1. These Regulations may be cited as the Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 and come into force on exit day.
2. The Human Medicines Regulations 2012(1) are amended in accordance with Parts 2 to 19.
3. Schedule 1 amends the Medicines (Products for Human Use) (Fees) Regulations 2016(2) and makes saving provision.
4. After regulation 2, insert—
2A.—(1) In these Regulations, “advanced therapy medicinal product” means any of the following products—
(a)a gene therapy medicinal product;
(b)a somatic cell therapy medicinal product; or
(c)a tissue engineered product.
(2) A “gene therapy medicinal product” is a biological medicinal product which has the following characteristics—
(a)it contains an active substance which contains or consists of a recombinant nucleic acid used in or administered to human beings with a view to regulating, repairing, replacing, adding or deleting a genetic sequence; and
(b)its therapeutic, prophylactic or diagnostic effect relates directly to the recombinant nucleic acid sequence it contains, or to the product of genetic expression of this sequence.
(3) A vaccine against infectious diseases is not to be treated as a gene therapy medicinal product.
(4) A “somatic cell medicinal product” is a medicinal product which has the following characteristics—
(a)it contains or consists of cells or tissues that—
(i)have been subject to substantial manipulation so that biological characteristics, physiological functions or structural properties relevant for the intended clinical use have been altered, or
(ii)are not intended to be used for the same essential function in the recipient as in the donor; and
(b)it is presented as having properties for, or is used in or administered to human beings with a view to, treating, preventing or diagnosing a disease through the pharmacological, immunological or metabolic action of its cells or tissues.
(5) A “tissue engineered product” is a medicinal product which—
(a)contains or consists of engineered cells or tissues; and
(b)is presented as having properties for, or is used in or administered to human beings with a view to, regenerating, repairing or replacing a human tissue.
(6) A tissue engineered product may contain—
(a)cells or tissues of human or animal origin;
(b)viable or non-viable cells or tissues; and
(c)additional substances, including cellular products, bio-molecules, biomaterials, chemical substances, scaffolds or matrices.
(7) A product is not a tissue engineered product if it—
(a)contains or consists exclusively of non-viable human or animal cells or tissues;
(b)does not contain any viable cells or tissues; and
(c)does not act principally by pharmacological, immunological or metabolic action.
(8) Cells or tissues are engineered if they—
(a)have been subject to substantial manipulation, so that biological characteristics, physiological functions or structural properties relevant for the intended regeneration, repair or replacement are achieved; or
(b)are not intended to be used for the same essential function in the recipient as in the donor.
(9) The following manipulations are not substantial manipulations for the purposes of paragraphs (4)(a) and (8)(a)—
(a)cutting;
(b)grinding;
(c)shaping;
(d)centrifugation;
(e)soaking in antibiotic or antimicrobial solutions;
(f)sterilisation;
(g)irradiation;
(h)cell separation, concentration or purification;
(i)filtering;
(j)lyophilisation;
(k)freezing;
(l)cryopreservation; and
(m)vitrification.
(10) In these Regulations, “combined advanced therapy medicinal product” means an advanced therapy medicinal product—
(a)which incorporates, as an integral part of the product, one or more medical devices or one or more active implantable medical devices; and
(b)the cellular part of which—
(i)contains viable cells or tissues; or
(ii)contains non-viable cells or tissues which are liable to act upon the human body with action that can be considered as primary to that of the medical devices.
(11) Where an advanced therapy medicinal product contains viable cells or tissues, the pharmacological, immunological or metabolic action of those cells or tissues is to be treated as the principal mode of action of the product.
(12) An advanced therapy medicinal product containing both autologous and allogeneic cells or tissues is to be treated as being for allogeneic use.
(13) A product which falls within the definition of a tissue engineered product and within the definition of a somatic cell therapy medicinal product is to be treated as a tissue engineered product.
(14) A product which falls within the definition of—
(a)a somatic cell therapy medicinal product or a tissue engineered product; and
(b)a gene therapy medicinal product,
is to be treated as a gene therapy medicinal product.”.
5.—(1) Regulation 3 is amended as follows.
(2) In paragraph (12)(d)—
(a)in paragraph (i) insert “UK” before “marketing authorisation”;
(b)at the end of paragraph (ii) insert “or”; and
(c)omit paragraph (iv) (and “or” immediately preceding it).
(3) In paragraph (15)—
(a)in sub-paragraph (a) insert “UK” before “marketing authorisation”; and
(b)at the end of sub-paragraph (b) insert “or”; and
(c)omit sub-paragraph (d) (and “or” immediately preceding it).
6. In regulation 4(4)(d)—
(a)in paragraph (i) insert “UK” before “marketing authorisation”;
(b)at the end of paragraph (ii) insert “or”; and
(c)omit paragraph (iv) (and “or” immediately preceding it).
7.—(1) Regulation 5 is amended as follows.
(2) Omit paragraph (1)(b) (and “or” immediately preceding it).
(3) In paragraph (2)—
(a)at the end of sub-paragraph (b), insert “or”; and
(b)omit sub-paragraph (d) (and “or” immediately preceding it).
(4) In paragraph (3)—
(a)omit sub-paragraph (b); and
(b)in paragraph (d), omit “or (b)”.
(5) In paragraph (4), omit sub-paragraph (b) (and “or” immediately preceding it).
(6) In paragraph (5)—
(a)omit sub-paragraph (b); and
(b)in paragraph (d), omit “or (b)”.
8. In Schedule 1(3), in each place where it occurs, insert “UK” before “marketing authorisation”.
9. In regulation 6—
(a)in paragraph (3) omit sub-paragraph (b) (and “or” immediately preceding it); and
(b)omit paragraphs (4) and (5).
10.—(1) Regulation 8(4) is amended as follows.
(2) In paragraph (1), at the appropriate places, insert—
““active implantable medical device”—
““agreed paediatric investigation plan” means a paediatric investigation plan which the licensing authority has agreed in accordance with regulation 50B;”;
““Annex I to the 2001 Directive” means Annex I to the 2001 Directive, as modified in accordance with Schedule 8B;”;
““approved country for batch testing list” means the list published by the licensing authority under paragraph 14(3) of Schedule 7 (obligations of qualified persons) and “approved country for batch testing” means a country included in that list;”;
““approved country for import list” means the list published by the licensing authority under regulation 18A (approved country for import) and “approved country for import” means a country included in that list;”;
““the Committee for Medicinal Products for Human Use” means the committee established under Article 5(1) of Regulation (EC) No 726/2004;”;
““conditional marketing authorisation” means a UK marketing authorisation granted under regulation 49(1)(a) in accordance with regulation 58F;”;
““country” means a country or territory;”;
““Directive 2001/18/EC” means Directive 2001/18/EC of the European Parliament and of the Council of 12 March 2001 on the deliberate release into the environment of genetically modified organisms and repealing Council Directive 90/220/EEC – Commission Declaration(7);”;
““EU Exit Regulations” means the Human Medicines Regulations 2012 (Amendment etc.) (EU Exit) Regulations 2019;”;
““medical device”—
has the meaning given in regulation 2 of the Medical Devices Regulations 2002; or
to the extent necessary for the practical application of that definition, also or instead has the meaning given in regulation 69 of those Regulations(8);”;
““orphan criteria” means the criteria listed in regulation 50G(2);”;
““orphan marketing authorisation” means a UK marketing authorisation granted under regulation 49(1)(a) in accordance with regulation 58C;”;
““Orphan Regulation” means Regulation (EC) No 141/2000 of the European Parliament and of the Council of 16 December 1999 on orphan medicinal products(9) as it has effect in EU law;”;
““paediatric indication” means a term of a UK marketing authorisation enabling the medicinal product to which the authorisation relates to be used by or administered to persons under the age of 18 years;”;
““paediatric population” means that part of the population consisting of persons under the age of 18 years;”;
““supplementary protection certificate” has the meaning given in section 128B(2) of the Patents Act 1977(10);”; and
““variation to the terms of a UK marketing authorisation” means any change to—
the information provided in accordance with regulations 50 to 57 and Schedule 8; or
the terms of the decision granting the UK marketing authorisation, including the summary of the product characteristics and any conditions, obligations, or restrictions affecting that UK marketing authorisation, or changes to the labelling or the package leaflet connected with changes to the summary of the product characteristics,
and “vary” and “variation” in relation to a UK marketing authorisation are to be construed accordingly;.”.
