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The Human Medicines Regulations 2012

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U.K.

Statutory Instruments

2012 No. 1916

Medicines

The Human Medicines Regulations 2012

Made

19th July 2012

Laid before Parliament

24th July 2012

Coming into force

14th August 2012

The Secretary of State and the Minister for Health, Social Services and Public Safety make the following Regulations. They do so in exercise of the powers conferred by section 2(2) and (5) of the European Communities Act 1972M1, having been designated for the purposes of section 2(2) of that Act in relation to medicinal productsM2 and to measures in the veterinary and phytosanitary fields for the protection of public healthM3. They do so in exercise also of the powers conferred by sections 87(1), 88(1) and (2), 91(2), and 129(1), (2) and (5) of the Medicines Act 1968M4, having consulted such organisations as appear to them to be representative of interests likely to be substantially affected by these Regulations in accordance with section 129(6) of that Act.

Modifications etc. (not altering text)

Marginal Citations

M11972 c.68. Section 2(2) was amended by section 27(1)(a) of the Legislative Reform Act 2006 (2006 c,51) and section 3(3) of and Part 1 of the Schedule to the European Union (Amendment) Act 2008 (2008 c.7). Section 2(5) was amended by section 41(1) of and Part 1 of Schedule 6 to the Northern Ireland Constitution Act 1973 (1973 c.36).

PART 1U.K.General

Citation and commencementU.K.

1.—(1) These Regulations may be cited as the Human Medicines Regulations 2012.

(2) These Regulations come into force on 14th August 2012.

Medicinal productsU.K.

2.—(1) In these Regulations “medicinal product” means—

(a)any substance or combination of substances presented as having properties of preventing or treating disease in human beings; or

(b)any substance or combination of substances that may be used by or administered to human beings with a view to—

(i)restoring, correcting or modifying a physiological function by exerting a pharmacological, immunological or metabolic action, or

(ii)making a medical diagnosis.

(2) These Regulations do not apply to—

(a)whole human blood; or

(b)any human blood component, other than plasma prepared by a method involving an industrial process.

Modifications etc. (not altering text)

C2Reg. 2 applied (with modifications) by The Medicines for Human Use (Clinical Trials) Regulations 2004 (S.I. 2004/1031), reg 47(1), Sch. 9 (as substituted (14.8.2012) by S.I. 2012/1916, reg. 1(2), Sch. 34 paras. 57(b), 64 (with Sch. 32))

Scope of these Regulations: special provisionsU.K.

3.—(1) Regulation 17(1) (manufacturing of medicinal products: requirement for licence) shall not apply in circumstances where paragraph (4) applies.

(2) Regulations 17(1) (manufacturing of medicinal products: requirement for licence) and 46 (requirement for authorisation) shall not apply in circumstances where paragraph (5) or (6) applies.

(3) These Regulations do not apply where paragraph (7) applies.

(4) This paragraph applies where a medicinal product is assembled by a registered nurse or a registered midwife if—

(a)the nurse or midwife is acting in the course of his or her profession; and

(b)the conditions in paragraphs (8) and (9) are met.

(5) This paragraph applies where a medicinal product is manufactured or assembled by a doctor or dentist and the conditions in paragraphs (8) and (9) are met.

(6) This paragraph applies where a herbal medicinal product is manufactured or assembled by a person (“A”) if—

(a)the manufacture or assembly takes place on premises occupied by A and from which A can exclude the public;

(b)the product is for administration to a person (“B”) and A has been requested by or on behalf of B, and in B's presence, to use A's judgment as to the treatment required;

(c)the product does not contain a substance specified in Part 1 of Schedule 20;

(d)the product does not contain a substance listed in Part 2 of that Schedule, unless the product is sold or supplied—

(i)in or from containers or packages labelled to show a dose not exceeding the maximum dose or maximum daily dose specified in column 2 of that Part, or

(ii)in the case of a product for external use only, with a percentage of the substance in the product that does not exceed the percentage specified in column 3 of that Part; and

(e)the condition in paragraph (9) is met.

(7) This paragraph applies where the product is a radionuclide that is in the form of a sealed source.

(8) This condition is that the medicinal product is supplied—

(a)to a patient in the course of the treatment of that patient; or

(b)in a case to which paragraph (5) applies, to a patient of another doctor or dentist who is a member of the same medical or dental practice.

(9) This condition is that the medicinal product is not manufactured or, as the case may be, assembled—

(a)on a large scale; or

(b)by an industrial process.

(10) Chapter 1 of Part 13 (requirements for packaging and package leaflets relating to medicinal products) does not apply to a medicinal product that is sold or supplied in circumstances where paragraph (11) or (12) applies in relation to the product, except to the extent set out in paragraph (14), but the requirements of paragraph (13) shall apply.

(11) This paragraph applies where a medicinal product is the result of a process of manufacture to which regulation 17(1) does not apply by virtue of paragraph (5) or (6).

(12) This paragraph applies in the case of a medicinal product where—

(a)the product is the result of a process of assembly of an authorised medicinal product;

(b)regulation 17(1) does not apply to the process of assembly by virtue of paragraph (4) or (5);

(c)the process of assembly results in a change in the presentation of the authorised medicinal product; and

(d)by reason of that change the product so assembled is not sold or supplied in accordance with the terms of—

(i)the marketing authorisation,

(ii)the certificate of registration,

(iii)the traditional herbal registration, or

(iv)the Article 126a authorisation,

that relates to the authorised medicinal product.

(13) The information specified in Part 1 of Schedule 26 must appear on the outer packaging, or, if there is no outer packaging, on the immediate packaging of a medicinal product that is sold or supplied in circumstances—

(a)where paragraph (11) applies to the product, except in the case of a product manufactured in accordance with paragraph (6); or

(b)where paragraph (12) applies in relation to the product.

(14) Regulations 269 (offences relating to packaging and package leaflets: other persons) and 271 (offences: penalties) shall have effect in relation to paragraph (13) as if that paragraph were a requirement of Part 13.

(15) For the purposes of this regulation and regulation 4 (special provisions for pharmacies etc), a medicinal product is authorised if there is in force for the product—

(a)a marketing authorisation;

(b)a certificate of registration;

(c)a traditional herbal registration; or

(d)an Article 126a authorisation.

Special provisions for pharmacies etcU.K.

4.—(1) Regulations 17(1) (manufacturing of medicinal products: requirement for licence) and 46 (requirement for authorisation) do not apply where any provision of section 10 of the Medicines Act 1968 M5 so provides.

(2) Chapter 1 of Part 13 (requirements for packaging and package leaflets relating to medicinal products) does not apply to a medicinal product that is sold or supplied in circumstances where paragraph (3) or (4) applies in relation to the product, except to the extent set out in paragraph (6), but the requirements of paragraph (5) shall apply.

(3) This paragraph applies in a case where a medicinal product is the result of a process of manufacture to which regulation 17(1) does not apply by virtue of any provision of section 10 of the Medicines Act 1968.

(4) This paragraph applies in the case of a medicinal product where—

(a)the product is the result of a process of assembly of a medicinal product that is an authorised medicinal product within the meaning of regulation 3(15);

(b)regulation 17(1) does not apply to the process of assembly by virtue of any provision of section 10 of the Medicines Act 1968;

(c)the process of assembly results in a change in the presentation of the authorised medicinal product; and

(d)by reason of that change the product so assembled is not sold or supplied in accordance with the terms of—

(i)the marketing authorisation,

(ii)the certificate of registration,

(iii)the traditional herbal registration, or

(iv)the Article 126a authorisation,

that relates to the authorised medicinal product.

(5) The information specified in Part 2 of Schedule 26 must appear on the outer packaging, or, if there is no outer packaging, on the immediate packaging of a medicinal product that is sold or supplied in circumstances where paragraph (3) or (4) applies in relation to the product.

(6) Regulations 269 (offences relating to packaging and package leaflets: other persons) and 271 (offences: penalties) shall have effect in relation to paragraph (5) as if that paragraph were a requirement of Part 13.

Marginal Citations

M5Section 10(1) was amended by paragraph 10(a) of Part 1 of Schedule 8 to S.I. 2006/2407, paragraph 5(a) of Schedule 3 to the Regulation of Care (Scotland) Act 2001, and article 3 of S.I. 1971/1445. Section 10(2) was repealed by paragraph 10(b) and (3)(b) was repealed by paragraph 10(c) of Part 1 of Schedule 8 to S.I. 2006/2407. Section 10(4) was amended and section 10(5) and (6) inserted by article 3 of S.I. 1971/1445. Section 10(6A) was repealed by paragraph 10(d) of Part 1 of Schedule 8 to S.I. 2006/2407. Section 10(7) was inserted by article 3 of S.I. 1971/1445, and amended by regulation 3 of S.I. 1993/834. Section 10(7A) to (7C) was inserted by the Health Act 2006 section 26(1), and section 10(7A) was amended by paragraph 10(e) of Part 1 of Schedule 8 to S.I. 2006/2407. Section 10(8) was inserted by S.I. 1971/1445 article 3. Section 10(9) was inserted by paragraph 5(a) of Schedule 3 to the Regulation of Care (Scotland) Act 2001.

Classification of medicinal productsU.K.

5.—(1) In these Regulations references to a medicinal product subject to general sale are to a product that is not a prescription only medicine or a pharmacy medicine but is—

(a)a product that is covered by an authorisation of which it is a term that the product is to be available on general sale; or

(b)a product that—

(i)is covered by an EU marketing authorisation, and

(ii)is not classified in the authorisation as a prescription only medicine, and

(iii)the licensing authority has determined should be available on general sale.

(2) In paragraphs (1)(a) and (5)(a) “authorisation” means—

(a)a UK marketing authorisation;

(b)a certificate of registration;

(c)a traditional herbal registration; or

(d)an Article 126a authorisation.

(3) In these Regulations references to a prescription only medicine are to any of the following—

(a)a medicinal product that is covered by an authorisation of which it is a term that the product is to be available only on prescription;

(b)a medicinal product that—

(i)is covered by an EU marketing authorisation, and

(ii)is classified in the authorisation as a prescription only medicine;

(c)a medicinal product that is a prescription only medicine by virtue of Part 1 of Schedule 1; or

(d)a medicinal product that is the result of—

(i)the assembly, or

(ii)the reformulation (including the combining with other substances),

of a medicinal product that is a prescription only medicine by virtue of sub-paragraph (a) or (b).

(4) In paragraph (3)(a) “authorisation” means—

(a)a UK marketing authorisation; or

(b)an Article 126a authorisation.

(5) In these Regulations references to a pharmacy medicine are to a medicinal product that is not a prescription only medicinal product or a medicinal product subject to general sale but is—

(a)covered by an authorisation of which it is a term that the product is to be available only from a pharmacy;

(b)a product that—

(i)is covered by an EU marketing authorisation, and

(ii)is not classified in the authorisation as a prescription only medicine,

other than a product to which paragraph (1)(b)(iii) applies;

(c)available only from a pharmacy by virtue of Part 2 of Schedule 1; or

(d)the result of—

(i)the assembly, or

(ii)the reformulation (including the combining with other substances),

of a medicinal product that is a pharmacy medicine by virtue of sub-paragraph (a) or (b).

The licensing authority and the MinistersU.K.

6.—(1) The licensing authority is responsible for the grant, renewal, variation, suspension and revocation of licences, authorisations, certificates and registrations under these Regulations.

(2) In these Regulations “the licensing authority” means either or both of the Ministers.

(3) Any function that—

(a)is conferred on “the licensing authority” by these Regulations; or

(b)is a function within paragraph (4),

may be exercised by either of the Ministers acting alone or by both of them acting jointly.

(4) The functions of a member State, or of the competent authority of a member State, under any of the relevant EU provisions are to be exercised by the licensing authority if—

(a)they relate to medicinal products; and

(b)they are to be exercised by, or by any authority of, the United Kingdom.

(5) Paragraph (4) does not apply to any function that is conferred by these Regulations on a person or body other than the licensing authority.

(6) In these Regulations “the Ministers” means—

(a)the Secretary of State; and

(b)the Minister for Health, Social Services and Public Safety.

(7) Any function that is conferred on “the Ministers” by these Regulations is to be exercised by the Ministers acting jointly.

(8) Paragraph (7) does not apply where these Regulations provide for a function of the Ministers to be exercised by either of them acting alone or both of them acting jointly.

Advertisements relating to medicinal productsU.K.

7.—(1) In these regulations “advertisement”, in relation to a medicinal product, includes anything designed to promote the prescription, supply, sale or use of that product.

(2) This includes, in particular, the following activities—

(a)door-to-door canvassing;

(b)visits by medical sales representatives to persons qualified to prescribe or supply medicinal products;

(c)the supply of samples;

(d)the provision of inducements to prescribe or supply medicinal products by the gift, offer or promise of any benefit or bonus, whether in money or in kind, except where the intrinsic value of such inducements is minimal;

(e)the sponsorship of promotional meetings attended by persons qualified to prescribe or supply medicinal products; and

(f)the sponsorship of scientific congresses attended by persons qualified to prescribe or supply medicinal products, including the payment of their travelling and accommodation expenses in that connection.

(3) But references in these Regulations to an “advertisement” do not include any of the following—

(a)a medicinal product's package or package leaflet;

(b)reference material and announcements of a factual and informative nature, including—

(i)material relating to changes to a medicinal product's package or package leaflet,

(ii)adverse reaction warnings,

(iii)trade catalogues, and

(iv)price lists,

provided that no product claim is made; or

(c)correspondence, which may be accompanied by material of a non-promotional nature, answering a specific question about a medicinal product.

(d)In this regulation “person qualified to prescribe or supply medicinal products” has the meaning given in regulation 277(1) (interpretation: Part 14 advertising).

General interpretationU.K.

8.—(1) In these Regulations (unless the context otherwise requires)—

[F1“the 2001 Directive” means Directive 2001/83/EC of the European Parliament and of the Council on the Community Code relating to medicinal products for human use;]

[F2“active substance” means any substance or mixture of substances intended to be used in the manufacture of a medicinal product and that, when used in its production, becomes an active ingredient of that product intended to exert a pharmacological, immunological or metabolic action with a view to restoring, correcting or modifying physiological functions or to make a medical diagnosis;]

administer” means administer to a human being—

(a)

orally, by injection, or by introduction into the body in any other way; or

(b)

by external application (whether or not by direct application to the body),

and any reference in these Regulations to administering anything is to administering it in its existing state or after it has been dissolved or dispersed in, or diluted or mixed with, a substance used as a vehicle;

advanced therapy medicinal product” means a medicinal product described in Article 2(1)(a) of Regulation (EC) No 1394/2007;

adverse reaction” means a response to a medicinal product that is noxious and unintended;

advisory body” has the meaning given by regulation 12(1);

appropriate practitioner” means an appropriate practitioner within the meaning of regulation 214;

Article 126a authorisation” means an authorisation granted by the licensing authority under Part 8 of these Regulations;

[F3“assemble”, in relation to a medicinal product or an active substance, includes the various processes of dividing up, packaging and presentation of the product or substance, and “assembly” has a corresponding meaning;]

“biological medicinal product” and “biological substance” have the meaning given in the third indent of paragraph 3.2.1.1.(b) of Annex I to the 2001 Directive;

blood component” means any of the following—

(a)

red cells;

(b)

white cells;

(c)

platelets; and

(d)

plasma;

the British Pharmacopoeia” means the British Pharmacopoeia referred to in regulation 317;

[F4“brokering” means all activities in relation to the sale or purchase of medicinal products, except for wholesale distribution, that do not include physical handling and that consist of negotiating independently and on behalf of another legal or natural person;]

business” includes—

(a)

a professional practice;

(b)

any activity carried on by a body of persons whether corporate or unincorporated; and

(c)

the provision of services by or on behalf of the Secretary of State, the Minister for Health, Social Services and Public Safety, the Welsh Ministers or the Scottish Ministers as the case may be under the following enactments—

(i)

the National Health Service Act 2006 M6,

(ii)

the Health and Personal Social Services (Northern Ireland) Order 1972 M7 and the Health and Social Care (Reform) Act (Northern Ireland) 2009 M8,

(iii)

the National Health Service (Wales) Act 2006 M9,

(iv)

the National Health Service (Scotland) Act 1978 M10;

certificate of registration” means a certificate of registration granted by the licensing authority under Part 6 of these Regulations;

clinical management plan” means a written plan relating to the treatment of an individual patient and agreed by—

(a)

the patient;

(b)

the doctor or dentist who is a party to the plan; and

(c)

any supplementary prescriber who is to prescribe, give directions for administration or administer under the plan;

clinical trial” has the meaning given by regulation 2 of the Clinical Trials Regulations;

the Clinical Trials Directive” means Directive 2001/20/EC of the European Parliament and of the Council on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use M11;

the Clinical Trials Regulations” means the Medicines for Human Use (Clinical Trials) Regulations 2004 M12;

the Commission” has the meaning given by regulation 9(1);

common name” in relation to a medicinal product, active substance or excipient means—

(a)

its international non-proprietary name recommended by the World Health Organisation; or

(b)

if such a name does not exist, its usual common name;

community practitioner nurse prescriber” means a person—

(a)

who is a registered nurse or a registered midwife; and

(b)

against whose name is recorded in the professional register an annotation signifying that the person is qualified to order drugs, medicines and appliances from the Nurse Prescribers' Formulary for Community Practitioners in the current edition of the British National Formulary;

contravention” includes failure to comply (and “contravene” has a corresponding meaning);

cosmetic” means any substance or preparation intended to be applied to the surfaces of the human body (including the epidermis, pilary system and hair, nails, lips and external genital organs), or the teeth or buccal mucosa, wholly or mainly for the purpose of—

(a)

perfuming them;

(b)

cleansing them;

(c)

protecting them;

(d)

caring for them or keeping them in condition;

(e)

modifying their appearance (for aesthetic purposes or otherwise); or

(f)

combating body odours or normal body perspiration;

dentist” means a person registered in the dentists register under section 14 of the Dentists Act 1984 M13;

Directive 2002/98/EC” means Directive 2002/98/EC of the European Parliament and of the Council of 27 January 2003 setting standards of quality and safety for the collection, testing, processing, storage and distribution of human blood and blood components and amending Directive 2001/83/EC M14;

Directive 2004/23/EC” means Directive 2004/23/EC of the European Parliament and of the Council of 31 March 2004 on setting standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells M15;

disease” includes any injury, ailment or adverse condition, whether of body or mind;

doctor” means a registered medical practitioner;

effervescent”, in relation to a tablet or capsule, means containing not less than 75 per cent, by weight of the tablet or capsule, of ingredients included wholly or mainly for the purpose of releasing carbon dioxide when the tablet or capsule is dissolved or dispersed in water;

electronic communication” means a communication transmitted (whether from one person to another, from one device to another or from a person to a device or vice versa)—

(a)

by means of an electronic communications network within the meaning of section 32(1) of the Communications Act 2003 M16; or

(b)

by other means but while in an electronic form;

the EMA” means the European Medicines Agency established by Regulation (EC) No 726/2004;

enactment” includes primary and secondary legislation of the devolved administrations in Wales, Scotland and Northern Ireland;

enforcement authority” means the Secretary of State, the Minister for Health, Social Services and Public Safety or a person on whom a function of enforcing a provision of these Regulations has been conferred by virtue of regulations 323 or 324;

EU marketing authorisation” means a marketing authorisation granted or renewed by the European Commission under Regulation (EC) No 726/2004;

“European Economic Area” or “EEA” means the European Economic Area created by the EEA agreement;

the European Pharmacopoeia” means the European Pharmacopoeia published by the European Directorate for the Quality of Medicines;

[F5“excipient” means any constituent of a medicinal product other than the active substance and the packaging material;]

exempt advanced therapy medicinal product” has the meaning given in regulation 171;

expert advisory group” has the meaning given by regulation 14(1);

[F6“export” means export, or attempt to export, from the United Kingdom, whether by land, sea or air;]

[F7“falsified medicinal product” means any medicinal product with a false representation of—

(a)

its identity, including its packaging and labelling, its name or its composition (other than any unintentional quality defect) as regards any of its ingredients including excipients and the strength of those ingredients;

(b)

its source, including its manufacturer, its country of manufacturing, its country of origin or its marketing authorisation holder; or

(c)

its history, including the records and documents relating to the distribution channels used;

Fees Regulations” means the Medicines (Products for Human Use) (Fees) Regulations 2013;]

the Good Manufacturing Practice Directive” means Commission Directive 2003/94/EC of 8 October 2003 laying down the principles and guidelines of good manufacturing practice in respect of medicinal products for human use and investigational medicinal products for human use M17;

the Health and Care Professions Council register” means the register established and maintained by the Health and Care Professions Council under article 5 of the Health and Social Work Professions Order 2001 M18;

health care professional” means—

(a)

a doctor;

(b)

a dentist;

(c)

a pharmacist;

(d)

a pharmacy technician registered in Part 2 or 5 of the Register of pharmacists and pharmacy technicians established and maintained under article 19(2) of the Pharmacy Order 2010 M19;

(e)

a registered nurse;

(f)

a registered midwife;

(g)

a registered optometrist;

(h)

a registered osteopath as defined in section 41 of the Osteopaths Act 1993 M20;

(i)

a registered chiropractor as defined in section 43 of the Chiropractors Act 1994 M21;

(j)

a person registered as a member of a relevant profession within the meaning of article 2 and paragraph 1 of Schedule 3 to the Health and Social Work Professions Order 2001 M22, other than a social worker, in the Health and Care Professions Council register; or

(k)

a person registered in the dental care professionals register established and maintained under section 36B of the Dentists Act 1984 M23 as a member of a profession complementary to dentistry specified by regulation 2 of the General Dental Council (Professions Complementary to Dentistry) Regulations 2006 M24;

health centre” means a health centre maintained under—

(a)

section 2 or 3 of the National Health Service Act 2006 M25;

(b)

section 2 or 3 of the National Health Service (Wales) Act 2006 M26;

(c)

section 36(1)(b) of the National Health Service (Scotland) Act 1978 M27; or

(d)

article 5 of the Health and Personal Social Services (Northern Ireland) Order 1972 M28;

herbal medicinal product” means a medicinal product whose only active ingredients are herbal substances or herbal preparations (or both);

herbal preparation” means a preparation obtained by subjecting herbal substances to processes such as extraction, distillation, expression, fractionation, purification, concentration or fermentation, and includes a comminuted or powdered herbal substance, a tincture, an extract, an essential oil, an expressed juice or a processed exudate;

herbal substance” means a plant or part of a plant, algae, fungi or lichen, or an unprocessed exudate of a plant, defined by the plant part used and the botanical name of the plant, either fresh or dried, but otherwise unprocessed;

homoeopathic medicinal product” means a medicinal product prepared from homoeopathic stocks in accordance with a homoeopathic manufacturing procedure described by—

(a)

the European Pharmacopoeia; or

(b)

in the absence of such a description in the European Pharmacopoeia, in any pharmacopoeia used officially in an EEA State;

hospital” includes a clinic, nursing home or similar institution;

immediate packaging” in relation to a medicinal product means the container or other form of packaging immediately in contact with the medicinal product;

[F8“import” means import, or attempt to import, into the United Kingdom, whether by land, sea or air;]

inspector” means a person authorised in writing by an enforcement authority for the purposes of Part 16 (enforcement) (and references to “the enforcement authority”, in relation to an inspector, are to the enforcement authority by whom the inspector is so authorised);

intermediate product” means a substance which—

(a)

has been manufactured for use in the manufacture of medicinal products; and

(b)

is intended for further processing by a manufacturer of such products;

investigational medicinal product” has the meaning given in regulation 2(1) of the Clinical Trials Regulations;

labelling” in relation to a container or package of medicinal products means affixing to or otherwise displaying on it a notice describing or otherwise relating to the contents (and “label” has a corresponding meaning);

the licensing authority” has the meaning given by regulation 6(2);

manufacture”, in relation to a medicinal product, includes any process carried out in the course of making the product, but does not include dissolving or dispersing the product in, or diluting or mixing it with, a substance used as a vehicle for the purpose of administering it;

manufacturer's licence” has the meaning given by regulation 17(1);

marketing authorisation” means—

(a)

a UK marketing authorisation; or

(b)

an EU marketing authorisation;

medicinal product subject to general sale” has the meaning given in regulation 5(1) (classification of medicinal products);

the Ministers” is to be construed in accordance with regulation 6(6) to (8);

name” in relation to a medicinal product means—

(a)

where the product has a UK marketing authorisation or traditional herbal registration, the name—

(i)

as approved by the licensing authority in granting the authorisation or registration, or

(ii)

where that name has been varied since that approval, as so amended;

(b)

where the product has an EU marketing authorisation, the name—

(i)

as approved by the European Commission in granting the authorisation, or

(ii)

where that name has been varied since that approval, as so amended; and

(c)

where the product has an Article 126a authorisation, the name—

(i)

as approved by the licensing authority to appear on the packaging and any package leaflet of the product under the authorisation, or

(ii)

where that name has been varied since that approval, as so amended;

the Narcotic Drugs Convention” means the Single Convention on Narcotic Drugs signed by the United Kingdom on 30thMarch 1961 as amended by the Protocol Amending the Single Convention on Narcotic Drugs signed by the United Kingdom on 25th March 1972;

NHS primary dental services” means—

(a)

in relation to England, primary dental services under the National Health Service Act 2006;

(b)

in relation to Wales, primary dental services under the National Health Service (Wales) Act 2006;

(c)

in relation to Scotland, dental services under the National Health Service (Scotland) Act 1978 or personal dental services in connection with a pilot scheme under the National Health Service (Primary Care) Act 1997 M29; and

(d)

in relation to Northern Ireland, general dental services under the Health and Personal Social Services (Northern Ireland) Order 1972 or personal dental services in connection with a pilot scheme under the Health Services (Primary Care) (Northern Ireland) Order 1997 M30;

NHS primary medical services” means—

(a)

in relation to England, primary medical services under the National Health Service Act 2006;

(b)

in relation to Wales, primary medical services under the National Health Service (Wales) Act 2006;

(c)

in relation to Scotland, primary medical services under the National Health Service (Scotland) Act 1978; and

(d)

in relation to Northern Ireland, primary medical services under the Health and Personal Social Services (Northern Ireland) Order 1972;

nurse independent prescriber” means a person who—

(a)

is a registered nurse or registered midwife; and

(b)

is noted in the professional register as qualified to order drugs, medicines and appliances as a nurse independent prescriber or a nurse independent / supplementary prescriber;

optometrist independent prescriber” means a person—

(a)

who is a registered optometrist; and

(b)

against whose name is recorded in the relevant register an annotation signifying that the person is qualified to order drugs, medicines and appliances as an optometrist independent prescriber;

outer packaging” in relation to a medicinal product means any packaging into which the immediate packaging of the medicinal product is placed;

package” in relation to a medicinal product, includes—

(a)

a container of the product;

(b)

any box, packet or other article in which one or more containers of the product are or are to be enclosed; and

(c)

any box, packet or other article in which a box, packet or other article mentioned in paragraph (b) or this paragraph is or is to be enclosed;

package leaflet” in relation to a medicinal product, means a leaflet that accompanies the product and contains information for the user of the product;

paediatric clinical trial” means a clinical trial conducted in whole or in part on persons under the age of 18 years;

paediatric investigation plan” means a research and development programme with the purpose of generating data determining the conditions in which a medicinal product may be authorised to treat persons under the age of 18 years;

the Paediatric Regulation” means Regulation (EC) No 1901/2006 of the European Parliament and of the Council of 12 December 2006 on medicinal products for paediatric use and amending Regulation (EEC) No 1768/92, Directive 2001/20/EC, Directive 2001/83/EC and Regulation (EC) No 726/2004 M31;

“periodic safety update report” or “PSUR” has the meaning given in regulation 191 (obligation on holder to submit periodic safety update reports: general requirements);

pharmacist” means—

(a)

in relation to Great Britain a person registered in Part 1 or 4 of the Register of pharmacists and pharmacy technicians maintained under article 19(2) of the Pharmacy Order 2010 M32; and

(b)

in relation to Northern Ireland a person registered in the register of pharmaceutical chemists for Northern Ireland or the register of visiting pharmaceutical chemists from a relevant European State maintained under articles 6 and 9 of the Pharmacy (Northern Ireland) Order 1976 M33;

pharmacist independent prescriber” means a person who—

(a)

is a pharmacist; and

(b)

is noted in the relevant register as qualified to order drugs, medicines and appliances as a pharmacist independent prescriber;

the Pharmacovigilance Risk Assessment Committee” means the committee of the EMA established by Article 56(1)(aa) of Regulation (EC) No 726/2004;

pharmacovigilance system” means a system used by the holder of a marketing authorisation, traditional herbal registration or Article 126a authorisation, or by the licensing authority, to fulfil the tasks and responsibilities set out in Part 11 and designed to monitor the safety of authorised or registered medicinal products and detect any change to their risk-benefit balance;

pharmacovigilance system master file” means a detailed description of the pharmacovigilance system used by the holder of a marketing authorisation, traditional herbal registration or Article 126a authorisation with respect to one or more authorised or registered medicinal products;

pharmacy medicine” has the meaning given in regulation 5(5) (classification of medicinal products);

[F9“physiotherapist independent prescriber” means a person—

(a)

who is a registered physiotherapist; and

(b)

against whose name is recorded in the relevant register an annotation signifying that the person is qualified to order drugs, medicines and appliances as a physiotherapist independent prescriber;

“podiatrist independent prescriber” means a person—

(a)

who is a registered podiatrist; and

(b)

against whose name is recorded in the relevant register an annotation signifying that the person is qualified to order drugs, medicines and appliances as a podiatrist independent prescriber;]

post-authorisation efficacy study” means any study relating to a medicinal product to which a marketing authorisation relates that is conducted with the aim of considering the efficacy of that product;

post-authorisation safety study” means any study relating to a medicinal product to which a marketing authorisation, traditional herbal registration or Article 126a authorisation relates that is conducted with the aim of—

(a)

identifying, characterising or quantifying a safety hazard;

(b)

confirming the safety profile of the medicinal product; or

(c)

measuring the effectiveness of risk management measures;

prescription only medicine” has the meaning given in regulation 5(3) (classification of medicinal products);

product information” in relation to a medicinal product means—

(a)

the summary of the product characteristics;

(b)

the immediate and outer packaging; and

(c)

the package leaflet;

the professional register” means the register maintained by the Nursing and Midwifery Council under article 5 of the Nursing and Midwifery Order 2001 M34;

the Psychotropic Substances Convention” means the Convention on Psychotropic Substances signed by the United Kingdom on 21st February 1971;

“qualified person”, except in relation to the expression “appropriately qualified person”, means—

(a)

a person who satisfies the requirements specified in Part 1 or 2 of Schedule 7; or

(b)

where an application for a licence is made before 30th April 2013, in so far as the application relates to activities in respect of traditional herbal medicinal products, a person who has been engaged in activities in respect of traditional herbal medicinal products equivalent to those in Part 3 of Schedule 7 on or before 30th April 2011 and continues to be so engaged at the time when the application is made;

radionuclide” means a radioactive isotope;

radionuclide generator” means any system incorporating a fixed parent radionuclide from which is produced a daughter radionuclide which is to be removed by elution or by any other method and is to be used in a radiopharmaceutical;

radionuclide kit” means any preparation to be reconstituted or combined with radionuclides in the final radiopharmaceutical, usually prior to its administration;

radionuclide precursor” means any radionuclide produced for the radio-labelling of another substance prior to administration, other than a radionuclide that is incorporated in or produced from a generator or is included in a radiopharmaceutical;

radiopharmaceutical” means a medicinal product which, when ready for use, contains one or more radionuclides included for a medicinal purpose;

registered midwife” means a person registered in the Midwives Part of the professional register;

registered nurse” means a person registered in the Nurses Part or the Specialist Community Public Health Nurses Part of the professional register;

registered optometrist” means a person whose name is entered in the register of optometrists maintained under section 7(a) of the Opticians Act 1989 M35 or the register of visiting optometrists from relevant European States maintained under section 8B(1)(a) M36 of that Act;

registered pharmacy” means—

(a)

in relation to Great Britain, premises entered in the register required to be kept under article 19 of the Pharmacy Order 2010 for the purposes of sections 74A and 74J of the Medicines Act 1968 M37; and

(b)

in relation to Northern Ireland, premises entered in the register required to be kept under section 75 M38 of the Medicines Act 1968;

registrable homoeopathic medicinal product” means a homoeopathic medicinal product to which regulation 102 applies;

[F10“Regulation (EC) No 726/2004” means Regulation (EC) 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency;]

Regulation (EC) No 1394/2007” means Regulation (EC) No 1394/2007 of the European Parliament and of the Council of 13 November 2007 on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004 M39;

Regulation (EC) No 1234/2008” means Commission Regulation (EC) No 1234/2008 of 24 November 2008 concerning the examination of variations to the terms of marketing authorisations for medicinal products for human use and veterinary medicinal products M40;

the relevant EU provisions” means the provisions of legislation of the European Union relating to medicinal products for human use, except to the extent that any other enactment provides for any function in relation to any such provision to be exercised otherwise than by the licensing authority;

relevant European State” means an EEA State or Switzerland;

relevant medicinal product” has the meaning given by regulation 48;

the relevant register” means—

(a)

in relation to a pharmacist—

(i)

in Great Britain, Part 1 of the Register of pharmacists and pharmacy technicians maintained under article 19(2) of the Pharmacy Order 2010, or

(ii)

in Northern Ireland, the register maintained in pursuance of articles 6 and 9 of the Pharmacy (Northern Ireland) Order 1976;

(b)

in relation to a registered nurse or registered midwife, the professional register;

(c)

in relation to a registered optometrist, the register of optometrists maintained under section 7(a) of the Opticians Act 1989 or the register of visiting optometrists from relevant European States maintained under section 8B(1)(a) of that Act; and

(d)

in relation to a chiropodist or podiatrist, a physiotherapist or a radiographer, the part of the Health and Care Professions Council register relating to—

(i)

chiropodists and podiatrists,

(ii)

physiotherapists, or

(iii)

radiographers;

retail pharmacy business” means a business (other than a professional practice carried on by a doctor or dentist) which consists of or includes the retail sale of medicinal products that are not subject to general sale;

risk management plan” means a detailed description of the risk management system;

risk management system” means a set of pharmacovigilance activities and interventions designed to identify, characterise, prevent or minimise risks relating to a medicinal product, including an assessment of the effectiveness of those activities and interventions;

serious adverse reaction” means an adverse reaction that—

(a)

results in a person's death;

(b)

threatens a person's life;

(c)

results in a person being hospitalised as an inpatient or prolongs a person's existing stay in hospital;

(d)

results in a person's persistent or significant disability or incapacity; or

(e)

results in a congenital anomaly or birth defect;

special medicinal product” means a product within the meaning of regulation 167 or any equivalent legislation in an EEA State other than the United Kingdom;

substance” means any matter regardless of its origins and includes—

(a)

human substances (such as human blood and human blood products);

(b)

animal substances (such as micro-organisms, whole animals, parts of organs, animal secretions, toxins, extracts and blood products);

(c)

vegetable substances (such as micro-organisms, plants, parts of plants, vegetable secretions and extracts);

(d)

chemical substances (such as elements, naturally occurring chemical materials and chemical products obtained by chemical change or synthesis); and

(e)

gases and vapours;

the summary of the product characteristics” in relation to a medicinal product means—

(a)

where the product has a UK marketing authorisation or traditional herbal registration, the summary of the product characteristics—

(i)

as approved by the licensing authority in granting the authorisation or registration, or

(ii)

where the summary has been varied since that approval, as so amended; or

(b)

where the product has an EU marketing authorisation, the summary of the product characteristics—

(i)

as approved by the European Commission in granting the authorisation, or

(ii)

where the summary has been varied since that approval, as so amended;

supplementary prescriber” means a person who is noted in the relevant register as qualified to order drugs, medicines and appliances as a supplementary prescriber (or, in the case of a registered nurse or registered midwife, as a nurse independent/supplementary prescriber) and is—

(a)

a pharmacist;

(b)

a registered midwife;

(c)

a registered nurse;

(d)

a chiropodist, podiatrist, physiotherapist or radiographer; or

(e)

a registered optometrist;

suspected” in relation to an adverse reaction means that there is at least a reasonable possibility of there being a causal relationship between a medicinal product and an adverse event;

third country” means a country or territory outside the EEA:

traditional herbal medicinal product” means a herbal medicinal product to which regulation 125 applies;

traditional herbal registration” means a traditional herbal registration granted by the licensing authority under these Regulations;

UK marketing authorisation” means a marketing authorisation granted by the licensing authority under—

(a)

Part 5 of these Regulations; or

(b)

Chapter 4 of Title III to the 2001 Directive (mutual recognition and decentralised procedure);

vaccine” means an antigenic substance which consists wholly or partly of—

(a)

any micro-organisms, viruses or other organisms in any state;

(b)

any toxins of microbial origin which have been detoxified (toxoids); or

(c)

any extracts or derivatives of any micro-organisms or of any viruses,

being substances which, when administered to human beings, are used for the prevention of specific diseases;

wholesale dealer's licence” has the meaning given by regulation 18(1).

(2) In these Regulations, references to distribution of a product by way of wholesale dealing are to be construed in accordance with regulation 18(7) and (8).

(3) In these Regulations, references to selling by retail, or to retail sale, are references to selling a product to a person who buys it otherwise than for a purpose specified in regulation 18(8).

(4) In these Regulations, references to supplying anything in circumstances corresponding to retail sale are references to supplying it, otherwise than by way of sale, to a person who receives it otherwise than for a purpose specified in regulation 18(8);

(5) References in these Regulations to the terms of—

(a)a marketing authorisation include the information supplied in relation to the authorisation in accordance with—

(i)regulation 50 and Schedule 8, and

(ii)(if appropriate) Schedule 10 (national homoeopathic products),

as updated in accordance with regulation 57, as approved upon grant under regulation 49 and as varied under regulation 68;

(b)a certificate of registration include the information supplied in relation to the certificate in accordance with regulation 103, as approved upon grant under regulation 103 and as varied under regulation 110; and

(c)a traditional herbal registration include the information supplied in relation to the registration in accordance with regulation 128 and Schedule 12, as updated in accordance with regulation 129, as approved upon grant under regulation 127 and as varied under regulation 135.

(6) References in these Regulations to a condition of—

(a)a marketing authorisation is to a condition to which the authorisation is subject by virtue of regulation 59(1) or 60(1); and

(b)a certificate of registration is to a condition to which the certificate is subject by virtue of regulation 105(1).

(7) For the purposes of these Regulations medicinal products are of the same description if—

(a)they are manufactured to the same specification, and

(b)they are in the same pharmaceutical form.

[F11(8) References in these Regulations to—

(a)good manufacturing practice for active substances relate to the principles and guidelines for good manufacturing practice adopted by the European Commission under the third paragraph of Article 47 of the 2001 Directive;

(b)good distribution practice for active substances relate to the guidelines on good distribution practices for active substances adopted by the European Commission under the fourth paragraph of Article 47 of the 2001 Directive.]

Modifications etc. (not altering text)

C3Reg. 8(1) applied (with modifications) by The Medicines for Human Use (Clinical Trials) Regulations 2004 (S.I. 2004/1031), reg 47(1), Sch. 9 (as substituted (14.8.2012) by S.I. 2012/1916, reg. 1(2), Sch. 34 paras. 57(b), 64 (with Sch. 32))

Marginal Citations

M11OJ No L 121, 1.5.2001, p.34. Directive 2001/20/EC was last amended by Regulation (EC) No 596/2009 (OJ No L 188, 18.7.2009, p.14).

M12S.I. 2004/1031, to which there are amendments not relevant to these Regulations.

M131984 c.24. Section 14 was substituted by the Dentists Act 1984 (Amendment) Order 2005 (S.I. 2005/2011) articles 2 and 6 and further amended by the European Qualifications (Health and Social Care Professions) Regulations 2007 (S.I. 2007/3101), regulations 109 and 111. Other amendments of the Dentists Act are not relevant to these Regulations.

M14OJ No L 33, 8.2.2003, p. 30.

M15OJ No L 102, 7.4.2004, p. 48.

M17OJ L 91, 30.3.2004, p.25.

M18S.I. 2002/254, as amended by S.I. 2009/1182. There are other amendments that are not relevant.

M201993 c.21. Section 41 was amended by S.I. 2007/3101 regulations 206 and 214.

M231984 c.24. Section 36B was inserted by S.I. 2005/2011, articles 2(1) and 29.

M271978 c.29. Concurrent functions under section 36(1) were transferred to the National Waiting Times Board by article 4(2)(c) and (4) of S.S.I. 2002/305.

M28S.I. 1972/1265 (N.I. 14), as amended by S.I. 1984/1158 (N.I. 8), S.I. 1986/595 ( N.I. 4) and 2004/311 (N.I. 2).

M31OJ No L 378, 27.12.2006, p.1. Regulation (EC) No 1901/2006, as amended by Regulation (EC) No 1902/2006 (OJ No L 378, 27.12.2006, p.20) .

M351989 c.44; section 7(a) was amended by S.I. 2005/848, articles 2 and 7(1).

M36Section 8B was inserted by S.I. 2007/3101, regulations 178 and 180.

M371968 c.67. Sections 74A and 74J were inserted by article 68 of and paragraph 1 of Schedule 4 to S.I. 2010/231.

M38Section 75 was amended by article 68 of and paragraph 1 of Schedule 4 to S.I. 2010/231

M39OJ No L 324, 10.12.2007, p.121.

M40OJ No L 334, 12.12.2008, p.7.

PART 2U.K.Administration

Commission on Human MedicinesU.K.

9.—(1) There is to continue to be a body known as the Commission on Human Medicines (referred to in these Regulations as “the Commission”).

(2) The Commission is to perform the functions conferred on it by these Regulations.

(3) The Commission is to have at least eight members.

(4) The members of the Commission are to be appointed by the Ministers.

(5) The Ministers must appoint one of the members of the Commission to chair it.

(6) The Ministers must consult the Scottish Ministers before exercising their functions under paragraphs (4) and (5).

Functions of the CommissionU.K.

10.—(1) The Commission must give advice to either or both of the Ministers in relation to the matters listed in paragraph (2) if—

(a)the Minister, or Ministers, request it; or

(b)the Commission considers it appropriate to give it.

(2) The matters mentioned in paragraph (1) are matters—

(a)relating to the execution of any duty imposed by these Regulations or the Clinical Trials Regulations;

(b)relating to the exercise of any power conferred by these Regulations or the Clinical Trials Regulations; or

(c)otherwise relating to medicinal products.

(3) Without prejudice to paragraphs (1) and (2), or to any other functions conferred on the Commission by or under these Regulations, the Commission must—

(a)give advice with respect to the safety, quality and efficacy of medicinal products; and

(b)promote the collection and investigation of information relating to adverse reactions, for the purposes of enabling such advice to be given.

(4) The Commission must also advise the licensing authority if—

(a)the licensing authority is required under Schedule 11 (advice and representations) or the Clinical Trials Regulations to consult the Commission about any matter arising under those provisions; or

(b)the licensing authority consults the Commission about any matter arising under those provisions.

British Pharmacopoeia CommissionU.K.

11.—(1) There is to continue to be a committee called the British Pharmacopoeia Commission (referred to as “the BPC” in this regulation).

(2) The BPC is to continue to have the following functions—

(a)the preparation under regulation 317(1) of editions of the British Pharmacopoeia;

(b)the preparation of compendia under regulation 317(3);

(c)the preparation under regulation 318 (which provides for the preparation and publication of lists of names to be used as headings to monographs in the British Pharmacopoeia) of lists of names; and

(d)the preparation of any other document under regulation 319.

(3) The BPC is to have at least eight members.

(4) The members of the BPC are to be appointed by the Ministers.

(5) The Ministers must appoint one of the members of the BPC to chair it.

(6) The Ministers must consult the Scottish Ministers before exercising their functions under paragraphs (4) and (5).

(7) In this regulation, a reference to preparation includes revision or amendment.

Reporting to MinistersU.K.

12.—(1) In this Part “advisory body” means—

(a)the Commission, or

(b)the British Pharmacopoeia Commission.

(2) Each advisory body must give a report to the Ministers each year about—

(a)the performance of its functions; and

(b)the performance of the functions of any expert advisory group appointed by it under regulation 14 (including any expert advisory group appointed jointly with the other advisory body).

(3) Each advisory body must give its report to the Ministers at the time specified by the Ministers.

(4) The Secretary of State must lay a copy of each report before Parliament.

Co-option of additional members of advisory bodiesU.K.

13.—(1) An advisory body may co-opt one or more additional members for the purposes of a meeting.

(2) A person co-opted as a member of an advisory body for the purposes of a meeting ceases to be a member at the end of the meeting.

Appointment of expert advisory groupsU.K.

14.—(1) An advisory body, or the advisory bodies acting jointly, may with the approval of the licensing authority appoint one or more sub-committees, to be known as expert advisory groups.

(2) The licensing authority may direct an advisory body to appoint an expert advisory group to advise on the matters specified in the direction.

(3) An expert advisory group may include, or consist of, persons who are not members of the advisory body or bodies which appointed the expert advisory group.

(4) The advisory body or bodies which appointed the expert advisory group must appoint a member of the group as its chair.

(5) The chair of an expert advisory group may co-opt additional members of the group for the purposes of a meeting.

(6) Before co-opting additional members under paragraph (5) the chair of the group must consult the chair of the advisory body or bodies which appointed the group.

(7) A person co-opted as a member of an expert advisory group for the purposes of a meeting ceases to be a member of the group at the end of the meeting.

Delegation of functions to expert advisory groupsU.K.

15.—(1) An advisory body may delegate any of its functions, other than the functions specified in paragraph (2), to an expert advisory group.

(2) The functions which may not be delegated are functions of providing advice to the licensing authority in any case where the licensing authority is required to consult the advisory body under—

(a)Schedule 11 (advice and representations); and

(b)the Clinical Trials Regulations.

(3) But an advisory body may arrange for an expert advisory group to provide advice to the advisory body in relation to the performance of a function referred to in paragraph (2).

Further provision about advisory bodies and expert advisory groups etcU.K.

16.  Schedule 2 (which makes further provision about advisory bodies and expert advisory groups, and provision about payment and expenses of expert committees appointed by the licensing authority) has effect.

PART 3U.K.[F12Manufacture and distribution of medicinal products and active substances

F12 Pt. 3 heading and Pt. 3 Ch. 1 inserted (20.8.2013) by The Human Medicines (Amendment) Regulations 2013 (S.I. 2013/1855), regs. 1(1), 4

CHAPTER 1U.K.Interpretation

InterpretationU.K.

A17.  In this Part “manufacture”, in relation to an active substance, includes any process carried out in the course of making the substance and the various processes of dividing up, packaging, and presentation of the active substance.]

[F13CHAPTER 2]U.K.Manufacturing and wholesale dealing

Grant etc of licencesU.K.

Manufacturing of medicinal productsU.K.

17.—(1) A person may not except in accordance with a licence (a “manufacturer's licence”)—

(a)manufacture, assemble or import from a state other than an EEA State any medicinal product; or

(b)possess a medicinal product for the purpose of any activity in sub-paragraph (a).

(2) Paragraph (1) is subject to paragraphs (3) to (5).

(3) Paragraph (1) applies in relation to an investigational medicinal product only—

(a)if the product has a marketing authorisation, Article 126a authorisation, certificate of registration or traditional herbal registration; and

(b)to the extent that the manufacture or assembly of the product is in accordance with the terms and conditions of that authorisation, certificate or registration.

(4) In paragraph (3), “marketing authorisation” means—

(a)a marketing authorisation issued by a competent authority in accordance with the 2001 Directive; or

(b)an EU marketing authorisation.

(5) Paragraph (1) does not apply to a person who, in connection with the importation of a medicinal product from a state other than an EEA State—

(a)provides facilities solely for transporting the product; or

(b)acting as an import agent, imports the medicinal product solely to the order of another person who holds a manufacturer's licence authorising the importation of the product.

(6) Paragraph (1) does not apply to a person who imports a medicinal product for administration to himself or herself or to any other person who is a member of that person's household.

[F14Wholesale dealing in medicinal productsU.K.

18.(1) A person may not except in accordance with a licence (a “wholesale dealer’s licence”)—

(a)distribute a medicinal product by way of wholesale dealing; or

(b)possess a medicinal product for the purpose of such distribution.

(2) Paragraph (1)—

(a)does not apply—

(i)to anything done in relation to a medicinal product by the holder of a manufacturer’s licence in respect of that product,

(ii)where the product concerned is an investigational medicinal product, or

(iii)if the product is a radiopharmaceutical in which the radionuclide is in the form of a sealed source; and

(b)is subject to regulation 19.

(3) Distribution of a medicinal product by way of wholesale dealing, or possession for the purpose of such distribution, is not to be taken to be in accordance with a wholesale dealer’s licence unless the distribution is carried on, or as the case may be the product held, at premises located in the UK and specified in the licence.

(4) In these Regulations a reference to distributing a product by way of wholesale dealing is a reference to—

(a)selling or supplying it; or

(b)procuring or holding it or exporting it for the purposes of sale or supply,

to a person who receives it for a purpose within paragraph (5).

(5) Those purposes are—

(a)selling or supplying the product; or

(b)administering it or causing it to be administered to one or more human beings,

in the course of a business carried on by that person.

(6) A wholesale dealer’s licence does not authorise the distribution of a medicinal product by way of wholesale dealing, or possession for the purpose of such distribution, unless a marketing authorisation, Article 126a authorisation, certificate of registration or traditional herbal registration is in force in respect of the product but this—

(a)does not apply in relation to distribution by a person to a person in a third country; and

(b)is subject to the exceptions in regulation 43(6).

(7) In paragraph (6), “marketing authorisation” means—

(a)a marketing authorisation issued by a competent authority of a member State in accordance with the 2001 Directive; or

(b)an EU marketing authorisation.]

Exemptions from requirement for wholesale dealer's licenceU.K.

19.—(1) Regulation 18 does not apply to the sale or offer for sale of a medicinal product by way of wholesale dealing, or possession for the purpose of such sale or offer, where paragraph (2) applies and the person selling or offering the product for sale is—

(a)the holder of a marketing authorisation, Article 126a authorisation, certificate of registration or traditional herbal registration, (an “authorisation”) which relates to the product, including a holder of an authorisation who manufactured or assembled the product; or

(b)a person who is not the holder of an authorisation in relation to the product but manufactured or assembled the product to the order of a person who is the holder of an authorisation relating to the product.

(2) This paragraph applies if—

(a)until the sale, the medicinal product has been kept on the premises of the person who manufactured or assembled the product (in this regulation referred to as “authorised premises”); and

(b)those premises are premises authorised for use for manufacture or assembly by that person's manufacturer's licence.

(3) For the purposes of this regulation, a medicinal product is regarded as having been kept on authorised premises at a time when—

(a)it was being moved from one set of authorised premises to another, or from one part of authorised premises to another part; or

(b)it was being moved from authorised premises by way of delivery to a purchaser.

(4) Regulation 18 does not apply to a person who in connection with the importation of a medicinal product—

(a)provides facilities solely for transporting the product; or

(b)acting as an import agent, handles the product where the product is imported solely to the order of another person who intends to sell the product or offer it for sale by way of wholesale dealing or to distribute it in any other way.

F15(5) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Mixing of medicinesU.K.

20.—(1) Regulation 17(1) (manufacturing of medicinal products) does not apply to the mixing of medicines by—

(a)a nurse independent prescriber;

(b)a pharmacist independent prescriber;

(c)a supplementary prescriber, if the mixing of medicines forms part of the clinical management plan for an individual patient;

[F16(ca)physiotherapist independent prescriber;

(cb)podiatrist independent prescriber;]

(d)a person acting in accordance with the written directions of a—

(i)doctor,

(ii)dentist,

(iii)nurse independent prescriber, F17...

[F18(iv)pharmacist independent prescriber,

(v)physiotherapist independent prescriber, or

(vi)podiatrist independent prescriber; or]

(e)a person acting in accordance with the written directions of a supplementary prescriber, if the mixing of medicines forms part of the clinical management plan for an individual patient.

(2) In this regulation “mixing of medicines” means the combining of two or more medicinal products together for the purposes of administering them to meet the needs of an individual patient.

F17Word in reg. 20(1)(d)(iii) omitted (20.8.2013) by virtue of The Human Medicines (Amendment) Regulations 2013 (S.I. 2013/1855), regs. 1(1), 7(b)

F18Reg. 20(1)(d)(iv)-(vi) substituted for reg. 20(1)(d)(iv) (20.8.2013) by The Human Medicines (Amendment) Regulations 2013 (S.I. 2013/1855), regs. 1(1), 7(c)

Application for manufacturer's or wholesale dealer's licenceU.K.

21.—(1) An application for a grant of a licence under this Part must—

(a)be made to the licensing authority;

(b)be made in the way and form specified in Schedule 3; and

(c)contain or be accompanied by the information, documents, samples and other material specified in that Schedule.

(2) An application must indicate the descriptions of medicinal products in respect of which the licence is required, either by specifying the descriptions of medicinal products in question or by way of an appropriate general classification.

Factors relevant to determination of application for manufacturer's or wholesale dealer's licenceU.K.

22.—(1) In dealing with an application for a manufacturer's licence the licensing authority must in particular take into consideration—

(a)the operations proposed to be carried out under the licence;

(b)the premises in which those operations are to be carried out;

(c)the equipment which is or will be available on those premises for carrying out those operations;

(d)the qualifications of the persons under whose supervision the operations will be carried out; and

(e)the arrangements made or to be made for securing the safekeeping of, and the maintenance of adequate records in respect of, medicinal products manufactured or assembled in pursuance of the licence.

(2) In dealing with an application for a wholesale dealer's licence the licensing authority must in particular take into consideration—

(a)the premises on which medicinal products of the descriptions to which the application relates will be stored;

(b)the equipment which is or will be available for storing medicinal products on those premises;

(c)the equipment and facilities which are or will be available for distributing medicinal products from those premises; and

(d)the arrangements made or to be made for securing the safekeeping of, and the maintenance of adequate records in respect of, medicinal products stored on or distributed from those premises.

Grant or refusal of licenceU.K.

23.—(1) Subject to the following provisions of these Regulations, on an application to the licensing authority for a licence under this Part the licensing authority may—

(a)grant a licence containing such provisions as it considers appropriate; or

(b)refuse to grant a licence if having regard to the provisions of these Regulations and any European Union obligation it considers it necessary or appropriate to do so.

(2) The licensing authority must grant or refuse an application for a licence under this Part within the period of 90 days beginning immediately after the day on which it receives the application.

(3) Paragraph (2) applies to an application only if the requirements of Schedule 3 have been met.

(4) If a notice under regulation 30 requires the applicant to provide the licensing authority with information, the information period is not to be counted for the purposes of paragraph (2).

(5) In paragraph (4), the “information period” means the period—

(a)beginning with the day on which the notice is given, and

(b)ending with the day on which the licensing authority receives the information or the applicant shows to the licensing authority's satisfaction that the applicant is unable to provide it.

(6) The licensing authority must give the applicant a notice stating the reasons for its decision in any case where—

(a)the licensing authority refuses to grant an application for a licence; or

(b)the licensing authority grants a licence otherwise than in accordance with the application and the applicant requests a statement of its reasons.

Standard provisions of licencesU.K.

24.—(1) The standard provisions set out in Schedule 4 may be incorporated by the licensing authority in a licence under this Part granted on or after the date on which these Regulations come into force.

(2) The standard provisions may be incorporated in a licence with or without modifications and either generally or in relation to medicinal products of a particular class.

Duration of licenceU.K.

25.  A licence granted under this Part remains in force until—

(a)the licence is revoked by the licensing authority; or

(b)the licence is surrendered by the holder.

General power to suspend, revoke or vary licencesU.K.

26.—(1) The licensing authority may in accordance with the procedure specified in regulation 27—

(a)suspend a licence under this Part for such period as the authority thinks fit;

(b)revoke a licence under this Part; or

(c)vary the provisions of a licence under this Part.

(2) The suspension or revocation of a licence may be—

(a)total;

(b)limited to medicinal products of one or more descriptions; or

(c)limited to medicinal products manufactured, assembled or stored on specified premises or a specified part of any premises.

(3) The powers conferred by this regulation may not be exercised in relation to a manufacturer's licence or a wholesale dealer's licence except on one or more of the grounds specified in—

(a)paragraph (4) (in relation to either a manufacturer's licence or a wholesale dealer's licence);

(b)paragraph (5) (in relation to a manufacturer's licence); or

(c)paragraph (6) (in relation to a wholesale dealer's licence).

(4) Those grounds are that—

(a)the information in the application as a result of which the licence was granted was false or incomplete in a material respect;

(b)a material change of circumstances has occurred in relation to any of the matters stated in the application;

(c)the holder of the licence has materially contravened a provision of it; or

(d)the holder of the licence has without reasonable excuse failed to supply information to the licensing authority with respect to medicinal products of a description to which the licence relates when required to do so under regulation 30(2).

(5) In relation to a manufacturer's licence, the powers conferred by this regulation may also be exercised on either or both of the following grounds—

(a)that the holder of the manufacturer's licence has manufactured or assembled medicinal products to the order of a person who holds a marketing authorisation, Article 126a authorisation, certificate of registration or traditional herbal registration (an “authorisation”) and has habitually failed to comply with the provisions of that authorisation; or

(b)that the holder of the manufacturer's licence does not have appropriate facilities to carry out processes of manufacture or assembly authorised by the licence.

(6) In relation to a wholesale dealer's licence, the powers conferred by this regulation may also be exercised on the grounds that the equipment and facilities available to the holder of the licence for storing or distributing medicinal products are inadequate to maintain the quality of medicinal products of one or more descriptions to which the licence relates.

Procedure where licensing authority proposes to suspend, revoke or vary licenceU.K.

27.—(1) This regulation applies where—

(a)the provisions of regulation 28 do not apply; and

(b)the licensing authority proposes to suspend, vary or revoke a licence under regulation 26.

(2) The licensing authority must notify the licence holder in writing of—

(a)its proposal;

(b)the reasons for it; and

(c)the date (which must be no earlier than 28 days from the notice given by the licensing authority) on which it is proposed that the suspension, revocation or variation should take effect.

(3) The licence holder may before the date specified in the notice—

(a)make written representations to the licensing authority with respect to the proposal; or

(b)notify the licensing authority that the holder wishes the licensing authority to submit the proposal to review upon oral representations.

(4) If the licence holder makes written representations in accordance with paragraph 3(a) the licensing authority must take those representations into account before making a decision in the matter.

[F19(5) If the licence holder notifies the licensing authority that the holder wishes the licensing authority to submit the proposal to review upon oral representations in accordance with paragraph (3)(b)—

(a)Schedule 5 has effect; and

(b)the licence holder must pay a fee for a review upon oral representations in accordance with the Fees Regulations.]

(6) If the licensing authority proceeds to suspend, revoke or vary a licence in accordance with the provisions of regulation 26 it must give a notice to the licence holder.

(7) The notice must—

(a)give particulars of the suspension, revocation or variation; and

(b)give reasons for the decision to suspend, revoke or vary the licence.

(8) Paragraphs (6) and (7) are without prejudice to any requirement of Schedule 5 as to notification.

Suspension of licence in cases of urgencyU.K.

28.—(1) Notwithstanding anything in the preceding provisions of this Part, where it appears to the licensing authority that in the interests of safety it is necessary to suspend a licence under this Part with immediate effect, the licensing authority may do so for a period not exceeding three months.

(2) This paragraph applies where—

(a)a licence has been suspended under paragraph (1); and

(b)it appears to the licensing authority that it is necessary to consider whether the licence should be further suspended, revoked or varied.

(3) Where paragraph (2) applies, the licensing authority must proceed as set out in regulation 27 (but this is subject to paragraphs (4) and (5)).

(4) Paragraph (5) applies where, in circumstances where paragraph (2) applies, the licensing authority proceeds as set out in regulation 27 and any proceedings under that regulation have not been finally disposed of before the end of the period for which the licence was suspended under paragraph (1) or further suspended under paragraph (5).

(5) If it appears to the licensing authority to be necessary in the interests of safety to do so, the authority may further suspend the licence for a period which (in the case of each further suspension) is not to exceed three months.

(6) In the event that any challenge against a decision under regulation 27 to suspend, vary or revoke the licence is made on an application to the High Court under regulation 322(4) paragraph (5) shall apply, but this is without prejudice to regulation 322(6)(a).

Variation of licence on the application of the holderU.K.

29.—(1) This regulation applies if the holder of a licence under this Part applies to the licensing authority for a variation of the licence.

(2) The application must—

(a)be in writing;

(b)specify the variation requested;

(c)be signed by or on behalf of the applicant;

(d)be accompanied by such information as may be required to enable the licensing authority to consider the application; and

(e)be accompanied by the required fee (if any).

(3) The licensing authority must consider an application made in accordance with this regulation.

(4) If paragraph (5) applies, the licensing authority must vary the licence or refuse to vary it before the end of the period allowed for considering the application.

(5) This paragraph applies to a variation which would have the effect of altering—

(a)the types of medicinal product in respect of which the licence was granted;

(b)any operation carried out under the licence; or

(c)any premises, equipment or facilities in respect of which the licence was granted.

(6) The period allowed for consideration of an application under this regulation is—

(a)in a case where the licensing authority considers that it is necessary to inspect premises to which the licence relates, 90 days beginning with the day after the date when the licensing authority receives the application; and

(b)in any other case 30 days beginning with that day.

(7) The licensing authority may give a notice to the applicant requiring the applicant to supply further information in connection with the application.

(8) If a notice under paragraph (7) requires the applicant to provide the licensing authority with information, the information period is not to be counted for the purposes of paragraph (6).

(9) In paragraph (8), the “information period” means the period—

(a)beginning with the day on which the notice is given; and

(b)ending with the day on which the licensing authority receives the information or the applicant shows to the licensing authority's satisfaction that the applicant is unable to provide it.

(10) Nothing in this regulation affects the powers conferred by regulation 26.

Provision of informationU.K.

30.—(1) Where an application has been made to the licensing authority for a licence under this Part, the licensing authority may, before determining the application, require the applicant to provide such information as the licensing authority thinks necessary, within the period specified by the licensing authority.

(2) The licensing authority may give a notice to the holder of a licence under this Part, requiring the holder to provide information of a kind specified in the notice within the period specified in the notice.

(3) A notice under paragraph (2) may not be given to the holder of a licence unless it appears to the licensing authority, or representations are made to the licensing authority by the Commission, an expert advisory group of the Commission, or an expert committee appointed by the licensing authority, that it is necessary for the licensing authority to consider whether the licence should be varied, suspended or revoked.

(4) A notice under paragraph (2) may specify information which the licensing authority, or the Commission, an expert advisory group of the Commission, or an expert committee appointed by the licensing authority, thinks necessary for considering whether the notice should be varied, suspended or revoked.

Miscellaneous and offencesU.K.

Certification of manufacturer's licenceU.K.

31.—(1) The licensing authority must issue a certificate in accordance with the following paragraphs of this regulation in relation to a manufacturer's licence relating to the manufacture or assembly of medicinal products if requested to do so by—

(a)subject to paragraph (5), the holder of the licence;

(b)a person who intends to export a medicinal product manufactured or assembled by the holder under the licence; or

(c)the competent authorities of a country other than an EEA State into which a medicinal product manufactured or assembled under the licence is, or is proposed to be, imported.

(2) The certificate must contain —

(a)information sufficient to identify the holder of the manufacturer's licence;

(b)details of the medicinal products that may be manufactured or assembled under the licence; and

(c)any other information concerning the holder, the product or the licence that the licensing authority thinks it appropriate to include, including information relating to clinical trials.

(3) If—

(a)a request is made—

(i)under paragraph (1)(a) in relation to the export or the proposed export of a product, or

(ii)under paragraph (1)(b) or (c); and

(b)there is a marketing authorisation or a traditional herbal registration in force for any product to which the licence relates,

the certificate must be accompanied by the summary of the product characteristics relating to that product.

(4) The licensing authority may restrict the information provided under sub-paragraphs (2)(a) and (b) and paragraph (3) to information relating to the specific medicinal products mentioned in the request made under paragraph (1).

(5) A licence holder who makes a request under paragraph (1) must—

(a)produce to the licensing authority a marketing authorisation, certificate of registration or traditional herbal registration in relation to any product to which the certificate is to relate; or

(b)make a declaration to the licensing authority explaining why no marketing authorisation, certificate of registration or traditional herbal registration is available.

(6) The licensing authority must have regard to the prevailing administrative arrangements of the World Health Organisation when issuing the certificate.

Sale and supply of starting materialsU.K.

F2032.  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Offence concerning data for advanced therapy medicinal productsU.K.

33.—(1) A person who is, or immediately before its revocation or suspension was, the holder of a manufacturer's licence relating to an advanced therapy medicinal product is guilty of an offence if the person fails to—

(a)keep the data referred to in Article 15(1) of Regulation (EC) No 1394/2007 in accordance with the requirements of Article 15(4) of that Regulation; or

(b)transfer the data referred to in Article 15(1) to the licensing authority in the event of that person's bankruptcy or liquidation,

but this is subject to paragraphs (2) and (3).

(2) Sub-paragraph (1)(b) does not apply if—

(a)the person is bankrupt or in liquidation and has transferred the data to another person; or

(b)the period for which the person was required to keep the data in accordance with the requirements of Article 15(4) mentioned in sub-paragraph (1)(a) has expired.

(3) It is a defence for a person charged with an offence under paragraph (1) to prove that the person took all reasonable precautions and exercised all due diligence to avoid commission of the offence.

(4) Where evidence is adduced that is sufficient to raise an issue with respect to the defence in paragraph (3), the court or jury must presume that the defence is satisfied unless the prosecution proves beyond reasonable doubt that it is not.

Offences: breach of regulations and false information and defence concerning starting materialsU.K.

34.—(1) A person is guilty of an offence if the person contravenes the provisions of regulation 17(1) [F21or 18(1)].

(2) A person is guilty of an offence if the person knowingly gives false information in response to a notice under regulation 30(1).

(3) A person is guilty of an offence if, without reasonable excuse, the person fails to comply with a notice under regulation 30(2).

(4) The defence in paragraph (5) applies to a person who is charged under paragraph (1) with an offence of contravening regulation 17(1) (prohibition on manufacturing a medicinal product except in accordance with a licence) by virtue of a breach of regulation [F2237(3)] (requirement that active substances used as starting materials are manufactured or assembled in accordance with the Good Manufacturing Practice Directive).

(5) It is a defence for the person to show that the person could not, by taking all reasonable precautions and exercising all due diligence, have discovered that an active substance was not manufactured in accordance with regulation [F2237(3)].

PenaltiesU.K.

35.—(1) A person guilty of an offence under regulation 33(1) or regulation 34(1) or (2) is liable—

(a)on summary conviction to a fine not exceeding the statutory maximum; or

(b)on conviction on indictment to a fine, to imprisonment for a term not exceeding two years, or to both.

(2) A person guilty of an offence under regulation 34(3) is liable on summary conviction to a fine not exceeding level 3 on the standard scale.

Conditions for holding a manufacturer's licenceU.K.

Conditions for manufacturer's licenceU.K.

36.—(1) Regulations 37 to 41 apply to the holder of a manufacturer's licence (referred to in those regulations as “the licence holder”) and have effect as if they were provisions of the licence (but the provisions specified in paragraph (2) do not apply to the holder of a manufacturer's licence insofar as the licence relates to the manufacture or assembly of exempt advanced therapy medicinal products).

(2) Those provisions are regulations [F2337(3)], 38, 39(6)(a) and (8) , 40 and 41.

(3) The requirements of Part 1 of Schedule 6 apply to the holder of a manufacturer's licence insofar as the licence relates to the manufacture or assembly of exempt advanced therapy medicinal products, and have effect as if they were provisions of the licence.

[F24Manufacturing and assemblyU.K.

37.(1) This regulation applies in relation to a manufacturer’s licence relating to the manufacture or assembly of medicinal products.

(2) The licence holder must comply with the principles and guidelines for good manufacturing practice set out in the Good Manufacturing Practice Directive.

(3) Unless paragraph (10) applies, the licence holder shall use active substances as starting materials only if—

(a)those substances have been manufactured in accordance with good manufacturing practice for active substances; and

(b)those substances have been distributed in accordance with the guidelines on good distribution practice for active substances.

(4) The licence holder shall verify—

(a)that the manufacturer or distributor of an active substance used by the licence holder has complied with the requirements of good manufacturing practice and good distribution practice for active substances by means of audits performed—

(i)directly by the licence holder, or

(ii)by a person acting on behalf of the licence holder under a contract;

(b)that unless the active substance is imported from a third country, any manufacturers, importers or distributors supplying active substances to the licence holder are registered with the competent authority of a member State in which they are established; and

(c)the authenticity and quality of the active substance.

(5) The licence holder shall ensure that—

(a)excipients are suitable for use in a medicinal product by—

(i)ascertaining what the appropriate good manufacturing practice is, and

(ii)ensuring that the ascertained good manufacturing practice is applied;

(b)the suitability of the excipient is ascertained on the basis of a formalised risk assessment as described in paragraph 5 of Article 47 of the 2001 Directive;

(c)the assessment under sub-paragraph (b) takes account of—

(i)the source,

(ii)requirements under other quality systems,

(iii)intended use of the excipients, and

(iv)previous instances of quality defects,

(d)the authenticity and quality of any excipient used is verified; and

(e)the measures taken under this paragraph are documented by the licence holder.

(6) The licence holder must maintain such staff, premises and equipment as are necessary for the stages of manufacture and assembly of medicinal products undertaken by the licence holder in accordance with—

(a)the manufacturer’s licence; and

(b)the marketing authorisations, Article 126a authorisations, certificates of registration or traditional herbal registrations applying to the medicinal products.

(7) The licence holder must not manufacture or assemble medicinal products, or classes of medicinal products, other than those specified in the licence.

(8) The licence holder must not manufacture or assemble medicinal products on premises other than those specified in the licence as approved by the licensing authority for the purpose.

(9) The licence holder must ensure that blood, or blood components, imported into the United Kingdom and used as a starting material or raw material in the manufacture of a medicinal product meet—

(a)the standards of quality and safety specified in Commission Directive 2004/33/EC of 22 March 2004 implementing Directive 2002/98/EC of the European Parliament and of the Council as regards certain technical requirements for blood and blood components; or

(b)equivalent standards.

(10) The requirements in paragraphs (3) to (5) do not apply in relation to the manufacture or assembly of special medicinal product to which regulation 167 (supply to fulfil special needs) applies.

(11) The licence holder must immediately inform the competent authority of a member State and, where applicable, the marketing authorisation holder, of medicinal products which come within the scope of manufacturing authorisation which the licence holder—

(a)knows or suspects; or

(b)has reasonable grounds for knowing or suspecting,

to be falsified.]

Imports from states other than EEA StatesU.K.

38.—(1) This regulation applies in relation to a manufacturer's licence relating to the import of medicinal products.

(2) The licence holder must comply with the conditions set out in this regulation in relation to the import of medicinal products from a state other than an EEA State.

(3) The licence holder must—

(a)comply with the principles and guidelines on good manufacturing practice in the Good Manufacturing Practice Directive in so far as they are relevant to the import of medicinal products; and

(b)ensure that active substances have been used as starting materials in the manufacture of medicinal products, other than special medicinal products, imported from a state other than an EEA State only if those substances have been manufactured or assembled in accordance with the principles and guidelines mentioned in paragraph (a), in so far as those principles and guidelines relate to starting materials.

Further requirements for manufacturer's licenceU.K.

39.—(1) This regulation applies in relation to any manufacturer's licence.

(2) The licence holder must maintain such staff, premises, equipment and facilities for the handling, control, storage and distribution of medicinal products under the licence as are appropriate in order to maintain the quality of the medicinal products.

(3) The licence holder must ensure that any arrangements made for the handling, control, storage and distribution of medicinal products are adequate to maintain the quality of the products.

(4) The licence holder must not handle, control, store or distribute medicinal products on any premises other than those specified in the licence as approved by the licensing authority for the purpose.

(5) The licence holder must inform the licensing authority before making a material alteration to the premises or facilities used under the licence, or to the purposes for which those premises or facilities are used.

(6) The licence holder must inform the licensing authority of any proposed change to—

(a)the qualified person; and

(b)any person named in the licence as having responsibility for quality control.