(3) In paragraph (1), amend or substitute (as the case may be) the following definitions—
(a)in the definition of “the Good Manufacturing Practice Directive” insert at the end “as modified in accordance with Schedule 2A”;
(b)in the definition of “homoeopathic medicinal product”, in paragraph (b), for “in any pharmacopoeia used officially in an EEA State” substitute “the British Pharmacopoeia, or in any pharmacopoeia used officially in a country that is included in a list published by the licensing authority for this purpose”;
(c)in the definition of “import”(11), insert at the end “and “imported” is to be construed accordingly”;
(d)in the definition of “name”, omit paragraphs (b) and (c);
(e)in the definition of “pharmacovigilance system”, “pharmacovigilance system master file” and “post-authorisation safety study”, for “marketing authorisation, traditional herbal registration or Article 126a authorisation” substitute “UK marketing authorisation or traditional herbal registration”;
(f)in the definition of “post-authorisation efficacy study”, insert “UK” before “marketing authorisation”;
(g)at the end of the definition of “Regulation (EC) No 726/2004”, insert “, as it has effect in EU law”;
(h)at the end of the definition of “Regulation (EC) No 1234/2008”, insert “, as it has effect in EU law”;
(i)in the definition of “special medicinal product” for “an EEA State” substitute “a country”;
(j)in the definition of “the summary of the product characteristics”, omit paragraph (b) (and “or” immediately preceding it); and
(k)in the definition of “UK marketing authorisation”, omit paragraph (b) (and “or” immediately preceding it).
(4) In paragraph (1), omit the following definitions—
(i)“advanced therapy medicinal product”,
(ii)“Article 126a authorisation”,
(iii)“care home”(12),
(iv)“Commission Regulation 2016/161”(13),
(v)“Directive 2002/98/EC”,
(vi)“Directive 2004/23/EC”,
(vii)“healthcare institution”(14),
(viii)“hospice”(15),
(ix)“marketing authorisation”,
(x)“Paediatric Regulation”,
(xi)“the Pharmacovigilance Risk Assessment Committee”,
(xii)“Regulation (EC) No 1394/2007”, and
(xiii)“third country”.
(5) In paragraph (5)(a) insert “UK” before “marketing authorisation”.
(6) In paragraph (6)(a)—
(a)insert “UK” before “marketing authorisation”; and
(b)for “or 60(1)” substitute “, 60(1) or 60A”.
(7) In paragraph (8)(16), for “References” substitute “Subject to regulation C17(6), references”.
11. Schedule 2 inserts a new Schedule 8B after Schedule 8A.
12. Schedule 3 inserts a new Schedule 2A after Schedule 2.
13.—(1) After regulation A17(17) insert—
B17.—(1) The Ministers may by regulations set out principles and guidelines of good manufacturing practice in respect of medicinal products and investigational medicinal products.
(2) Regulations under paragraph (1) may in particular make provisions as to—
(a)inspections;
(b)compliance with good manufacturing practice and, where relevant, the UK marketing authorisation;
(c)quality assurance systems;
(d)personnel;
(e)premises and equipment;
(f)documentation;
(g)production;
(h)quality control;
(i)the contracting out of work;
(j)complaints and product recall;
(k)self-inspection.
(3) Subject to any provision made in regulations under paragraph (1), the principles and guidelines set out in the Good Manufacturing Practice Directive have effect on and after exit day as they had effect immediately before exit day, but subject to the modifications specified in Schedule 2A.
(4) The Ministers may by regulations amend or revoke Schedule 2A.
C17.—(1) The licensing authority may publish—
(a)detailed guidelines of good manufacturing practice in respect of medicinal products, and investigational medicinal products, referred to in Article 46(f) of the 2001 Directive, including guidelines as to the formalised risk assessment for ascertaining the appropriate good manufacturing practice for excipients;
(b)principles and guidelines of good manufacturing practice for active substances, referred to in the first paragraph of point (f) of Article 46 and in Article 46b of that Directive;
(c)principles and guidelines of good distribution practice referred to in the first paragraph of point (f) of Article 46, and Article 84, of that Directive.
(2) Guidelines or principles under paragraph (1) may replace, amend or otherwise modify any guidelines or principles published or adopted by the European Commission under the second, third, fourth or fifth paragraph of Article 47, or Article 84, of the 2001 Directive.
(3) Unless replaced by principles or guidelines published under paragraph (1), principles and guidelines published or adopted by the European Commission under the second, third, fourth or fifth paragraph of Article 47, or Article 84, of the 2001 Directive, as they applied immediately before exit day(18), continue to apply on and after exit day (subject to any amendments or modifications published under paragraph (1)).
(4) Before exercising the power under paragraph (1), the licensing authority must consult such persons as it considers appropriate.
(5) The licensing authority may only exercise its power under paragraph (1) if it considers that it is necessary in order to take account of technical or scientific progress.
(6) If the licensing authority publishes principles and guidelines under paragraph (1), any reference in these Regulations to any principle or guideline adopted under the provisions of the 2001 Directive specified in those paragraphs is instead to be read as a reference to the principle or guideline published under paragraph (1), or that principle or guideline as amended or modified (as the case may be).”.
14.—(1) Regulation 17 is amended as follows.
(2) In paragraph (1)(a), for “state other than an EEA State” substitute “country other than an approved country for import”.
(3) In paragraph (3)(a), for “a marketing authorisation, Article 126a authorisation” substitute “a UK marketing authorisation”.
(4) Omit paragraph (4).
(5) In paragraph (5), for “state other than EEA State” substitute “country other than an approved country for import”.
15.—(1) Regulation 18(19) is amended as follows.
(2) In paragraph (1)—
(a)in sub-paragraph (a), omit “or”;
(b)in sub-paragraph (b) for “distribution.” substitute “distribution; or”;
(c)insert at the end—
“(c)import a medicinal product from an approved country for import for either purpose.”.
(3) In paragraph (6), for “a marketing authorisation, Article 126a authorisation” substitute “a UK marketing authorisation”.
(4) Omit paragraph (7).
16. After regulation 18, insert—
18A.—(1) The licensing authority must—
(a)publish a list of countries from which medicinal products may be imported under a wholesale dealing licence (“approved country for import list”); and
(b)only include in that list a country which is included in the approved country for batch testing list.
(2) In order to determine whether a country should be included in the approved country for import list, the licensing authority may, in particular, take into account—
(a)the country’s system for ensuring that each batch of a medicinal product has been manufactured and checked in accordance with the requirements of its legislation and any authorisation in respect of that product;
(b)the country’s rules for good distribution practice;
(c)the regularity of inspections to verify compliance with good distribution practice;
(d)the effectiveness of enforcement of good distribution practice;
(e)the regularity and rapidity of information provided by that country relating to non-compliant manufacturers and distributers of medicinal products;
(f)any on-site review of that country’s regulatory system undertaken by the licensing authority;
(g)any on-site inspection of a manufacturing site in that country observed by the licensing authority; and
(h)any other relevant documentation available to the licensing authority.
(3) The licensing authority must—
(a)remove a country from the approved country for import list if that country is removed from the approved country for batch testing list;
(b)in any event review the countries it has included in the approved country for import list to determine if it is still satisfied that the country should remain on that list, and if it is not so satisfied, remove that country from the list; and
(c)undertake that review at least every three years beginning with the date on which that country is included in that list.”.
17.—(1) Regulation 19(20) is amended as follows.
(2) In paragraph (1)(a), for “marketing authorisation, Article 126a authorisation” substitute “UK marketing authorisation”.
(3) In paragraph (1)(b), after “or assembled the product” insert “in the United Kingdom”.
18.—(1) Schedule 3 is amended as follows.
(2) In paragraph 1(2)(g), for “marketing authorisation, Article 126a authorisation,” substitute “UK marketing authorisation”.
(3) In paragraph 2(1), for “state other than an EEA state” substitute “country other than an approved country for import”.
(4) In paragraph 3—
(a)in sub-paragraph (2)(d) at the end insert “or the responsible person (import)”.
(b)in sub-paragraph (3)(b)—
(i)in paragraph (i), insert “UK” before “marketing authorisation”,
(ii)omit paragraph (iv), and
(iii)after paragraph (iii) insert—
“(v)an authorisation granted by an authority in a country other than the United Kingdom to sell or supply the medicinal product in that other country;”;
(c)in sub-paragraph (3)(d)—
(i)in paragraph (i) omit “or”,
(ii)in paragraph (ii) for “etc);” substitute “etc), or”,
(iii)at the end insert—
“(iii)to be distributed by means of export to an approved country for import;”; and
(d)for sub-paragraph (4) substitute—
“(4) In sub-paragraph (2)(d)—
“the responsible person” means the person who has the functions described in regulation 45(2);
“the responsible person (import)” means the person who has the functions described in regulation 45AA(4).”.
19. In regulation 23(1)(b), omit “and any European Union obligation”.
20.—(1) Schedule 4 is amended as follows.
(2) In paragraph 13(b), for “marketing authorisation, Article 126a authorisation” substitute “UK marketing authorisation”.
(3) In the heading of Part 2, for “State Other Than an EEA State” substitute “Country other than an Approved Country for Import”.
(4) In paragraphs 15, 22(1) and 23, for “state other than an EEA State” substitute “country other than an approved country for import”.