(7) For the purposes of enabling the licensing authority to determine whether there are grounds for suspending, revoking or varying the licence, the licence holder must permit a person authorised in writing by the licensing authority to do anything that the licensing authority could have done for the purposes of verifying a statement made in an application for a licence.

(8) In distributing a medicinal product by way of wholesale dealing, the licence holder must comply with regulations 43(1), (2) and (5) and [F2544(4) to (6)] as if the licence holder were the holder of a wholesale dealer's licence.

Obligation to provide information relating to control methodsU.K.

40.—(1) This regulation applies in relation to any manufacturer's licence.

(2) The licensing authority may require the licence holder to provide the authority with proof of the control methods employed by the holder in relation to a medicinal product.

Requirements as to qualified personsU.K.

41.—(1) This regulation applies in relation to any manufacturer's licence.

(2) The licence holder must ensure that there is at the disposal of the holder at all times at least one qualified person who is responsible for carrying out, in relation to medicinal products manufactured, assembled or imported under the licence, the duties specified in Part 3 of Schedule 7.

(3) If the licence holder satisfies the requirements of Part 1 or 2 of Schedule 7 the licence holder may act as a qualified person.

(4) A qualified person may be treated by the licence holder as satisfying the requirements of Part 1 or 2 of Schedule 7 if that person produces evidence that he or she—

(a)is a member of a body specified in paragraph (5); and

(b)is regarded by that body as satisfying those requirements.

(5) Those bodies are—

(a)the Society of Biology;

(b)the Royal Pharmaceutical Society;

(c)the Pharmaceutical Society of Northern Ireland;

(d)the Royal Society of Chemistry; and

(e)such other body as may be specified by the licensing authority for the purpose of this paragraph.

(6) Where the qualified person changes, the licence holder must give the licensing authority advance notification of—

(a)that change; and

(b)the name, address and qualifications of the new qualified person.

(7) The licence holder must not permit any person to act as a qualified person other than the person named in the licence or another person notified to the licensing authority under paragraph (6).

(8) Paragraph (9) applies if the licensing authority thinks, after giving the licence holder and a person acting as a qualified person the opportunity to make representations (orally or in writing), that the person—

(a)does not satisfy the requirements of Part 1 or 2 of Schedule 7 in relation to qualifications or experience;

(b)does not satisfy paragraph (b) of the definition of “qualified person” in regulation 8; or

(c)is failing to carry out the duties referred to in paragraph (2) adequately or at all.

(9) Where this paragraph applies, the licensing authority must notify the licence holder in writing that the person is not permitted to act as a qualified person.

(10) The licence holder must at all times provide and maintain such staff, premises and equipment as are necessary to enable the qualified person to carry out the duties referred to in paragraph (2).

(11) The licence holder is not obliged to meet the requirements of this regulation in relation to any activity under the licence which relates to special medicinal products or to products authorised on a temporary basis under regulation 174 (supply in response to spread of pathogenic agents etc).

Conditions for holding a wholesale dealer's licenceU.K.

Conditions for wholesale dealer's licenceU.K.

42.—(1) Regulations 43 to 45 apply to the holder of a wholesale dealer's licence (referred to in those regulations as “the licence holder”) and have effect as if they were provisions of the licence (but the provisions specified in paragraph (2) do not apply to the holder of a wholesale dealer's licence insofar as the licence relates to exempt advanced therapy medicinal products).

[F26(2) Those provisions are regulations 43(2) and (8) and 44.]

(3) The requirements in Part 2 of Schedule 6 apply to the holder of a wholesale dealer's licence insofar as the licence relates to exempt advanced therapy medicinal products, and have effect as if they were provisions of the licence.

Obligations of licence holderU.K.

43.—(1) The licence holder must comply with the guidelines on good distribution practice published by the European Commission in accordance with Article 84 of the 2001 Directive.

(2) The licence holder must ensure, within the limits of the holder's responsibility, the continued supply of medicinal products to pharmacies, and other persons who may lawfully sell medicinal products by retail or supply them in circumstances corresponding to retail sale, so that the needs of patients in the United Kingdom are met.

(3) The licence holder must provide and maintain such staff, premises, equipment and facilities for the handling, storage and distribution of medicinal products under the licence as are necessary—

(a)to maintain the quality of the products; and

(b)to ensure their proper distribution.

(4) The licence holder must inform the licensing authority of any proposed structural alteration to, or discontinuance of use of, premises to which the licence relates or which have otherwise been approved by the licensing authority.

(5) Subject to paragraph (6), the licence holder must not sell or supply a medicinal product, or offer it for sale or supply, unless—

(a)there is a marketing authorisation, Article 126a authorisation, certificate of registration or traditional herbal registration (an “authorisation”) in force in relation to the product; and

(b)the sale or supply, or offer for sale or supply, is in accordance with the authorisation.

(6) The restriction in paragraph (5) does not apply to—

(a)the sale or supply, or offer for sale or supply, of a special medicinal product;

(b)the export to an EEA State, or supply for the purposes of such export, of a medicinal product which may be placed on the market in that State without a marketing authorisation, Article 126a authorisation, certificate of registration or traditional herbal registration by virtue of legislation adopted by that State under Article 5(1) of the 2001 Directive; or

(c)the sale or supply, or offer for sale or supply, of an unauthorised medicinal product where the Secretary of State has temporarily authorised the distribution of the product under regulation 174.

(7) The licence holder must—

(a)keep documents relating to the sale or supply of medicinal products under the licence which may facilitate the withdrawal or recall from sale of medicinal products in accordance with paragraph (b);

(b)maintain an emergency plan to ensure effective implementation of the recall from the market of a medicinal product where recall is—

(i)ordered by the licensing authority or by the competent authority of any EEA State, or

(ii)carried out in co-operation with the manufacturer of, or the holder of the marketing authorisation, Article 126a authorisation, certificate of registration or traditional herbal registration for, the product; and

[F27(c)keep records in relation to the receipt, dispatch or brokering of medicinal products, of—

(i)the date of receipt,

(ii)the date of despatch,

(iii)the date of brokering,

(iv)the name of the medicinal product,

(v)the quantity of the product received, dispatched or brokered,

(vi)the name and address of the person from whom the products were received or to whom they are dispatched,

(vii)the batch number of medicinal products bearing safety features referred to in point (o) of Article 54 of the 2001 Directive.]

[F27(8) A licence holder (“L”) who imports from another EEA State a medicinal product in relation to which L is not the holder of a marketing authorisation, Article 126a authorisation, certificate of registration or a traditional herbal registration shall—

(a)notify the intention to import that product to the holder of the authorisation and—

(i)in the case of a product which has been granted a marketing authorisation under Regulation (EC) No 726/2004, to the EMA; or

(ii)in any other case, the licensing authority; and

(b)pay a fee to the EMA in accordance with Article 76(4) of the 2001 Directive or the licensing authority as the case may be, in accordance with the Fees Regulations,

but this paragraph does not apply in relation to the wholesale distribution of medicinal products to a person in a third country.]

(9) For the purposes of enabling the licensing authority to determine whether there are grounds for suspending, revoking or varying the licence, the licence holder must permit a person authorised in writing by the licensing authority, on production of identification, to carry out any inspection, or to take any samples or copies, which an inspector could carry out or take under Part 16 (enforcement).

[F28(10) The holder (“L”) must verify in accordance with paragraph (11) that any medicinal products received by L that are required by Article 54a of the Directive to bear safety features are not falsified but this paragraph does not apply in relation to the distribution of medicinal products received from a third country by a person to a person in a third country.

(11) Verification under this paragraph is carried out by checking the safety features on the outer packaging, in accordance with the requirements laid down in the delegated acts adopted under Article 54a(2) of the 2001 Directive.

(12) The licence holder must maintain a quality system setting out responsibilities, processes and risk management measures in relation to their activities.

(13) The licence holder must immediately inform the licensing authority and, where applicable, the marketing authorisation holder, of medicinal products which the licence holder receives or is offered which the licence holder—

(a)knows or suspects; or

(b)has reasonable grounds for knowing or suspecting,

to be falsified.

(14) Where the medicinal product is obtained through brokering, the licence holder must verify that the broker involved fulfils the requirements set out in regulation 45A(1)(b).

(15) In this regulation, “marketing authorisation” means—

(a)a marketing authorisation issued by a competent authority in accordance with the 2001 Directive; or

(b)an EU marketing authorisation.]

F28Reg. 43(10)-(15) substituted for reg. 43(10) (20.8.2013) by The Human Medicines (Amendment) Regulations 2013 (S.I. 2013/1855), regs. 1(1), 14(b)

[F29Requirement for wholesale dealers to deal only with specified personsU.K.

44.(1) Unless paragraph (2) applies, the licence holder must not obtain supplies of medicinal products from anyone except—

(a)the holder of a manufacturer’s licence or wholesale dealer’s licence in relation to products of that description;

(b)the person who holds an authorisation granted by another EEA State authorising the manufacture of products of the description or their distribution by way of wholesale dealing; or

(c)where the supplier is not the holder of a manufacturer’s licence, where the supply is in accordance with the principles and guidelines of good distribution practice,

but this paragraph does not apply in relation to the distribution of medicinal products directly received from a third country but not imported into the EU.

(2) From 28th October 2013 the licence holder must not obtain supplies of medicinal products from anyone except—

(a)the holder of a manufacturer’s licence or wholesale dealer’s licence in relation to products of that description;

(b)the person who holds an authorisation granted by another EEA State authorising the manufacture of products of the description or their distribution by way of wholesale dealing;

(c)where the medicinal product is directly received from a third country (“A”) for export to a third country (“B”), the supplier of the medicinal product in country A is a person who is authorised or entitled to supply such medicinal products in accordance with the legal and administrative provisions in country A; or

(d)where the supplier is not the holder of a manufacturer’s licence, where the supply is in accordance with the principles and guidelines of good distribution practice.

(3) Where a medicinal product is obtained in accordance with paragraph (1), (2)(a) or (b), the licence holder must verify that—

(a)the wholesale dealer who supplies the product complies with the principles and guidelines of good distribution practices; or

(b)the manufacturer or importer who supplies the product holds a manufacturing authorisation.

(4) Unless paragraph (5) applies, the licence holder may distribute medicinal products by way of wholesale dealing only to—

(a)the holder of a wholesale dealer’s licence relating to those products;

(b)the holder of an authorisation granted by the competent authority of another EEA State authorising the supply of those products by way of wholesale dealing;

(c)a person who may lawfully sell those products by retail or may lawfully supply them in circumstances corresponding to retail sale; or

(d)a person who may lawfully administer those products,

but this paragraph does not apply in relation to medicinal products which are distributed by way of wholesale dealing to a person in a third country.

(5) From 28th October 2013, the licence holder may distribute medicinal products by way of wholesale dealing only to—

(a)the holder of a wholesale dealer’s licence relating to those products;

(b)the holder of an authorisation granted by the competent authority of another EEA State authorising the supply of those products by way of wholesale dealing;

(c)a person who may lawfully sell those products by retail or may lawfully supply them in circumstances corresponding to retail sale;

(d)a person who may lawfully administer those products; or

(e)in relation to supply to persons in third countries, a person who is authorised or entitled to receive medicinal products for wholesale distribution or supply to the public in accordance with the applicable legal and administrative provisions of the third country concerned.

(6) Where a medicinal product is supplied to a person who is authorised or entitled to supply medicinal products to the public in accordance with paragraph (4)(c), (5)(c) or (e), the licence holder must enclose with the product a document stating the—

(a)date on which the supply took place;

(b)name and pharmaceutical form of the product supplied;

(c)quantity of product supplied;

(d)name and address of the licence holder; and

(e)batch number of the medicinal products bearing the safety features referred to in point (o) of Article 54 of the 2001 Directive.

(7) The licence holder must—

(a)keep a record of information supplied in accordance with paragraph (6) for at least five years beginning immediately after the date on which the information is supplied; and

(b)ensure that the record is available to the licensing authority for inspection.]

Requirement as to responsible personsU.K.

45.—(1) The licence holder must ensure that there is available at all times at least one person (referred to in this regulation as the “responsible person”) who in the opinion of the licensing authority—

(a)has knowledge of the activities to be carried out and of the procedures to be performed under the licence which is adequate to carry out the functions mentioned in paragraph (2); and

(b)has adequate experience relating to those activities and procedures.

(2) Those functions are—

(a)ensuring that the conditions under which the licence was granted have been, and are being, complied with; and

(b)ensuring that the quality of medicinal products handled by the licence holder is being maintained in accordance with the requirements of the marketing authorisations, Article 126a authorisations, certificates of registration or traditional herbal registrations applicable to those products.

(3) The licence holder must notify the licensing authority of—

(a)any change to the responsible person; and

(b)the name, address, qualifications and experience of the responsible person.

(4) The licence holder must not permit any person to act as a responsible person other than the person named in the licence or another person notified to the licensing authority under paragraph (3).

(5) Paragraph (6) applies if, after giving the licence holder and a person acting as a responsible person the opportunity to make representations (orally or in writing), the licensing authority thinks that the person—

(a)does not satisfy the requirements of paragraph (1) in relation to qualifications or experience; or

(b)is failing to carry out the functions referred to in paragraph (2) adequately or at all.

(6) Where this paragraph applies, the licensing authority must notify the licence holder in writing that the person is not permitted to act as a responsible person.

[F30CHAPTER 3U.K.Brokering

Brokering in medicinal productsU.K.

45A.(1) A person may not broker a medicinal product unless—

(a)that product is covered by an authorisation granted—

(i)under Regulation (EC) No 726/2004; or

(ii)by a competent authority of a member State; and

(b)that person—

(i)is validly registered as a broker with a competent authority of a member State,

(ii)except where the person is validly registered with the competent authority of another EEA state, has a permanent address in the United Kingdom, and

(iii)complies with the guidelines on good distribution practice published by the European Commission in accordance with Article 84 of the 2001 Directive insofar as those guidelines apply to brokers.

(2) A person is not validly registered for the purpose of paragraph (1)(b) if—

(a)the person’s permanent address is not entered into a register of brokers kept by a competent authority of a member State;

(b)the registration is suspended; or

(c)the person has notified the competent authority of a member State to remove that person from the register.

(3) Paragraph (1)(b)(i) does not apply until 20th October 2013 in relation to a person who brokered any medicinal product before 20th August 2013.

Application for brokering registrationU.K.

45B.(1) The licensing authority may not register a person as a broker unless paragraphs to (7) are complied with.

(2) An application for registration must be made containing—

(a)the name of the person to be registered;

(b)the name under which that person is trading (if different to the name of that person);

(c)that person’s—

(i)permanent address in the United Kingdom,

(ii)e-mail address, and

(iii)telephone number;

(d)a statement of whether the medicinal products to be brokered are—

(i)prescription only medicines,

(ii)pharmacy medicines, or

(iii)medicines subject to general sale;

(e)an indication of the range of medicinal products to be brokered;

(f)evidence that that person can comply with regulations 45A(1)(b)(iii), 45E(3)(a) to (f) and 45F(1); and

(g)any fee payable in connection with the application in accordance with the Fees Regulations.

(3) Where the address at which the emergency plan, documents or record necessary to comply with regulation 45E(3)(b) to (d) are kept is different from the address notified in accordance with sub-paragraph (2)(c)(i), the application must contain—

(a)that address where the plan or records are to be kept;

(b)the name of a person who can provide access to that address for the purpose of regulation 325 (rights of entry); and

(c)that person’s—

(i)address,

(ii)e-mail address, and

(iii)telephone number.

(4) Unless paragraph (6) applies, the application for registration must—

(a)be in English; and

(b)be signed by the person seeking a brokering registration.

(5) The pages of the application must be serially numbered.

(6) Where the application is made on behalf of the person seeking a brokering registration by another person (“A”), the application must—

(a)contain the name and address of A; and

(b)be signed by A.

Procedure for determining an application for broker’s registrationU.K.

45C.(1) The licensing authority must grant or refuse an application for registration under regulation 45B within the period of 90 days beginning immediately after the day on which it receives the application.

(2) Paragraph (1) applies to an application only if the requirements of regulation 45B(2) have been met.

(3) Before determining an application for a brokering registration, the licensing authority may notify the applicant of a requirement to provide such information as the licensing authority thinks necessary, within the period specified by the licensing authority.

(4) If a notice under paragraph (3) requires the applicant to provide the licensing authority with information, the information period is not to be counted for the purposes of paragraph (1).

(5) In paragraph (4), the “information period” means the period—

(a)beginning with the day on which the notice is given, and

(b)ending with the day on which the licensing authority receives the information or the applicant shows to the licensing authority’s satisfaction that the applicant is unable to provide it.

Grant or refusal of broker’s registrationU.K.

45D.(1) Subject to regulations 45E and 45F, on an application to the licensing authority for a brokering registration, the licensing authority must, if it considers it necessary and appropriate to do so—

(a)register the applicant as a broker; or

(b)refuse registration as a broker, having regard to—

(i)the provisions of these Regulations, and

(ii)any EU obligation.

(2) The licensing authority must give the applicant a notice stating the reasons for its decision in any case where the licensing authority—

(a)refuses to grant an application for registration; or

(b)grants registration otherwise than in accordance with the application and the applicant requests a statement of its reasons.

(3) The licensing authority must register the applicant or refuse registration under this Chapter within the period of 90 days beginning immediately after the day on which it receives the application.

(4) Where the licensing authority registers a person as a broker, the licensing authority must enter the following information into a publicly available register—

(a)the person’s name;

(b)the name under which that person is trading (if different from the person’s name);

(c)the person’s permanent address in the United Kingdom.

(5) The licensing authority must make the register of brokers publicly available.

Criteria of broker’s registrationU.K.

45E.(1) Registration of a broker is conditional on that broker—

(a)complying with regulation 45A(1); and

(b)satisfying—

(i)the criteria in paragraphs (3), (4) and (7), and

(ii)such other criteria as the licensing authority considers appropriate and notifies the broker of.

(2) The criteria referred to in paragraph (1)(b)(ii) may include (but are not limited to) the criteria specified in paragraphs (5) and (6).

(3) The broker must—

(a)have a permanent address in the United Kingdom;

(b)maintain an emergency plan to ensure effective implementation of the recall from the market of a medicinal product where recall is—

(i)ordered by the licensing authority or by the competent authority of any EEA State, or

(ii)carried out in co-operation with the manufacturer of, or the holder of the marketing authorisation, for the product;

(c)keep documents relating to the sale or supply of medicinal products under the licence which may facilitate the withdrawal or recall from sale of medicinal products in accordance with sub-paragraph (b);

(d)record in relation to the brokering of each medicinal product—

(i)the name of the medicinal product,

(ii)the quantity of the product brokered,

(iii)the batch number of the medicinal product bearing the safety features referred to in point (o) of Article 54 of the 2001 Directive,

(iv)the name and address of the—

(aa)supplier, or

(bb)consignee, and

(v)the date on which the sale or purchase of the product is brokered;

(e)maintain a quality system setting out responsibilities, processes and risk management measures in relation to their activities; and

(f)keep the documents or record required by sub-paragraph (c) or (d) available to the licensing authority for a period of five years; and

(g)comply with regulation 45F(1), (2) and (4).

(4) Where the address at which the plan or records necessary to comply with paragraph (3)(b) to (d) are kept is different from the address notified in accordance with regulation 45B(2)(c)(i), the broker must—

(a)ensure that the plan or records are kept at an address in the United Kingdom; and

(b)inform the licensing authority of the address at which the plan or records are kept.

(5) The broker must provide such information as may be requested by the licensing authority concerning the type and quantity of medicinal products brokered within the period specified by the licensing authority.

(6) The broker must take all reasonable precautions and exercise all due diligence to ensure that any information provided by that broker to the licensing authority in accordance with regulation 45F is not false or misleading.

(7) For the purposes of enabling the licensing authority to determine whether there are grounds for suspending, revoking or varying the registration, the broker must permit a person authorised in writing by the licensing authority, on production of identification, to carry out any inspection, or to take any copies, which an inspector may carry out or take under regulations 325 (rights of entry) and 327 (powers of inspection, sampling and seizure).

Provision of informationU.K.

45F.(1) A broker registered in the UK must immediately inform—

(a)the licensing authority; and

(b)where applicable, the marketing authorisation holder,

of medicinal products which the broker identifies as, suspects to be, or has reasonable grounds for knowing or suspecting to be, falsified.

(2) On or before the date specified in paragraph (3), a broker who is, or has applied to the licensing authority to become, a registered broker in the United Kingdom must submit a report to the licensing authority, which—

(a)includes a declaration that the broker has in place an appropriate system to ensure compliance with regulations 45A, 45B and this regulation; and

(b)details the system which the broker has in place to ensure such compliance.

(3) The date specified for the purposes of this paragraph is—

(a)in relation to any application made before 31st March 2014, the date of the application; and

(b)in relation to each subsequent reporting year, 30th April following the end of that year.

(4) The broker must without delay notify the licensing authority of any changes to the matters in respect of which evidence has been supplied in relation to paragraph (2) which might affect compliance with the requirements of this Chapter.

(5) Any report or notification to the licensing authority under paragraph (2) or (4) must be accompanied by the appropriate fee in accordance with the Fees Regulations.

(6) The licensing authority may give a notice to a registered broker requiring that broker to provide information of a kind specified in the notice within the period specified in the notice.

(7) A notice under paragraph (6) may not be given to a registered broker unless it appears to the licensing authority that it is necessary for the licensing authority to consider whether the registration should be varied, suspended or revoked.

(8) A notice under paragraph (6) may specify information which the licensing authority thinks necessary for considering whether the registration should be varied, suspended or revoked.

(9) In paragraph (3)(b), “reporting year” means a period of twelve months ending on 31st March.

Power to suspend or vary a broker’s registration or remove a broker from the registerU.K.

45G.(1) The licensing authority may in accordance with regulation 45H—

(a)suspend a broker’s registration for such period as the authority thinks fit;

(b)vary a broker’s registration; or

(c)remove a person from the register.

(2) The suspension of registration or removal from the register may be—

(a)total;

(b)limited to medicinal products of one or more descriptions; or

(c)limited to medicinal products manufactured, assembled or stored on specified premises or a specified part of any premises.

(3) The powers conferred by this regulation may not be exercised in relation to a broker’s registration except on one or more of the following grounds—

(a)the information in the application as a result of which the broker’s registration was granted was false or incomplete in a material respect;

(b)a material change of circumstances has occurred in relation to any of the matters stated in the application;

(c)the broker has materially contravened a criterion of registration; or

(d)the broker has without reasonable excuse failed to supply information to the licensing authority with respect to medicinal products of a description to which the registration relates when required to do so under regulation 45F(6).

Procedure where licensing authority proposes to suspend or vary a broker’s registration or remove a broker from the registerU.K.

45H.(1) This regulation applies where—

(a)regulation 45I does not apply; and

(b)the licensing authority proposes to exercise the power in regulation 45G(1).

(2) The licensing authority must notify the broker in writing of—

(a)its proposal;

(b)the reasons for it; and

(c)the date (which must be no earlier than 28 days from the notice given by the licensing authority) on which it is proposed that the suspension, variation or revocation should take effect.

(3) The registered broker may before the date specified in the notice—

(a)make written representations to the licensing authority with respect to the proposal; or

(b)notify the licensing authority that the broker wishes the licensing authority to submit the proposal to review upon oral representations.

(4) If the broker makes written representations in accordance with paragraph (3)(a) the licensing authority must take those representations into account before making a decision in the matter.

(5) Schedule 5 has effect if the registered broker—

(a)notifies the licensing authority of the proposal to review upon oral representations in accordance with paragraph (3)(b); and

(b)pays the fee for a review upon oral representations in accordance with the Fees Regulations.

(6) If the licensing authority proceeds to suspend or vary a registration or remove a broker from the register in accordance with the provisions of regulation 45G it must give a notice to the broker.

(7) A notice under paragraph (6) must—

(a)give particulars of the suspension, variation or removal; and

(b)give reasons for the decision to suspend, vary or remove a broker from the register.

(8) Paragraphs (6) and (7) are without prejudice to any requirement of Schedule 5 as to notification.

Suspension of a broker registration in cases of urgencyU.K.

45I.(1) The licensing authority may immediately suspend a broker’s registration for a period not exceeding three months where it appears to the licensing authority that in the interests of safety it is appropriate to do so.

(2) This paragraph applies where—

(a)a broker’s registration has been suspended under paragraph (1); and

(b)it appears to the licensing authority that it is necessary to consider whether the broker’s registration should be—

(i)further suspended or varied, or

(ii)removed from the brokers’ register.

(3) Where paragraph (2) applies, the licensing authority must proceed as set out in regulation 45H (but this is subject to paragraph (4)).

(4) Paragraph (5) applies where, in circumstances where paragraph (2) applies, the licensing authority proceeds as set out in regulation 45H and any proceedings under that regulation have not been finally disposed of before the end of the period for which the registration was suspended under paragraph (1) or further suspended under paragraph (5).

(5) If it appears to the licensing authority to be necessary in the interests of safety to do so, the authority may further suspend the registration for a period which (in the case of each further suspension) is not to exceed three months.

(6) In the event that any challenge against a decision under regulation 45H to suspend, vary or revoke the registration is made on an application under regulation 322(4), paragraph (5) shall apply, but this is without prejudice to regulation 322(6)(a) (validity of decisions and proceedings).

Variation of a broker’s registration on the application of the brokerU.K.

45J.(1) This regulation applies if the person registered as a broker applies to the licensing authority for a variation of the registration.

(2) The application must—

(a)be in writing;

(b)specify the variation requested;

(c)be signed by or on behalf of the applicant;

(d)be accompanied by such information as may be required to enable the licensing authority to consider the application;

(e)include the appropriate fee in accordance with the Fees Regulations.

(3) The licensing authority must vary a broker’s registration or refuse to vary it within 30 days beginning with the day after the date when the licensing authority receives the application.

(4) The licensing authority may give a notice to the applicant requiring the applicant to supply further information in connection with the application within the period specified in the notice.

(5) If a notice under paragraph (4) requires the applicant to provide the licensing authority with information, the information period is not to be counted for the purposes of paragraph (3).

(6) In paragraph (5), the “information period” means the period—

(a)beginning with the day on which notice is given; and

(b)ending with the day on which the licensing authority receives the information or the applicant shows to the licensing authority’s satisfaction that the applicant is unable to provide it.

(7) Nothing in this regulation affects the powers conferred by regulations 45G and 45I.

Offences: breach of regulations and false informationU.K.

45K.(1) A person is guilty of an offence if the person—

(a)contravenes regulation 45A(1); or

(b)brokers a medicinal product otherwise than in accordance with the criteria under regulation 45E relating to that person’s brokering registration.

(2) A person is guilty of an offence if the person knowingly gives false information in—

(a)an application for a broker registration under regulation 45B(2);

(b)a notification to the licensing authority under regulation 45F(4);

(c)an application for a variation under regulation 45J(1); or

(d)response to a notice under regulation 45C(3) or 45J(5).

(3) A person is guilty of an offence if, without reasonable excuse, the person fails to comply with a notice under regulation 45F(6) or 45J(5).

PenaltiesU.K.

45L.(1) A person guilty of an offence under regulation 45K(1) or (2) is liable—

(a)on summary conviction to a fine not exceeding the statutory maximum; or

(b)on conviction on indictment to a fine, to imprisonment for a term not exceeding two years, or to both.

(2) A person guilty of an offence under regulation 45K(3) is liable on summary conviction to a fine not exceeding level 3 on the standard scale.]

[F30CHAPTER 4U.K.Importation, manufacture and distribution of active substances

Criteria for importation, manufacture or distribution of active substancesU.K.

45M.(1) A person may not—

(a)import;

(b)manufacture; or

(c)distribute,

an active substance unless that person is registered with the licensing authority in accordance with regulation 45N and the requirements in regulation 45O are met.

(2) Paragraph (1) applies in relation to an active substance which is to be used in an investigational medicinal product only—

(a)if the product has a marketing authorisation, Article 126a authorisation, certificate of registration or traditional herbal registration; and

(b)to the extent that the manufacture of the active substance is in accordance with the terms and conditions of that authorisation, certificate or registration.

(3) Paragraph (1)(a) does not apply to a person who, in connection with the importation of an active substance from a state other than an EEA state—

(a)provides facilities solely for transporting the active substance; or

(b)acting as an import agent, imports the active substance solely to the order of another person who holds a certificate of good manufacturing practice issued by the licensing authority.

Registration in relation to active substancesU.K.

45N.(1) For registration in relation to active substances, the licensing authority must have received a valid registration form from the applicant for import, manufacture or, as the case may be, distribution of an active substance and—

(a)60 days have elapsed since receipt and the licensing authority have not notified the applicant that an inspection will be carried out; or

(b)the licensing authority—

(i)notified the applicant within 60 days of receipt of a registration form that an inspection will be carried out; and

(ii)within 90 days of that inspection the licensing authority have issued that person with a certificate of good manufacturing practice or, as the case may be, of good distribution practice; and

(c)that person has not instructed the licensing authority to end that person’s registration.

(2) The person applying for registration under paragraph (1) must notify the licensing authority of any changes which have taken place as regards the information in the registration form—

(a)immediately where such changes may have an impact on quality or safety of the active substances that are manufactured, imported or distributed;

(b)in any other case, on each anniversary of the receipt of the application form by the licensing authority.

(3) For the purpose of paragraph (2), changes which are notified in accordance with that paragraph shall be treated as incorporated in the application form.

(4) Any notification to the licensing authority under paragraph (2) must be accompanied by the appropriate fee in accordance with the Fees Regulations.

(5) A registration form is valid for the purpose of paragraph (1) if—

(a)it is provided to the licensing authority; and

(b)is completed in the way and form specified in Schedule 7A.

(6) Paragraph (1) does not apply until 20th October 2013 in relation to a person who had, before 20th August 2013, commenced the activity for which the person would, apart from this provision, need to send a registration form to the licensing authority.

Requirements for registration as an importer, manufacturer or distributor of an active substanceU.K.

45O.(1) Where the Commission has adopted principles and guidelines of good manufacturing practice under the third paragraph of Article 47 of the 2001 Directive which applies to an active substance manufactured in the UK, the manufacturer must comply with good manufacturing practice in relation to that active substance.

(2) Where the Commission has adopted principles and guidelines of good distribution practice under the fourth paragraph of Article 47 of the 2001 Directive which applies to an active substance distributed in the United Kingdom, the distributor must comply with good distribution practice in relation to that active substance.

(3) Without prejudice to regulation 37(4) (manufacture and assembly in relation to active substances) and paragraph 9A of Schedule 8 (material to accompany an application for a UK marketing authorisation in relation to an active substance), where the Commission has adopted principles and guidelines of good manufacturing practice under the third paragraph of Article 47 of the 2001 Directive which applies to an active substance imported into the UK and where an active substance is imported from a third country—

(a)the importer must comply with good manufacturing practice and good distribution practice in relation to the active substance;

(b)the active substances must have been manufactured in accordance with standards which are at least equivalent to good manufacturing practice; and

(c)the active substances must be accompanied by a written confirmation from the competent authority of the exporting third country of the following—

(i)the standards of manufacturing practice applicable to the plant manufacturing the exported active substance are at least equivalent to good manufacturing practice,

(ii)the manufacturing plant concerned is subject to regular, strict and transparent controls and to the effective enforcement of standards of manufacturing practice at least equivalent to good manufacturing practice, including repeated and unannounced inspections, so as to ensure a protection of public health at least equivalent to that in the Union, and

(iii)in the event of findings relating to non-compliance, information on such findings is supplied by the exporting third country to the Union without any delay.

(4) Paragraph (3)(c) does not apply—

(a)where the country from where the active substance is exported is included in the list referred to in Article 111b of the 2001 Directive; or

(b)for a period not exceeding the validity of the certificate of good manufacturing practice, where—

(i)in relation to a plant where active substances are manufactured where the competent authority of a member State has found, upon inspection, that a plant complies with the principles and guidelines of good manufacturing practice, and

(ii)the licensing authority is of the opinion that it is necessary to waive the requirement to ensure availability of the active substance.

(5) The criteria in this regulation apply regardless of whether an active substance is intended for export.

Provision of informationU.K.

45P.(1) In this regulation—

“R” means a person who is, or has applied to the licensing authority to become, a registered importer, manufacturer or distributor of active substances;

“reporting year” means a period of twelve months ending on 31st March.

(2) On or before the date specified in paragraph (3), R must submit a report to the licensing authority which—

(a)includes a declaration that R has in place an appropriate system to ensure compliance with regulations 45N, 45O and this regulation; and

(b)details the system which R has in place to ensure such compliance.

(3) The date specified for the purposes of this paragraph is—

(a)in relation to any application made before 31st March 2014, the date of the application; and

(b)in relation to each subsequent reporting year, 30th April following the end of that year.

(4) R must without delay notify the licensing authority of any changes to the matters in respect of which evidence has been supplied in relation to paragraph (2) which might affect compliance with the requirements of this Chapter.

(5) Any report or notification to the licensing authority under paragraph (2) or (4) must be accompanied by the appropriate fee in accordance with the Fees Regulations.

(6) The licensing authority may give a notice to R, requiring R to provide information of a kind specified in the notice within the period specified in the notice.

(7) A notice under paragraph (6) may not be given to R unless it appears to the licensing authority that it is necessary for the licensing authority to consider whether the registration should be varied, suspended or removed from the active substance register.

(8) A notice under paragraph (6) may specify information which the licensing authority thinks necessary for considering whether the registration should be varied, suspended or removed from the active substance register.

Power to suspend or vary or remove an active substance registrationU.K.

45Q.(1) The licensing authority may in accordance with regulation 45R—

(a)suspend an active substance registration for such period as the authority thinks fit;

(b)vary an active substance registration; or

(c)remove a person from the active substance register.

(2) The suspension of registration may be—

(a)total;

(b)limited to active substances of one or more descriptions; or

(c)limited to active substances imported, manufactured, assembled or stored on specified premises or a specified part of any premises.

(3) The powers conferred by this regulation may not be exercised in relation to an active substance registration except on one or more of the following grounds—

(a)the information in the application as a result of which the active substance registration was granted was false or incomplete in a material respect;

(b)a material change of circumstances has occurred in relation to any of the matters stated in the application;

(c)the person with an active substance registration has materially contravened a criterion of registration; or

(d)the person with an active substance registration has without reasonable excuse failed to supply information to the licensing authority with respect to active substances of a description to which the registration relates when required to do so under regulation 45P(6).

Procedure where licensing authority proposes to suspend or vary an active substance registration or remove a person from the active substance registerU.K.

45R.(1) This regulation applies where—

(a)the provisions of regulation 45S do not apply; and

(b)the licensing authority proposes to exercise the power in regulation 45Q(1).

(2) The licensing authority must notify the person with an active substance registration in writing of—

(a)its proposal;

(b)the reasons for it; and

(c)the date (which must be no earlier than 28 days from the notice given by the licensing authority) on which it is proposed that the suspension, variation or removal from the active substance register should take effect.

(3) The person with an active substance registration may before the date specified in the notice—

(a)make written representations to the licensing authority with respect to the proposal; or

(b)notify the licensing authority that the person wishes the licensing authority to submit the proposal to review upon oral representations.

(4) If the person with an active substance registration makes written representations in accordance with sub-paragraph (3)(a) the licensing authority must take those representations into account before making a decision in the matter.

(5) If the person with an active substance registration notifies the licensing authority that the person wishes the licensing authority to submit the proposal to review upon oral representations in accordance with paragraph (3)(b)—

(a)Schedule 5 has effect; and

(b)the person with an active substance registration must pay a fee for a review upon oral representations in accordance with the Fees Regulations.

(6) If the licensing authority proceeds to suspend or vary a registration or remove a person from the active substance register in accordance with the provisions of regulation 45Q it must give a notice to that person.

(7) The notice must—

(a)give particulars of the suspension, variation or removal; and

(b)give reasons for the decision to suspend, vary or remove a person’s entry on the active substance register.

(8) Paragraphs (6) and (7) are without prejudice to any requirement of Schedule 5 as to notification.

Suspension of an active substance registration in cases of urgencyU.K.

45S.(1) The licensing authority may immediately suspend a person’s active substance registration for a period not exceeding three months where it appears to the licensing authority that in the interests of safety it is appropriate to do so.