(5) In paragraph 25(m), for the words “referred to in Article 8(2) of Directive 2004/23/EC”, substitute—
“assigned by a tissue establishment pursuant to—
(a)paragraph 1 of Schedule 3A to the Human Fertilisation and Embryology Act 1990(21), as regards human gametes and embryos; and
(b)paragraph 1 of Schedule 2 to the Human Tissue (Quality and Safety for Human Application) Regulations 2007(22), as regards other human tissues and cells.”.
(6) In paragraph 33, for “another EEA State” substitute “an approved country for import”.
21. In regulation 26(5)(a), for “marketing authorisation, Article 126a authorisation” substitute “UK marketing authorisation”.
22.—(1) Schedule 5(23) is amended as follows.
(2) In paragraph 1(2)(e), 3(11)(b) and 5(2)(d) after—
(a)“UK marketing authorisation,” in each place it appears, insert “parallel import licence,”; and
(b)“an authorisation,” or “the authorisation,” in each place it appears, insert “licence,”.
(3) In paragraph 3 omit sub-paragraph (11)(b)(iii).
(4) In paragraph 5 omit sub-paragraph (2)(c).
23. In regulation 29(5)—
(a)in sub-paragraph (b) omit “or”;
(b)in sub-paragraph (c) for “granted.” substitute “granted; or”; and
(c)at the end insert—
“(d)the responsible person (import) under regulation 45AA.”.
24.—(1) Regulation 31 is amended as follows.
(2) In paragraph (1)(c), for “an EEA State” substitute “the United Kingdom”.
(3) In paragraphs (3)(b), (5)(a) and (5)(b) insert “UK” before “marketing authorisation”.
25.—(1) Regulation 33 is amended as follows.
(2) In paragraph (1)(a)—
(a)for “Article 15(1) of Regulation 1394/2007” substitute “paragraph 8 of Schedule 6”; and
(b)for “Article 15(4) of that Regulation” substitute “paragraph 9 of that Schedule”.
(3) In paragraph (1)(b), for “Article 15(1)” substitute “paragraph 8”.
(4) In paragraph (2) for “Article 15(4)” substitute “paragraph 9”.
26.—(1) Schedule 6 is amended as follows.
(2) In paragraph 3, for “Directive 2004/23/EC”, substitute—
“requirements imposed pursuant to—
(a)paragraphs 6 to 9 of Schedule 3A to the Human Fertilisation and Embryology Act 1990, as regards gametes and embryos; and
(b)paragraphs 9 to 12 of Schedule 2 to the Human Tissue (Quality and Safety for Human Application) Regulations 2007, as regards other tissues and cells.”.
(3) In paragraph 4, for the words “laid down in” to the end, substitute—
“imposed pursuant to—
(a)Schedule 3A to the Human Fertilisation and Embryology Act 1990, as regards gametes and embryos; and
(b)Schedule 2 to the Human Tissue (Quality and Safety for Human Application) Regulations 2007, as regards other tissues and cells.”.
(4) In paragraph 5, for the words from “Commission” to the end substitute “the Blood Quality and Safety Regulations 2005(24)”.
(5) In paragraph 11, for the words from “laid down in” to the end, substitute—
“imposed pursuant to—
(a)as regards gametes and embryos, sections 12(3), and 33A to 33D of, and paragraph 1 of Schedule 3A to, the Human Fertilisation and Embryology Act 1990(25);
(b)as regards blood cells, regulations 8, 9(e) and 14 of the Blood Safety and Quality Regulations 2005; and
(c)as regards other cells and tissues, regulations 13 and 16 of, and paragraph 1 of Schedule 2 to, the Human Tissue (Quality and Safety for Human Application) Regulations 2007;”.
27. In regulation 36(26), omit paragraphs (4) to (7).
28.—(1) Regulation 37(27) is amended as follows.
(2) In paragraph (4)(b)—
(a)for “third country” substitute “country other than an approved country for import”; and
(b)for “competent authority of a member State” substitute “appropriate authority for the registration of such persons in the approved country for import”.
(3) In paragraph (5)(b), for “paragraph 5 of Article 47 of the 2001 Directive” substitute “the guidelines which apply under or by virtue of regulation C17”.
(4) In paragraph (6)(b), for “marketing authorisations, Article 126a authorisations” substitute “UK marketing authorisations”.
(5) In paragraph (9)(a), from “Commission” to the end substitute “the Blood Quality and Safety Regulations 2005(28); or”.
(6) In paragraph (11)—
(a)for “competent authority of a member State” substitute “licensing authority”; and
(b)insert “UK” before “marketing authorisation”.
29.—(1) Regulation 38(29) is amended as follows.
(2) In the heading, for “states other than EEA states” substitute “countries other than approved countries for import”.
(3) In paragraphs (2) and (3)(b), for “state other than an EEA State” substitute “country other than an approved country for import”.
30. In regulation 39(8)(30), omit “, 43A”.
31.—(1) Regulation 42(31) is amended as follows.
(2) In paragraph (1), for “45” substitute “45AA”.
(3) Omit paragraphs (4) and (5).
32.—(1) Schedule 7(32) is amended as follows.
(2) In Part 1—
(a)in paragraph 3, for “the member State in which it is studied” substitute “the licensing authority”;
(b)in paragraph 6, for “the member State in which the courses take place” substitute “the licensing authority”.
(3) In Part 3 (obligations of qualified person)—
(a)in paragraph 12—
(i)the existing text becomes sub-paragraph (1),
(ii)in paragraph (a) of that sub-paragraph—
(aa)for “marketing authorisation, Article 126a authorisation” substitute “UK marketing authorisation”,
(bb)after “herbal registration” insert “, or an equivalent authorisation,”, and
(cc)insert “and” at the end,
(iii)in paragraph (b) of that sub-paragraph—
(aa)for “medicinal products imported from a non-EEA State, irrespective of whether the products have been manufactured in an EEA State” substitute “medicinal products imported from a country other than approved country for import, irrespective of whether the products have been manufactured in the United Kingdom or an approved country for import”, and
(bb)in paragraph (iii), for “marketing authorisation, Article 126a authorisation” substitute “UK marketing authorisation”, and
(cc)after “herbal registration” insert “, or an equivalent authorisation,”,
(iv)omit paragraph (c) of that sub-paragraph, and
(v)after that sub-paragraph insert—
“(2) In this paragraph “equivalent authorisation” means, in respect of a medicinal product that does not have a UK marketing authorisation, certificate of registration or traditional herbal registration, such equivalent authorisation or registration granted by an appropriate authority for the licensing of medicinal products in an approved country for import.”.
(b)omit paragraph 13;
(c)in paragraph 14—
(i)in sub-paragraph (1)(a) for “country other than an EEA State” substitute “country other than approved country for import”,
(ii)in sub-paragraph (1)(b)—
(aa)for “European Union” substitute “licensing authority”,
(bb)for “that country” substitute “the country from which those products are imported”, and
(cc)in sub-paragraph (i), for “laid down by the European Union” substitute “in the Good Manufacturing Practice Directive, as supplemented by the guidelines and principles which apply under, or by virtue of, regulation C17”,
(iii)at the end insert—
“(3) The licensing authority must publish a list of the countries with whom it has made appropriate arrangements under sub-paragraph (1)(b) (“approved country for batch testing list”).
(4) A country may be included in the approved country for batch testing list subject to any condition or restriction that the licensing authority considers appropriate, including as to categories of medicinal product, and any such condition or restriction must be included in the list.
(5) In order to satisfy itself of the matters specified in sub-paragraph (1)(b)(i) and (ii), the licensing authority may, in particular, take into account—
(a)the country’s rules for good manufacturing practice;
(b)the regularity of inspections to verify compliance with good manufacturing practice;
(c)the effectiveness of enforcement of good manufacturing practice;
(d)the regularity and rapidity of information provided by that country relating to non-compliant manufacturers;
(e)any on-site review of that country’s regulatory system undertaken by the licensing authority;
(f)any on-site inspection of a manufacturing site in that country observed by the licensing authority;
(g)any other relevant documentation available to the licensing authority.
(6) The licensing authority must—
(a)review any appropriate arrangements it has made under sub-paragraph (1)(b) to determine if that country still satisfies the requirements of sub-paragraph (1)(b)(i) and (ii), and whether any condition or restriction in those arrangements remains appropriate;
(b)if it is not so satisfied, remove that country from the approved country for batch testing list or, as the case may be, amend or remove that condition or restriction; and
(c)undertake such a review at least every three years beginning with the date on which the country is included in that list.”.
33.—(1) Regulation 43(33) is amended as follows.
(2) In paragraph (1), for “by the European Commission in accordance with Article 84 of the 2001 Directive” substitute “under, or that apply by virtue of, regulation C17”.
(3) In paragraph (5)(a) and 7(b)(ii), for “marketing authorisation, Article 126a authorisation”, substitute “UK marketing authorisation”.