(2) This paragraph applies where—

(a)a person’s active substance registration has been suspended under paragraph (1); and

(b)it appears to the licensing authority that it is necessary to consider whether a person’s active substance registration should be—

(i)further suspended or varied, or

(ii)removed from the active substance register.

(3) Where paragraph (2) applies, the licensing authority must proceed as set out in regulation 45R (but this is subject to paragraph (4)).

(4) Paragraph (5) applies where, in circumstances where paragraph (2) applies, the licensing authority proceeds as set out in regulation 45R and any proceedings under that regulation have not been finally disposed of before the end of the period for which the registration was suspended under paragraph (1) or further suspended under paragraph (5).

(5) If it appears to the licensing authority to be necessary in the interests of safety to do so, the authority may further suspend the registration for a period which (in the case of each further suspension) is not to exceed three months.

(6) In the event that any challenge against a decision under regulation 45R to suspend, vary or remove a person’s active substance registration is made on an application to the High Court under regulation 322(4), paragraph (5) shall apply, but this is without prejudice to regulation 322(6)(a) (validity of decisions and proceedings).

Variation of an active substance registration on an application from the registered personU.K.

45T.(1) This regulation applies if a person with an active substance registration applies to the licensing authority for a variation of the registration.

(2) The application must—

(a)be in writing;

(b)specify the variation requested;

(c)be signed by or on behalf of the applicant;

(d)be accompanied by such information as may be required to enable the licensing authority to consider the application; and

(e)include the appropriate fee in accordance with the Fees Regulations.

(3) The licensing authority must vary an active substance registration or refuse to vary it within 30 days beginning with the day after the date when the licensing authority receives the application.

(4) The licensing authority may give a notice to the applicant requiring the applicant to supply further information in connection with the application within the period specified in the notice.

(5) If a notice under paragraph (4) requires the applicant to provide the licensing authority with information, the information period is not to be counted for the purposes of paragraph (3).

(6) In paragraph (5), the “information period” means the period—

(a)beginning with the day on which notice is given; and

(b)ending with the day on which the licensing authority receives the information or the applicant shows to the licensing authority’s satisfaction that the applicant is unable to provide it.

(7) Nothing in this regulation affects the powers conferred by regulations 45Q and 45S.

Offences: breach of regulations and false informationU.K.

45U.(1) A person is guilty of an offence if the person imports, manufactures or distributes an active substance in breach of regulation 45M(1).

(2) A person is guilty of an offence if the person knowingly gives false information in—

(a)a registration form received by the licensing authority under regulation 45N(1);

(b)a notification to the licensing authority under regulation 45N(2) or 45P(4);

(c)an application for a variation under regulation 45T(2); or

(d)response to a notice under regulation 45T(4).

(3) A person is guilty of an offence if, without reasonable excuse, the person fails to comply with a notice under regulation 45P(6) or 45T(4).

PenaltiesU.K.

45V.(1) A person guilty of an offence under regulation 45U(1) or (2) is liable—

(a)on summary conviction to a fine not exceeding the statutory maximum; or

(b)on conviction on indictment to a fine, to imprisonment for a term not exceeding two years, or to both.

(2) A person guilty of an offence under regulation 45U(3) is liable on summary conviction to a fine not exceeding level 3 on the standard scale.]

PART 4U.K.Requirement for authorisation

Requirement for authorisationU.K.

46.—(1) A person may not sell or supply, or offer to sell or supply, an unauthorised medicinal product.

(2) A person may not sell or supply, or offer to sell or supply, a medicinal product otherwise than in accordance with the terms of—

(a)a marketing authorisation;

(b)a certificate of registration;

(c)a traditional herbal registration; or

(d)an Article 126a authorisation.

(3) A person may not possess an unauthorised medicinal product if the person knows or has reasonable cause to believe that the product is intended to be sold or supplied to another person within the European Economic Area.

(4) A person may not in the circumstances mentioned in paragraph (5)—

(a)manufacture or assemble a medicinal product; or

(b)procure the sale, supply, manufacture or assembly of a medicinal product.

(5) Those circumstances are that the person knows or has reasonable cause to believe that the medicinal product has been or is intended to be sold or supplied contrary to paragraph (1).

(6) For the purposes of this regulation a medicinal product is unauthorised if none of the following is in force for the product—

(a)a marketing authorisation;

(b)a certificate of registration;

(c)a traditional herbal registration; or

(d)an Article 126a authorisation.

(7) This regulation is subject to—

(a)Part 10 (exceptions to requirement for marketing authorisation etc); and

(b)Article 83 of Regulation (EC) No 726/2004 (authorisation of placing on the market of medicinal product for compassionate reasons).

(8) A medicinal product is not unauthorised for the purposes of this regulation if—

(a)it is sold or supplied, or offered for sale or supply, for export to an EEA State; and

(b)the product may lawfully be sold or supplied in that state by virtue of legislation adopted by that state in compliance with the 2001 Directive.

(9) Paragraphs (1) and (2) do not apply to the sale, supply, or offer for sale or supply, of a medicinal product to a person outside the European Economic Area.

(10) Paragraphs (1) and (2) do not apply to the sale, supply, or offer for sale or supply, of an investigational medicinal product to a person specified in regulation 13(1) of the Clinical Trials Regulations for the purposes of administering that product in a clinical trial, provided that the conditions specified in regulation 13(2) of those Regulations are satisfied.

(11) Paragraph (3) does not apply to possession of an investigational medicinal product by a person who knows or has reasonable cause to believe—

(a)that the investigational medicinal product is intended to be sold or supplied within the European Economic Area; and

(b)that paragraph (10) will apply to the sale or supply.

Breach of requirementU.K.

47.—(1) A person who breaches regulation 46 is guilty of an offence.

(2) A person guilty of an offence under this regulation is liable—

(a)on summary conviction to a fine not exceeding the statutory maximum; or

(b)on conviction on indictment to a fine, to imprisonment not exceeding two years or to both.

(3) It is to be presumed for the purposes of regulation 46(3) that, if a person (“P”) knows or has reasonable cause to believe that a medicinal product is intended to be sold or supplied to another person, P knows or has reasonable cause to believe that the other person is within the European Economic Area.

(4) Paragraph (3) does not apply if P proves that P did not know or have reasonable cause to believe that the person was within the European Economic Area.

(5) Where evidence is adduced that is sufficient to raise an issue with respect to the defence in paragraph (4), the court or jury must assume that the defence is satisfied unless the prosecution proves beyond reasonable doubt that it is not.

(6) Paragraph (7) applies if the holder of a marketing authorisation, certificate of registration, traditional herbal registration or Article 126a authorisation is charged with an offence under this regulation in respect of anything that—

(a)has been manufactured or assembled to the holder's order by another person; and

(b)has been so manufactured or assembled as not to comply with the terms of the authorisation, certificate or registration.

(7) Where this paragraph applies, it is a defence for the holder to prove that—

(a)the holder communicated the terms of the authorisation, certificate or registration to the other person; and

(b)the holder did not know and could not by the exercise of reasonable care have known that those terms had not been complied with.

PART 5U.K.Marketing authorisations

Application of this PartU.K.

48.—(1) This Part applies to relevant medicinal products.

(2) In this Part—

generic medicinal product” has the meaning given in Article 10(2)(b) of the 2001 Directive;

relevant medicinal product” means a medicinal product that is not—

(a)

a registrable homoeopathic medicinal product; or

(b)

a traditional herbal medicinal product; and

reference medicinal product” has the meaning given in Article 10(2)(a) of the 2001 Directive.

Application for UK marketing authorisationU.K.

Application for grant of UK marketing authorisationU.K.

49.—(1) The licensing authority may, subject to regulation 58, grant a UK marketing authorisation for a relevant medicinal product in response to an application made in accordance with this Part.

(2) A marketing authorisation granted under paragraph (1) shall contain terms approved by the licensing authority.

(3) The applicant must be established in the European Union.

(4) The application must be—

(a)made in writing;

(b)signed by or on behalf of the applicant; and

(c)unless the licensing authority directs otherwise, accompanied by any fee payable in connection with the application.

(5) An application is treated as signed for the purposes of paragraph (4)(b) if it is signed with an electronic signature.

(6) The application and any accompanying material must be in English.

(7) The application must include a statement indicating whether the product to which the application relates should be available—

(a)only on prescription;

(b)only from a pharmacy; or

(c)on general sale.

(8) The application must include a statement indicating—

(a)whether any terms of the authorisation are proposed relating to the method of sale or supply of the product (including, in particular, any proposed restrictions affecting the circumstances of the use or promotion of the product); and

(b)if so, what terms are proposed.

Accompanying materialU.K.

50.—(1) An applicant for the grant of a UK marketing authorisation for a relevant medicinal product must provide the material specified in Schedule 8 in relation to the product.

(2) An applicant for the grant of a UK marketing authorisation for a radionuclide generator must, in addition, provide—

(a)a general description of the system together with a detailed description of the components of the system which may affect the composition or quality of the daughter nucleid preparation; and

(b)qualitative and quantitative particulars of the eluate or the sublimate.

(3) The applicant must also, if requested by the licensing authority to do so, provide the licensing authority with material or information that the licensing authority reasonably considers necessary for dealing with the application.

(4) If any of the medicinal products to which the application relates is liable to be imported from a country other than an EEA State, the material or information referred to in paragraph (3) may include an undertaking from the manufacturer of the product to comply with the matters set out in Schedule 9.

(5) Material that is submitted under this regulation must be submitted in accordance with the applicable provisions of Annex I to the 2001 Directive.

(6) This regulation is subject to—

(a)regulation 51 (applications relating to generic medicinal products);

(b)regulation 52 (applications relating to certain medicinal products that do not qualify as generic etc);

(c)regulation 53 (applications relating to certain biological medicinal products);

(d)regulation 54 (applications relating to products in well-established medicinal use);

(e)regulation 55 (applications relating to new combinations of active substances);

(f)regulation 56 (applications containing information supplied in relation to another medicinal product with consent); and

(g)Schedule 10 (applications relating to national homoeopathic products).

Applications relating to generic medicinal productsU.K.

51.—(1) An applicant for a UK marketing authorisation for a relevant medicinal product that is a generic medicinal product may provide information in relation to the application in accordance with Article 10(1), (5) and (6) of the 2001 Directive.

(2) If the licensing authority grants a UK marketing authorisation for the generic medicinal product in accordance with paragraph (1), it is a term of the authorisation that the product must not be sold or supplied, or offered for sale or supply, in the United Kingdom before the time at which it may be placed on the market in accordance with—

(a)Article 10(1) of the 2001 Directive; or

(b)in a case where the application for the marketing authorisation for the reference medicinal product referred to in the application was submitted on or before 30th October 2005, Article 10(1) of the 2001 Directive as it stood before it was amended by Article 1(8) of Directive 2004/27/EC of the European Parliament and of the Council of 31 March 2004 amending the 2001 Directive M41 (“Directive 2004/27/EC”), in accordance with Article 2 of Directive 2004/27/EC .

Marginal Citations

M41OJ No L 136, 30.4.2004, p. 34.

Applications relating to certain medicinal products that do not qualify as generic etcU.K.

52.—(1) This regulation applies where—

(a)an application is made for a UK marketing authorisation in respect of a product by reference to another medicinal product as reference medicinal product; and

(b)one or more of the circumstances listed in Article 10(3) of the 2001 Directive applies in respect of the application.

(2) The applicant must provide information in accordance with Article 10(3) and (6) of the 2001 Directive.

(3) Regulation 51(2) shall apply to the application as it applies in relation to an application made in accordance with regulation 51(1).

Applications relating to similar biological medicinal productsU.K.

53.—(1) This regulation applies if an applicant for a UK marketing authorisation for a biological medicinal product is not able to show that it meets a condition for its being a generic version of a similar medicinal product because of any of the reasons described in Article 10(4) of the 2001 Directive.

(2) The applicant must provide information in accordance with Article 10(4) and (6) of the 2001 Directive.

(3) Regulation 51(2) shall apply to the application as it applies in relation to an application made in accordance with regulation 51(1).

Applications relating to products in well-established medicinal useU.K.

54.—(1) This regulation applies if an applicant for a UK marketing authorisation for a relevant medicinal product is able to demonstrate that the active substances of the product have been in well-established medicinal use within the European Union for at least 10 years, with recognised efficacy and an acceptable level of safety in terms of the conditions set out in Annex I to the 2001 Directive.

(2) The applicant must provide information in accordance with Article 10a of the 2001 Directive.

Applications relating to new combinations of active substancesU.K.

55.—(1) This paragraph applies to an application for a UK marketing authorisation for a relevant medicinal product that contains active substances that—

(a)have been used in medicinal products that have been the subject of a marketing authorisation under these Regulations, the 2001 Directive or Regulation (EC) No 726/2004; but

(b)have not been used in that combination for therapeutic purposes.

(2) The applicant must provide information in accordance with Article 10b of the 2001 Directive.

Applications containing information supplied in relation to another product with consentU.K.

56.—(1) This regulation applies to an application for a UK marketing authorisation for a relevant medicinal product where—

(a)the product that is the subject of the application (“product A”) has the same qualitative and quantitative composition in terms of active substances and the same pharmaceutical form as a product (“product B”);

(b)product B is the subject of a UK marketing authorisation; and

(c)the holder of the marketing authorisation for product B has allowed use to be made of the pharmaceutical, pre-clinical and clinical documentation contained in the file on product B with a view to examining subsequent applications relating to other medicinal products possessing the same qualitative and quantitative composition in terms of active substances and the same pharmaceutical form.

(2) The documentation referred to in paragraph (1)(c) in relation to product B may be used in relation to the application in relation to product A, in accordance with Article 10c of the 2001 Directive.

Obligation to update information supplied in connection with applicationU.K.

57.—(1) The applicant for a UK marketing authorisation must update information supplied in accordance with paragraphs 18 to 21 of Schedule 8 (material to accompany an application for a UK marketing authorisation) in connection with the application.

(2) The applicant must update information supplied in connection with the application to include any further information that is relevant to the evaluation of the safety, quality or efficacy of the product concerned.

(3) Updated information within paragraphs (1) or (2) must be provided as soon as is reasonably practicable after the applicant becomes aware of it.

Consideration of applicationU.K.

Consideration of applicationU.K.

58.—(1) The licensing authority must take all reasonable steps to ensure that it makes a decision to grant or refuse a UK marketing authorisation before the end of 210 days beginning immediately after the day on which the application for the authorisation is submitted in accordance with regulations 49 to 55.

(2) If the licensing authority requests the applicant to provide any further information or material, the period referred to in paragraph (1) is suspended for the period—

(a)beginning with the date on which the request is made; and

(b)ending with the date on which the information or material is provided.

(3) If the licensing authority requests the applicant to give an oral or written explanation of the application, the period referred to in paragraph (1) is suspended for the period—

(a)beginning with the date on which the request is made; and

(b)ending with the date on which the explanation is provided.

(4) The licensing authority may grant the application only if, having considered the application and the accompanying material, the authority thinks that—

(a)the applicant has established the therapeutic efficacy of the product to which the application relates;

(b)the positive therapeutic effects of the product outweigh the risks to the health of patients or of the public associated with the product;

(c)the application and the accompanying material complies with regulations 49 to 55; and

(d)the product's qualitative and quantitative composition is as described in the application and the accompanying material.

(5) Schedule 11 makes provision about advice and representations in relation to an application for the grant of a UK marketing authorisation.

(6) This regulation does not apply to an application that—

(a)has been submitted to the licensing authority in accordance with Article 28 of the 2001 Directive; or

(b)has been referred to the Committee for Medicinal Products for Human Use established under Regulation (EC) No 726/2004 for the application of the procedure laid down in Articles 32 to 34 of the 2001 Directive.

(7) An application to which paragraph (6) applies is to be determined by the licensing authority in accordance with Chapter 4 of Title III of the 2001 Directive.

Conditions of UK marketing authorisation: generalU.K.

59.—(1) The licensing authority may—

(a)grant a UK marketing authorisation subject to one or more of the conditions in paragraph (2); or

(b)vary or remove a condition in paragraph (2) to which the UK marketing authorisation is subject.

(2) Those conditions are—

(a)to take certain measures for ensuring the safe use of the medicinal product and include them in the risk management plan;

(b)to conduct post-authorisation safety studies;

(c)to comply with obligations on the recording or reporting of suspected adverse reactions which are stricter than those referred to in Part 11;

(d)any other conditions or restrictions with regard to the safe and effective use of the medicinal product;

(e)the existence of an adequate pharmacovigilance system; and

(f)to conduct post-authorisation efficacy studies where concerns relating to some aspects of the efficacy of the medicinal product are identified and can be resolved only after the medicinal product has been marketed.

(3) An obligation to conduct such studies as are referred to in paragraph (2)(f) must be based on the delegated acts adopted pursuant to Article 22b of the 2001 Directive, while taking into account the scientific guidance referred to in Article 108a of the 2001 Directive.

(4) The marketing authorisation must lay down deadlines for the fulfilment of the conditions in paragraph (2) where necessary.

(5) The licensing authority must notify the EMA of any marketing authorisation that it has granted subject to a condition included in accordance with this regulation.

(6) The holder of the authorisation must incorporate any condition included in a marketing authorisation in accordance with this regulation into the risk management system for the product.

(7) Schedule 11 makes provision about advice and representations in relation to proposals to vary or remove a condition to which a UK marketing authorisation is subject.

Conditions of UK marketing authorisation: exceptional circumstancesU.K.

60.—(1) The licensing authority may—

(a)grant a UK marketing authorisation subject to conditions in accordance with the following paragraphs of this regulation; or

(b)vary or remove such a condition to which the UK marketing authorisation is subject.

(2) The powers in paragraph (1) may be exercised only after consultation with the applicant for the authorisation or (as the case may be) its holder.

(3) The power in paragraph (1)(a) to grant an authorisation subject to conditions may be exercised only—

(a)in exceptional circumstances; and

(b)when the applicant can show that the applicant is unable to provide comprehensive data on the efficacy and safety of the medicinal product under normal conditions of use.

(4) The conditions must relate to a matter addressed by Annex I to the 2001 Directive.

(5) The conditions may, in particular, relate to the safety of the product to which the authorisation relates.

(6) The conditions may, in particular, require that, where there is a serious adverse reaction relating to the use of the product—

(a)the reaction must be reported to the licensing authority; and

(b)such other action as may be specified in the conditions must be taken.

(7) The licensing authority must keep under review—

(a)the conditions under this regulation to which a UK marketing authorisation is subject; and

(b)the holder's compliance with those conditions.

(8) The licensing authority must consider those matters no less frequently than—

(a)at the end of the period of one year beginning with the date on which the authorisation was granted; and

(b)at the end of each subsequent period of one year.

(9) The licensing authority must notify the EMA of any marketing authorisation that it has granted subject to a condition included in accordance with this regulation.

(10) The holder of the authorisation must incorporate any condition included in a marketing authorisation in accordance with this regulation into the risk management system for the product.

(11) Schedule 11 makes provision about advice and representations in relation to proposals to vary or remove a condition to which a UK marketing authorisation is subject.

Conditions of UK marketing authorisation: new obligations post-authorisationU.K.

61.—(1) After the granting of a UK marketing authorisation, the licensing authority may impose an obligation on the holder of the authorisation in accordance with either or both of —

(a)paragraph (4), in a case where paragraph (2) applies; or

(b)paragraph (5), in a case where paragraph (3) applies.

(2) This paragraph applies if there are concerns about the risks of a medicinal product that is the subject of a marketing authorisation.

(3) This paragraph applies if the understanding of the disease or the clinical methodology indicate that previous efficacy evaluations might have to be revised significantly.

(4) The obligation in this paragraph is to conduct a post-authorisation safety study.

(5) The obligation in this paragraph is to conduct a post-authorisation efficacy study.

(6) If concerns as described in paragraph (2) apply to more than one medicinal product, the licensing authority shall, following consultation with the Pharmacovigilance Risk Assessment Committee, encourage the marketing authorisation holders concerned to conduct a joint post-authorisation safety study.

(7) The obligation under paragraph (5) shall be based on the delegated acts adopted pursuant to Article 22b of the 2001 Directive while taking account of the scientific guidance referred to in Article 108a of the 2001 Directive.

(8) Where the licensing authority imposes an obligation under paragraph (4) or (5), it must without delay give written notice to the holder of —

(a)the imposition of the obligation;

(b)the justification for the imposition;

(c)the objectives and timeframe for submission and conduct of the study; and

(d)the opportunity to present written observations in accordance with paragraph (9) and the time limit specified for doing so.

(9) Where the holder so requests within the period of thirty days beginning on the day after the receipt by the holder of the notice referred to in paragraph (8), the licensing authority must provide the holder of the authorisation with an opportunity to present written observations in response to the imposition of the obligation within the time limit specified by the licensing authority in the notice.

(10) Where the holder presents written observations under paragraph (9), the licensing authority must withdraw or confirm the imposition of the obligation under paragraph (4) or (5) on the basis of the written observations as soon as is reasonably practicable.

(11) Paragraph (12) applies where the licensing authority—

(a)imposes an obligation under paragraph (4) or (5) and the holder does not present written representations under paragraph (9); or

(b)confirms the imposition of an obligation under paragraph (10).

(12) Where this paragraph applies, the licensing authority must vary the marketing authorisation to include the obligation as a condition of the marketing authorisation as if it were a condition imposed under regulation 59 (conditions of UK marketing authorisations: general).

(13) The licensing authority must notify the EMA that the marketing authorisation is subject to a condition included in accordance with paragraph (12).

(14) The holder of the authorisation must incorporate any condition included in a marketing authorisation in accordance with paragraph (12) into the risk management system for the product.

(15) Schedule 11, which makes provision about advice and representations in relation to proposals to vary or remove a condition to which a UK marketing authorisation is subject, shall apply in relation to the variation or removal of a condition included in a marketing authorisation in accordance with paragraph (12).

Classification of UK marketing authorisationU.K.

62.—(1) A UK marketing authorisation must include a term that the product to which the authorisation relates is to be available—

(a)only on prescription;

(b)only from a pharmacy; or

(c)on general sale.

(2) In making a determination under paragraph (1), the licensing authority must have regard to the following in relation to the product—

(a)the maximum single dose;

(b)the maximum daily dose;

(c)the strength of the product;

(d)its pharmaceutical form;

(e)its packaging; and

(f)such other circumstances relating to its use as the licensing authority considers relevant.

(3) A UK marketing authorisation must be granted subject to a condition that the product to which the authorisation relates is to be available only on prescription if the licensing authority considers that the product—

(a)is likely to present a direct or indirect danger to human health, even when used correctly, if used without the supervision of a doctor or dentist;

(b)is frequently and to a very wide extent used incorrectly, and as a result is likely to present a direct or indirect danger to human health;

(c)contains substances, or preparations of substances, of which the activity requires, or the side effects require, further investigation; or

(d)is normally prescribed by a doctor or dentist for parenteral administration.

(4) In deciding whether paragraph (3) applies to a product, the licensing authority must take into account whether the product—

(a)contains a substance listed in any of Schedules I, II or IV to the Narcotics Drugs Convention (where the product is not a preparation listed in Schedule III to that Convention);

(b)contains a substance listed in any of Schedules I to IV of the Psychotropic Substances Convention (where the product is not a preparation which may be exempted from measures of control in accordance with paragraphs 2 and 3 of article 3 of that Convention);

(c)is likely, if incorrectly used—

(i)to present a substantial risk of medicinal abuse,

(ii)to lead to addiction, or

(iii)to be used for illegal purposes;

(d)contains a substance that, by reason of its novelty or properties, might fall within paragraph (c), but as to which there is insufficient information available to determine whether it does so fall;

(e)by reason of its pharmaceutical characteristics or novelty, or in the interests of public health, is reserved for treatments that can only be followed in a hospital;

(f)is used in the treatment of conditions that must be diagnosed in a hospital or in an institution with special diagnostic facilities (although administration and subsequent supervision may be carried out elsewhere); or

(g)is intended for outpatients but may produce very serious side effects which would require a prescription drawn up as required by a specialist and special supervision throughout the treatment.

(5) A UK marketing authorisation may include a term that the product to which the authorisation relates is to be available on general sale only if the licensing authority considers that the product can with reasonable safety be sold or supplied otherwise than by, or under the supervision of, a pharmacist.

Frequency of periodic safety update reportsU.K.

63.—(1) The licensing authority must, if paragraph (2) applies, include in a UK marketing authorisation a term that specifies the frequency, calculated from the date on which the authorisation is granted, with which the holder of the authorisation must submit periodic safety update reports in accordance with regulation 191(8) (obligation on holder to submit periodic safety update reports: general requirements).

(2) This paragraph applies in the case of a medicinal product in relation to which regulation 191(8) applies by virtue of regulation 191(1).

Duties of licensing authority in connection with determinationU.K.

64.—(1) This regulation applies if the licensing authority grants a UK marketing authorisation.

(2) The licensing authority must inform the holder of the authorisation of the summary of the product characteristics as approved by the authority.

(3) The licensing authority must ensure that the summary of the product characteristics continues to match the version it has approved, subject to any changes it approves.

(4) As soon as is reasonably practicable after granting the marketing authorisation, the licensing authority must make available publicly—

(a)the marketing authorisation;

(b)the package leaflet;

(c)the summary of the product characteristics;

(d)any conditions established in accordance with Articles 21a, 22 and 22a of the 2001 Directive; and

(e)any deadlines for the fulfilment of those conditions.

(5) The licensing authority must draw up an assessment report and make comments on the file as regards—

(a)the results of the pharmaceutical and pre-clinical tests, the clinical trials, the risk management system and the pharmacovigilance system of the product to which the authorisation relates; or

(b)in the case of a national homoeopathic medicinal product within the meaning of Schedule 10, the information submitted under paragraphs 3 to 5 of that Schedule.

(6) The licensing authority must—

(a)revise the assessment report whenever new information becomes available that is of importance for the evaluation of the quality, safety or efficacy of the medicinal product;

(b)make the assessment report publicly available (with the omission of information of a commercially confidential nature) as soon as is reasonably practicable after it has been prepared or revised; and

(c)include in the assessment report a summary, written in a manner that is understandable to the public, that contains, in particular, a section relating to the conditions of use of the medicinal product.

(7) The assessment must be provided separately for each indication that is authorised.

Validity of UK marketing authorisationU.K.

Validity of UK marketing authorisationU.K.

65.—(1) Subject to the following paragraphs, a UK marketing authorisation remains in force—

(a)for an initial period of five years beginning with the date on which it is granted; and

(b)if the authorisation is renewed in accordance with regulation 66, for an unlimited period after its renewal.

(2) The licensing authority may, on the first application for renewal of an authorisation, determine on grounds relating to pharmacovigilance, including exposure of an insufficient number of patients to the medicinal product concerned, that it should be necessary for the holder to make one further application for renewal.

(3) In that event the authorisation remains in force—

(a)for a further period of five years beginning with the date on which it is first renewed; and

(b)if the authorisation is further renewed under regulation 66, for an unlimited period after its further renewal.

(4) If an application for the renewal or further renewal of an authorisation is made in accordance with regulation 66 the authorisation remains in force until the licensing authority notifies the applicant of its decision on the application.

(5) This regulation is subject to—

(a)regulation 67 (failure to place on the market etc); and

(b)regulation 68 (revocation etc of marketing authorisations).

Application for renewal of authorisationU.K.

66.—(1) The licensing authority may renew a UK marketing authorisation in response to an application made in accordance with this regulation.

(2) The applicant must be established in the European Union.

(3) The application must be—

(a)made in writing;

(b)signed by or on behalf of the applicant; and

(c)unless the licensing authority directs otherwise, accompanied by any fee payable in connection with the application.

(4) An application is treated as signed for the purposes of paragraph (3)(b) if it is signed with an electronic signature.

(5) The application must be made so that it is received by the licensing authority before the beginning of the period of nine months ending with the expiry of the period mentioned in paragraph (1)(a) or (as the case may be) (3)(a) of regulation 65 (initial and further period of validity).

(6) The holder must provide a consolidated version of the file in respect of quality, safety and efficacy, including—

(a)the evaluation of data contained in suspected adverse reaction reports and periodic safety update reports submitted in accordance with Part 11; and

(b)all amendments made since the authorisation was granted.

(7) The licensing authority may renew a UK marketing authorisation only if, having considered the application and the material accompanying it, the authority thinks that the positive therapeutic effects of the product to which the authorisation relates outweigh the risks of the product to the health of patients or of the public.

(8) Schedule 11 makes provision about advice and representations in relation to an application for the renewal of a UK marketing authorisation.

Failure to place on the market etcU.K.

67.—(1) A UK marketing authorisation ceases to be in force if the product to which it relates is not placed on the market in the United Kingdom during the period of three years beginning immediately after the day on which it was granted.

(2) A UK marketing authorisation for a product which has been placed on the market ceases to be in force if the product to which it relates is not sold or supplied in the United Kingdom for a period of three years.

(3) This regulation does not apply if the licensing authority grants an exemption from its operation.

(4) An exemption may be granted—

(a)in response to an application in writing by the holder of the UK marketing authorisation; or

(b)by the licensing authority of its own motion.

(5) An exemption may be granted only—

(a)in exceptional circumstances; and

(b)on public health grounds.

(6) An exemption—

(a)has effect for the period determined by the licensing authority, which may not exceed three years beginning with the day on which it is granted; and

(b)may be renewed or further renewed.

Revocation, variation and suspension of marketing authorisationU.K.

Revocation, variation and suspension of UK marketing authorisationU.K.

68.—(1) The licensing authority may revoke, vary or suspend a UK marketing authorisation if any of the following conditions is met.

(2) Condition A is that the licensing authority thinks that—

(a)the product to which the authorisation relates is harmful;

(b)the positive therapeutic effects of the product do not outweigh the risks of the product to the health of patients or of the public;

(c)the product lacks therapeutic efficacy, in that therapeutic results cannot be obtained from the product; or

(d)the product's qualitative or quantitative composition is not as described in the application for the authorisation or the material supplied with it.

(3) Condition B is that the licensing authority thinks that the application or the material supplied with it is incorrect.

(4) Condition C is that the licensing authority thinks that there has been a breach of—

(a)a term of the authorisation; or

(b)a requirement imposed by Part 13 (packaging and leaflets).

(5) Condition D is that the licensing authority thinks that a condition to which the authorisation is subject by virtue of regulations 59 (conditions of UK marketing authorisations: general), 60 (conditions of UK marketing authorisations: exceptional circumstances) or 61 (conditions of UK marketing authorisations: new obligations post-authorisation) has not been fulfilled.

(6) Condition E is that the licensing authority thinks that the holder of the authorisation has not complied with regulation 75(1) to (3) (requirements to provide information).

(7) Condition F is that the holder of the authorisation has ceased to be established in the European Union.

(8) Condition G is that—

(a)the product to which the authorisation relates is manufactured in the United Kingdom; and

(b)the licensing authority thinks that the holder of the manufacturer's licence for the product has failed to comply in relation to the product with regulations 37 (manufacturing and assembly), 38 (imports from states other than EEA States), 39 (further requirements for manufacturer's licence), 40 (obligation to provide information relating to control methods) or 41 (requirements as to qualified persons).

(9) Condition H is that—

(a)the product to which the authorisation relates is manufactured in a member State other than the United Kingdom; and

(b)the licensing authority thinks that the licensee under the manufacturer's licence for the product has failed to comply in relation to the product with provision giving effect to Article 41 of the 2001 Directive (requirements relating to manufacturing authorisations) in that member State.

(10) Condition I is that the licensing authority thinks that urgent action to protect public health is necessary, in which case it—

(a)may suspend the authorisation; and

(b)must notify the suspension to the EMA, the European Commission, and all other member States by the end of the next working day following the day on which the suspension comes into force.

(11) Condition J is that—

(a)the holder applies to vary the authorisation; and

(b)the licensing authority thinks that the application should be granted.

[F31(11A) Condition K is that the manufacture of the product to which the authorisation relates is not carried out in compliance with the particulars provided under paragraphs 5 and 9 of Schedule 8.]

(12) Schedule 11 makes provision about advice and representations in relation to a proposal to revoke, vary or suspend a UK marketing authorisation, other than a proposal to vary an authorisation on the application of its holder.

(13) This regulation is subject to regulation 70 (authorisations granted under Chapter 4 of Title III of the 2001 Directive).

Suspension of use etc of relevant medicinal productU.K.

69.—(1) The licensing authority may, if any of the following conditions are met, suspend the use, sale, supply or offer for sale or supply within the United Kingdom of a product to which a UK marketing authorisation relates.

(2) Condition A is that the licensing authority thinks that—

(a)the product to which the authorisation relates is harmful;

(b)the positive therapeutic effects of the product do not outweigh the risks of the product to the health of patients or of the public;

(c)the product lacks therapeutic efficacy, in that therapeutic results cannot be obtained from the product; or

(d)the product's qualitative or quantitative composition is not as described in the application for the authorisation or the material supplied with it.

(3) Condition B is that the licensing authority thinks that the holder of the authorisation has not complied with regulation 75(7) (requirements to provide proof of controls on manufacturing process).

(4) Condition C is that the licensing authority thinks that there has been a breach of—

(a)a term of the authorisation; or

(b)a requirement imposed by Part 13 (packaging and leaflets).

(5) Condition D is that the licensing authority thinks that paragraph (4) or (5) of regulation 26 (power to revoke, suspend or vary manufacturers' licences) applies in relation to the manufacturer's licence for the product to which the authorisation relates.

(6) A suspension under this regulation may relate to batches of the product.

(7) The licensing authority must give notice in writing of a suspension under this regulation to the holder of the UK marketing authorisation.

(8) The licensing authority must provide in the notice that the suspension—

(a)is to take effect immediately or from a date specified in the notice; and

(b)is to apply for the period specified in the notice.

(9) Where a medicinal product is the subject of a suspension under this regulation, the licensing authority may—

(a)in exceptional circumstances; and

(b)for such a transitional period as the licensing authority may determine,

allow the supply of the medicinal product to patients who are already being treated with the medicinal product.

(10) This regulation is subject to regulation 70 (authorisations granted under Chapter 4 of Title III of the 2001 Directive).

Authorisations granted under Chapter 4 of Title III of the 2001 DirectiveU.K.

70.—(1) Regulations 68 and 69 do not apply in relation to a UK marketing authorisation that—

(a)was granted in accordance with the provisions of Chapter 4 of Title III of the 2001 Directive (mutual recognition procedure and decentralised procedure);

(b)was granted before 1st January 1995 in accordance with Article 4 of Council Directive 87/22/EEC of 22 December 1986 on the approximation of national measures relating to the placing on the market of high-technology medicinal products, particularly those derived from biotechnology M42; or

(c)was subject to the procedure laid down in Articles 32 to 34 of the 2001 Directive following a referral under Article 30 or 31 of that Directive, unless the procedure was limited to certain specific parts of the authorisation.

(2) A proposal by the licensing authority to vary, suspend or revoke a marketing authorisation within paragraph (1), or an application by the holder of such an authorisation to vary or revoke it, is to be determined in accordance with Chapter 4 of Title III of the 2001 Directive.

Marginal Citations

M42OJ No L 15, 17.1.1987. p.38.

Withdrawal of medicinal product from the marketU.K.

71.—(1) This regulation applies if—

(a)under regulation 68, regulation 70(2), Article 34(3) of the 2001 Directive or Regulation (EC) No 726/2004 the licensing authority or the European Commission revokes or suspends a marketing authorisation, or

(b)under regulation 69 or Article 20(4) of Regulation (EC) No 726/2004 the licensing authority suspends the use, sale, supply or offer for sale or supply within the United Kingdom of a product to which a marketing authorisation relates.

(2) The licensing authority may give written notice to the person who is, or immediately before its revocation was, the holder of the authorisation requiring that person to comply with both of the following requirements.

(3) Requirement A is to take all reasonably practicable steps to inform wholesalers, retailers, medical practitioners, patients and others who may be in possession of the product to which the authorisation relates of—

(a)the revocation or suspension;

(b)the reasons for the revocation or suspension; and

(c)any action to be taken to restrict or prevent further use, sale, supply or offer for sale or supply of the product.

(4) Requirement B is to take all reasonably practicable steps to withdraw from the market in the United Kingdom and recover possession of—

(a)the product; or

(b)the batches of the product specified in the notice,

within the time and for the period specified in the notice.

Sale etc of suspended medicinal productU.K.