(4) In paragraph (6)—
(a)in sub-paragraph (a), insert at the end “in the United Kingdom”; and
(b)for sub-paragraph (b), substitute—
“(b)the export to an approved country for import, or supply for the purposes of such export, of a medicinal product which may be placed on the market in that country without—
(i)a marketing authorisation, certificate of registration or traditional herbal registration within the meaning of the 2001 Directive, by virtue of legislation adopted by that country under Article 5(1) of that Directive, where the approved country for import is an EEA State, or
(ii)such equivalent authorisation, certificate or registration in the approved country for import, under legislation in that country that makes provision that is equivalent to Article 5(1) of the 2001 Directive, where the approved country for import is not an EEA State.”.
(5) In paragraph (7)—
(a)in sub-paragraph (b)—
(i)in sub-paragraph (i), for “the competent authority of any EEA State” substitute “an appropriate authority for the licensing of medicinal products in an approved country for import”, and
(ii)in sub-paragraph (ii), for “marketing authorisation, Article 126a authorisation” substitute “UK marketing authorisation”; and
(b)omit sub-paragraph (c)(vii).
(6) For paragraph (8) substitute—
“(8) Paragraph (8A) applies to a person (“P”) who—
(a)imports a medicinal product, other than for the sole purpose of wholesale distribution of that product to a person in a country other than the United Kingdom; but
(b)is not the holder of a UK marketing authorisation, certificate of registration or traditional herbal registration in respect of that product.
(8A) Where this paragraph applies, P must—
(a)notify—
(i)the holder of any authorisation, certificate or registration, granted by an authority in the country from which the product is exported, to sell or supply that product in that country, and
(ii)the licensing authority,
of the intention to import that product; and
(b)pay a fee to the licensing authority in accordance with the Fees Regulations.”.
(7) Omit paragraphs (10) and (11).
(8) In paragraph (13), insert “UK” before “marketing authorisation holder”.
(9) Omit paragraph (15).
34. Omit regulation 43A(34).
35.—(1) Regulation 44(35) is amended as follows.
(2) In paragraph (2)—
(a)in sub-paragraph (b), for “another EEA State” substitute “an approved country for import”; and
(b)in sub-paragraph (c), for “from a third country (“A”) for export to a third country (“B”)”, substitute “from a country that is not an approved country for import (“A”), for export to a country that is not an approved country for import (“B”)”.
(3) In paragraph (5)(b), for “competent authority of another EEA State” substitute “appropriate authority of an approved country for import that is responsible for”.
(4) In paragraph (5)(e)—
(a)for “third countries” substitute “countries other than approved countries for import”; and
(b)for “third country concerned” substitute “country to which the product is supplied”.
(5) In paragraph (6)—
(a)insert “and” at the end of sub-paragraph (c); and
(b)omit sub-paragraph (e) (and “and” immediately preceding it).
36.—(1) Regulation 45 is amended as follows.
(2) In paragraph (1), for “The licence holder” insert substitute “Subject to regulation 45AA, the licence holder”.
(3) In paragraph (2)(b) for “marketing authorisations, Article 126a authorisations” substitute “UK marketing authorisations”.
37. After regulation 45, insert—
45AA.—(1) Subject to paragraph (2), this regulation applies where the licence holder imports a medicinal product from an approved country for import under a wholesale dealer’s licence.
(2) The requirements of this regulation do not apply where an unlicensed medicinal product falling under paragraph (1) is imported—
(a)from an approved country for import for the sole purpose of distribution by way of wholesale dealing as a special medicinal product; or
(b)for the sole purpose of wholesale distribution of that product to a person in a country other than an approved country for import.
(3) 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 (import)”) whose name is included in the register established under regulation 45AB.
(4) A responsible person (import) must—
(a)carry out the functions under regulation 45(2), unless a responsible person under regulation 45 is performing those functions in respect of the licence; and
(b)ensure that there is appropriate evidence to confirm that each production batch of a medicine imported from an approved country for import under the licence has been certified as provided for in Article 51 of the 2001 Directive, or such equivalent certification procedure as applies in the approved country for import.
(5) The licensing authority must publish guidance on the documentation that it considers to be appropriate evidence for the purposes of paragraph (4)(b).
(6) Guidance published under paragraph (5) may be taken into account by the licensing authority in determining whether it considers there has been a failure to comply with this regulation.
(7) The licence holder must apply to vary the licence if a change is proposed to the responsible person (import).
(8) The licence holder must not permit any person to act as a responsible person (import) other than the person named in the licence.
(9) Paragraph (10) applies if—
(a)the person acting as responsible person (import) in respect of the licence is no longer included in the register under 45AB;
(b)the licensing authority thinks, after giving the licence holder and a person acting as a responsible person (import) the opportunity to make representations (orally or in writing), that the responsible person (import) is failing to carry out the functions referred to in paragraph (4) adequately or at all.
(10) Where this paragraph applies the licensing authority—
(a)must notify the licence holder in writing that the person is not permitted to act as a responsible person (import) in respect of that licence; and
(b)may, subject to regulation 45AB(3)(b), remove that person’s name from the register under regulation 45AB.
(11) In this regulation, “unlicensed medicinal product” means a medicinal product in respect of which—
(a)there is no marketing authorisation, within the meaning of the 2001 Directive, in any EEA State in respect of that product, where the product is imported from an approved country for import that is an EEA State; or
(b)there is no licence or authorisation in respect of that product as regards its sale or supply in the approved country for import, where the product is imported from an approved country for import that is not an EEA State.
45AB.—(1) The licensing authority must maintain a register of persons (“the responsible person (import) register”) who may carry out the role of responsible person (import) under regulation 45AA.
(2) The licensing authority may only include a person’s name in the responsible person (import) register if that person—
(a)holds—
(i)a diploma, certificate or other evidence of formal qualifications awarded on completion of a university or other higher education course of study in pharmacy, chemistry, medicine, biology or a related life science, or
(ii)such other qualification as the licensing authority is satisfied is equivalent;
(b)is a member of—
(i)the Royal Society of Biology,
(ii)the Royal Pharmaceutical Society,
(iii)the Pharmaceutical Society of Northern Ireland,
(iv)the Royal Society of Chemistry, or
(v)such other body as may be specified by the licensing authority for the purpose of this paragraph; and
(c)has a minimum of 2 years’ experience in performing the functions of a responsible person under regulation 45, or in performing such other functions that appear to the licensing authority to be equivalent.
(3) The licensing authority—
(a)may remove a person’s name from the responsible person (import) register if it no longer considers that the person satisfies the requirements of paragraph (2); but
(b)it may not exercise that power unless it has given that person the opportunity to make representations to it (orally or in writing).”.
38.—(1) Regulation 45A(36) is amended as follows.
(2) In paragraph (1)—
(a)in sub-paragraph (a) for paragraphs (i) and (ii) substitute—
“(i)by the licensing authority, or
(ii)by an appropriate authority responsible for the licensing of medicinal products in an approved country for import,”;
(b)in sub-paragraph (b)—
(i)in paragraph (i), for “a competent authority of a member State” substitute “the licensing authority”,
(ii)in paragraph (ii), omit “except where the person is validly registered with the competent authority of another EEA State”, and
(iii)in paragraph (iii), for “published by the European Commission in accordance with Article 84 of the 2001 Directive” substitute “which apply under, or by virtue of, regulation C17”.
(3) In paragraph (2)—
(a)in sub-paragraph (a), for “a competent authority of a member State” substitute “the licensing authority”;
(b)in sub-paragraph (c), for “competent authority of a member State” substitute “licensing authority”.
(4) Omit paragraph (3).
39. In regulation 45D(1)(b)(37) omit sub-paragraph (ii) (and “and” immediately preceding it).
40. In regulation 45E(3)(38)—
(a)in sub-paragraph (b)(i), for “the competent authority of any EEA State” substitute “an appropriate authority responsible for the licensing of medicinal products in an approved country for import”; and
(b)omit sub-paragraph (d)(iii).
41. In regulation 45F(1)(39) for sub-paragraph (b) substitute—
“(b)either—
(i)the UK marketing authorisation holder; or
(ii)where applicable, the holder of the licence or authorisation granted by an appropriate authority responsible for the licensing of medicinal products in an approved country for import;”.
42.—(1) Regulation 45M(40) is amended as follows.
(2) In paragraph (2)(a), for “marketing authorisation, Article 126a authorisation” substitute “UK marketing authorisation”.
(3) In paragraph (3), omit “from a state other than an EEA State”.
43.—(1) Schedule 7A(41) is amended as follows.
(2) In paragraph 13(b), omit “from third countries”.
(3) In paragraph 15(c), omit “to a third country”.
44.—(1) Regulation 45O(42) is amended as follows.
(2) In paragraph (1), for “the Commission has adopted principles and guidelines of good manufacturing practice under the third paragraph of Article 47 of the 2001 Directive which applies” substitute “principles and guidelines of good manufacturing practice have been published under, or apply by virtue of, regulation C17, which apply”.
(3) In paragraph (2), for “the Commission has adopted principles and guidelines of good distribution practice under the fourth paragraph of Article 47 of the 2001 Directive which applies” substitute “principles and guidelines of good distribution practice have been published under, or apply by virtue of, regulation C17, which apply”.
(4) In paragraph (3)—
(a)for “the Commission has adopted principles and guidelines of good manufacturing practice under the third paragraph of Article 47 of the 2001 Directive which applies” substitute “principles and guidelines of good manufacturing practice have been published under, or apply by virtue of, regulation C17, which apply”;
(b)for “imported from a third country” substitute “so imported”;
(c)in sub-paragraph (c)—
(i)omit “third” in both places it appears,
(ii)in paragraph (ii), for “Union” substitute “United Kingdom”, and
(iii)in paragraph (iii), for “Union” substitute “licensing authority”.
(5) In paragraph (4)—
(a)in sub-paragraph (a), for “Article 111b of the 2001 Directive” substitute “paragraph (6)”; and
(b)in sub-paragraph (b)(i), for “competent authority of a member State” substitute “licensing authority or an appropriate authority responsible for the licensing of medicinal products in a country included in a list under paragraph (6)”.
(6) At the end insert—
“(6) The licensing authority may publish a list of countries which it is satisfied have a regulatory framework applicable to active substances exported to the United Kingdom that is equivalent to the regulatory framework in the United Kingdom, in that the respective control and enforcement activities in those countries ensures an equivalent level of protection of public health.
(7) Before including a country in the list under paragraph (6), the licensing authority must assess the equivalence referred to in that paragraph by—
(a)reviewing relevant documentation; and
(b)unless the country is included in the approved country for batch testing list, carrying out—
(i)an on-site review of the country’s regulatory system, and
(ii)if the licensing authority considers it necessary, an inspection of one or more of that country’s manufacturing sites for active substances.
(8) In carrying out an assessment under paragraph (7) the licensing authority must in particular take account of the—
(a)country’s rules for good manufacturing practice;
(b)regularity of inspections to verify compliance with good manufacturing practice;
(c)effectiveness of enforcement of good manufacturing practice; and
(d)regularity and rapidity of information provided by that country relating to non-compliant producers of active substances.
(9) The licensing authority must—
(a)review the list under paragraph (6) to determine if a country included in it still satisfies the requirements for inclusion in the list, and if it is not so satisfied, remove that country; and
(b)undertake such a review at least every three years, beginning with the date on which a country is included in the list .”.
45.—(1) Regulation 46 is amended as follows.
(2) In paragraph (2)—
(a)in sub-paragraph (a), before “marketing authorisation”, insert “UK”;
(b)at the end of sub-paragraph (b), insert “or”; and
(c)omit sub-paragraph (d) (and “or” immediately preceding it).
(3) In paragraph (3), before “European Economic Area” insert “United Kingdom or the”.
(4) In paragraph (6)—
(a)in sub-paragraph (a), before “marketing authorisation”, insert “UK”;
(b)at the end of sub-paragraph (b), insert “or”; and
(c)omit sub-paragraph (d) (and “or” immediately preceding it).
(5) In paragraph (7), omit sub-paragraph (b) (and “and” immediately preceding it).
(6) In paragraph (9), before “European Economic Area” insert “United Kingdom or the”.
(7) In paragraph (11)(a), before “European Economic Area” insert “United Kingdom or the”.
46.—(1) Regulation 47 is amended as follows.
(2) In paragraphs (3) and (4), before “European Economic Area”, insert “United Kingdom or the”.
(3) In paragraph (6), for “marketing authorisation, certificate of registration, traditional herbal registration or Article 126a authorisation”, substitute “UK marketing authorisation, certificate of registration or traditional herbal registration”.
47.—(1) Regulation 48(43) is amended as follows.
(2) In paragraph (2)—
(a)at the appropriate place insert—
““EU reference medicinal product” means a medicinal product which falls within paragraph (b) of the definition of “reference medicinal product”;”;
(b)for the definition of “generic medicinal product”, substitute—
““generic medicinal product”, in relation to a reference medicinal product, means a medicinal product—
that has the same qualitative and quantitative composition in active substances as the reference medicinal product;
that has the same pharmaceutical form as the reference medicinal product; and
whose bioequivalence with the reference medicinal product has been demonstrated by appropriate bioavailability studies;”;
(c)for the definition of “parallel import licence” substitute—
““parallel import licence” means a licence that is granted by the licensing authority under this Part authorising the holder to place on the market a medicinal product imported in to the United Kingdom from an EEA State where that product—
has been granted an EU marketing authorisation or a marketing authorisation in an EEA State under the 2001 Directive; and
is essentially similar to a product that has been granted a UK marketing authorisation;”; and
(d)for the definition of “reference medicinal product”, substitute—
““reference medicinal product” means a medicinal product—
authorised under regulation 49(1)(a), in accordance with the provisions of regulation 50; or
in relation to which an EU marketing authorisation was in force on exit day, but in relation to which no UK marketing authorisation is in force because the holder of the EU marketing authorisation notified the licensing authority in accordance with paragraph 6(3) of Schedule 33A that it did not wish to be the holder of a converted EU marketing authorisation.”.
(3) After paragraph (2) insert—
“(3) In this Part, references to a medicinal product to be imported that is “essentially similar to a product that has been granted a UK marketing authorisation” are to be read as references to a medicinal product to be imported that—
(a)has been manufactured to the same formulation as a product that has been granted a UK marketing authorisation (“the UK product”);
(b)contains the same active ingredients as the UK product;
(c)has the same therapeutic effect as the UK product,
and for the purposes of sub-paragraph (a), any differences in a product’s formulation are to be ignored in so far as they are considered to be immaterial by the licensing authority.
(4) For the purposes of the definition of generic medicinal product—
(a)the different salts, esters, ethers, isomers, mixtures of isomers, complexes or derivatives of an active substance are considered to be the same active substance, unless they differ significantly in properties with regard to safety or efficacy; and
(b)the various immediate-release oral pharmaceutical forms are considered to be the same pharmaceutical form.
(5) When a medicinal product has been granted a UK marketing authorisation under regulation 49(1)(a) in accordance with the provisions of regulation 50 (“initial marketing authorisation”), any additional strengths, pharmaceutical forms, administration routes, presentations, variations and extensions in relation to which a UK marketing authorisation is granted under regulation 49(1)(a), or which are included in the initial UK marketing authorisation, belong to the same “global marketing authorisation”.
(6) Paragraph (7) applies if a medicinal product—
(a)belongs to a global marketing authorisation but is not the initial marketing authorisation; and
(b)is used as a reference medicinal product in accordance with regulations 51 to 53.
(7) Where this paragraph applies, the medicinal product is treated for the purposes of the application of regulation 51(1) and (8) as it if had been authorised on the date of authorisation of the medicinal product to which the initial marketing authorisation relates.
(8) Paragraph (9) applies in relation to a medicinal product if—
(a)it is an EU reference medicinal product;
(b)it is used as a reference medicinal product in accordance with regulations 51 to 53; and
(c)it belongs to a global marketing authorisation, as described in the second paragraph of Article 6(1) of the 2001 Directive; but
(d)it is not the initial marketing authorisation for the purposes of that global marketing authorisation.
(9) Where this paragraph applies, the medicinal product is treated for the purposes of the application of regulation 51(1) and (8) as if it had been authorised on the date of authorisation of the initial marketing authorisation for the purposes of the global marketing authorisation to which the product belongs.”.
48.—(1) Regulation 49(44) is amended as follows.
(2) In paragraph (1), after “regulation 58,” insert “58C, 58E, 58F and 58G,”.
(3) After paragraph (1) insert—
“(1A) The licensing authority may only grant a parallel import licence if it is able to obtain the information necessary, whether from a competent authority of an EEA State or otherwise, to satisfy itself that the medicinal product to be imported—
(a)has been granted an EU marketing authorisation or a marketing authorisation under the 2001 Directive; and
(b)is essentially similar to a product that has already been granted a UK marketing authorisation.”.
(4) In paragraph (3), for “European Union” substitute “United Kingdom.”
(5) After paragraph (3) insert—
“(3A) An application for a parallel import licence may not be made by—
(a)the holder of the marketing authorisation, within the meaning of the 2001 Directive, or the EU marketing authorisation, in respect of the relevant medicinal product to be imported; or
(b)a company which is in the same group as the holder of that marketing authorisation.”.
(6) At the end insert—
“(9) In this regulation “group” has the same meaning as in Part 15 of the Companies Act 2006(45) (see section 474(1) of that Act).”.
49.—(1) Regulation 50(46) is amended as follows.