72.—(1) This regulation applies if the use, sale, supply or offer for sale or supply of a medicinal product is suspended in accordance with regulation 69 or 70(2) or Article 20(4) of Regulation (EC) No 726/2004.

(2) A person must not—

(a)sell, supply or offer to sell or supply the product; or

(b)procure the sale, supply or offer for sale or supply of the product,

knowing, or having reasonable cause to believe, that such use, sale, supply or offer for sale or supply is suspended.

Obligations of holder of marketing authorisationU.K.

Obligation to notify placing on the market etcU.K.

73.—(1) The holder of a UK marketing authorisation must notify the licensing authority of the date on which the product to which the authorisation relates is placed on the market in the United Kingdom, taking account of the various presentations authorised.

(2) A notification under paragraph (1) must be given before the end of the period of two months beginning with the date on which the product is placed on the market.

(3) The holder of a UK marketing authorisation must notify the licensing authority if the product to which the authorisation relates is to be withdrawn from the market in the United Kingdom (whether temporarily or permanently).

(4) A notification under paragraph (3) must be given before the beginning of the period of two months ending with the date on which the product is to be withdrawn from the market unless it is not reasonably practicable to do so.

(5) In that event, the notification must be given as far as is reasonably practicable in advance of the date on which the product is withdrawn from the market.

[F32(5A) The holder of a UK marketing authorisation must notify the licensing authority forthwith if the holder takes action to—

(a)request the cancellation of the authorisation;

(b)not apply for the renewal of the authorisation; or

(c)withdraw the product to which the authorisation relates from the market in a third country (whether temporarily or permanently) and the action is based on any of the grounds set out in Article 116 or 117(1) of the 2001 Directive.

(5B) A notification under paragraph (3) or (5A) must include the reasons for the action, in particular declaring if the action is based on any of the grounds set out in Article 116 or 117(1) of the 2001 Directive.

(5C) The holder of a UK marketing authorisation must also notify the EMA forthwith where the action which is the subject of a notification by the holder under paragraph (3) or (5A) is based on any of the grounds set out in Article 116 or 117(1) of the 2001 Directive.]

(6) The licensing authority may require the holder of a UK marketing authorisation to provide—

(a)information relating to the volume of sales in the United Kingdom of the product to which the authorisation relates; or

(b)information of which the holder is aware relating to the volume of prescriptions in the United Kingdom for the product.

(7) The holder of a UK marketing authorisation must provide the licensing authority with information that it requires under paragraph (6)—

(a)where the period within which the information must be provided is specified in a written notice given to the holder by the licensing authority, before the end of that period; or

(b)otherwise, as soon as is reasonably practicable after receipt of the request.

Obligation to take account of scientific and technical progressU.K.

74.—(1) The holder of a UK marketing authorisation must keep under review the methods of manufacture and control of the product to which the authorisation relates, taking account of scientific and technical progress.

(2) As soon as is reasonably practicable after becoming aware of the need to do so, the holder must apply to vary the marketing authorisation to make any changes to those methods that are required to ensure they are generally accepted scientific methods.

Obligation to provide information relating to safety etcU.K.

75.—(1) The holder of a UK marketing authorisation must provide the licensing authority with any new information that might entail the variation of the authorisation.

(2) The holder must, in particular, provide the licensing authority with the following information—

(a)information about any prohibition or restriction imposed in relation to the product to which the authorisation relates by the competent authority of any country in which the product is on the market;

(b)positive and negative results of clinical trials or other studies in all indications and populations, whether or not included in the marketing authorisation;

(c)data on the use of the medicinal product where such use is outside the terms of the marketing authorisation; and

(d)any other information that the holder considers might influence the evaluation of the benefits and risks of the product.

(3) Information within paragraph (1) or (2) must be provided as soon as is reasonably practicable after the holder becomes aware of it.

(4) The licensing authority may require the holder of a UK marketing authorisation to provide the authority with information that—

(a)is specified by the licensing authority; and

(b)demonstrates that the positive therapeutic effects of the product to which the authorisation relates continue to outweigh the risks of the product to the health of patients or of the public.

(5) The information that may be required under paragraph (4) includes information arising from use of the product—

(a)in a country which is not an EEA State; or

(b)outside the terms of the marketing authorisation,

including use in clinical trials.

(6) If the information supplied under paragraph (1), (2) or (4) entails the variation of the UK marketing authorisation, the holder must make an application to the licensing authority to that effect as soon as is reasonably practicable after becoming aware of the information.

(7) The licensing authority may require the holder of a UK marketing authorisation to provide the authority with proof of the control methods employed by the manufacturer of the product to which the authorisation relates.

(8) The holder of a UK marketing authorisation must provide the licensing authority with information it requests under paragraphs (4) or (7)—

(a)where the period within which the information must be provided is specified in a written notice given to the holder by the licensing authority, before the end of that period; or

(b)otherwise, as soon as is reasonably practicable after receipt of the request.

Obligation in relation to product informationU.K.

76.—(1) The holder of a UK marketing authorisation for a medicinal product must ensure that the product information relating to the product is kept up to date with current scientific knowledge.

(2) In this regulation “current scientific knowledge” includes the conclusions of the assessment and recommendations made public by means of the European medicines web-portal established in accordance with Article 26 of Regulation (EC) No 726/2004.

Record-keeping obligationsU.K.

77.  The holder of a marketing authorisation must keep any documents or information that will facilitate the withdrawal or recall from sale or supply of any product to which the authorisation relates.

Obligation to ensure appropriate and continued suppliesU.K.

78.  The holder of a marketing authorisation must take all reasonable steps to ensure appropriate and continued supplies of the product to which the authorisation relates to pharmacies and persons authorised to supply the product so that the needs of patients in the United Kingdom are met.

Offences relating to specific requirementsU.K.

Failure to provide information on marketing authorisations to EMAU.K.

79.—(1) The holder of a marketing authorisation is guilty of an offence if the holder—

(a)has not submitted information to the EMA as required by Article 57(2)(b) of Regulation (EC) No 726/2004 (information on all existing medicinal products for human use authorised or registered in the EU) in relation to any medicinal product that is the subject of a marketing authorisation granted before 2nd July 2012; and

(b)fails to do so as soon as is reasonably practicable after the coming into force of these Regulations.

(2) The holder of a marketing authorisation is guilty of an offence if the holder fails to submit information to the EMA as required by Article 57(2)(c) of Regulation (EC) No 726/2004 (information on any new or varied authorisations granted in the EU) in relation to any medicinal product that is the subject of a marketing authorisation granted on or after 2nd July 2012 as soon as is reasonably practicable after the grant of the authorisation.

Urgent safety restrictionsU.K.

80.  The holder of a marketing authorisation is guilty of an offence if the holder —

(a)fails to inform the licensing authority or the European Commission in accordance with Article 22(1) of Regulation (EC) No 1234/2008 that the holder has taken urgent safety restrictions on the holder's own initiative;

(b)fails to implement an urgent safety restriction imposed on the holder by the licensing authority or the European Commission under Article 22(2) of that Regulation; or

(c)fails to submit an application for variation of the marketing authorisation to the licensing authority or the European Commission in accordance with Article 22(3) of that Regulation before the end of a period of fifteen days beginning on the day after—

(i)the taking under Article 22(1) or, as the case may be,

(ii)the imposition under Article 22(2),

of that Regulation of an urgent safety restriction.

Offences relating to EU marketing authorisationsU.K.

Obligation to update information supplied in connection with EU applicationU.K.

81.  An applicant for an EU marketing authorisation is guilty of an offence if that person fails to supply updated information to the EMA in accordance with Article 8(3) of the 2001 Directive as applied by Article 6(1) of Regulation (EC) No 726/2004.

EU marketing authorisations: failure to notify placing on market etcU.K.

82.—(1) The holder of an EU marketing authorisation is guilty of an offence if the holder fails to notify the EMA in accordance with—

(a)the first paragraph of Article 13(4) of Regulation (EC) No 726/2004 (requirement to notify date of placing of product on the market); F33...

(b)the second paragraph of Article 13(4) of Regulation (EC) No 726/2004 (requirement to notify that product is to be withdrawn from the [F34market); or]

[F35(c)Article 14b of Regulation (EC) No 726/2004 (requirement to notify suspending of marketing of the product etc).]

(2) The holder of an EU marketing authorisation is guilty of an offence if the holder fails to provide the EMA with information that it requires under the third paragraph of Article 13(4) of Regulation (EC) No 726/2004 (information as to sales and prescriptions)—

(a)where the period within which the information must be provided is specified in a written notice given to the holder by the EMA, before the end of that period; or

(b)otherwise, as soon as is reasonably practicable after receipt of the request.

EU marketing authorisations: failure to take account of technical and scientific progressU.K.

83.  The holder of an EU marketing authorisation is guilty of an offence if the holder fails to apply to vary the marketing authorisation as required by Article 16(1) of Regulation (EC) No 726/2004 (obligation to take account of scientific and technical progress).

EU marketing authorisations: failure to provide information as to safety etcU.K.

84.—(1) The holder of an EU marketing authorisation is guilty of an offence if the holder fails to provide information to the EMA, the Commission or the licensing authority as required by Article 16(2) of Regulation (EC) No 726/2004 (new information which might entail amendment of particulars or documents) as soon as is reasonably practicable after becoming aware of the information.

(2) The holder of an EU marketing authorisation is guilty of an offence if the holder fails to provide the EMA with information that it requests as required by the first paragraph of Article [F3616(3a)] of Regulation (EC) No 726/2004 (data on risk-benefit balance).

EU marketing authorisations: failure to update product informationU.K.

85.—(1) The holder of an EU marketing authorisation for a medicinal product is guilty of an offence if the holder fails to ensure that the product information relating to the product is kept up to date with current scientific knowledge, as required by Article 16(3) of Regulation (EC) No 726/2004.

(2) In this regulation “current scientific knowledge” includes the conclusions of the assessment and recommendations made public by means of the European medicines web-portal established in accordance with Article 26 of Regulation (EC) No 726/2004.

EU marketing authorisations: breach of pharmacovigilance condition etcU.K.

86.—(1) The holder of an EU marketing authorisation is guilty of an offence if the holder fails to comply with—

(a)any obligation to which the marketing authorisation is subject by virtue of Articles 10a(1) or 14(7); or

(b)any condition to which the authorisation is subject by virtue of Article 14(8),

of Regulation (EC) No 726/2004.

(2) The holder of an EU marketing authorisation is guilty of an offence if the holder fails to incorporate into the risk management system for the product as required by Article 14a of Regulation (EC) No 726/2004

(a)any recommendation referred to in Article 9(4)(c), (ca), (cb) or (cc);

(b)any obligation to which the authorisation is subject by virtue of Articles 10a(1) or 14(7) ; or

(c)any condition to which the marketing authorisation is subject by virtue of Article 14(8),

of Regulation (EC) No 726/2004.

Offences relating to advanced therapy medicinal productsU.K.

Offences in connection with risk management systems and traceability systemsU.K.

87.—(1) The holder of an EU marketing authorisation for an advanced therapy medicinal product is guilty of an offence if the holder fails to—

(a)submit an additional report evaluating the effectiveness of a risk management system and the results of studies within the period of 21 days beginning on the day following receipt of a request made under the second sub-paragraph of Article 14(2) of Regulation (EC) No 1394/2007, or such longer period as the EMA may specify; or

(b)include in any periodic safety update report referred to in Article 28(2) of Regulation (EC) No 726/2004 an evaluation of the effectiveness of a risk management system or of the results of any study performed pursuant to the first sub-paragraph of Article 14(2) of Regulation (EC) No 1394/2007, as required by the third sub-paragraph of Article 14(2).

(2) A person who is, or who immediately before its revocation or withdrawal was, the holder of an EU marketing authorisation for an advanced therapy medicinal product is guilty of an offence if the person fails to—

(a)establish and maintain a traceability system in accordance with the requirements set out in Article 15(1) of Regulation (EC) No 1394/2007;

(b)where the product contains human cells or tissues, to ensure that the traceability system is complementary to and compatible with the requirements laid down in Articles 8 and 14 of Directive 2004/23/EC, as regards human cells and tissues other than blood cells, and Articles 14 and 24 of Directive 2002/98/EC, as regards blood cells; or

(c)to keep the data to which the traceability system relates in accordance with the requirements of Article 15(4) of Regulation (EC) No 1394/2007.

Offence concerning data for advanced therapy medicinal productsU.K.

88.—(1) A person who is, or immediately before its revocation or suspension was, the holder of an EU marketing authorisation relating to an advanced therapy medicinal product is guilty of an offence if the person fails to—

(a)keep the data referred to in Article 15(1) of Regulation (EC) No 1394/2007 in accordance with the requirements of Article 15(4) of that Regulation; or

(b)transfer the data referred to in Article 15(1) to the EMA in the event of that person's bankruptcy or liquidation in accordance with Article 15(5),

but this is subject to paragraph (2).

(2) Paragraph (1)(b) does not apply if—

(a)the person is bankrupt or in liquidation and has transferred the data to another person; or

(b)the period for which the person was required to keep the data in accordance with the requirements of Article 15(4) mentioned in paragraph (1)(a) has expired.

Offences relating to the Paediatric RegulationU.K.

Offences in connection with withdrawal of product from the marketU.K.

89.—(1) This regulation applies to a person (“H”) if—

(a)H is the holder of a UK marketing authorisation;

(b)H has benefited from one or more rewards or incentives under any of Articles 36, 37 and 38 of the Paediatric Regulation in relation to the product to which the authorisation relates, and

(c)all of the periods of protection provided pursuant to those Articles have expired in relation to H.

(2) H is guilty of an offence if H ceases to supply the product without previously in accordance with Article 35 of the Paediatric Regulation —

(a)transferring the UK marketing authorisation to another person who has declared an intention to continue to supply the product; or

(b)allowing such a person to use the pharmaceutical, pre-clinical and clinical documentation contained in the file on that product as provided for in regulation 56.

(3) H is guilty of an offence if H—

(a)ceases to supply the product; and

(b)does not in accordance with Article 35 of the Paediatric Regulation inform the EMA of H's intention to do so before the beginning of the period of six months ending immediately before the day on which H does so.

Failure to place on the market taking account of paediatric indicationU.K.

90.—(1) A person (“P”) is guilty of an offence if—

(a)P is the holder of a UK marketing authorisation;

(b)P obtains a paediatric indication in respect of the product to which the authorisation relates following completion of an agreed paediatric investigation plan;

(c)the product was placed on the market for other indications before P obtained that paediatric indication; and

(d)P fails to place the product on the market taking account of the paediatric indication in accordance with Article 33 of the Paediatric Regulation before the end of the period of two years beginning immediately after the day on which the paediatric indication is authorised.

(2) In this regulation “paediatric indication” means a term of the marketing authorisation enabling the product to which it relates to be used by or administered to persons under the age of 18 years.

Failure to notify results of third country clinical trialsU.K.

91.—(1) This regulation applies to a person (“P”) if—

(a)a decision by the EMA in respect of a paediatric investigation plan is addressed to P;

(b)the plan refers to clinical trials carried out in third countries (“third country clinical trials”); and

(c)P is established in the United Kingdom.

(2) P is guilty of an offence if P does not enter into the database referred to in Article 11 of the Clinical Trials Directive the details set out in that Article in relation to the third country clinical trials in accordance with Article 41(1) of the Paediatric Regulation within whichever is the later of—

(a)the period of one month beginning after the day on which the decision was received; or

(b)the period of one month beginning after the day on which the necessary permission to conduct the clinical trial was received from the competent authorities in the country where the clinical trial is to take place.

(3) P is guilty of an offence if P does not submit the results of those clinical trials to the EMA in accordance with Article 41(2) of the Paediatric Regulation within the period of—

(a)six months, if P is the holder of a marketing authorisation for the medicinal product concerned; or otherwise

(b)twelve months,

beginning with the day on which the last of those trials ended.

(4) Paragraph (3) does not apply, and regulation 93(3) shall apply, in the case of a clinical trial that forms part of a paediatric study to which regulation 93 applies.

Failure of sponsor of UK paediatric clinical trial to notify results of trialU.K.

92.—(1) This regulation applies to the sponsor (“S”) of a paediatric clinical trial in the United Kingdom in respect of a medicinal product if—

(a)the product has a UK marketing authorisation but S is not the holder of the authorisation; or

(b)the product does not have a marketing authorisation.

(2) S is guilty of an offence if S does not submit the results of the clinical trial to the EMA in accordance with Article 41(2) of the Paediatric Regulation within the period of twelve months beginning with the day on which the trial ended.

Failure to notify results of paediatric studyU.K.

93.—(1) This regulation applies to a person (“H”) if—

(a)H is the holder of a UK marketing authorisation; and

(b)H sponsors a paediatric study in respect of the product to which the authorisation relates.

(2) H is guilty of an offence if H does not submit the results of the study to the licensing authority in accordance with Article 46(1) of the Paediatric Regulation within the period of six months beginning with the day on which the study ended.

(3) H is guilty of an offence if H does not submit the results of any clinical trial that forms part of that study to the EMA in accordance with Article 41(2) of the Paediatric Regulation within the period of six months beginning with the day on which the trial ended.

Failure to submit report to EMAU.K.

94.  The holder of a marketing authorisation is guilty of an offence if the holder fails to submit an annual report to the EMA as required by Article 34(4) of the Paediatric Regulation.

General provisions relating to offencesU.K.

Offences in connection with applicationU.K.

95.  A person is guilty of an offence if, in the course of an application for the grant, renewal or variation of a marketing authorisation for a relevant medicinal product, the person—

(a)fails to provide the licensing authority with any information that is relevant to the evaluation of the safety, quality or efficacy of the product;

(b)provides to the licensing authority any information that is relevant to the evaluation of the safety, quality or efficacy of the product but that is false or misleading in a material particular;

(c)fails to provide the EMA with any information that is relevant to the evaluation of the safety, quality or efficacy of the product as required by paragraph (7) or (11) in the “Introduction and general principles” of Annex 1 to the 2001 Directive as applied by Article 6(1) of Regulation (EC) No 726/2004; or

(d)provides to the EMA any information of the kind described in sub-paragraph (c) that is false or misleading in a material particular.

Provision of false or misleading informationU.K.

96.—(1) The holder of a marketing authorisation is guilty of an offence if the holder provides any information to which paragraph (2) applies that is relevant to the evaluation of the safety, quality or efficacy of a medicinal product but that is false or misleading in a material particular to—

(a)the licensing authority;

(b)the EMA; or

(c)the competent authorities of other EEA States.

(2) This paragraph applies to information about the product that is supplied pursuant to the obligations in—

(a)these Regulations; or

(b)Regulation (EC) No 726/2004.

(3) This regulation is without prejudice to the operation of regulation 95.

Breach of pharmacovigilance conditionU.K.

97.  The holder of a marketing authorisation is guilty of an offence if the holder fails to comply with a condition to which the marketing authorisation is subject by virtue of any of regulations 59 (conditions of UK marketing authorisation: general), 60 (conditions of UK marketing authorisation: exceptional circumstances) or 61 (conditions of UK marketing authorisation: new obligations post-authorisation).

General offence of breach of provision of this PartU.K.

98.—(1) A person is guilty of an offence if that person commits a breach of a provision in this Part.

(2) A breach of a provision in this Part includes any—

(a)failure by the holder of a marketing authorisation to comply with any requirement or obligation in this Part:

(b)contravention by any person of any prohibition in this Part; or

(c)failure to comply with any requirement imposed on a person by the licensing authority pursuant to this Part.

(3) Paragraph (1) is without prejudice to any offence established by any other provision in this Part.

PenaltiesU.K.

99.—(1) A person guilty of an offence under this Part, other than a breach of regulation 79 (failure to provide information on marketing authorisations to EMA), is liable—

(a)on summary conviction, to a fine not exceeding the statutory maximum; or

(b)on conviction on indictment, to a fine, to imprisonment for a term not exceeding two years or to both.

(2) A person guilty of a breach of regulation 79 is liable—

(a)on summary conviction, to a fine not exceeding the statutory maximum; or

(b)on conviction on indictment, to a fine.

Persons liableU.K.

100.  If a breach of regulation 95 (offences in connection with application) is committed by a person acting as employee or agent, the employer or principal of that person is guilty of the same offence and is liable to be proceeded against and punished accordingly.

DefencesU.K.

101.—(1) Paragraph (2) applies if the holder of a marketing authorisation is charged with an offence under this Part in respect of anything that—

(a)has been manufactured or assembled to the holder's order by another person; and

(b)has been so manufactured or assembled as not to comply with the terms of the authorisation.

(2) It is a defence for the holder to prove that—

(a)the holder communicated the terms of the authorisation to the other person; and

(b)the holder did not know and could not by the exercise of reasonable care have known that those terms had not been complied with.

(3) It is a defence for a person charged with an offence consisting of a breach of regulations 73(3) or 78, or an offence under any of regulations 88 to 93, 95 and 96, to prove that the person took all reasonable precautions and exercised all due diligence to avoid commission of that offence.

(4) Where evidence is adduced that is sufficient to raise an issue with respect to the defence in paragraph (3), the court or jury must presume that the defence is satisfied unless the prosecution proves beyond reasonable doubt that it is not.

PART 6U.K.Certification of homoeopathic medicinal products

Application of PartU.K.

Application of PartU.K.

102.—(1) This Part applies to a homoeopathic medicinal product (a “registrable homoeopathic medicinal product”) that meets the following conditions.

(2) Condition A is that the product is administered orally or externally.

(3) Condition B is that no specific therapeutic indication appears—

(a)on the labelling of the product; or

(b)in any information supplied with the product.

(4) Condition C is that—

(a)the product contains no more than one part per 10,000 of the mother tincture; and

(b)in a case where the product's active substance is a relevant allopathic substance, the product contains no more than 1/100th of the smallest concentration of that substance used in allopathy.

(5) In this regulation “relevant allopathic substance” means an active substance whose presence in an allopathic medicinal product means that the product is only available on prescription.

(6) For this purpose—

(a)allopathic medicinal product” means a medicinal product other than a homoeopathic medicinal product; and

(b)allopathy” means treatment using an allopathic medicinal product.

Application for certificate of registration and consideration of applicationU.K.

Application for certificate of registrationU.K.

103.—(1) The licensing authority may, subject to regulation 104, grant an application for a certificate of registration for a registrable homoeopathic medicinal product in response to an application made in accordance with this Part.

(2) A certificate granted under paragraph (1) shall contain terms approved by the licensing authority.

(3) The application may relate to two or more homoeopathic medicinal products derived from the same homoeopathic stock or the same combination of homoeopathic stocks.

(4) The applicant must be established in the European Union.

(5) The application must be—

(a)made in writing;

(b)signed by or on behalf of the applicant; and

(c)unless the licensing authority directs otherwise, accompanied by any fee payable in connection with the application.

(6) An application is treated as signed for the purposes of paragraph (5)(b) if it is signed with an electronic signature.

(7) The application and any accompanying material must be in English.

(8) The applicant must provide each of the following for each product to which the application relates—

(a)a statement of the scientific name, or other name given in a pharmacopoeia, of the homoeopathic stock or stocks from which the product is derived;

(b)a statement of the routes of administration, pharmaceutical forms and degree of dilution of the product;

(c)a dossier describing how the homoeopathic stock or stocks are obtained and controlled and justifying their homoeopathic use on the basis of an adequate bibliography;

(d)a manufacturing and control file for each pharmaceutical form and a description of the method of dilution and potentisation of the product;

(e)evidence that each manufacturer of the medicinal product is authorised to manufacture it (which, in the case of a product manufactured in the United Kingdom or another EEA State, means the manufacturer's licence or (as the case may be) its equivalent in that EEA State);

(f)where an authorisation to place the product on the market has been granted by another member State, a copy of the authorisation;

(g)a mock-up of the outer and immediate packaging of the product; and

(h)data concerning the stability of the product.

(9) This material, taken as a whole, must be such as to demonstrate the pharmaceutical quality and batch to batch homogeneity of each product to which the application relates.

(10) The applicant must also, if requested by the licensing authority to do so, provide the licensing authority with material or information that the licensing authority reasonably considers necessary for considering the application.

Consideration of applicationU.K.

104.—(1) The licensing authority must take all reasonable steps to ensure that it makes a decision to grant or refuse a certificate of registration before the end of the period of 210 days beginning immediately after the day on which an application for the certificate is submitted in accordance with regulation 103.

(2) If the licensing authority requests the applicant to provide any further information or material, the period referred to in paragraph (1) is suspended for the period—

(a)beginning with the date on which the request is made; and

(b)ending with the date on which the information or material is provided.

(3) The licensing authority may grant a certificate only if, having considered the application and the accompanying material, the authority thinks that—

(a)the risks to the health of patients or of the public associated with the product do not outweigh any beneficial effects of the homoeopathic medicinal product in question;

(b)the application and the accompanying material complies with regulation 103; and

(c)the product's qualitative or quantitative composition is as described in the application and the accompanying material.

(4) Schedule 11 makes provision about advice and representations in relation to an application for the grant of a certificate of registration.

(5) This regulation does not apply to an application that—

(a)has been submitted to the licensing authority in accordance with Article 28 of the 2001 Directive; or

(b)has been referred to the Committee for Medicinal Products for Human Use for the application of the procedure laid down in Articles 32 to 34 of the 2001 Directive.

(6) An application to which paragraph (5) applies is to be determined by the licensing authority in accordance with Chapter 4 of Title III of the 2001 Directive.

Conditions of certificate of registrationU.K.

105.—(1) The licensing authority may—

(a)grant a certificate of registration subject to conditions; or

(b)vary or remove a condition to which the certificate of registration is subject.

(2) The powers in paragraph (1) may be exercised only after consultation with the applicant for the certificate or (as the case may be) its holder.

(3) The power in paragraph (1)(a) to grant an authorisation subject to conditions may be exercised only—

(a)in exceptional circumstances; and

(b)when the applicant can show that the applicant is unable to provide comprehensive data on the safety of the medicinal product under normal conditions of use.

(4) The conditions must relate to a matter addressed by Annex I to the 2001 Directive.

(5) The conditions may, in particular, relate to the safety of the product to which the certificate relates.

(6) The conditions may, in particular, require that, where there is an incident relating to the use of the product—

(a)the incident must be reported to the licensing authority; and

(b)such other action as may be specified in the conditions must be taken.

(7) The licensing authority must keep under review—

(a)the conditions to which a certificate of registration is subject; and

(b)the holder's compliance with those conditions.

(8) The licensing authority must consider those matters no less frequently than—

(a)at the end of the period of one year beginning with the date on which the certificate was granted; and

(b)at the end of each subsequent period of one year.

(9) Schedule 11 makes provision about advice and representations in relation to proposals to vary or remove a condition to which a certificate of registration is subject.

Classification of certificate of registrationU.K.

106.—(1) A certificate of registration must include a term that the product to which the certificate relates is to be available—

(a)only from a pharmacy; or

(b)on general sale.

(2) A certificate of registration may include a term that the product to which the certificate relates is to be available on general sale only if the licensing authority considers that the product can with reasonable safety be sold or supplied otherwise than by, or under the supervision of, a pharmacist.

Validity of certificate of registrationU.K.

107.—(1) Subject to the following paragraphs, a certificate of registration remains in force—

(a)for an initial period of five years beginning with the date on which it is granted; and

(b)if the authorisation is renewed under regulation 108 for an unlimited period after its renewal.

(2) The licensing authority may, on the first application for renewal of a certificate, determine on grounds relating to pharmacovigilance, including exposure of an insufficient number of patients to the medicinal product concerned, that it should be necessary for the holder to make one further application for renewal.

(3) In that event, the certificate remains in force—

(a)for a further period of five years beginning with the date on which it is first renewed; and

(b)if the authorisation is further renewed under regulation 108 for an unlimited period after its further renewal.

(4) If an application for the renewal or further renewal of a certificate is made in accordance with regulation 108 the certificate remains in force until the licensing authority notifies the applicant of its decision on the application.

(5) This regulation is subject to—

(a)regulation 109 (failure to place on the market etc); and

(b)regulation 110 (revocation etc of certificate of registration).

Application for renewal of certificateU.K.

108.—(1) An application for the renewal of a certificate of registration must be made to the licensing authority.

(2) The applicant must be established in the European Union.

(3) The application must be—

(a)made in writing;

(b)signed by or on behalf of the applicant; and

(c)unless the licensing authority directs otherwise, accompanied by any fee payable in connection with the application.

(4) An application is treated as signed for the purposes of paragraph (3)(b) if it is signed with an electronic signature.

(5) The application must be made so that it is received by the licensing authority before the beginning of the period of nine months ending with the expiry of the period mentioned in paragraph (1)(a) or (as the case may be) (3)(a) of regulation 107 (initial and further period of validity).

(6) The holder must provide a consolidated version of the file in respect of quality, safety and efficacy (including all amendments made since the authorisation was granted).

(7) The licensing authority may renew a certificate only if, having considered the application and the material accompanying it, the authority thinks that the risks to the health of patients or of the public associated with the homoeopathic medicinal product to which the certificate relates do not outweigh any beneficial effects of the product.

(8) Schedule 11 makes provision about advice and representations in relation to an application for the renewal of a certificate of registration.

Failure to place on the market etcU.K.

109.—(1) A certificate of registration ceases to be in force if the product to which it relates is not placed on the market in the United Kingdom during the period of three years beginning immediately after the day on which it was granted.

(2) A certificate of registration for a product which has been placed on the market ceases to be in force if the product to which it relates is not sold or supplied in the United Kingdom for a period of three years.

(3) This regulation does not apply if the licensing authority grants an exemption from its operation.

(4) An exemption may be granted—

(a)in response to an application in writing by the holder of the certificate of registration; or

(b)by the licensing authority of its own motion.

(5) An exemption may be granted only—

(a)in exceptional circumstances; and

(b)on public health grounds.

(6) An exemption—

(a)has effect for the period determined by the licensing authority, which may not exceed three years beginning with the day on which it is granted; and

(b)may be renewed or further renewed.

Revocation, variation and suspension of certificate of registrationU.K.

Revocation, variation and suspension of certificate of registrationU.K.

110.—(1) The licensing authority may revoke, vary or suspend a certificate of registration if any of the following conditions are met.

(2) Condition A is that the licensing authority thinks that—

(a)the product to which the certificate relates is harmful;

(b)the risks of the product to the health of patients or of the public outweigh any beneficial effects of the product; or

(c)the product's qualitative or quantitative composition is not as described in the application for the certificate or the material supplied with it.

(3) Condition B is that the licensing authority thinks that the application or the material accompanying it is incorrect.

(4) Condition C is that the licensing authority thinks that there has been a breach of—

(a)a term of the certificate; or

(b)a requirement imposed by Chapter 1 of Part 13 (packaging and leaflets).

(5) Condition D is that the licensing authority thinks that a condition to which the certificate is subject by virtue of regulation 105 (conditions of certificate or registration) has not been fulfilled.

(6) Condition E is that the licensing authority thinks that the holder of the certificate has not complied with regulation 115(1) to (3) (requirements to provide information).

(7) Condition F is that the holder of the certificate has ceased to be established in the European Union.

(8) Condition G is that—

(a)the holder applies to vary the certificate; and

(b)the licensing authority thinks that the application should be granted.

[F37(8A) Condition H is that the manufacture and control of the product to which the certificate relates is not in compliance with the particulars provided under regulation 103(8)(c) and (d).]

(9) Schedule 11 makes provision about advice and representations in relation to a proposal to revoke, vary or suspend a certificate of registration, other than a proposal to vary a certificate on the application of its holder.

(10) This regulation is subject to regulation 111 (certificates granted under Chapter 4 of Title III of the 2001 Directive).

Certificates granted under Chapter 4 of Title III of the 2001 DirectiveU.K.

111.—(1) Regulation 110 does not apply in relation to a certificate of registration that was granted in accordance with the provisions of Chapter 4 of Title III of the 2001 Directive (mutual recognition procedure and decentralised procedure).

(2) A proposal by the licensing authority to vary, suspend or revoke a certificate of registration within paragraph (1), or an application by the holder of such a certificate to vary or revoke it, is to be determined in accordance with Chapter 4 of Title III of the 2001 Directive.

Withdrawal of homoeopathic medicinal product from the marketU.K.

112.—(1) This regulation applies if under regulation 110 or regulation 111(2) the licensing authority revokes or suspends a certificate of registration.

(2) The licensing authority may give written notice to the person who is, or immediately before its revocation was, the holder of the certificate requiring the holder to comply with the following requirement.

(3) That requirement is to take all reasonably practicable steps to withdraw from the market in the United Kingdom and recover possession of—

(a)the product to which the certificate relates; or

(b)the batches of the product specified in the notice,

within the time and for the period specified in the notice.

(4) The notice must specify the grounds for giving the notice.

Obligations of holder of certificate of registrationU.K.

Obligation to notify placing on the market etcU.K.

113.—(1) The holder of a certificate of registration must notify the licensing authority of the date on which the product to which the certificate relates is placed on the market in the United Kingdom taking account of the various presentations authorised.

(2) A notification under paragraph (1) must be given before the end of the period of two months beginning with the date on which the product is placed on the market.

(3) The holder of a certificate of registration must notify the licensing authority if the product to which the certificate relates is to be withdrawn from the market in the United Kingdom (whether temporarily or permanently).

[F38(3A) A notification under paragraph (3) must include the reasons for the withdrawal in accordance with article 123(2) of the 2001 Directive.]

(4) A notification under paragraph (3) must be given before the beginning of the period of two months ending with the date on which the product is to be withdrawn from the market unless it is not reasonably practicable to do so.

(5) In that event, the notification must be given as far as is reasonably practicable in advance of the date on which the product is withdrawn from the market.

(6) The licensing authority may require the holder of a certificate of registration to provide information relating to the volume of sales in the United Kingdom of the product to which the certificate relates.

(7) The holder of a certificate of registration must provide the licensing authority with information that it requires under paragraph (6)—

(a)where the period within which the information must be provided is specified in a written notice given to the holder by the licensing authority, before the end of that period; or

(b)otherwise, as soon as is reasonably practicable after receipt of the request.

Obligation to take account of scientific and technical progressU.K.

114.—(1) The holder of a certificate of registration must keep under review the methods of manufacture and control of the product to which the certificate relates, taking account of scientific and technical progress.

(2) As soon as is reasonably practicable after becoming aware of the need to do so, the holder must apply to vary the certificate of registration to make any changes to those methods that are required to ensure they are generally accepted scientific methods.

Obligation to provide information relating to safety etcU.K.

115.—(1) The holder of a certificate of registration must provide the licensing authority with any new information that might entail the variation of the certificate.

(2) The holder must, in particular, provide the licensing authority with the following information—

(a)information about any prohibition or restriction imposed in relation to the product to which the certificate relates by the competent authority of any country in which the product is on the market;

(b)positive and negative results of clinical trials or other studies in all indications and populations, whether or not included in the certificate of registration;

(c)data on the use of the product where such use is outside the terms of the certificate of registration; and

(d)any other information that the holder considers might influence the evaluation of the benefits and risks of the product.

(3) Information within paragraph (1) or (2) must be provided as soon as is reasonably practicable after the holder becomes aware of it.

(4) The licensing authority may require the holder of a certificate of registration to provide the authority with information that—

(a)is specified by the licensing authority; and

(b)demonstrates that the risks of the product to the health of patients or of the public do not outweigh any beneficial effects of the product to which the certificate relates.

(5) The information that may be required under paragraph (4) includes information arising from use of the product—

(a)in a country which is not an EEA State; or

(b)outside the terms of the certificate of registration.

(6) If the information supplied under paragraph (1), (2) or (4) entails the variation of the certificate of registration, the holder must make an application to the licensing authority to that effect as soon as is reasonably practicable after becoming aware of the information.

(7) The licensing authority may require the holder of a certificate of registration to provide the authority with proof of the control methods employed by the manufacturer of the product to which the certificate relates.

(8) The licensing authority may notify the holder of a certificate of registration that it requires the holder to provide to the licensing authority information of any description specified in the notice, within the period specified in the notice, subject to paragraph (9).

(9) A notice under paragraph (8) must not be served unless it appears to the licensing authority, or it is represented to the licensing authority by the Commission or by an expert committee appointed by the licensing authority—

(a)that circumstances exist by reason of which it is necessary to consider whether the certificate of registration should be varied, suspended or revoked; and

(b)that the information required by the notice is needed to consider that question.