(2) In paragraph (4), omit “from a country other than an EEA State”.
(3) After paragraph (5) insert—
“(5A) The Ministers may by regulations amend Schedule 8B (modifications of Annex I) for the purpose of further modifying Annex I to the 2001 Directive in order to take account of scientific and technical progress.
(5B) The licensing authority may publish, for the purposes of applications made pursuant to this regulation—
(a)guidance on the presentation and content of the material specified in Schedule 8;
(b)scientific guidelines relating to the quality, safety and efficacy of medicinal products; and
(c)guidelines describing the active substance manufacturing process and process controls.
(5C) Unless replaced by guidance or guidelines published under the power conferred by paragraph (5B), the following guidance and guidelines continue to apply as they applied immediately before exit day (subject to any amendments or variations published under that paragraph)—
(a)the guidance published by the European Commission in the rules governing medicinal products in the European Community, Volume 2B, Notice to Applicants, Medicinal Products for human use, Presentation and content of the dossier, Common Technical Document(47);
(b)the scientific guidelines relating to the quality, safety and efficacy of medicinal products as adopted by the Committee for Medicinal Products for Human Use and published by the EMA and the other pharmaceutical Community guidelines published by the European Commission in the different volumes of the rules governing medicinal products in the European Community(48); and
(c)guidelines published by the EMA for the purposes of paragraph 3.2.1.2 of Part I of Annex I to the 2001 Directive(49).”.
(4) In paragraph (6), before sub-paragraph (a), insert—
“(za)regulation 50A (requirement for certain applications to include results of paediatric investigation plan);
(zb)regulation 50E (application for paediatric use marketing authorisation);
(zc)regulation 50F (other applications including paediatric indications);
(zd)regulation 50G (applications relating to orphan medicinal products);
(ze)regulation 50H (applications relating to advanced therapy medicinal products);
(zf)regulation 50I (applications relating to conditional marketing authorisations);
(zg)regulation 50J (applications relating to medicinal products containing or consisting of genetically modified organisms);”.
(5) After paragraph (6), insert—
“(7) The licensing authority may make appropriate arrangements with any EEA State or the EMA in order to obtain the information it considers necessary to satisfy itself that a product to be imported under a parallel import licence is essentially similar to a product that has been granted a UK marketing authorisation.
(8) If the licensing authority makes arrangements under paragraph (7), it must publish a list of the EEA States or the organisation with which it has made such arrangements.”.
50.—(1) Schedule 8(50) is amended as follows.
(2) In paragraph 12—
(a)in sub-paragraph (a), after “pharmacovigilance” insert “who is ordinarily resident, and operates, in the United Kingdom”;
(b)omit sub-paragraph (b); and
(c)in paragraph (e) at the end insert “or, if kept in electronic form, from which it can be accessed, which in either case, must be in the United Kingdom”.
(3) For paragraph 18 substitute—
“18. Where an application for authorisation for the medicinal product to be placed on the market is under consideration in a country other than the United Kingdom, or by the EMA, notification of that fact.”.
(4) In paragraph 19, for “a member state or by a third country”, substitute “a country other than the United Kingdom or by the European Commission”.
(5) Omit paragraph 20.
(6) In paragraph 21, for “a member state or by a third country”, substitute “a country other than the United Kingdom”.
(7) Omit paragraph 22.
(8) In paragraph 23—
(a)for “Article 23 of Regulation (EC) No 726/2004” substitute “regulation 202A”;
(b)before “statement”, insert “symbol and”; and
(c)before “This”, insert “▼”.
(9) After paragraph 25, insert—
“25A. In the case of an advanced therapy medicinal product which contains cells or tissues, a detailed description of those cells or tissues and of their specific origin, including the species of animal in cases of non-human origin.”.
(10) After paragraph 35, insert—
“36. In the case of an advanced therapy medicinal product—
(a)references in this Part of this Schedule to administration of a product include references to the advanced therapy medicinal product’s use, application or implantation; and
(b)descriptions, instructions and warnings must include explanatory drawings and pictures where necessary.”.
51. Paragraph 6 of Schedule 8A(51) is amended as follows—
(a)in sub-paragraph (a), after “pharmacovigilance” insert “who resides and operates in the United Kingdom”;
(b)omit sub-paragraph (b); and
(c)in paragraph (e) at the end inset “or, if kept in electronic form, from which it can be accessed, which in either case, must be in the United Kingdom”.
52.—(1) Schedule 9 is amended as follows.
(2) In the heading, for “EEA” substitute “United Kingdom”.
(3) In each place where it occurs, insert “UK” before “marketing authorisation”.
53. After regulation 50, insert—
50A.—(1) This regulation applies in relation to an application—
(a)under regulation 49 for a UK marketing authorisation for a relevant medicinal product which is an initial marketing authorisation for the purposes of a global marketing authorisation, as described in regulation 48(5), or
(b)under regulation 49 or 65C for a new indication (including a paediatric indication), a new pharmaceutical form or a new route of administration in relation to a relevant medicinal product which is already the subject of a UK marketing authorisation.
(2) Paragraph (1)(b) only applies if the medicinal product in relation to which the new indication, new pharmaceutical form or new route of administration is sought is protected in the United Kingdom by a supplementary protection certificate or a patent which qualifies for the granting in the United Kingdom of a supplementary protection certificate.
(3) An applicant making an application to which this regulation applies must, in addition to the material specified in regulation 50, or in Schedule 10A, provide to the licensing authority the results of all studies performed, and details of all information collected, in compliance with an agreed paediatric investigation plan.
(4) Where paragraph (1)(b) applies, the material provided pursuant to paragraph (3) must cover both the existing and new indication, pharmaceutical form or route of administration.
(5) Paragraph (3) does not apply–
(a)to the extent that the licensing authority has, in relation to all or part of the paediatric population, granted—
(i)a deferral under regulation 50C of the initiation or completion of some or all of the measures set out in a paediatric investigation plan, or
(ii)a waiver under regulation 50D of the obligation to produce the information referred to in paragraph (3); or
(b)if one of regulations 51 to 54 applies to the application.
(6) The applicant making an application to which this regulation applies must include in the application details of the measures intended to ensure the follow up of efficacy and of possible adverse reactions to the paediatric use of the medicinal product.
50B.—(1) Any person may prepare a paediatric investigation plan and submit it to the licensing authority with a request for agreement.
(2) A paediatric investigation plan must—
(a)specify the timing and measures proposed to assess the safety, quality and efficacy of a medicinal product in the paediatric population; and
(b)describe any measures to adapt the formulation of the medicinal product so as to make its use more acceptable, easier, safer or more effective for different subsets of the paediatric population.
(3) A person who requests the agreement of a paediatric investigation plan must submit it to the licensing authority not later than upon completion of the human pharmaco-kinetic studies in adults in relation to the medicinal product to which the plan relates, as specified in section 5.2.3 of Part I of Annex I to the 2001 Directive, unless the licensing authority agrees to accept a later request.
(4) The licensing authority may request the person applying for agreement of a paediatric investigation plan to supply further information in relation to the plan or to submit proposed modifications to it.
(5) The licensing authority must decide whether or not—
(a)the proposed studies will ensure the generation of the necessary data determining the conditions in which the medicinal product may be used to treat the paediatric population or subsets of it; and
(b)the expected therapeutic benefits of the medicinal product justify the studies proposed; and
in doing so must consider whether or not the measures proposed to adapt the formulation of the medicinal product for use in different subsets of the paediatric population are appropriate.
(6) If, following a decision by the licensing authority to agree a paediatric investigation plan, the person carrying out the plan encounters such difficulties with its implementation as to render the plan unworkable or no longer appropriate, that person may propose changes or request a deferral or a waiver, by submitting a request to the licensing authority, explaining the grounds for the request.
(7) Schedule 11 makes provision about advice and representations in relation to proposals to agree, or to refuse to agree, a paediatric investigation plan under paragraph (5) or to grant, or to refuse to grant, a deferral or waiver requested under paragraph (6).
50C.—(1) At the same time as the paediatric investigation plan is submitted under regulation 50B(1), the person requesting agreement of it may request the agreement of the licensing authority to a deferral of the initiation or completion of some or all of the measures set out in the plan.
(2) If the licensing authority is satisfied that a deferral of the initiation or completion of some or all of the measures set out in a paediatric investigation plan can be justified on scientific and technical grounds, or on grounds related to public health, it may—
(a)agree to a request by the applicant to grant a deferral; or
(b)decide of its own motion to grant a deferral.
(3) If the licensing authority is satisfied as set out in paragraph (2), it must decide to grant a deferral where it is satisfied that—
(a)it is appropriate to conduct studies in adults prior to initiating studies in the paediatric population; or
(b)studies in the paediatric population will take longer to conduct than studies in adults.