(10) The holder of a certificate of registration must provide the licensing authority with information that it requires under paragraphs (4) or (7)—

(a)where the period within which the information must be provided is specified in a written notice given to the holder by the licensing authority, before the end of that period; or

(b)otherwise, as soon as is reasonably practicable after receipt of the request.

Obligation in relation to product informationU.K.

116.—(1) The holder of the certificate of registration for a medicinal product must ensure that the product information relating to the product is kept up to date with current scientific knowledge.

(2) In this regulation “current scientific knowledge” includes the conclusions of the assessment and recommendations made public by means of the European medicines web-portal established in accordance with Article 26 of Regulation (EC) No 726/2004.

Record-keeping obligationU.K.

117.  The holder of a certificate of registration must keep any documents or information that will facilitate the withdrawal or recall from sale or supply of the product to which the certificate relates.

Obligation to ensure appropriate and continued suppliesU.K.

118.  The holder of a certificate of registration must take all reasonable steps to ensure appropriate and continued supplies of the product to which the certificate relates to pharmacies and persons authorised to supply the product so that the needs of patients in the United Kingdom are met.

Provisions relating to offencesU.K.

Offences in connection with applicationsU.K.

119.  A person is guilty of an offence if, in the course of an application for the grant, renewal or variation of a certificate of registration for a registrable homoeopathic medicinal product, the person—

(a)fails to provide the licensing authority with any information that is relevant to an evaluation of the quality of the product; or

(b)provides to the licensing authority any information that is relevant to an evaluation of the quality of the product that is false or misleading in a material particular.

Provision of false or misleading informationU.K.

120.—(1) The holder of a certificate of registration for a medicinal product is guilty of an offence if the person provides the licensing authority with any information that is relevant to the quality of the product but that is false or misleading in a material particular.

(2) Paragraph (1) is without prejudice to the operation of regulation 119.

General offence of breach of provision of this PartU.K.

121.—(1) A person is guilty of an offence if that person commits a breach of a provision in this Part.

(2) A breach of a provision in this Part includes any—

(a)failure by the holder of a certificate of registration to comply with any requirement or obligation in this Part;

(b)contravention by any person of any prohibition in this Part; or

(c)failure to comply with any requirement imposed on a person by the licensing authority pursuant to this Part.

(3) Paragraph (1) is without prejudice to any offence established by any other provision in this Part.

PenaltiesU.K.

122.  A person guilty of an offence under this Part is liable—

(a)on summary conviction to a fine not exceeding the statutory maximum; or

(b)on conviction on indictment, to a fine, to imprisonment for a term not exceeding two years or to both.

Persons liableU.K.

123.  If an offence under regulation 119 (offences in connection with applications) is committed by a person acting as employee or agent, the employer or principal of that person is guilty of the same offence and is liable to be proceeded against and punished accordingly.

DefencesU.K.

124.—(1) Paragraph (2) applies if the holder of a certificate of registration is charged with an offence under this Part in respect of anything that—

(a)has been manufactured or assembled to the holder's order by another person; and

(b)has been so manufactured or assembled as not to comply with the terms of the certificate.

(2) It is a defence for the holder to prove that—

(a)the holder communicated the terms of the certificate to the other person; and

(b)the holder did not know and could not by the exercise of reasonable care have known that those terms had not been complied with.

(3) It is a defence for a person charged with an offence consisting of a breach of regulation 113(3) or 118 or an offence under regulation 119 or 120 to prove that the person took all reasonable precautions and exercised all due diligence to avoid commission of that offence.

(4) Where evidence is adduced that is sufficient to raise an issue with respect to the defence in paragraph (3), the court or jury must presume that the defence is satisfied unless the prosecution proves beyond reasonable doubt that it is not.

PART 7U.K.Traditional herbal registrations

Application of PartU.K.

Traditional herbal medicinal productsU.K.

125.—(1) This Part applies to a herbal medicinal product (a “traditional herbal medicinal product”) if the following conditions are met.

(2) Condition A is met if by virtue of its composition and indications the product is appropriate for use without the need for a medical practitioner to—

(a)diagnose the condition to be treated by the product;

(b)prescribe the product; or

(c)monitor the product's use.

(3) Condition B is met if the product is intended to be administered at a particular strength and in accordance with a particular posology.

(4) Condition C is met if the product is intended to be administered externally, orally or by inhalation.

(5) Condition D is met if—

(a)the product has been in medicinal use for a continuous period of at least 30 years, and

(b)the product has been in medicinal use in the European Union for a continuous period of at least 15 years.

(6) It is immaterial for the purposes of condition D whether or not during a period mentioned in that condition—

(a)the sale or supply of the product has been based on a specific authorisation; or

(b)the number or quantity of the ingredients (or any of them) has been reduced.

(7) Condition E is met if there is sufficient information about the use of the product as mentioned in condition D (referred to in this Part as its “traditional use”), so that (in particular)—

(a)it has been established that the traditional use of the product is not harmful; and

(b)the pharmacological effects or efficacy of the product are plausible on the basis of long-standing use and experience.

Addition of vitamins or mineralsU.K.

126.  The addition to a traditional herbal medicinal product of a vitamin or mineral does not prevent a traditional herbal registration from being granted for the product if—

(a)there is well-documented evidence of the safety of the vitamin or mineral; and

(b)the action of the vitamin or mineral is ancillary to the action of the product's active herbal ingredients in connection with the use authorised by the traditional herbal registration.

Application for traditional herbal registrationU.K.

Application for grant of traditional herbal registrationU.K.

127.—(1) The licensing authority may, subject to regulation 130, grant an application for a traditional herbal registration for a traditional herbal medicinal product in response to an application made in accordance with this Part.

(2) A registration granted under paragraph (1) shall contain terms approved by the licensing authority.

(3) The applicant must be established in the European Union.

(4) The application must be—

(a)made in writing;

(b)signed by or on behalf of the applicant; and

(c)unless the licensing authority directs otherwise, accompanied by any fee payable in connection with the application.

(5) An application is treated as signed for the purposes of paragraph (4)(b) if it is signed with an electronic signature.

(6) The application and any accompanying material must be in English.

(7) The application must include a statement indicating whether the product to which the application relates should be available—

(a)only from a pharmacy; or

(b)on general sale.

(8) The application must include a statement indicating—

(a)whether any terms of the registration are proposed relating to the method of sale or supply of the product (including, in particular, any proposed restrictions affecting the circumstances of the use or promotion of the product); and

(b)if so, what terms are proposed.

Accompanying materialU.K.

128.—(1) The applicant for the grant of a traditional herbal registration must provide the material specified in Schedule 12 in relation to the product.

(2) The applicant must also, if requested by the licensing authority to do so, provide the licensing authority with material or information that the licensing authority reasonably considers necessary for considering the application.

(3) If the application relates to a product that is contained in the list referred to in Article 16f(1) of the 2001 Directive—

(a)the applicant does not need to provide the material referred to in paragraphs 16 to 20 of Part 1 of Schedule 12; and

(b)paragraph (2) of this regulation does not apply.

(4) Material that is submitted under this regulation must be submitted in accordance with Annex I to the 2001 Directive, so far as applicable to traditional herbal medicinal products.

Obligation to update information supplied in connection with applicationU.K.

129.—(1) The applicant for a traditional herbal registration must update information supplied in connection with the application to include any further information that is relevant to the evaluation of the safety, quality or efficacy of the product concerned.

(2) Updated information within paragraph (1) must be provided as soon as is reasonably practicable after the applicant becomes aware of it.

Consideration of applicationU.K.

Consideration of applicationU.K.

130.—(1) The licensing authority must take all reasonable steps to ensure that it makes a decision to grant or refuse a traditional herbal registration before the end of the period of 210 days beginning immediately after the day on which an application for the registration is submitted in accordance with regulation 128.

(2) If the licensing authority requests the applicant to provide any further information or material, the period referred to in paragraph (1) is suspended for the period—

(a)beginning with the date on which the request is made; and

(b)ending with the date on which the information or material is provided.

(3) If the licensing authority requests the applicant to give an oral or written explanation of the application, the period referred to in paragraph (1) is suspended for the period—

(a)beginning with the date on which the request is made; and

(b)ending with the date on which the explanation is provided.

(4) The licensing authority may grant the application only if, having considered the application and the accompanying material, the authority thinks that—

(a)the product complies with conditions A to E of regulation 125 (conditions for a product to be a traditional herbal medicinal product);

(b)the product to which the application relates is not harmful under normal conditions of use;

(c)the application and the accompanying material complies with the requirements of this Part;

(d)the product's qualitative and quantitative composition is as described in the application and the accompanying material; and

(e)the product's pharmaceutical quality has been satisfactorily demonstrated.

(5) The licensing authority need not take into account any updated information supplied in connection with the application under regulation 129 (obligation to update information supplied in connection with application), unless it thinks that the information is unfavourable in respect of the safety, quality or efficacy of the product concerned

(6) The licensing authority may refuse the application on the ground that it is more appropriate to consider whether to authorise the placing of the product on the market in response to an application for a marketing authorisation or certificate of registration for the product.

(7) Paragraph (4)(a) is subject to Article 16c(4) of the 2001 Directive (procedure where product has been used in the European Union for less than 15 years).

(8) If the application relates to a herbal medicinal product that is contained in the list referred to Article 16f(1) of the 2001 Directive—

(a)paragraph (4)(a) applies as if it referred to conditions A to D of regulation 125; and

(b)paragraph (4)(b) does not apply.

(9) Where Article 16d(1) of the 2001 Directive (products to which the mutual recognition procedure and decentralised procedure apply) does not apply to the product, the licensing authority must, in considering the application, take into account any registrations granted by other member States in accordance with Chapter 2a of Title III of the 2001 Directive.

(10) The licensing authority must take into account—

(a)any herbal monograph of the kind referred to in Article 16h(3) of the 2001 Directive that the authority thinks relevant to the application; or

(b)if no relevant monograph within sub-paragraph (a) has been established, such other monographs, publications or data as the authority thinks relevant.

(11) Schedule 11 makes provision about advice and representations in relation to an application for the grant of a traditional herbal registration.

(12) This regulation does not apply where Article 16d(1) applies to the product and the application—

(a)has been submitted to the licensing authority in accordance with Article 28 of the 2001 Directive; or

(b)has been referred to the Committee for Herbal Medicinal Products for the application of the procedure laid down in Articles 32 to 34 of the 2001 Directive.

(13) An application to which paragraph (12) applies is to be determined by the licensing authority in accordance with Chapter 4 of Title III of the 2001 Directive.

Classification of traditional herbal registrationU.K.

131.—(1) A traditional herbal registration must include a term that the product to which the registration relates is to be available—

(a)only from a pharmacy; or

(b)on general sale.

(2) A traditional herbal registration may include a term that the product to which the registration relates is to be available on general sale only if the licensing authority considers that the product can with reasonable safety be sold or supplied otherwise than by, or under the supervision of, a pharmacist.

Validity of traditional herbal registrationU.K.

Validity of traditional herbal registrationU.K.

132.—(1) Subject to the following paragraphs, a traditional herbal registration remains in force—

(a)for an initial period of five years beginning with the date on which it is granted; and

(b)if the registration is renewed under regulation 133 for an unlimited period after its renewal.

(2) The licensing authority may on the first application for renewal of a registration determine on grounds relating to pharmacovigilance, including exposure of an insufficient number of patients to the medicinal product concerned, that it should be necessary for the holder to make one further application for renewal.

(3) In that event, the registration remains in force—

(a)for a further period of five years beginning with the date on which it is first renewed; and

(b)if the registration is further renewed under regulation 133 for an unlimited period after its further renewal.

(4) If an application for the renewal or further renewal of a registration is made in accordance with regulation 133 the certificate remains in force until the licensing authority notifies the applicant of its decision on the application.

(5) This regulation is subject to—

(a)regulation 134 (failure to place on the market); and

(b)regulation 135 (revocation etc of traditional herbal registration).

Application for renewal of registrationU.K.

133.—(1) An application for the renewal of a traditional herbal registration must be made to the licensing authority.

(2) The applicant must be established in the European Union.

(3) The application must be—

(a)made in writing;

(b)signed by or on behalf of the applicant; and

(c)unless the licensing authority directs otherwise, accompanied by any fee payable in connection with the application.

(4) An application is treated as signed for the purposes of paragraph (3)(b) if it is signed with an electronic signature.

(5) The application must be made so that it is received by the licensing authority before the beginning of the period of nine months ending with the expiry of the period mentioned in paragraph (1)(a) or (3)(a) of regulation 132 (initial and further period of validity), as the case may be.

(6) The holder must provide a consolidated version of the file in respect of quality, safety and efficacy including—

(a)the evaluation of data contained in suspected adverse reaction reports and periodic safety update reports submitted in accordance with Part 11; and

(b)all variations introduced since the traditional herbal registration was granted.

(7) The licensing authority may renew a traditional herbal registration only if, having considered the application and the material accompanying it, the authority thinks that the positive therapeutic effects of the product to which the registration relates outweigh the risks of the product to the health of patients or of the public.

(8) Schedule 11 makes provision about advice and representations in relation to an application for the renewal of a traditional herbal registration.

Failure to place on the market etcU.K.

134.—(1) A traditional herbal registration ceases to be in force if the product to which it relates is not placed on the market in the United Kingdom during the period of three years beginning immediately after the day on which it was granted.

(2) A traditional herbal registration for a product which has been placed on the market ceases to be in force if the product to which it relates is not sold or supplied in the United Kingdom for a period of three years.

(3) This regulation does not apply if the licensing authority grants an exemption from its operation.

(4) An exemption may be granted—

(a)in response to an application in writing by the holder of the traditional herbal registration; or

(b)by the licensing authority of its own motion.

(5) An exemption may only be granted only—

(a)in exceptional circumstances; and

(b)on public health grounds.

(6) An exemption—

(a)has effect for the period determined by the licensing authority, which may not exceed three years beginning with the day on which it is granted; and

(b)may be renewed or further renewed.

Revocation, variation and suspension of traditional herbal registrationU.K.

Revocation, variation and suspension of traditional herbal registrationU.K.

135.—(1) The licensing authority may revoke, vary or suspend a traditional herbal registration if any of the following conditions are met.

(2) Condition A is that the licensing authority thinks that—

(a)the product to which the registration relates is harmful;

(b)the pharmacological effects or efficacy of the product are no longer plausible; or

(c)the product's qualitative or quantitative composition is not as described in the application for the registration or the material accompanying it.

(3) Condition B is that the licensing authority thinks that the application or the material supplied with it is incorrect.

(4) Condition C is that the licensing authority thinks that there has been a breach of—

(a)a term of the registration; or

(b)a requirement imposed by Chapter 1 of Part 13 (packaging and leaflets).

(5) Condition D is that the licensing authority thinks that the holder of the registration has not complied with regulation 145(1) to (3) (requirement to provide information that may entail amendment of authorisation).

(6) Condition E is that the holder of the registration has ceased to be established in the United Kingdom.

(7) Condition F is that—

(a)the product to which the registration relates is manufactured in the United Kingdom; and

(b)the licensing authority thinks that the holder of the manufacturer's licence for the product has failed to comply in relation to the product with regulations 37 (manufacturing and assembly), 38 (imports from states other than EEA States), 39 (further requirements for manufacturer's licence), 40 (obligation to provide information relating to control methods) or 41 (requirements as to qualified persons).

(8) Condition G is that—

(a)the product to which the registration relates is manufactured in an EEA State other than the United Kingdom; and

(b)the licensing authority thinks that the holder of the manufacturer's licence for the product has failed to comply in relation to the product with provision giving effect to Article 41 of the 2001 Directive (requirements relating to manufacturing authorisations) in that member State.

(9) Condition H is that the licensing authority thinks that urgent action to protect public health is necessary, in which case it—

(a)may suspend the registration; and

(b)must notify the suspension to the EMA, the European Commission, and all other member States by the end of the next working day following the day on which the suspension comes into force.

(10) Condition I is that—

(a)the holder applies to vary the registration; and

(b)the licensing authority thinks that the application should be granted.

[F39(10A) Condition J is that the manufacture of the product to which registration relates is not carried out in compliance with the particulars provided under paragraphs 5 and 9 of Schedule 12.]

(11) This regulation is subject to regulation 139 (registrations granted under Chapter 4 of Title III of the 2001 Directive).

Revocation by licensing authority: further provisionsU.K.

136.—(1) The licensing authority must revoke a traditional herbal registration if—

(a)the application for the registration was submitted in accordance with regulation 128(3) on the basis that the herbal medicinal product to which it relates was contained in the list referred to Article 16f(1) of the 2001 Directive; and

(b)the product ceases to be contained in that list.

(2) Paragraph (1) does not apply if within the period of three months beginning immediately after the day on which product ceases to be contained on the list the holder—

(a)submits to the licensing authority the material specified in Schedule 12 (including that referred to in paragraphs 16 to 20 of Part 1 of that Schedule) in relation to the product; and

(b)provides the licensing authority with any material or information that the licensing authority reasonably considers necessary for considering the application and requests the holder to provide.

(3) This regulation is subject to regulation 139 (registrations granted under Chapter 4 of Title III of the 2001 Directive).

Procedures for revocation, variation or suspensionU.K.

137.  Schedule 11 makes provision about advice and representations in relation to a proposal to revoke, vary or suspend a traditional herbal registration, other than a proposal to vary a registration on the application of its holder.

Suspension of use etc of traditional herbal medicinal productU.K.

138.—(1) The licensing authority may suspend the use, sale, supply or offer for sale or supply within the United Kingdom of a product to which a traditional herbal registration relates if any of the following conditions are met.

(2) Condition A is that the licensing authority thinks that—

(a)the product is harmful;

(b)the pharmacological effects or efficacy of the product are no longer plausible; or

(c)the product's qualitative or quantitative composition is not as described in the application for the registration or the material accompanying it.

(3) Condition B is that the licensing authority thinks that the holder has not complied with regulation 145(7) (requirements to provide proof of controls on manufacturing process).

(4) Condition C is that the licensing authority thinks that there has been a breach of—

(a)a term of the registration; or

(b)a requirement imposed by Chapter 1 of Part 13 (packaging and leaflets).

(5) Condition D is that the licensing authority thinks that paragraph (4) or (5) of regulation 23 (power to revoke, suspend or vary manufacturers' licences) applies in relation to the manufacturer's licence for the product.

(6) A suspension under this regulation may relate to batches of the product.

(7) The licensing authority must give notice in writing of a suspension under this regulation to the holder of the registration.

(8) The licensing authority must provide in the notice that the suspension—

(a)is to take effect immediately or from a date specified in the notice; and

(b)is to apply for the period specified in the notice.

(9) Where a medicinal product is the subject of a suspension under this regulation, the licensing authority may—

(a)in exceptional circumstances; and

(b)for such a transitional period as the licensing authority may determine,

allow the supply of the medicinal product to patients who are already being treated with the medicinal product.

(10) This regulation is subject to regulation 139 (registrations granted under Chapter 4 of Title III of the 2001 Directive).

Registrations granted under Chapter 4 of Title III of the 2001 DirectiveU.K.

139.—(1) Regulations 135 to 138 do not apply in relation to a traditional herbal registration that—

(a)was granted in accordance with the provisions of Chapter 4 of Title III of the 2001 Directive (mutual recognition procedure and decentralised procedure); or

(b)was subject to the procedure laid down in Articles 32 to 34 of the 2001 Directive following a referral under Article 30 or 31 of that Directive, unless the procedure was limited to certain specific parts of the registration.

(2) A proposal by the licensing authority to vary, suspend or revoke a traditional herbal registration within paragraph (1), or an application by the holder of such a registration to vary or revoke it, is to be determined in accordance with Chapter 4 of Title III of the 2001 Directive.

Withdrawal of traditional herbal medicinal product from the marketU.K.

140.—(1) This regulation applies if—

(a)under regulation 135, 136, 139(2) or Article 34(3) of the 2001 Directive the licensing authority revokes or suspends a traditional herbal registration; or

(b)under regulation 138 the licensing authority suspends the use, sale, supply or offer for sale or supply within the United Kingdom of a product to which a traditional herbal registration relates.

(2) The licensing authority may give written notice to the person who is, or immediately before its revocation was, the holder of the registration requiring the holder to comply with both of the following requirements.

(3) Requirement A is to take all reasonably practicable steps to inform wholesalers, retailers, medical practitioners, patients and others who may be in possession of the product to which the registration relates of—

(a)the revocation or suspension;

(b)the reasons for the revocation or suspension; and

(c)any action to be taken to restrict or prevent further use, sale, supply or offer for sale or supply of the product.

(4) Requirement B is to take all reasonably practicable steps to withdraw from the market in the United Kingdom and recover possession of—

(a)the product; or

(b)the batches of the product specified in the notice,

within the time and for the period specified in the notice.

Sale etc of suspended traditional herbal medicinal productU.K.

141.—(1) This regulation applies if the use, sale, supply or offer for sale or supply of a traditional herbal medicinal product is suspended in accordance with regulation 138 or 139(2).

(2) A person must not—

(a)sell, supply or offer to sell or supply the product; or

(b)procure the sale, supply or offer for sale or supply of the product,

knowing, or having reasonable cause to believe, that such use, sale, supply or offer for sale or supply is suspended.

Obligations of holder of traditional herbal registrationU.K.

Obligation to notify placing on the market etcU.K.

142.—(1) The holder of a traditional herbal registration must notify the licensing authority of the date on which the product to which the registration relates is placed on the market in the United Kingdom taking account of the various presentations authorised.

(2) A notification under paragraph (1) must be given before the end of the period of two months beginning with the date on which the product is placed on the market.

(3) The holder of a traditional herbal registration must notify the licensing authority if the product to which the registration relates is to be withdrawn from the market in the United Kingdom (whether temporarily or permanently).

(4) A notification under paragraph (3) must be given before the beginning of the period of two months ending with the date on which the product is to be withdrawn from the market unless it is not reasonably practicable to do so.

(5) In that event, the notification must be given as far as is reasonably practicable in advance of the date on which the product is withdrawn from the market.

[F40(5A) The holder of a traditional herbal registration must notify the licensing authority forthwith if the holder takes action to—

(a)request the cancellation of the registration;

(b)not apply for the renewal of the registration; or

(c)withdraw the product to which the registration relates from the market in a third country (whether temporarily or permanently) and the action is based on any of the grounds set out in Article 116 or 117(1) of the 2001 Directive.

(5B) A notification under paragraph (3) or (5A) must include the reasons for the action, in particular declaring if the action is based on any of the grounds set out in Article 116 or 117(1) of the 2001 Directive.

(5C) The holder of a traditional herbal registration must notify the EMA forthwith where the action which is the subject of a notification by the holder under paragraph (3) or (5A) is based on any of the grounds set out in Article 116 or 117(1) of the 2001 Directive.]

(6) The licensing authority may require the holder of a traditional herbal registration to provide information relating to the volume of sales in the United Kingdom of the product to which the registration relates.

(7) The holder of a traditional herbal registration must provide the licensing authority with information that it requires under paragraph (6)—

(a)where the period within which the information must be provided is specified in a written notice given to the holder by the licensing authority, before the end of that period; or

(b)otherwise, as soon as is reasonably practicable after receipt of the request.

Obligation to take account of scientific and technical progressU.K.

143.—(1) The holder of a traditional herbal registration must keep under review the methods of manufacture and control of the product to which the registration relates, taking account of scientific and technical progress.

(2) As soon as is reasonably practicable after becoming aware of the need to do so, the holder must apply to vary the traditional herbal registration to make any changes to those methods that are required to ensure they are generally accepted scientific methods.

Obligation following new herbal monographU.K.

144.  Where a new herbal monograph of the kind referred to in Article 16h(3) of the 2001 Directive is established the holder of a traditional herbal registration for a product to which the monograph relates must as soon as is reasonably practicable—

(a)consider whether to modify the registration dossier; and

(b)notify any modification to the licensing authority.

Obligation to provide information relating to safety etcU.K.

145.—(1) The holder of a traditional herbal registration must provide the licensing authority with any new information that might entail the variation of the registration.

(2) The holder must, in particular, provide the licensing authority with the following information—

(a)information about any prohibition or restriction imposed in relation to the product to which the registration relates by the competent authority of any country in which the product is on the market;

(b)positive and negative results of clinical trials or other studies in all indications and populations, whether or not included in the traditional herbal registration;

(c)data on the use of the product where such use is outside the terms of the traditional herbal registration; and

(d)any other information that the holder considers might influence the evaluation of the benefits and risks of the product.

(3) Information within paragraph (1) or (2) must be provided as soon as is reasonably practicable after the holder becomes aware of it.

(4) The licensing authority may require the holder of a traditional herbal registration to provide the authority with information that—

(a)is specified by the licensing authority; and

(b)demonstrates that the positive therapeutic effects of the product to which the registration relates outweigh the risks of the product to the health of patients or of the public.

(5) The information that may be required under paragraph (4) includes information arising from use of the product—

(a)in a country which is not an EEA State; or

(b)outside the terms of the traditional herbal registration,

including use in clinical trials.

(6) If the information supplied under paragraph (1), (2) or (4) entails the variation of the traditional herbal registration, the holder must make an application to the licensing authority to that effect as soon as is reasonably practicable after becoming aware of the information.

(7) The licensing authority may require the holder of a traditional herbal registration to provide the authority with proof of the control methods employed by the manufacturer of the product to which the registration relates.

(8) The holder of a traditional herbal registration must provide the licensing authority with information that it requires under paragraph (4) or (7)—

(a)where the period within which the information must be provided is specified in a written notice given to the holder by the licensing authority, before the end of that period; or

(b)otherwise, as soon as is reasonably practicable after receipt of the request.

Obligation in relation to product informationU.K.

146.—(1) The holder of the traditional herbal registration for a medicinal product must ensure that the product information relating to the product is kept up to date with current scientific knowledge.

(2) In this regulation “current scientific knowledge” includes the conclusions of the assessment and recommendations made public by means of the European medicines web-portal established in accordance with Article 26 of Regulation (EC) No 726/2004.

Record-keeping obligationsU.K.

147.  The holder of a traditional herbal registration must keep any documents or information that will facilitate the withdrawal or recall from sale or supply of any product to which the registration relates.

Obligation to ensure appropriate and continued suppliesU.K.

148.  The holder of a traditional herbal registration must take all reasonable steps to ensure appropriate and continued supplies of the product to which the registration relates to pharmacies and persons authorised to supply the product so that the needs of patients in the United Kingdom are met.

Offences relating to traditional herbal registrationsU.K.

Urgent safety restrictionsU.K.

149.  The holder of a traditional herbal registration is guilty of an offence if the holder—

(a)fails to inform the licensing authority or the European Commission in accordance with Article 22(1) of Regulation (EC) No. 1234/2008 that the holder has taken urgent safety restrictions on the holder's own initiative;

(b)fails to implement an urgent safety restriction imposed on the holder by the licensing authority or the European Commission under Article 22(2) of that Regulation; or

(c)fails to submit an application for variation of the traditional herbal registration to the licensing authority or the European Commission in accordance with Article 22(3) of that Regulation before the end of a period of fifteen days beginning on the day after—

(i)the taking under Article 22(1) or, as the case may be,

(ii)the imposition under Article 22(2),

of that Regulation of an urgent safety restriction.

Offences in connection with applicationsU.K.

150.  A person is guilty of an offence if in the course of an application for the grant, renewal or variation of a traditional herbal registration for a traditional herbal medicinal product the person—

(a)fails to provide the licensing authority with any information that is relevant to the evaluation of the safety, quality or efficacy of the product; or

(b)provides to the licensing authority any information that is relevant to the evaluation of the safety, quality or efficacy of the product that is false or misleading in a material particular.

Provision of false or misleading informationU.K.

151.—(1) The holder of a traditional herbal registration is guilty of an offence if the holder provides to the licensing authority any information that is relevant to the evaluation of the safety, quality or efficacy of a traditional herbal medicinal product but that is false or misleading in a material particular.

(2) Paragraph (1) is without prejudice to regulation 150.

General offence of breach of provision of this PartU.K.

152.—(1) A person is guilty of an offence if that person commits a breach of a provision in this Part.

(2) A breach of a provision in this Part includes any—

(a)failure by the holder of a traditional herbal registration to comply with any requirement or obligation in this Part;

(b)contravention by any person of any prohibition in this Part; or

(c)failure to comply with any requirement imposed on a person by the licensing authority pursuant to this Part.

(3) Paragraph (1) is without prejudice to any offence established by any other provision in this Part.

PenaltiesU.K.

153.  A person guilty of an offence under this Part is liable—

(a)on summary conviction, to a fine not exceeding the statutory maximum; or

(b)on conviction on indictment, to a fine, to imprisonment for a term not exceeding two years or to both.

Persons liableU.K.

154.  If an offence under regulation 150 (offences in connection with applications) is committed by a person acting as employee or agent, the employer or principal of that person is guilty of the same offence and is liable to be proceeded against and punished accordingly.

DefencesU.K.

155.—(1) Paragraph (2) applies if the holder of a traditional herbal registration is charged with an offence under this Part in respect of anything that—

(a)has been manufactured or assembled to the holder's order by another person; and

(b)has been so manufactured or assembled as not to comply with the terms of the authorisation.

(2) It is a defence for the holder to prove that—

(a)the holder communicated the terms of the registration to the other person; and

(b)the holder did not know and could not by the exercise of reasonable care have known that those terms had not been complied with.

(3) It is a defence for a person charged with an offence consisting of a breach of regulation 142(3) or 148 or an offence under regulation 150 or 151 to prove that the person took all reasonable precautions and exercised all due diligence to avoid commission of that offence.

(4) Where evidence is adduced that is sufficient to raise an issue with respect to the defence in paragraph (3), the court or jury must presume that the defence is satisfied unless the prosecution proves beyond reasonable doubt that it is not.

PART 8U.K.Article 126a authorisations

Article 126a authorisationsU.K.

156.—(1) The licensing authority may grant an Article 126a authorisation for a medicinal product if the following conditions are met.

(2) Condition A is that no United Kingdom marketing authorisation, certificate of registration or traditional herbal registration is in force for the product.

(3) Condition B is that no application is pending in the United Kingdom for a marketing authorisation, certificate of registration or traditional herbal registration for the product.

(4) Condition C is that the licensing authority considers that the placing of the product on the market in the United Kingdom is justified for public health reasons.

(5) Condition D is that the product is imported from another member State that has, in accordance with the 2001 Directive, authorised the placing on the market of the product in that member State.

(6) Condition E is that the person to whom the authorisation is granted is established in the European Union.

(7) Before granting an Article 126a authorisation, the licensing authority must notify the authorisation holder in the member State mentioned in paragraph (5) of the proposal to grant the Article 126a authorisation.

(8) Before granting an Article 126a authorisation, the licensing authority may request the competent authority in the member State mentioned in paragraph (5) to provide in accordance with Article 126a(3)(b) of the 2001 Directive a copy of—

(a)the assessment report for that product as mentioned in Article 21(4) of the 2001 Directive; and

(b)the authorisation in force for that product.

(9) An Article 126a authorisation remains in force for the period specified in it unless revoked before the end of that period.

(10) That period may be specified by reference to the occurrence or non-occurrence of a particular event or events.

Requests from other member StatesU.K.

157.—(1) Paragraph (2) applies where the licensing authority is requested by the competent authority of another member State to provide in accordance with Article 126a(3)(b) of the 2001 Directive a copy of—

(a)the assessment report for a medicinal product as mentioned in regulation 64(5) (duties of licensing authority in connection with determination); and

(b)the marketing authorisation in force for that product.

(2) The licensing authority must supply those documents to the competent authority before the end of the period of thirty days beginning on the day after the request is received.

Application of these RegulationsU.K.

158.  The following provisions of Part 5 (marketing authorisations) apply to an Article 126a authorisation as they apply to a marketing authorisation—

(a)regulation 62 (classification of marketing authorisation);

(b)regulation 63 (frequency of periodic safety update reports);

(c)regulation 68 (revocation etc of marketing authorisation) and Schedule 11 (advice and representations in connection with revocations etc) so far as relating to that regulation;

(d)regulation 69 (suspension of use etc of medicinal product);

(e)regulation 71 (withdrawal of medicinal products from the market);

(f)regulation 72 (sale etc of suspended medicinal product);

(g)regulation 80 (urgent safety restrictions); and

(h)regulations 98 (general offence of breach of provision of this Part), 99 (penalties) and 101(1) and (2) (defences), so far as relating to the regulations mentioned in sub-paragraphs (a) and (e) to (f).

PART 9U.K.Borderline products

Provisional determinationU.K.

159.—(1) This regulation applies if the licensing authority thinks that a product without a marketing authorisation, traditional herbal registration, certificate of registration or Article 126a authorisation is a medicinal product.

(2) The licensing authority may give a notice in writing (a “provisional determination notice”) to any person (the “recipient”)—

(a)who has sold or supplied the product, or has offered to sell or supply it; or

(b)whom the licensing authority thinks may sell or supply the product.

(3) The provisional determination notice must—

(a)advise the recipient that the licensing authority has made a provisional determination that the product is a medicinal product;

(b)give reasons for the provisional determination;

(c)advise the recipient of the recipient's rights to challenge the provisional determination in accordance with regulation 160 and

(d)specify a period of at least six weeks beginning immediately after the date on which the provisional determination notice is given to the recipient (in this Part “the determination date”) within which any written representations in accordance with regulation 160(2)(a) must be made to the licensing authority.

Challenge to provisional determinationU.K.

160.—(1) A recipient of a provisional determination notice may, within the period of four weeks beginning immediately after the determination date, give notice in writing to the licensing authority requesting the authority to submit the provisional determination to review.

(2) If the recipient gives such notice the recipient must—

(a)within the period specified in the provisional determination notice, make written representations to the licensing authority explaining why the recipient thinks the product is not a medicinal product; or

(b)within the period of four weeks beginning immediately after the determination date, inform the licensing authority in writing that the recipient wants to make oral representations explaining why the recipient thinks the product is not a medicinal product.

(3) If—

(a)the recipient has informed the licensing authority that the recipient wants to make written representations in accordance with paragraph (2)(a); and

(b)the licensing authority thinks that, because of exceptional circumstances or the nature or complexity of the issues involved, additional time is needed for the preparation of written representations,

the licensing authority may alter the period for making written representations.

(4) The licensing authority must inform the recipient in writing of an alteration under paragraph (3) and of the reasons for it.

Written representations procedureU.K.

161.—(1) If a recipient makes written representations in accordance with regulation 160(2)(a) the licensing authority must appoint a panel of at least two persons (“the reviewers”) to advise on the provisional determination.

(2) The licensing authority must provide the reviewers with—

(a)the recipient's written representations; and

(b)any written representations of the licensing authority.

(3) The reviewers must advise the licensing authority on the authority's provisional determination taking account of—

(a)the written representations; and

(b)any other evidence submitted to them.

(4) The licensing authority must take into account the reviewers' advice and make a final determination as to whether the product is a medicinal product.

(5) The licensing authority must—

(a)inform the recipient in writing of its final determination and of the reasons for it; and

(b)if the licensing authority disagrees with the reviewers' advice, inform the recipient in writing of the reasons for that disagreement.

Oral representations procedureU.K.

162.—(1) If a recipient informs the licensing authority in accordance with regulation 160(2)(b) that the recipient wants to make oral representations, the licensing authority must—

(a)appoint a panel of at least two persons (“the reviewers”) to conduct the review; and

(b)after consultation with the recipient set a date for the hearing.

(2) The licensing authority may alter the date of the hearing at the request of the recipient or of its own motion if it thinks that because of exceptional circumstances or the nature or complexity of the issues involved additional time is needed for preparation for the hearing.

(3) The licensing authority must inform the recipient in writing of any alteration under paragraph (2) and of the reasons for it.

(4) The recipient and the licensing authority may make oral representations at the hearing.

(5) The reviewers must advise the licensing authority on the authority's provisional determination, taking account of—

(a)the oral representations made and any other evidence submitted by the recipient at the hearing;

(b)any oral representations made or other evidence submitted by the licensing authority at the hearing; and

(c)any other evidence heard by the review panel.

(6) The licensing authority must take into account the reviewers' advice and make a final determination as to whether the product is a medicinal product.

(7) The licensing authority must—

(a)inform the recipient in writing of its final determination and of the reasons for it; and

(b)if the licensing authority disagrees with the reviewers' advice, inform the recipient in writing of the reasons for that disagreement.

Final determination without representationsU.K.

163.—(1) This regulation applies if the recipient—

(a)does not give notification to the licensing authority that the recipient wishes to challenge its provisional determination within the period of four weeks beginning immediately after the determination date;

(b)gives such notification, but fails to make written representations to the licensing authority within the period for making those representations; or

(c)gives such notification, but fails to make oral representations at a hearing before the reviewers appointed for the purposes of advising on the provisional determination.

(2) The licensing authority must—

(a)make a final determination as to whether the product is a medicinal product; and

(b)inform the recipient in writing of its final determination and of the reasons for it.

Effect of final determinationU.K.

164.—(1) If the licensing authority makes a final determination that a product is a medicinal product, it may give a notice to any person—

(a)who has sold or supplied the product, or has offered to sell or supply it; or

(b)whom the licensing authority thinks may sell or supply the product.

(2) The notice must require the person—

(a)to cease to sell, supply or offer to sell or supply the product from the date specified in the notice until a marketing authorisation, traditional herbal registration, certificate of registration or Article 126a authorisation is granted in respect of the product; or

(b)not to sell, supply or offer to sell or supply the product unless a marketing authorisation, traditional herbal registration, certificate of registration or Article 126a authorisation is granted in respect of the product.

Determination in other casesU.K.

165.  Nothing in this Part prevents the licensing authority from determining that a product is a medicinal product without following the procedures in this Part when it thinks it appropriate.

Offences relating to borderline productsU.K.

166.—(1) A person is guilty of an offence if that person sells or supplies, or offers to sell or supply a product in breach of a notice under regulation 164(1) imposing a requirement under—

(a)regulation 164(2)(a); or

(b)regulation 164(2)(b).

(2) A person guilty of an offence under this regulation is liable—

(a)on summary conviction to a fine not exceeding the statutory maximum; or

(b)on conviction on indictment, to a fine, to imprisonment for a term not exceeding two years or to both.

PART 10U.K.Exceptions to requirement for marketing authorisation etc

ExceptionsU.K.

Supply to fulfil special patient needsU.K.

167.—(1) The prohibitions in regulation 46 (requirement for authorisation) do not apply in relation to a medicinal product (a “special medicinal product”) if—

(a)the medicinal product is supplied in response to an unsolicited order;

(b)the medicinal product is manufactured and assembled in accordance with the specification of a person who is a doctor, dentist, nurse independent prescriber, pharmacist independent prescriber or supplementary prescriber;

(c)the medicinal product is for use by a patient for whose treatment that person is directly responsible in order to fulfil the special needs of that patient; and

(d)the following conditions are met.

(2) Condition A is that the medicinal product is supplied—

(a)to a doctor, dentist, nurse independent prescriber, pharmacist independent prescriber or supplementary prescriber; or

(b)for use under the supervision of a pharmacist in a registered pharmacy, a hospital or a health centre.

(3) Condition B is that no advertisement relating to the medicinal product is published by any person.

(4) Condition C is that—

(a)the manufacture and assembly of the medicinal product are carried out under such supervision; and

(b)such precautions are taken,

as are adequate to ensure that the medicinal product meets the specification of the doctor, dentist, nurse independent prescriber, pharmacist independent prescriber or supplementary prescriber who requires it.

(5) Condition D is that written records of the manufacture or assembly of the medicinal product in accordance with condition C are maintained and are available to the licensing authority or to the enforcement authority on request.

(6) Condition E is that if the medicinal product is manufactured or assembled in the United Kingdom or imported into the United Kingdom from a country other than an EEA State—

(a)it is manufactured, assembled or imported by the holder of a manufacturer's licence that relates specifically to the manufacture, assembly or importation of special medicinal products; or

(b)it is manufactured, assembled or imported as an investigational medicinal product by the holder of a manufacturing authorisation granted by the licensing authority for the purposes of regulation 36 of the Clinical Trials Regulations.

(7) Condition F is that if the product is imported from an EEA State—

(a)it is manufactured or assembled in that State by a person who is the holder of an authorisation in relation to its manufacture or assembly in accordance with the provisions of the 2001 Directive as implemented in that State; or

(b)it is manufactured or assembled as an investigational medicinal product in that State by the holder of an authorisation in relation to its manufacture or assembly in accordance with Article 13 of the Clinical Trials Directive as implemented in that State.

(8) Condition G is that if the product is distributed by way of wholesale dealing by a person (“P”), who has not, as the case may be, manufactured, assembled or imported the product in accordance with paragraph (6)(a) or (7)(a), P must be the holder of a wholesale dealer's licence in relation to the product in question.

(9) In this regulation “publish” has the meaning given in regulation 277(1) (interpretation: Part 14 advertising).

Use of non-prescription medicines in the course of a businessU.K.

168.—(1) The prohibitions in regulation 46 (requirement for authorisation) do not apply to anything done in relation to a medicinal product if the following conditions are met.

(2) Condition A is that the medicinal product is not a prescription only medicine.

(3) Condition B is that the medicinal product is sold or supplied to a person who is a health care professional (“P”) exclusively for use by P—

(a)in the course of a business carried on by P, and

(b)for the purposes of administering it or causing it to be administered otherwise than by selling it.

(4) Condition C is that the medicinal product is—

(a)manufactured and assembled in accordance with the specification of P; and

(b)for use by a patient for whose treatment P is directly responsible in order to fulfil the special needs of that patient

(5) Condition D is that if sold or supplied through the holder of a wholesale dealer's licence the medicinal product is sold or supplied to such a person and for such use as mentioned in condition B.

(6) Condition E is that no advertisement relating to the medicinal product is published by any person.

(7) Condition F is that the sale or supply of the medicinal product is in response to an unsolicited order.

(8) Condition G is that if the medicinal product is —

(a)manufactured or assembled in the United Kingdom or imported into the United Kingdom from a country other than an EEA State, it is manufactured, assembled or imported by the holder of a manufacturer's licence that relates specifically to the manufacture, assembly or importation of special medicinal products; or

(b)imported from an EEA State, it is manufactured or assembled in that State by a person who is the holder of an authorisation in relation to its manufacture or assembly in accordance with the provisions of the 2001 Directive as implemented in that State.

(9) In this regulation “publish” has the meaning given in regulation 277(1) (interpretation: Part 14 advertising).

Mixing of general sale medicinal productsU.K.

169.—(1) The prohibitions in regulation 46 (requirement for authorisation) do not apply to a medicinal product (“the product”) in respect of which the following conditions are met.

(2) Condition A is that the product is manufactured by the mixing of authorised medicinal products with other authorised medicinal products, or with substances that are not medicinal products.

(3) Condition B is that any authorised medicinal product that is so mixed is subject to general sale.

(4) Condition C is that the product is manufactured by a person (“H”) who is the holder of a manufacturer's licence that—

(a)relates specifically to the manufacture of medicinal products in accordance with this regulation; and

(b)was granted or renewed not more than five years before the date on which the product is sold or supplied in accordance with paragraphs (5) and (6),

and that the product is manufactured in accordance with the terms of that licence.

(5) Condition D is that the product is sold or supplied by H to a person (“P”) for administration to P or to a member of P's household.

(6) Condition E is that P is present and asks H to use H's judgment as to the treatment required.

(7) Condition F is that no advertisement relating to the product is published by any person.

(8) Condition G is that written records of the manufacture of the product and of the sale or supply of the product are maintained and are made available to the licensing authority or to the enforcement authority on request.

(9) In this regulation, “authorised medicinal product” means a medicinal product that is the subject of—

(a)a marketing authorisation;

(b)a certificate of registration; or

(c)a traditional herbal registration.

Record-keeping requirementsU.K.

170.—(1) Where the sale or supply of a medicinal product relies on the exemptions under regulations 167, 168 or, subject to paragraph (4), 169, the person who sells or supplies the product must maintain for at least five years a record showing—

(a)the source from which and the date on which the person obtained the product;

(b)the person to whom and the date on which the sale or supply was made;

(c)the quantity of the sale or supply;

(d)the batch number of the batch of that product from which the sale or supply was made; and

(e)details of any suspected adverse reaction to the product so sold or supplied of which the person is aware or subsequently becomes aware.

(2) The person must make the records available for inspection by the licensing authority on request.

(3) The person must notify the licensing authority of any suspected adverse reaction to the medicinal product which is a serious adverse reaction.

(4) In the case of a medicinal product that is sold or supplied in reliance on the exemption in regulation 169—

(a)the reference in paragraph (1)(a) to “the product” means all the medicinal products that were mixed in the course of the manufacture of the product; and

(b)paragraph (1)(d) shall not apply.

Exempt advanced therapy medicinal productsU.K.

171.—(1) The prohibitions in regulation 46 (requirement for authorisation) do not apply in relation to an advanced therapy medicinal product (an “exempt advanced therapy medicinal product”) if the following conditions are met.

(2) Condition A is that the product is prepared—

(a)on a non-routine basis;

(b)in the United Kingdom; and

(c)according to specific quality standards equivalent to those provided for advanced therapy medicinal products authorised under Regulation (EC) No 726/2004.

(3) Condition B is that the product is used—

(a)in a hospital in the United Kingdom;

(b)under the exclusive professional responsibility of a doctor; and

(c)in order to comply with an individual medical prescription for a product made to order for an individual patient.

(4) Condition C is that no advertisement relating to the medicinal product is published by any person.

(5) Condition D is that the sale or supply of the medicinal product is in response to an unsolicited order.

(6) In this regulation “publish” has the meaning given in regulation 277(1) (interpretation Part 14 advertising).

Parallel import licencesU.K.

172.—(1) The prohibitions in regulation 46 (requirement for authorisation) do not prevent—

(a)the holder of a parallel import licence from placing the medicinal product to which the licence relates on the market; or

(b)the sale or supply, or offer for sale or supply, of a medicinal product to which a parallel import licence relates, in accordance with the terms of that licence.

(2) In this regulation “parallel import licence” means a licence that—

(a)is granted by the licensing authority in compliance with the rules of European Union law relating to parallel imports; and

(b)authorises the holder to place on the market a medicinal product imported into the United Kingdom from another EEA State.

Exemption for certain radiopharmaceuticalsU.K.

173.  Regulation 46 (requirement for authorisation) does not apply where a radiopharmaceutical is prepared—

(a)at the time when it is intended to be administered;

(b)in accordance with the manufacturer's instructions and by the person by whom it is to be administered;

(c)from radionuclide generators, radionuclide kits and radionuclide precursors in respect of which a marketing authorisation is in force; and

(d)for administration in accordance with regulation 2 of the Medicines (Administration of Radioactive Substances) Regulations 1978 M43.

Marginal Citations

M43S.I. 1978/1006, as amended by S.I. 1995/2147 and S.I. 2006/2806; there are other amendments not relevant to these Regulations.

Supply in response to spread of pathogenic agents etcU.K.

174.  The prohibitions in regulation 46 (requirement for authorisation) do not apply where the sale or supply of a medicinal product is authorised by the licensing authority on a temporary basis in response to the suspected or confirmed spread of—

(a)pathogenic agents;

(b)toxins;

(c)chemical agents; or

(d)nuclear radiation,

which may cause harm to human beings.

OffencesU.K.

Offences relating to exceptionsU.K.

175.—(1) A person to whom this paragraph applies is guilty of an offence if the person provides to the licensing authority any information that is relevant to the evaluation of the safety, quality or efficacy of a medicinal product that is false or misleading in a material particular.

(2) Paragraph (1) applies to any person who for the purposes of regulation 167 (special patient needs)—

(a)sells or supplies the product; or

(b)provides a specification for the product.

(3) A person is guilty of an offence if the person fails to—

(a)maintain any record required by regulation 170(1) (records in connection with special medicinal products etc);

(b)make any record available as required by regulation 170(2); or

(c)notify the licensing authority of any suspected serious adverse reaction as required by regulation 170(3).

Penalties and supplementary provision about offencesU.K.

176.—(1) A person guilty of an offence under regulation 175 is liable—

(a)on summary conviction to a fine not exceeding the statutory maximum; or

(b)on conviction on indictment, to a fine, to imprisonment for a term not exceeding two years or to both.

(2) It is a defence for a person charged with an offence under regulation 175(1) to prove that the person took all reasonable precautions and exercised all due diligence to avoid commission of that offence.

(3) Where evidence is adduced that is sufficient to raise an issue with respect to the defence in paragraph (2), the court or jury must presume that the defence is satisfied unless the prosecution proves beyond reasonable doubt that it is not.

PART 11U.K.Pharmacovigilance

Application of this Part and interpretationU.K.

177.—(1) This Part and Schedule 33 apply, except to the extent set out in paragraph (4)(b), in relation to medicinal products that are the subject of—

(a)a UK marketing authorisation;

(b)a traditional herbal registration; or

(c)an Article 126a authorisation.

(2) References in this Part to a “holder” are to the holder of—

(a)a UK marketing authorisation;

(b)a traditional herbal registration; or

(c)an Article 126a authorisation,

and, in relation to such references, “product” means the product to which the authorisation or registration relates.

(3) References to an “authorisation or registration” in this Part and in Schedule 33 are references to—

(a)a UK marketing authorisation;

(b)a traditional herbal registration; or

(c)an Article 126a authorisation

and “authorised or registered” is to be read accordingly.

[F41(4) The following provisions of this Part and Schedule 33 apply in relation to medicinal products that are the subject of an EU marketing authorisation—

(a)regulation 206 (infringement notices);

(b)regulation 210 (offences relating to pharmacovigilance obligations under Regulation (EC) No 726/2004), and paragraphs 2 and 4 of Schedule 33 (transitional arrangements: pharmacovigilance), but that regulation and those paragraphs do not apply in relation to the medicinal products specified in paragraph (1); and

(c)regulation 210A (offences in relation to pharmacovigilance obligations under the Implementing Regulation).]

(5) In this Part and in Schedule 33—

co-ordination group” means the group of that name established under Article 27 of the 2001 Directive;

Eudravigilance database” means the database and data-processing network set up and maintained by the EMA under Article 24 of Regulation (EC) No 726/2004;

[F42“Implementing Regulation” means Commission Implementing Regulation (EU) No 520/2012 of 19 June 2012 on the performance of pharmacovigilance activities provided for in Regulation (EC) No 726/2004 of the European Parliament and of the Council and Directive 2001/83/EC of the European Parliament and of the Council.]

infringement notice” has the meaning given to it in regulation 206 (infringement notices);

relevant competent authorities” means the competent authority of each EEA state other than the United Kingdom which has granted in relation to a medicinal product—

(a)

an authorisation in accordance with Chapter 1 of Title III to the 2001 Directive (marketing authorization);

(b)

an authorisation in accordance with Chapter 4 of Title III to the 2001 Directive (mutual recognition and decentralised procedure);

(c)

a registration in accordance with Chapter 2a of Title III to the 2001 Directive (traditional use registration for herbal medicinal products); or

(d)

an authorisation in accordance with Article 126a of the 2001 Directive;

relevant post-authorisation safety study” means a post-authorisation safety study which—

(a)

is non-interventional;

(b)

is initiated, managed or financed by the holder voluntarily or pursuant to conditions imposed under regulation 59 (conditions of a UK marketing authorisation: general) or 61 (conditions of a UK marketing authorisation: new obligations post-authorisation); and

(c)

involves the collection of safety data from patients or health care professionals; and

UK web-portal” has the meaning given in regulation 203 (obligations on licensing authority in relation to national medicines web-portal).

Obligations on licensing authority in relation to pharmacovigilanceU.K.

General obligations of the licensing authorityU.K.

178.  The licensing authority must—

(a)take all appropriate measures to encourage the reporting to it of suspected adverse reactions;

(b)facilitate reporting through the provision of alternative reporting formats in addition to web-based formats;

(c)take all appropriate measures to obtain accurate and verifiable data for the scientific evaluation of suspected adverse reaction reports;

(d)ensure that the public is given important information on pharmacovigilance concerns relating to the use of a medicinal product in a timely manner, through publication on the UK web-portal, and through other means of publicly available information as necessary; and

(e)ensure that all appropriate measures are taken to identify any biological medicinal product (including name and batch number) prescribed, dispensed or sold in the United Kingdom which is the subject of a suspected adverse reaction report through—

(i)the methods for collecting data, and

(ii)where necessary, the follow up of suspected adverse reaction reports.

Obligation on licensing authority to operate pharmacovigilance systemU.K.

179.—(1) The licensing authority must operate a pharmacovigilance system.

(2) The pharmacovigilance system must in particular enable the collection of information on the risks that medicinal products present to patients' health or public health, including information on—

(a)adverse reactions in humans arising from use of a medicinal product (irrespective of whether the use was within the terms of an authorisation or registration); and

(b)adverse reactions associated with occupational exposure.

(3) The licensing authority must on an ongoing basis—

(a)evaluate scientifically the information collected under the pharmacovigilance system;

(b)consider options for minimising and preventing risks presented by medicinal products; and

(c)take appropriate regulatory action, if any.

Obligation on licensing authority to audit pharmacovigilance systemU.K.

180.—(1) The licensing authority must perform a regular audit of its pharmacovigilance system and report the results of that audit to the European Commission.

(2) The results of the audit referred to in paragraph (1) must be reported to the European Commission—

(a)on the first occasion no later than 21st September 2013; and

(b)every two years after the first occasion.

Delegation of obligations under this PartU.K.

181.—(1) The licensing authority may delegate any of its obligations under this Part to another EEA State where the conditions in paragraph (2) are met.

(2) The conditions in this paragraph are that the EEA State to whom the obligations are to be delegated—

(a)has given its written agreement to the delegation; and

(b)is not performing delegated obligations under this Part on behalf of another EEA State.

(3) Where the licensing authority has delegated any of its obligations under paragraph (1), it must—

(a)inform the European Commission, the EMA and all other EEA States in writing of the delegation as soon as is reasonably practicable; and

(b)make the delegation public as soon as is reasonably practicable.

(4) The licensing authority may agree to carry out any of the obligations of another EEA State under Title IX of the 2001 Directive on a delegated basis, but may carry out obligations under that Title only for one EEA State at any time.

Obligations on holders in relation to pharmacovigilance systemU.K.

Obligation on holder to operate pharmacovigilance systemU.K.

182.—(1) The holder must operate a pharmacovigilance system.

(2) The holder must (as part of its pharmacovigilance system)—

(a)have permanently and continuously at its disposal an appropriately qualified person responsible for pharmacovigilance who resides and operates in the EU and is responsible for the establishment and maintenance of the pharmacovigilance system;

(b)maintain and make available on the request of the licensing authority a pharmacovigilance system master file;

(c)operate a risk management system for the product in accordance with the risk management plan (if any) for the product (subject to regulation 183);

(d)monitor the outcome of the risk minimisation measures which are contained in the risk management plan (if any) for the product or which are laid down as conditions of the authorisation of the product under regulations 59 to 61 (conditions of UK marketing authorisation); and

(e)update the risk management system for the product and monitor pharmacovigilance data to determine whether in relation to the product—

(i)there are new risks,

(ii)risks have changed, or

(iii)there are changes to the risk-benefit balance.

(3) The holder must keep the licensing authority F43... informed of the name and contact details of the appropriately qualified person mentioned in paragraph (2)(a) at all times.

(4) The holder must use its pharmacovigilance system to—

(a)evaluate scientifically all information relevant to the product;

(b)consider options for minimising and preventing the risk presented by the use of the product; and

(c)take appropriate measures as soon as is reasonably practicable to—

(i)investigate the potential risks of the product,

(ii)communicate the risks, and

(iii)implement actions for minimising and preventing the risks, including updating the risk management system for the product.

(5) Where the licensing authority requests that the pharmacovigilance system master file is made available under paragraph (2)(b), the holder must submit a copy of the pharmacovigilance system master file to the licensing authority before the end of the period of 7 days beginning on the day after the day when the request was made.

(6) This regulation is subject to regulation 212 (transitional arrangements).

Exception to obligation to operate risk management systemU.K.

183.—(1) The holder is not required to operate a risk management system under regulation 182(2)(c) in relation to a medicinal product which has an authorisation or registration that was granted before 21st July 2012.

(2) The licensing authority may impose an obligation on the holder to operate a risk management system in relation to a medicinal product referred to in paragraph (1) if there are concerns about new or changed risks affecting the risk-benefit balance of that product.

(3) Paragraphs (4) to (6) apply where the licensing authority imposes an obligation to operate a risk management system on the holder under paragraph (2).

(4) The licensing authority must without delay notify the holder in writing of—

(a)the imposition of the obligation;

(b)the justification for the obligation;

(c)the timeframe for submission of the detailed description of the risk management system required under paragraph (8)(a); and

(d)the opportunity to present written observations in accordance with paragraph (5).

(5) Where the holder so requests before the end of the period of thirty days beginning on the day after the receipt by the holder of the notice referred to in paragraph (4), the licensing authority must provide the holder with an opportunity to present written observations in response to the imposition of the obligation within such a time limit as the licensing authority may specify.

(6) Where a holder presents written observations under paragraph (5), the licensing authority must withdraw or confirm the imposition of the obligation under paragraph (2), having regard to the written observations, as soon as is reasonably practicable.

(7) Paragraphs (8) and (9) apply where the licensing authority—

(a)imposes an obligation under paragraph (2) and the holder does not present written obligations under paragraph (5); or

(b)confirms the imposition of the obligation under paragraph (2) pursuant to paragraph (6).

(8) The holder must—

(a)submit to the licensing authority in writing a detailed description of the risk management system which it intends to introduce for the product in accordance with the timeframe set out in the notification under paragraph (4); and

(b)comply with the obligation to operate a risk management system.

(9) Where the imposition relates to a product with a UK marketing authorisation, the licensing authority must vary the authorisation to include the measures to be taken as part of the risk management system as conditions of the authorisation as if they were conditions imposed under regulation 59 (conditions of UK marketing authorisations: general).

Obligation on holder to audit pharmacovigilance systemU.K.

184.—(1) The holder must—

(a)perform a regular audit of its pharmacovigilance system;

(b)place a note concerning the main findings of each audit on the pharmacovigilance system master file on completion of each audit; and

(c)ensure that an appropriate corrective action plan is prepared and implemented as soon as is reasonably practicable after completion of each audit.

(2) The holder may remove the note placed on the pharmacovigilance system master file under paragraph (1)(b) when all the measures in the corrective action plan under paragraph (1)(c) have been fully implemented.

Recording, reporting and assessment of pharmacovigilance dataU.K.

Recording obligations on the licensing authorityU.K.

185.  The licensing authority must record all suspected adverse reactions to medicinal products that—

(a)occur in the United Kingdom; and

(b)are reported to it by a patient or a patient's carer, a health care professional, a coroner or a procurator fiscal.

Reporting obligations on the licensing authorityU.K.

186.—(1) The licensing authority must—

(a)when it receives a suspected adverse reaction report from a person mentioned in regulation 185(b), follow up the report with that person as appropriate;

(b)ensure that reports of suspected adverse reactions in the United Kingdom may be submitted to it, whether by the UK web-portal or by other means;

(c)collaborate with the EMA and the holders of authorisations or registrations in the detection of duplicates of suspected adverse reaction reports;

(d)submit reports of serious suspected adverse reactions that it has recorded under regulation 185 electronically to the Eudravigilance database before the end of the period of 15 days beginning on the day following the day on which the report was received; and

(e)submit reports of non-serious suspected adverse reactions it has recorded under regulation 185 electronically to the Eudravigilance database before the end of the period of 90 days beginning on the day following the day on which the report was received.

(2) Paragraph (3) applies where the licensing authority has received a report of a suspected adverse reaction arising from an error associated with the use of a medicinal product.

(3) The licensing authority must (in addition to meeting the requirements in paragraph (1) in respect of the report) ensure that the report is made available to any statutory body with functions in relation to patient safety within the United Kingdom.

(4) This regulation is subject to regulation 212 (transitional arrangements).

Recording obligations on holdersU.K.

187.—(1) Subject to paragraph (2), the holder must record all suspected adverse reactions to the product occurring in the EEA or in third countries which are brought to its attention irrespective of whether the reaction—

(a)is reported spontaneously by patients or health care professionals; or

(b)occurred in the context of a post-authorisation study.

(2) Paragraph (1) does not apply where the suspected adverse reaction occurred in the context of a clinical trial within the meaning of the Clinical Trials Regulations.

(3) The holder must not refuse to consider reports of suspected adverse reactions to the product received electronically or by any other appropriate means from patients or from health care professionals.

(4) The holder must ensure that reports recorded under paragraph (1) are accessible (electronically or physically) at a single point within the EEA.

Reporting obligations on holdersU.K.

188.—(1) Subject to paragraph (2), the holder must in relation to the product—

(a)submit electronically to the Eudravigilance database a report on all serious suspected adverse reactions that occur in the EEA and third countries before the end of the period of 15 days beginning on the day following the day on which the holder gained knowledge of the reaction;

(b)submit electronically to the Eudravigilance database a report on all non-serious suspected adverse reactions that occur in the EEA before the end of the period of 90 days beginning on the day following the day on which the holder gained knowledge of the reaction;

(c)establish procedures in order to obtain accurate and verifiable data for the scientific evaluation of suspected adverse reaction reports;

(d)collect follow-up information on reports submitted under sub-paragraphs (a) or (b) and submit it electronically to the Eudravigilance database by way of an update to the original report within the specified time period; and

(e)collaborate with the EMA and the competent authorities of the EEA States in the detection of duplicates of suspected adverse reaction reports.

(2) The holder is not required to submit a report of a suspected adverse reaction to the product under paragraph (1)(a) or (b), or to provide follow-up information under paragraph (1)(d), where—

(a)the suspected adverse reaction relates to a medicinal product which contains a monitored active substance; and

(b)the suspected adverse reaction is recorded in a monitored publication.

(3) Paragraph (4) applies to medicinal products containing a monitored active substance.

(4) The holder must—

(a)monitor medical literature other than the monitored publications for reports of suspected adverse reactions to the product; and

(b)report suspected adverse reactions identified under sub-paragraph (a) in accordance with paragraph (1).

(5) In this regulation—

monitored active substance” means an active substance on the list of active substances being monitored by the EMA published under Article 27 of Regulation (EC) No 726/2004;

monitored publication” means a publication on the list of publications being monitored by the EMA published under Article 27 of Regulation (EC) No 726/2004; and

the specified time period” means—

(a)

in the case of serious adverse reactions, the period of 15 days beginning on the day following the day on which the follow up information became known to the holder; and

(b)

in the case of non-serious adverse reactions, the period of 90 days beginning on the day following the day on which the follow up information became known to the holder.

(6) This regulation is subject to regulation 212 (transitional arrangements).

Signal detectionU.K.

Signal detection: licensing authority obligationsU.K.

189.—(1) The licensing authority must in relation to each medicinal product—

(a)monitor the data in the Eudravigilance database to determine whether there are any relevant changes;

(b)assess updates to the risk management system for the product;

(c)monitor the outcome of risk minimisation measures contained in the risk management plan (if any); and

(d)monitor the outcome of conditions imposed under regulations 59 to 61 (conditions of UK marketing authorisations) (if any).

(2) The licensing authority must collaborate with the EMA in carrying out its functions under paragraph (1).

(3) The licensing authority must inform the bodies specified in paragraph (4) without delay if it detects any relevant changes in relation to a medicinal product.

(4) The bodies specified in this paragraph are—

(a)the EMA; and

(b)the relevant competent authorities.

(5) In this regulation “relevant changes” in relation to a medicinal product means—

(a)new risks;

(b)risks that have changed; or

(c)changes to the risk-benefit balance.

Signal detection: holder obligationU.K.

190.—(1) The holder must inform the EMA and the licensing authority without delay if it detects any relevant changes in relation to the product.

(2) In this regulation, “relevant changes” has the meaning given in regulation 189(5).

Periodic Safety Update ReportsU.K.

Obligation on holder to submit periodic safety update reports: general requirementsU.K.

191.—(1) The holder must submit reports known as periodic safety update reports (“PSURs”) in relation to the product to the EMA in accordance with this regulation, or in a case where paragraph (2) applies, in accordance with regulation 192.

(2) This paragraph applies to—

(a)a marketing authorisation granted pursuant to regulations 51 (applications for UK marketing authorisations relating to generic medicinal products) or 54 (application relating to products in well-established medicinal use); or

(b)a traditional herbal registration.

(3) In the following paragraphs of this regulation—

authorisation” means a UK marketing authorisation or an Article 126a authorisation;

the holder” means the holder of a UK marketing authorisation or an Article 126a authorisation; and

product” means a product to which a UK marketing authorisation or Article 126a authorisation relates.

(4) Each PSUR must contain—

(a)summaries of data relevant to the benefits and risks of the product, including results of all studies, with a consideration of their potential impact on the authorisation for the product;

(b)a scientific evaluation of the risk-benefit balance of the product; and

(c)all data relating to the volume of sales of the product and any data the holder has relating to the volume of prescriptions, including an estimate of the population exposed to the product.

(5) For the purposes of paragraph (4)(b), the scientific evaluation must be based on all available data, including data from clinical trials conducted outside the terms of the authorisation for the product.

(6) Each PSUR must be submitted electronically.

(7) PSURs must be submitted to the EMA with the frequency and on the dates as set out in paragraphs (8) to (10).

(8) In the case of an authorisation granted on or after 21st July 2012, the holder must submit PSURs with the frequency as specified in the authorisation for the product, with the dates of submission being calculated from the date of authorisation.

(9) In the case of an authorisation granted before 21st July 2012 which specifies the frequency and dates of submission of PSURs, the holder must submit PSURs with the frequency and on the dates as specified in the authorisation for the product.

(10) In the case of an authorisation granted before 21st July 2012 which does not specify the frequency and dates of submission of PSURs, the holder must submit a PSUR—

(a)immediately upon the request of the licensing authority;

(b)where the product has not yet been placed on the market within the EEA, at least every six months following authorisation until the placing on the market within the EEA; and

(c)where the product has been placed on the market within the EEA—

(i)at least every six months during the first two years following the initial placing on the market,

(ii)once a year for the following two years, and

(iii)every three years after that.

(11) This regulation is subject to regulation 212 (transitional arrangements).

Obligation on holder to submit periodic safety update reports: derogation from general requirementsU.K.

192.—(1) This regulation applies in relation to medicinal products granted—

(a)a marketing authorisation pursuant to regulations 51 (applications for UK marketing authorisations relating to generic medicinal products) or 54 (application relating to products in well-established medicinal use); or

(b)a traditional herbal registration.

(2) In the following paragraphs of this regulation—

authorisation or registration” means a marketing authorisation to which paragraph (1)(a) applies or a traditional herbal registration;

the holder” means the holder of a marketing authorisation to which paragraph (1)(a) applies or of a traditional herbal registration; and

product” means a product to which a marketing authorisation referred to in paragraph (1)(a) or a traditional herbal registration relates.

(3) The holder must submit PSURs in relation to the product to the EMA in accordance with paragraph (5)—

(a)where requested to do so by the licensing authority in accordance with paragraph (4); or

(b)in the case of a product to which paragraph (1)(a) applies, where it is a condition to which the marketing authorisation for the product is subject by virtue of regulations 59 (conditions of UK marketing authorisation: general) or 60 (conditions of UK marketing authorisation: exceptional circumstances) to do so.

(4) The licensing authority may request the holder to submit PSURs where—

(a)it has concerns relating to the product's pharmacovigilance data; or

(b)it considers there is a lack of PSUR data relating to an active substance of the product after the authorisation or registration is granted.

(5) The submission of PSURs under paragraph (3) must be in accordance with—

(a)where the PSUR is submitted pursuant to a request under paragraph (3)(a), the terms of the request; and

(b)where the PSUR is submitted pursuant to a condition under paragraph (3)(b), the terms of the condition.

(6) Each PSUR must contain—

(a)summaries of data relevant to the benefits and risks of the product, including results of all studies, with a consideration of their potential impact on the authorisation or registration for the product;

(b)a scientific evaluation of the risk-benefit balance of the product; and

(c)all data relating to the volume of sales of the product and any data the holder has relating to the volume of prescriptions, including an estimate of the population exposed to the product.

(7) For the purposes of paragraph (6)(b), the scientific evaluation must be based on all available data, including data from clinical trials conducted outside the terms of the authorisation or registration for the product.

(8) Each PSUR must be submitted electronically.

(9) Where the licensing authority requests submission of PSURs under paragraph (3)(a), it must communicate a PSUR assessment report to the EMA as soon as is reasonably practicable after each report is received.

(10) In this regulation “PSUR assessment report” means a report which evaluates the information provided in a PSUR.

(11) This regulation is subject to regulation 212 (transitional arrangements).

Harmonisation of PSUR frequency or date of submissionU.K.

193.—(1) Where products that are subject to different authorisations or registrations contain the same active substance or the same combination of active substances, the frequency and dates of submission may be amended and harmonised in accordance with—

(a)Article 107c(4) of the 2001 Directive; or

(b)paragraphs (2) to (4).

(2) The holder may, where one or more of the grounds in paragraph (3) is met, submit a request in relation to the product to the EMA—

(a)to determine an EU reference date; or

(b)to change the frequency of submission of the PSUR.

(3) The grounds in this paragraph are—

(a)reasons relating to public health;

(b)in order to avoid duplication of the assessment; or

(c)in order to achieve international harmonisation.

(4) The second paragraph of Article 107c(6) of the 2001 Directive has effect in relation to the submission and determination of a request under paragraph (2).

(5) Where the frequency or dates of submission of a PSUR are changed in accordance with Article 107c(4) or Article 107c(6) of the 2001 Directive, the holder must apply to vary the product's authorisation or registration to reflect the new frequency or date of submission before the end of the period of six months beginning on the day after the change is made public by the EMA.

(6) In this regulation, “EU reference date” in relation to a product means—

(a)the date of the first marketing authorisation in the EEA of a medicinal product containing the same active substance or the same combination of active substances as that product; or

(b)if the date referred to in point (a) cannot be ascertained, the earliest of the known dates of the marketing authorisations in the EEA for a medicinal product containing the same active substance or the same combination of active substances as that product.

Responding to a single assessment of PSUR under Article 107e of the 2001 DirectiveU.K.

194.—(1) This regulation applies where PSURs relating to a medicinal product have been assessed under the EU single assessment procedure.

(2) The licensing authority must implement—

(a)the necessary measures that are consequent upon any agreement reached under Article 107g(2) of the 2001 Directive as part of the EU single assessment process, in accordance with the implementation timetable determined in the agreement; or

(b)any decision adopted under Article 107g(4)(a) of the 2001 Directive before the end of the period of 30 days beginning on the day after the day on which the licensing authority received notification of the decision.

(3) Paragraph (4) applies where—

(a)an agreement reached under Article 107g(2) of the 2001 Directive requires a variation to be made to an authorisation or registration; and

(b)the terms of the agreement are known to the holder of that authorisation or registration.

(4) A holder of an authorisation or registration referred to in paragraph (3)(a) must submit to the licensing authority in accordance with the implementation timetable determined in the agreement an appropriate application for a variation, including—

(a)an updated summary of the product characteristics; and

(b)an updated package leaflet.

(5) In this regulation, “EU single assessment procedure” means the single assessment procedure laid down in Article 107e of the 2001 Directive, which covers—

(a)medicinal products that are authorised in more than one member State; and

(b)medicinal products that contain the same active substance or the same combination of active substances and for which a harmonised EU reference date and frequency of submission of PSURs have been established under Article 107c of the 2001 Directive.

Obligation on licensing authority to assess PSURs where EU single assessment procedure does not applyU.K.

195.—(1) This regulation applies where PSURs relating to a medicinal product have not been assessed under the EU single assessment procedure because—

(a)the medicinal product to which the PSUR relates has not been authorised to be placed on the market in accordance with the 2001 Directive in an EEA State other than the United Kingdom; and

(b)a harmonised EU reference date and frequency of submission of PSURs have not been established for that product under Article 107c of the 2001 Directive.

(2) The licensing authority must assess the PSURs to determine whether there are any relevant changes.

(3) Where the licensing authority has assessed a PSUR under paragraph (2) it must—

(a)consider whether any action concerning the authorisation or registration of the product to which the PSUR relates is necessary; and

(b)vary, suspend, or revoke the authorisation or registration as appropriate.

(4) In this regulation—

EU reference date” has the meaning given in regulation 193(6);

EU single assessment procedure” has the meaning given in regulation 194(5); and

relevant changes” in relation to a medicinal product means—

(a)

new risks,

(b)

risks that have changed, or

(c)

changes to the risk-benefit balance.