(4) If the licensing authority grants an application to which regulation 50A applies, it must, if it also grants a deferral in accordance with this regulation—
(a)record that fact in the product’s summary of product characteristics, and, if it considers that it would be appropriate to do so, in the package leaflet; and
(b)specify in the document notifying the applicant of the grant of the deferral the time limits for the initiation or completion of the measures to which the deferral relates.
(5) Schedule 11 makes provision about advice and representations in relation to proposals to grant, or to refuse to grant, a deferral under paragraph (2) or (3).
50D.—(1) The applicant making an application to which regulation 50A applies is exempt from the obligation to provide to the licensing authority the results of all studies performed, and details of all information collected, in compliance with an agreed paediatric investigation plan, if a waiver is granted in accordance with this regulation.
(2) The licensing authority may grant a waiver in accordance with this regulation if it is satisfied that there is evidence showing that—
(a)the medicinal product or class of medicinal products is likely to be ineffective or unsafe in all or part of the paediatric population;
(b)the disease or condition for which the medicinal product or class of medicinal products is intended occurs only in adult populations; or
(c)the medicinal product does not represent a significant therapeutic benefit over existing treatments for patients in the paediatric population.
(3) The licensing authority may grant a waiver in accordance with this regulation—
(a)in respect of the entire paediatric population, or a subset of it;
(b)in respect of all of the therapeutic indications for the medicinal product concerned, or only some of them;
(c)of its own motion, or at the request of the applicant; or
(d)in respect of a specific product or a class of medicinal products.
(4) A person who requests a waiver in accordance with this regulation must submit the request to the licensing authority not later than upon completion of the human pharmaco-kinetic studies in adults in relation to the medicinal product concerned, as specified in section 5.2.3 of Part I of Annex I to the 2001 Directive, unless the licensing authority agrees to accept a later application.
(5) The licensing authority must maintain and publish a list of waivers which are granted under this regulation in respect of a class of medicinal products.
(6) The licensing authority may review a waiver which it has granted under this regulation and may revoke it if it considers it appropriate, having regard to the matters specified in paragraph (2).
(7) If the licensing authority revokes a waiver granted under this regulation, the holder of the UK marketing authorisation to which the waiver relates must, at the end of the period of 36 months beginning with the date of publication of the decision to revoke the waiver, submit the information referred to in regulation 50A(3) to the licensing authority.
(8) If the licensing authority grants an application to which regulation 50A applies, it must, if it also grants a waiver in accordance with this regulation, record that fact in the product’s summary of product characteristics, and, if it considers that it would be appropriate to do so, in the package leaflet.
(9) Schedule 11 makes provision about advice and representations in relation to proposals to grant, or to refuse to grant, a waiver in response to a request made in accordance with paragraph (4) and to revoke a waiver under paragraph (6).
50E.—(1) This regulation applies in relation to an application for a UK marketing authorisation—
(a)for a relevant medicinal product which is not protected in the United Kingdom by a supplementary protection certificate or by a patent which qualifies for the granting of a supplementary protection certificate; and
(b)which covers exclusively therapeutic indications which are relevant for use in the paediatric population, or subsets of it, including the appropriate strength, pharmaceutical form or route of administration for that product.
(2) The applicant for a UK marketing authorisation to which this regulation applies must, in addition to the material specified in regulation 50, provide to the licensing authority material necessary to establish the quality, safety and efficacy of the product in the paediatric population, including any specific data needed to support an appropriate strength, pharmaceutical form or route of administration for the product, in accordance with an agreed paediatric investigation plan.
(3) An application to which this regulation applies may, in accordance with regulations 51 to 55, refer to material supplied by the holder of a UK marketing authorisation.
(4) The applicant for a UK marketing authorisation to which this regulation applies must include in the application details of the measures intended to ensure the follow up of efficacy and of possible adverse reactions to the paediatric use of the medicinal product.
50F.—(1) This regulation applies in relation to an application to which neither regulation 50A nor 50E applies and which is—
(a)an application for a UK marketing authorisation for a relevant medicinal product which includes a paediatric indication; or
(b)an application to include a paediatric indication in an existing UK marketing authorisation.
(2) The applicant making an application to which this regulation applies must include in the application details of the measures intended to ensure the follow up of efficacy and of possible adverse reactions to the paediatric use of the medicinal product.
50G.—(1) This regulation applies in relation to an application for a UK marketing authorisation for a relevant medicinal product in relation to which the applicant intends to demonstrate that the orphan criteria are met.
(2) The orphan criteria are that—
(a)the medicinal product is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition;
(b)either—
(i)the condition referred to in sub-paragraph (a) affects not more than five in 10,000 persons in the United Kingdom; or
(ii)the medicinal product is unlikely, when marketed, to generate sufficient financial return to justify the necessary investment; and
(c)there exists no satisfactory method of diagnosis, prevention or treatment of the condition in question that has been authorised in the United Kingdom, or if such method exists, the medicinal product will be of significant benefit to those affected by the condition.
(3) The applicant for a UK marketing authorisation to which this regulation applies must, in addition to the material specified in regulation 50, provide to the licensing authority material that demonstrates that the orphan criteria are met.
(4) Schedule 9A makes further provision about the orphan criteria and terms used in regulation 58D.
(5) The Ministers may by regulations amend Schedule 9A.
50H.—(1) This regulation applies in relation to an application for a UK marketing authorisation for a relevant medicinal product which is an advanced therapy medicinal product.
(2) The applicant for a UK marketing authorisation to which this regulation applies must, in addition to the material specified in regulation 50, provide to the licensing authority information about the measures the applicant envisages putting in place to ensure the follow up of the efficacy of the product and of any adverse reactions to it.
(3) In relation to an application for a UK marketing authorisation for a combined advanced therapy medicinal product, the applicant must, in addition to the material specified in regulation 50 and paragraph (2), provide to the licensing authority evidence of conformity with the requirements of the Medical Devices Regulations 2002(52), including, where available, the results of the assessment of a notified body in accordance with those Regulations.
50I.—(1) This regulation applies in relation to an application for a UK marketing authorisation for a relevant medicinal product which falls within paragraph (2).
(2) A relevant medicinal product falls within this paragraph if it is—
(a)aimed at the treatment, prevention or diagnosis of seriously debilitating or life-threatening diseases; or
(b)to be used in emergency situations, in response to public health threats.
(3) The applicant for a UK marketing authorisation to which this regulation applies may request that the licensing authority grant a conditional marketing authorisation if—
(a)comprehensive clinical data referring to the safety and efficacy of the medicinal product have not been supplied; and
(b)the applicant can demonstrate that—
(i)the positive therapeutic effects of the product outweigh the risks to the health of patients or of the public associated with the product,
(ii)it is likely that the applicant will be in a position to provide the comprehensive clinical data,
(iii)unmet medical needs will be fulfilled, and
(iv)the benefit to the public health of the immediate availability on the market of the medicinal product concerned outweighs the risk inherent in the fact that additional data are still required.
(4) In this regulation, “unmet medical needs” means medical needs in relation to a condition for which there exists no satisfactory method of diagnosis, prevention or treatment authorised in the United Kingdom, or, even if such method exists, in relation to which the medicinal product concerned will be of major therapeutic advantage to those affected.
(5) The applicant for a UK marketing authorisation to which this regulation applies must include in the application material which demonstrates that the criteria in paragraph (3)(b) are met.
50J.—(1) This regulation applies in relation to an application for a UK marketing authorisation for a relevant medicinal product which contains or consists of genetically modified organisms.
(2) The applicant for a UK marketing authorisation to which this regulation applies must, in addition to the material specified in regulation 50, provide to the licensing authority—
(a)a copy of the consent to the deliberate release into the environment of the genetically modified organisms for research and development purposes given pursuant to—
(i)regulation 21 of the Genetically Modified Organisms (Deliberate Release) Regulations 2002(53),
(ii)regulation 22 of the Genetically Modified Organisms (Deliberate Release) (Wales) Regulations 2002(54),
(iii)regulation 21 of the Genetically Modified Organisms (Deliberate Release) (Scotland) Regulations 2002(55), or
(iv)regulation 21 of the Genetically Modified Organisms (Deliberate Release) Regulations (Northern Ireland) 2003(56);
(b)a complete technical dossier supplying the information specified in Annexes III and IV to Directive 2001/18/EC;
(c)an environmental risk assessment in accordance with the principles set out in Annex II to Directive 2001/18/EC; and
(d)the results of any investigations performed for the purposes of research or development.
(3) In this regulation, “genetically modified organism” has the meaning given in Article 2(2) of Directive 2001/18/EC.”.
54. Schedule 4 inserts a new Schedule 9A after Schedule 9.
55. In paragraph 4(4)(a) of Schedule 10 (exceptions to requirement to submit safety data) insert “UK” before “marketing authorisation”.