Urgent actionU.K.

Urgent actionU.K.

196.[F44(1) The licensing authority must initiate the Section 4 procedure by informing the specified bodies where, on the basis of concerns resulting from the evaluation of data from pharmacovigilance activities,—

(a)it considers suspending or revoking an authorisation or registration of a medicinal product or class of medicinal products;

(b)it considers prohibiting the supply of a medicinal product or class of medicinal products;

(c)it considers refusing the renewal of an authorisation or registration of a medicinal product; or

(d)it is informed by a holder that, on the basis of safety concerns, the holder has—

(i)interrupted the sale or supply, or offer of sale or supply, of the product,

(ii)taken action to have the product’s authorisation or registration cancelled or intends to do so, or

(iii)not applied for the renewal of the product’s authorisation or registration.

(2) The licensing authority must inform the specified bodies where, on the basis of concerns resulting from the evaluation of data from pharmacovigilance activities, it considers it necessary to vary an authorisation or registration or a class of authorisations or registrations to include—

(a)a new contra-indication,

(b)a reduction to the recommended dose, or

(c)a restriction to the therapeutic indications.

(2A) The information provided under paragraph (2) must outline the action considered and the reasons for the action.

(2B) Where the licensing authority considers urgent action is necessary in relation to the information provided under paragraph (2), it must initiate the Section 4 procedure.

(2C) The information required to be provided under paragraph (1) or (2) must be provided by the end of the day on which the consideration arose under paragraph (1)(a) to (c) or (2) or the information was received under paragraph (1)(d) (as the case may be).]

(3) When informing the EMA under paragraph [F45(1) or] (2), the licensing authority must make available to the EMA in relation to the medicinal product or class of medicinal products—

(a)all relevant scientific information at its disposal; and

(b)any assessment it has carried out.

(4) Where the EU urgent action procedure does not apply in relation to the medicinal product or class of medicinal products referred to in [F46paragraph (1) or (2)], the licensing authority—

(a)must inform the holder that it has taken action under [F47paragraph (1) or (2) (as the case may be)]; and

(b)may take such steps as it sees fit to address the safety concerns.

(5) Where the EU urgent action procedure does apply in relation to the medicinal product or class of medicinal products referred to in [F48paragraph (1) or (2)], the licensing authority may where the conditions in paragraph (6) are met—

(a)suspend the authorisation or registration of the medicinal product or the authorisations and registrations for the class of medicinal products referred to in [F48paragraph (1) or (2)] (as the case may be); or

(b)prohibit its or their use within the United Kingdom.

(6) The conditions in this paragraph are that—

(a)urgent action is necessary to protect public health; and

(b)an agreement under Article 107k of the 2001 Directive in respect of the medicinal product or class of medicinal products has not been reached.

(7) Where the licensing authority takes action under paragraph (5), it must by the end of the next working day after the day on which the action is taken inform [F49the specified bodies] of the reasons for the action F50...

[F51(8) In this regulation—

EU urgent action procedure” means the procedure under Articles 107j and 107k of the 2001 Directive;

“Section 4 procedure” means the procedure under Section 4 of Chapter 3 of Title IX of the 2001 Directive; and

“specified bodies” means—

(a)

the competent authority of each EEA State other than the United Kingdom,

(b)

the EMA, and

(c)

the European Commission.]

EU urgent action procedureU.K.

197.—(1) Where the EU urgent action procedure is initiated in relation to a medicinal product or class of medicinal products, the licensing authority—

(a)may publicly announce the initiation of the EU urgent action procedure on the UK web-portal; and

(b)must implement the measures set out in any agreement reached under Article 107k of the 2001 Directive in relation to the medicinal product or class of medicinal products in accordance with the implementation timetable determined in the agreement.

(2) Paragraph (3) applies where an agreement under Article 107k of the 2001 Directive in relation to a medicinal product or class of medicinal products requires a variation to be made to one or more authorisation or registration.

(3) Each holder of an authorisation or registration covered by the agreement referred to in paragraph (2) must submit to the licensing authority in accordance with the terms of the agreement (including its implementation timetable) an application for a variation in respect of the authorisation or registration including—

(a)an updated summary of the product characteristics; and

(b)an updated package leaflet.

(4) In this regulation, “EU urgent action procedure” has the same meaning as it is given in regulation 196(8).

Post-authorisation safety studiesU.K.

Post-authorisation safety studies: general provisionsU.K.

198.—(1) A relevant post-authorisation safety study—

(a)may not be conducted where the act of conducting the study promotes the use of a medicinal product; and

(b)may not provide for payments to health care professionals for participating in the study except in compensation for time and expenses incurred.

(2) The licensing authority may require the holder for the product which is the subject of a relevant post-authorisation safety study to submit the protocol and progress reports for the study to the competent authorities of the EEA States in which the study is conducted.

(3) The holder for the product which is the subject of a relevant post-authorisation safety study must—

(a)comply with a requirement imposed by the licensing authority under paragraph (2) (if any);

(b)while the study is being conducted—

(i)monitor the data generated, and

(ii)consider its implications for the risk-benefit balance of the product which is the subject of the study;

(c)communicate to the relevant competent authorities any new information that arises at any point during the study which might influence the evaluation of the risk-benefit balance for that product as soon as is reasonably practicable after it becomes known to the holder; and

(d)send the final report on the study to the competent authorities of the EEA States in which the study was conducted before the end of the period of 12 months beginning on the day after the day on which data collection for the study ended.

(4) This regulation is subject to regulation 212 (transitional arrangements).

Submission of draft study protocols for required studiesU.K.

199.—(1) This regulation applies to a relevant post-authorisation safety study that is to be conducted pursuant to a condition of a UK marketing authorisation imposed under regulation 59 (conditions of a UK marketing authorisation: general) or 61 (conditions of a UK marketing authorisation: new obligations post-authorisation).

(2) The holder for the product which is the intended subject of the study must submit a draft protocol for the study to the body specified in paragraph (3) before the study is commenced.

(3) The body specified in this paragraph is—

(a)where the study is to be conducted in the United Kingdom only, the licensing authority; or

(b)in all other cases, the Pharmacovigilance Risk Assessment Committee.

(4) Paragraph (5) applies where a draft protocol is submitted to the licensing authority under paragraphs (2) and (3)(a).

(5) Where this paragraph applies, the licensing authority, before the end of the period of 60 days beginning on the day after the day on which the draft protocol is submitted, must issue—

(a)a letter endorsing the draft protocol;

(b)a letter objecting to the draft protocol on the grounds that—

(i)it considers that the conduct of the study promotes the use of a medicinal product, or

(ii)it considers that the design of the study does not fulfil the study objectives; or

(c)a letter notifying the holder for the product which is the intended subject of the study that the study is a clinical trial within the meaning of the Clinical Trials Regulations.

(6) A study may not commence unless a letter endorsing the draft protocol has been issued by—

(a)the licensing authority under paragraph (5)(a); or

(b)the Pharmacovigilance Risk Assessment Committee under Article 107n(2) of the 2001 Directive.

(7) Paragraph (8) applies where a letter endorsing the draft protocol has been issued by the Pharmacovigilance Risk Assessment Committee under Article 107n(2) of the 2001 Directive.

(8) Where this paragraph applies, the holder for the product which is the intended subject of the study must forward the protocol to the competent authorities of the EEA States in which the study is to be conducted before commencing the study.

(9) In this regulation, “a letter” includes email correspondence.

(10) This regulation is subject to regulation 212 (transitional arrangements).

Amendment to study protocols for required studiesU.K.

200.—(1) This regulation applies where a study to which regulation 199 applies has been commenced.

(2) The holder for the product which is the subject of the study must submit any substantial amendments to the study protocol to the body specified in paragraph (3) before their implementation.

(3) The body specified in this paragraph is—

(a)where the study is being conducted in the United Kingdom only, the licensing authority; or

(b)in all other cases, the Pharmacovigilance Risk Assessment Committee.

(4) Paragraph (5) applies where a proposed amendment to a study protocol is submitted to the licensing authority under paragraphs (2) and (3)(a).

(5) Where this paragraph applies, the licensing authority must as soon as is reasonably practicable—

(a)assess the amendment; and

(b)inform the holder of its endorsement of, or objection to, the proposed amendment.

(6) Paragraph (7) applies where the proposed amendment to a study protocol is submitted to the Pharmacovigilance Risk Assessment Committee under paragraphs (2) and (3)(b).

(7) Where this paragraph applies, the holder who submitted the amendment must inform the competent authorities of the EEA States in which the study is being conducted of any amendment to the study protocol approved by the Pharmacovigilance Risk Assessment Committee as soon as is reasonably practicable.

(8) This regulation is subject to regulation 212 (transitional arrangements).

Submission and evaluation of final study reports for required studiesU.K.

201.—(1) This regulation applies where a study to which regulation 199 applies has been completed.

(2) Subject to paragraph (4), the holder for the product which is the subject of the study must submit electronically, before the end of the period of 12 months beginning on the day after the day on which data collection for the study ended, to the body specified in paragraph (3)—

(a)a final study report; and

(b)an abstract of the study results.

(3) The body specified in this paragraph is—

(a)where the study was conducted in the United Kingdom only, the licensing authority; or

(b)in all other cases, the Pharmacovigilance Risk Assessment Committee.

(4) Paragraph (2) does not apply where a written waiver has been granted by the licensing authority for reports falling under paragraph (3)(a), or by the Pharmacovigilance Risk Assessment Committee for reports falling under paragraph (3)(b).

(5) The holder must without delay—

(a)evaluate whether the results of a final study report submitted under paragraph (2) have an impact on the authorisation or registration of the medicinal product to which the report relates; and

(b)if necessary, submit an application to vary the authorisation or registration for the product.

(6) This regulation is subject to regulation 212 (transitional arrangements).

Follow-up of final study reportsU.K.

202.—(1) This regulation applies where—

(a)the Pharmacovigilance Risk Assessment Committee has made recommendations concerning an authorisation or registration or a class of authorisations or registrations based on a final study report under Article 107q(1) of the 2001 Directive; and

(b)an agreement on the action to be taken in respect of the authorisation or registration or the class of authorisations or registrations has been reached by the co-ordination group under the procedure laid out in Article 107q(2) of the 2001 Directive (“the agreement”).

(2) The licensing authority must implement the measures set out in the agreement in accordance with the implementation timetable determined in the agreement.

(3) Paragraph (4) applies where—

(a)the agreement requires a variation to be made to one or more authorisation or registration; and

(b)the terms of the agreement are known to the holder or holders for the product or products which is, or which are, the subject of the agreement.

(4) Where this paragraph applies, each holder must submit to the licensing authority in accordance with the terms of the agreement (including its implementation timetable) an application for a variation including—

(a)an updated summary of the product characteristics; and

(b)an updated package leaflet.

(5) This regulation is subject to regulation 212 (transitional arrangements).

Transparency and communicationsU.K.

Obligations on licensing authority in relation to national medicines web-portalU.K.

203.—(1) The licensing authority must set up and maintain a national medicines web-portal (“the UK web-portal”) linked to the European medicines web-portal established in accordance with Article 26 of Regulation (EC) No 726/2004 (“the EU web-portal”).

(2) The licensing authority must make available publicly by means of the UK web-portal the following (at a minimum)—

(a)the assessment reports prepared or revised by the licensing authority under regulation 64(5) and (6) (duties of licensing authority in connection with determination), each with a summary;

(b)the summary of the product characteristics for the medicinal products concerned;

(c)the package leaflet for the medicinal products concerned;

(d)a summary of the risk management plan (if any) for the medicinal products concerned;

(e)the list of medicinal products that are subject to additional monitoring referred to in Article 23 of Regulation (EC) No 726/2004; and

(f)information on the different ways of reporting suspected adverse reactions to medicinal products to the licensing authority by patients or their carers, health care professionals, coroners or procurators fiscal (including by way of the web-based structured forms referred to in Article 25 of Regulation (EC) No 726/2004).

Obligation on licensing authority in relation to public announcementsU.K.

204.—(1) This regulation applies where the licensing authority intends to make a public announcement relating to information on pharmacovigilance concerns.

(2) Subject to paragraph (4), the licensing authority must inform the bodies specified in paragraph (3) not less than 24 hours prior to making the public announcement.

(3) The bodies specified in this paragraph are—

(a)the EMA;

(b)the European Commission; and

(c)the competent authority of each EEA State other than the United Kingdom.

(4) Paragraph (2) does not apply if the information in the announcement needs to be made public urgently for the protection of public health.

Obligations on holders in relation to public announcementsU.K.

205.—(1) This regulation applies where the holder intends to make a public announcement relating to information on pharmacovigilance concerns in relation to the use of a medicinal product.

(2) The holder must inform the bodies listed in paragraph (3) of its intention to make the public announcement—

(a)as soon as is practicable once it forms that intention; and

(b)in any event no later than at the same time as, or before, the public announcement is made.

(3) The bodies listed in this paragraph are—

(a)the licensing authority;

(b)the EMA; and

(c)the European Commission.

(4) The holder must ensure that the information in the public announcement—

(a)is presented objectively; and

(b)is not misleading.

EnforcementU.K.

Infringement noticesU.K.

206.[F52(1) If an enforcement authority has objective grounds for considering that any person (“P”) has contravened any relevant provision, it may serve upon P a notice in writing (referred to in this Part as an “infringement notice”)—

(a)informing P of the authority’s grounds for considering that P has contravened one or more relevant provision;

(b)specifying the relevant provision;

(c)specifying the measures which P must take in order to ensure that the contravention does not continue or, as the case may be, does not recur;

(d)requiring P to take those measures, within such period as may be specified in the notice;

(e)specifying the further action (if any) that the enforcement authority may take.]

(2) An infringement notice may include directions as to the measures to be taken by P to ensure that the contravention does not continue or, as the case may be, does not recur, including the different ways of securing compliance.

(3) If an enforcement authority serves an infringement notice in accordance with paragraph (1), it shall as soon as is reasonably practicable inform—

(a)the EMA; and

(b)the European Commission.

[F53(4) In this regulation “relevant provision” means a provision of—

(a)this Part;

(b)Chapter 3 of Title II of Regulation (EC) No 726/2004; or

(c)the Implementing Regulation.]

OffencesU.K.

207.—(1) A person is guilty of an offence if the person commits a breach of a provision in this Part, other than regulation 199(2) or (6) (submission of draft study protocols for required studies).

(2) A breach of a provision in this Part includes any—

(a)failure by a holder to comply with any requirement or obligation in this Part; or

(b)contravention by any person of any prohibition in this Part.

False and misleading informationU.K.

208.  A person is guilty of an offence if the person provides information to the licensing authority or the EMA, pursuant to an obligation in this Part, but that information is false or misleading in a material particular.

PenaltiesU.K.

209.—(1) Subject to paragraph (2), a person guilty of an offence under regulation 207 or 208 is liable—

(a)on summary conviction to a fine not exceeding the statutory maximum; or

(b)on conviction on indictment to a fine, to imprisonment for a term not exceeding two years or to both.

(2) A person guilty of an offence under regulation 207 which relates to a breach of a provision listed in paragraph (3) is liable—

(a)on summary conviction to a fine not exceeding the statutory maximum; or

(b)on conviction on indictment to a fine.

(3) Those provisions are regulations—

(a)182(2)(a) and (b), (3) and (5);

(b)183(8)(a);

(c)184(1)(a) and (b);

(d)187(4);

(e)188(1)(c) and (e);

(f)193(5);

(g)198(1) and (3)(a) and (d);

(h)199(8); and

(i)200(7).

Offences relating to pharmacovigilance obligations under Regulation (EC) No 726/2004U.K.

210.—(1) A person is guilty of an offence if the person—

(a)commits a breach of a provision of Regulation (EC) No 726/2004 listed in paragraph (3); or

(b)provides information which is false or misleading in a material particular to the licensing authority or the EMA pursuant to an obligation in Chapter 3 of Title II of Regulation (EC) No 726/2004.

(2) A breach of a provision listed in paragraph (3) includes any—

(a)failure to comply with any requirement or obligation contained in any of those provisions;

(b)contravention of any prohibition contained in any of those provisions; or

(c)failure to comply with any requirement imposed by the licensing authority or the EMA pursuant to any of those provisions.

(3) Those provisions are—

(a)Article [F5416(3a)], second paragraphM44;

(b)Article 20(8)M45;

(c)Article 21(1) and (2)M46;

(d)Article 22M47;

(e)Article 28(1), (2) and (5)M48;

(f)Article 28a(3)M49; and

(g)Article 28b(1)M50, except insofar as it imposes an obligation under Article 107n(1), or the first paragraph of Article 107n(3), of the 2001 Directive.

(4) Subject to paragraph (5), a person guilty of an offence under this regulation is liable—

(a)on summary conviction to a fine not exceeding the statutory maximum; or

(b)on conviction on indictment to a fine, to imprisonment for a term not exceeding two years or to both.

(5) A person guilty of an offence under this regulation in relation to a provision of Regulation (EC) No 726/2004 listed in paragraph (6) is liable—

(a)on summary conviction to a fine not exceeding the statutory maximum; or

(b)on conviction on indictment to a fine.

(6) Those provisions are—

(a)Article [F5516(3a)], second paragraph;

(b)Article 21(1) insofar as it relates to obligations set out in—

(i)the second paragraph of Article 104(2) of the 2001 Directive save the obligation regarding preparing and implementing a corrective action plan,

(ii)Article 104(3)(a) of the 2001 Directive,

(iii)Article 104(3)(b) of the 2001 Directive, or

(iv)the second paragraph of Article 104(3) of the 2001 Directive;

(c)Article 21(2) insofar as it relates to the obligation to submit a detailed description of a risk management system;

(d)Article 28(1) insofar as it relates to obligations set out in—

(i)the second paragraph of Article 107(1) of the 2001 Directive,

(ii)the first sentence of Article 107(4) of the 2001 Directive, or

(iii)Article 107(5) of the 2001 Directive;

(e)Article 28(2) insofar as it relates to the obligation set out in the third paragraph of Article 107c(4) of the 2001 Directive; and

(f)Article 28b(1) insofar as it relates to prohibitions or obligations set out in—

(i)Article 107m(3) to (6) of the 2001 Directive,

(ii)the second paragraph of Article 107n(3) of the 2001 Directive, or

(iii)the last sentence of Article 107o of the 2001 Directive.

(7) This regulation is subject to regulation 212 (transitional arrangements).

F54Word in reg. 210(3)(a) substituted (20.8.2013) by The Human Medicines (Amendment) Regulations 2013 (S.I. 2013/1855), regs. 1(1), 24

F55Word in reg. 210(6)(a) substituted (20.8.2013) by The Human Medicines (Amendment) Regulations 2013 (S.I. 2013/1855), regs. 1(1), 24

Marginal Citations

M44Article 16(4), second paragraph, of Regulation (EC) No 726/2004 (“the Regulation”) imposes an obligation identical to that set out in Article 23(4), second paragraph, of the 2001 Directive; Article 23(4), second paragraph, of the 2001 Directive is transposed at regulation 182(5).

M45Article 20(8) of the Regulation applies Article 107i of the 2001 Directive, which in turn applies Articles 107j and 107k of the 2001 Directive; Article 107k(2) second paragraph is implemented in regulation 197(3).

M46Article 21(1) of the Regulation, first paragraph, cross-refers to obligations set out in Article 104 of the 2001 Directive, implemented in regulation 182 and 185; Article 21(1), second paragraph, and 21(2) of the Regulation are similar in effect to Article 104a of the 2001 Directive, implemented in regulation 183.

M47Article 22 of the Regulation cross-refers to obligations set out in Article 106a(1) of the 2001 Directive; Article 106a(1) is implemented in regulation 205.

M48Article 28(1) and (2) of the Regulation cross-refers to obligations set out in Articles 107, 107a, 107b and 107c of the 2001 Directive; those Articles are implemented in regulations 185, 186, 187, 188, 191, 192 and 193; Article 28(5) of the Regulation applies Articles 107e to 107g of the 2001 Directive; Article 107g of the 2001 Directive is implemented in regulation 194.

M49Article 28a(3) of the Regulation imposes an obligation identical to that set out in the first sentence of Article 107h(3) of the 2001 Directive; Article 107h(3) first sentence is implemented in regulation 190.

M50Article 28b(1) of the Regulation cross-refers to prohibitions and obligations set out in Articles 107m, 107n, 107o, 107p and 107q of the 2001 Directive; those Articles are implemented in regulations 198, 199, 200, 201 and 202; Article 107n(1) and the first paragraph of Article 107n(3), implemented in regulation 199(2) and (6), are excluded as they are enforced otherwise than by way of criminal offence.

[F56Offences in relation to pharmacovigilance obligations under the Implementing RegulationU.K.

210A.(1) A holder is guilty of an offence if the holder—

(a)fails to comply with any requirement or obligation contained in a provision of the Implementing Regulation listed in paragraph (2); or

(b)provides information which is false or misleading in a material particular to the licensing authority or the EMA pursuant to an obligation in the Implementing Regulation.

(2) The provisions mentioned in paragraph (1)(a) are—

(a)Chapter I (pharmacovigilance system master file);

(b)Sections 1 and 2 of Chapter II (minimum requirements for the quality systems for the performance of pharmacovigilance activities);

(c)Chapter III (minimum requirements for the monitoring of data in the Eudravigilance database);

(d)Chapter V (transmission of reports of suspected adverse reactions);

(e)Article 32 of Chapter VI (updates of risk management plans);

(f)Chapter VII (periodic safety update reports); and

(g)Chapter VIII (post-authorisation safety studies).

(3) Subject to paragraph (4), a person guilty of an offence under this regulation is liable—

(a)on summary conviction to a fine not exceeding the statutory maximum; or

(b)on conviction on indictment to a fine.

(4) A person guilty of an offence under this regulation which relates to a breach of Article 34(5) or 36(3) of the Implementing Regulation is liable—

(a)on summary conviction to a fine not exceeding the statutory maximum; or

(b)on conviction on indictment to a fine, to imprisonment for a term not exceeding two years or to both.]

Persons liableU.K.

211.  If an offence under regulation 207(1) (offences) or regulation 210(1)(a) (offences relating to pharmacovigilance obligations under Regulation (EC) No 726/2004) is committed by a person acting as employee or agent, the employer or principal of that person is guilty of the same offence and is liable to be proceeded against and punished accordingly.

Transitional arrangementsU.K.

Transitional arrangementsU.K.

212.  Regulations 182, 186, 188, 191, 192, 198, 199, 200, 201, 202 and 210 are subject to the transitional provisions set out in Schedule 33 (transitional arrangements: pharmacovigilance).

PART 12U.K.Dealings with medicinal products

CHAPTER 1U.K.Interpretation

InterpretationU.K.

213.—(1) In this Part—

[F57clinical commissioning group” means a body established under section 14D of the National Health Service Act 2006;]

the Common Services Agency” means the Common Services Agency for the Scottish Health Service established under section 10 of the National Health Service (Scotland) Act 1978 M51;

controlled drug” means any substance or product for the time being specified in Schedule 1, 2 or 3 of the Misuse of Drugs Regulations 2001 M52 or in Schedule 1, 2 or 3 of the Misuse of Drugs Regulations (Northern Ireland) 2002 M53, except where the context requires otherwise;

the dental care professionals register” means the register established and maintained under section 36B of the Dentists Act 1984 M54;

EEA health professional” means—

(a)

a doctor who is lawfully engaged in medical practice in an EEA State other than the United Kingdom or in Switzerland; or

(b)

a dentist who is lawfully engaged in dental practice in an EEA State other than the United Kingdom or in Switzerland (including a person whose formal qualifications as a doctor are recognised for the purposes of the pursuit of the professional activities of a dental practitioner under Article 37 of Directive 2005/36/EC of the European Parliament and of the Council of 7 September 2005 on the recognition of professional qualifications M55),

and who is not otherwise a doctor or a dentist for the purpose of these Regulations;

EEA prescription” means a prescription given in an EEA State other than the United Kingdom or in Switzerland;

external use” in relation to a medicinal product—

(a)

means its use by application to the skin, teeth, mucosa of the mouth, throat, nose, ear, eye, vagina or anal canal in circumstances where local action only is necessary and systematic absorption is unlikely to occur; but

(b)

does not include its use by means of a throat spray, nasal spray, nasal inhalation or teething preparation or by means of throat pastilles, throat lozenges, throat tablets or nasal drops;

food” includes—

(a)

beverages;

(b)

confectionery;

(c)

articles and substances used as ingredients in the preparation of food; and

(d)

any manufactured substance—

(i)

to which there has been added any vitamin, and

(ii)

which is advertised as available and for sale to the general public as a dietary supplement;

health authority” means—

(a)

F58. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

(b)

in relation to Wales, a Local Health Board established under section 11 of the National Health Service (Wales) Act 2006 M56;

(c)

in relation to Scotland, a Health Board constituted under section 2(1)(a) of the National Health Service (Scotland) Act 1978 M57; and

(d)

in relation to Northern Ireland, the Regional Health and Social Care Board established under section 7 of the Health and Social Care (Reform) Act (Northern Ireland) 2009 M58;

health care” means services for or in connection with the prevention, diagnosis or treatment of disease;

health prescription” means a prescription issued by a doctor, dentist, supplementary prescriber, nurse independent prescriber, optometrist independent prescriber, pharmacist —independent prescriber or community practitioner nurse prescriber under—

(a)

in England, the National Health Service Act 2006;

(b)

in Wales, the National Health Service (Wales) Act 2006;

(c)

in Scotland, the National Health Service (Scotland) Act 1978; and

(d)

in Northern Ireland, the Health and Personal Social Services (Northern Ireland) Order 1972 M59;

F59. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

“independent clinic”—

(a)

in relation to England, means an establishment of either of the following kinds—

(i)

a walk-in centre, in which one or more medical practitioners provides services of a kind which, if provided in pursuance of the National Health Services Act 2006, would be provided as primary medical services under Part 4 of that Act, or

(ii)

a surgery or consulting room in which a medical practitioner who provides no services in pursuance of the National Health Services Act 2006 provides medical services of any kind (including psychiatric treatment), except where such medical services are provided only under arrangements made on behalf of the patients by—

(aa)

their employer,

(bb)

a government department or any executive agency of any government department,

(cc)

a prison or other establishment in which patients are held under custody, other than pursuant to any provision under the Mental Health Act 1983 M60, or

(dd)

an insurance provider with whom the patients hold an insurance policy, other than an insurance policy which is solely or primarily intended to provide benefits in connection with the diagnosis or treatment of physical or mental illness, disability or infirmity,

and where two or more medical practitioners use different parts of the same premises as a surgery or consulting room, or use the same surgery or consulting room at different times, each of the medical practitioners shall be regarded as carrying on a separate independent clinic unless they practise together;

(b)

in relation to Wales, has the meaning given by section 2(4) of the Care Standards Act 2000 M61;

(c)

in relation to Scotland, has the meaning given by section 10F(2) of the National Health Service (Scotland) Act 1978 M62; and

(d)

in relation to Northern Ireland, has the meaning given by article 2(2) of the Health and Personal Social Services (Quality, Improvement and Regulation) (Northern Ireland) Order 2003 M63;

“independent hospital”—

(a)

in relation to England, means a hospital as defined by section 275 of the National Health Service Act 2006 that is not a health service hospital as defined by that section;

(b)

in relation to Wales, has the meaning given by section 2(2) of the Care Standards Act 2000;

(c)

in relation to Scotland, has the meaning given by section 10F(2) of the National Health Act 1978; and

(d)

in relation to Northern Ireland, has the meaning given by article 2(2) of the Health and Personal Social Services (Quality, Improvement and Regulation) (Northern Ireland) Order 2003;

“independent medical agency”—

(a)

in relation to England, means an undertaking (not being an independent hospital) which consists of or includes the provision of services by medical practitioners, and the term “undertaking” in this definition includes any business or profession and—

(i)

in relation to a public or local authority includes the exercise of any functions of that authority, and

(ii)

in relation to any other body of persons, whether corporate or unincorporated, includes any of the activities of that body;

(b)

in relation to Wales, has the meaning given by section 2(5) of the Care Standards Act 2000;

(c)

in relation to Scotland means an undertaking which is neither an independent clinic nor an undertaking comprised in a hospital and which consists of or includes the provision of services, other than in pursuance of the National Health Service (Scotland) Act 1978, by a medical practitioner; and

(d)

in relation to Northern Ireland, has the meaning given by article 2(2) of the Health and Personal Social Services (Quality, Improvement and Regulation) (Northern Ireland) Order 2003;

[F60local authority” has the same meaning as in section 2B of the National Health Service Act 2006;]

“maximum daily dose” or “MDD”, in relation to a product for internal use, means the maximum quantity of the substance contained in the amount of the product that it is recommended should be taken or administered in any period of 24 hours;

“maximum dose” or “MD”, in relation to a product for internal use, means the maximum quantity of the substance contained in the amount of the product that it is recommended should be taken or administered at any one time;

NHS body” means—

(a)

the Common Services Agency;

(b)

a health authority;

(c)

a special health authority;

(ca)

[F61a clinical commissioning group;

(cb)

the National Health Service Commissioning Board;]

(d)

F62. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

(e)

an NHS trust; or

(f)

an NHS foundation trust;

NHS foundation trust” has the meaning given by section 30(1) of the National Health Service Act 2006;

“NHS trust”—

(a)

in relation to England, means an NHS trust established under section 25(1) of the National Health Service Act 2006;

(b)

in relation to Wales, means an NHS trust established under section 18(1) of the National Health Service (Wales) Act 2006;

(c)

in relation to Scotland, means an NHS trust established under section 12A of the National Health Service (Scotland) Act 1978 M64; and

(d)

in relation to Northern Ireland, means a Health and Social Care trust established under Article 10 of the Health and Personal Social Services (Northern Ireland) Order 1991 M65;

nursing home” has the meaning given by article 11 of the Health and Personal Social Services (Quality, Improvement and Regulation) (Northern Ireland) Order 2003 M66;

parenteral administration” means administration by breach of the skin or mucous membrane;

“patient group direction” or “PGD” means a written direction that relates to the sale or supply and to the administration of a description or class of medicinal product and that—

(a)

is signed—

(i)

by a doctor or dentist and by a pharmacist, and

(ii)

by any other person who may be required to sign it in the circumstances specified for its use in any provision of this Part; and

(b)

relates to sale or supply and to administration to persons generally (subject to any exclusions that may be specified in the PGD);

F63. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

prison service” means—

(a)

in relation to England and Wales, a Minister of the Crown exercising functions in relation to prisons (within the meaning of the Prison Act 1952 M67);

(b)

in relation to Scotland, the Scottish Ministers exercising functions in relation to prisons (within the meaning of the Prisons (Scotland) Act 1989 M68); and

(c)

in relation to Northern Ireland, the Department of Justice exercising functions in relation to prisons (within the meaning of the Prison Act (Northern Ireland) 1953 M69);

registered chiropodist” means a person who is registered in Part 2 of the Health and Care Professions Council register;

registered dental hygienist” means a person registered under that title in the dental care professionals register;

registered dental therapist” means a person registered under that title in the dental care professionals register;

registered dietitian” means a person who is registered in Part 4 of the Health and Care Professions Council register;

registered dispensing optician” means a person whose name is entered in the register of dispensing opticians maintained under section 7(b) of the Opticians Act 1989 M70 or the register of visiting dispensing opticians from relevant European States maintained under section 8B(1)(b) M71 of that Act;

registered occupational therapist” means a person who is registered in Part 6 of the Health and Care Professions Council register;

registered orthoptist” means a person who is registered in Part 7 of the Health and Care Professions Council register;

registered orthotist and prosthetist” means a person who is registered in Part 10 of the Health and Care Professions Council register;

registered paramedic” means a person who is registered in Part 8 of the Health and Care Professions Council register;

registered physiotherapist” means a person who is registered in Part 9 of the Health and Care Professions Council register;

registered podiatrist” means a person who is registered in Part 2 of the Health and Care Professions Council register;

“registered provider”—

(a)

in England, in relation to an independent hospital, independent clinic, an independent medical agency, a dental clinic or a dental practice means the person who is registered as a service provider under Chapter 2 of Part 1 of the Health and Social Care Act 2008 M72 in respect of regulated activities (within the meaning of that Part) carried on in that hospital, clinic, agency, dental clinic or dental practice;

(b)

in Wales, in relation to an independent hospital, an independent clinic or an independent medical agency, means the person who is registered under Part 2 of the Care Standards Act 2000 as the person who carries on the hospital, clinic or agency;

(c)

in Scotland, in relation to an independent hospital, an independent clinic or an independent medical agency, means the person who is registered under section 10P of the National Health Service (Scotland) Act 1978 M73; and

(d)

in Northern Ireland, in relation to an independent hospital, an independent clinic, a nursing home or an independent medical agency, means the person who is registered under Part 3 of the Health and Personal Social Services (Quality, Improvement and Regulation) (Northern Ireland) Order 2003 as the person who carries on the hospital, clinic, nursing home or agency;

registered radiographer” means a person who is registered in Part 11 of the Health and Care Professions Council register;

registered speech and language therapist” means a person who is registered in Part 12 of Health and Care Professions Council register;

“relevant manager”—

(a)

in England, means—

(i)

a person, other than the registered provider, who is registered under Chapter 2 of Part 1 of the Health and Social Care Act 2008 as the manager of an independent hospital, independent clinic, an independent medical agency, a dental clinic or a dental practice, or

(ii)

if there is no such person, but the registered provider has appointed a person to manage the hospital, clinic, agency, dental clinic or dental practice, that person;

(b)

in Wales, means—

(i)

a person, other than the registered provider, who is registered under Part 2 of the Care Standards Act 2000 as the manager of an independent hospital, an independent clinic or an independent medical agency, or

(ii)

if there is no such person, but the registered provider has appointed a person to manage the hospital, clinic or agency, that person;

(c)

in Scotland, means a person, other than the registered provider, who was identified as an individual who is to manage an independent hospital, an independent clinic or an independent medical agency on the application for registration of that clinic, hospital or agency under section 10P of the National Health Service (Scotland) Act 1978; and

(d)

in Northern Ireland, means—

(i)

a person, other than the registered provider, who is registered under Part 3 of the Health and Personal Social Services (Quality, Improvement and Regulation) (Northern Ireland) Order 2003 as the manager of an independent hospital, an independent clinic, a nursing home or an independent medical agency, or

(ii)

if there is no such person, but the registered provider has appointed a person to manage the hospital, clinic, nursing home or agency, that person;

relevant prescriber” means any of the following—

(a)

a doctor;

(b)

a dentist;

(c)

a supplementary prescriber;

(d)

a nurse independent prescriber;

(e)

a pharmacist independent prescriber;

(f)

a community practitioner nurse prescriber;

(g)

an optometrist independent prescriber; and

(h)

an EEA health professional;

repeatable prescription” means a prescription that contains a direction that it may be dispensed more than once;

sell” means sell by retail (and “sale” has a corresponding meaning);

special health authority” means—

(a)

in relation to England, a Special Health Authority established under section 28 of the National Health Service Act 2006;

(b)

in relation to Wales, a Special Health Authority established under section 22 of the National Health Service (Wales) Act 2006;

(c)

in relation to Scotland, a Special Health Board constituted under section 2(1)(b) of the National Health Service (Scotland) Act 1978 M74; and

(d)

in relation to Northern Ireland, a special health and social care agency established under Article 3 of the Health and Personal Social Services (Special Agencies) (Northern Ireland) Order 1990 M75;

supply” means supply in circumstances corresponding to retail sale;

unit preparation” means a preparation, including a mother tincture, that—

(a)

is prepared by a process of—

(i)

solution,

(ii)

extraction, or

(iii)

trituration,

with a view to being diluted tenfold or one hundredfold, either once or repeatedly, in an inert dilutent; and

(b)

is used—

(i)

in that diluted form, or

(ii)

where applicable, by impregnating tablets, granules, powders or other inert substances,

for the purpose of being administered to human beings.

(2) In this Part—

(a)a reference to a product being sold or supplied for the purpose of being administered in accordance with the written directions of a doctor or dentist relating to a person includes a reference to it being supplied in accordance with such directions; and

(b)a reference to a product being sold or supplied for the purpose of being administered in accordance with a patient group direction includes a reference to it being supplied in accordance with a patient group direction.