56. For regulation 51 substitute—
“(1) An applicant for a UK marketing authorisation for a generic medicinal product may, by way of derogation from paragraph 10 of Schedule 8, omit from the application the results of pre-clinical tests and of clinical trials if the applicant can demonstrate that the medicinal product is a generic of a reference medicinal product which is or has been authorised for not less than eight years—
(a)under regulation 49(1)(a) (subject to paragraphs (2) and (3)); or
(b)if the product is an EU reference medicinal product, under Regulation (EC) No 726/2004.
(2) If, after exit day but before the date of grant of the UK marketing authorisation in relation to the reference medicinal product, an EU marketing authorisation took effect in relation to that product, the period of not less than eight years referred to in paragraph (1) is treated as having started on the date on which the EU marketing authorisation took effect.
(3) If, after exit day but before the date of grant of the UK marketing authorisation in relation to the reference medicinal product, the competent authority of an EEA state granted a marketing authorisation in relation to that product, the period of not less than eight years referred to in paragraph (1) is treated as having started on the date on which the marketing authorisation in the first EEA state in which the product was authorised took effect.
(4) In the case of an application under this regulation in relation to a salt, ester, ether, isomer, mixture of isomers, complex or derivative of an authorised active substance which differs significantly in properties with regard to safety or efficacy from the active substance in the reference medicinal product, the applicant must supply additional information providing proof of the safety or efficacy of the salt, ester, ether, isomer, mixture of isomers, complex or derivative.
(5) The applicant may omit bioavailability studies from an application under this regulation if the applicant can demonstrate that the generic medicinal product meets the relevant criteria as specified in the guidelines referred to in paragraph (6).
(6) The licensing authority may publish guidelines specifying the criteria to be met by generic medicinal products for the purpose of omitting bioavailability studies from an application in accordance with paragraph (5).
(7) Until replaced by guidelines published under paragraph (6), the guidelines published by the EMA under Article 10(2)(b) of the 2001 Directive(57) continue to apply on and after exit day as they applied immediately before exit day (subject to any amendments or variations published under paragraph (6)).
(8) If the licensing authority grants a UK marketing authorisation in relation to 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 expiry of ten years beginning with—
(a)the date on which the reference medicinal product was granted a UK marketing authorisation;
(b)the date referred to in paragraph (2) or (3), if earlier than the date in sub-paragraph (a); or
(c)if the reference medicinal product is an EU reference medicinal product, the date on which the EU marketing authorisation for the reference medicinal product took effect.
(9) Paragraph (10) applies where an EU reference medicinal product is used as a reference medicinal product for the purposes of this regulation.
(10) Where this paragraph applies, the terms of the marketing authorisation of the EU reference medicinal product are treated as being the terms of the product’s EU marketing authorisation as they stood immediately before exit day.
(11) Paragraph (12) applies if—
(a)during the first eight of the ten years referred to in paragraph (8) the marketing authorisation holder for the reference medicinal product obtained a UK marketing authorisation for one or more new therapeutic indications; and
(b)during the scientific evaluation prior to their authorisation, the licensing authority considers the new indications bring a significant clinical benefit in comparison with existing therapies.
(12) Where this paragraph applies, the period of ten years referred to in paragraph (8) is extended to eleven years, subject to the provisions of paragraphs (13) and (14).
(13) Where the European Commission, or an EEA state, has granted or varied a marketing authorisation in relation to the new therapeutic indication before the licensing authority does so, the one year extension of the period of ten years referred to in paragraph (8) is reduced by the period of time—
(a)beginning on the date on which the EU or EEA state marketing authorisation took effect or was varied; and
(b)ending immediately before the date on which the licensing authority granted or varied the UK marketing authorisation.
(14) If the period of time by which the one year extension is to be reduced in accordance with paragraph (13) is one year or longer, paragraph (12) does not apply.
(15) Paragraph (16) applies where—
(a)an application is made in relation to a new indication for a well-established substance; and
(b)significant pre-clinical or clinical studies were carried out in relation to the new indication.
(16) Where this paragraph applies, the applicant for a UK marketing authorisation under paragraph (1) or regulation 52 or 53 may not refer in its application to the studies mentioned in paragraph (15)(b) for the period of one year beginning on the date on which the licensing authority grants or varies a UK marketing authorisation in relation to the new indication (subject to paragraphs (17) and (18)).
(17) Where the European Commission, or an EEA state, has granted or varied a marketing authorisation in relation to the new indication before the licensing authority does so, the period of one year referred to in paragraph (10) is reduced by the period of time—
(a)beginning on the date on which the EU or EEA state marketing authorisation took effect or was varied; and
(b)ending immediately before the date on which the licensing authority granted or varied the UK marketing authorisation.
(18) If the period of time by which the one year period in paragraph (16) is to be reduced in accordance with paragraph (17) is one year or longer, paragraph (16) does not apply.”.
57.—(1) Regulation 52 is amended as follows.
(2) In paragraph (1)(a), for “as reference medicinal product” substitute—
“which is or has been authorised for not less than eight years—
(i)under regulation 49(1)(a) (subject to paragraphs (2) and (3) of regulation 51), or
(ii)if the reference medicinal product is an EU reference medicinal product, under Regulation (EC) No 726/2004; and”.
(3) For paragraph (1)(b) substitute—
“(b)one or more of the following circumstances applies in respect of the application—
(i)the medicinal product to which the application relates does not fall within the definition of generic medicinal product,
(ii)bioequivalence with the reference medicinal product cannot be demonstrated through bioavailability studies, or
(iii)the medicinal product to which the application relates differs from the reference medicinal product in terms of changes in the active substance, therapeutic indications, strength, pharmaceutical form or route of administration.”.
(4) For paragraph (2), substitute—
“(2) The applicant—
(a)may, by way of derogation from paragraph 10 of Schedule 8, omit from the application the results of pre-clinical tests and of clinical trials relating to the reference medicinal product; but
(b)must provide the results of the appropriate pre-clinical tests or clinical trials relating to the applicable circumstance in paragraph (1)(b).”.
(5) In paragraph (3)—
(a)for “Regulation 51(2)” substitute “Paragraphs (2) to (14) of regulation 51”; and
(b)for “it applies” substitute “they apply”.
58.—(1) Regulation 53 is amended as follows.
(2) In paragraph (1), for the words from “any of the reasons” to the end, substitute “differences relating to raw materials or differences in manufacturing processes of the biological medicinal product and the reference medicinal product.”
(3) For paragraph (2), substitute—
“(2) The applicant—
(a)may, by way of derogation from paragraph 10 of Schedule 8, omit from the application the results of pre-clinical tests and of clinical trials relating to the reference medicinal product; but
(b)must provide the results of appropriate pre-clinical tests or clinical trials relating to the differences referred to in paragraph (1).
(2A) The type and quantity of supplementary data to be provided by the applicant under paragraph (2)(b) must comply with the relevant criteria in Annex I to the 2001 Directive and in the related detailed guidelines published by the licensing authority under paragraph (2B), or (as the case may be) as mentioned in paragraph (2C).
(2B) The licensing authority may publish guidelines concerning the type and quantity of supplementary data to be provided by an applicant under paragraph (2)(b).
(2C) Unless replaced by guidelines published under paragraph (2B), the guidelines published by the EMA under Article 10(4) of the 2001 Directive(58) continue to apply on and after exit day as they applied immediately before exit day (subject to any amendments or variations published under that paragraph).”
(4) In paragraph (3) —
(a)for “Regulation 51(2)” substitute “Paragraphs (2) to (8) of regulation 51”; and
(b)for “it applies” substitute “they apply”.
59.—(1) Regulation 54 is amended as follows.
(2) In paragraph (1) before “European Union”, insert “United Kingdom or the”.
(3) For paragraph (2), substitute—
“(2) The applicant may, by way of derogation from paragraph 10 of Schedule 8, replace the results of pre-clinical tests or clinical trials with appropriate scientific literature.”.
60.—(1) Regulation 55 is amended as follows.
(2) In paragraph (1)(a), omit “, the 2001 Directive or Regulation (EC) No 726/2004”.
(3) For paragraph (2), substitute—
“(2) The applicant must provide the results of new pre-clinical tests or new clinical trials relating to that combination in accordance with paragraph 10 of Schedule 8, but does not need to provide scientific references relating to each individual active substance.”.
61. In regulation 56(2), omit “in accordance with Article 10c of the 2001 Directive”.
62.—(1) Regulation 58 is amended as follows.
(2) After paragraph (4), insert—
“(4A) When considering an application for a UK marketing authorisation, the licensing authority may, if it considers it appropriate, have regard to—
(a)an opinion of the Committee for Medicinal Products for Human Use; or
(b)the results of an assessment of an application for a marketing authorisation by the appropriate authority for the licensing of medicinal products of a country other than the United Kingdom ,
in respect of the medicinal product to which the application relates.
(4B) The licensing authority may under paragraph (4A)—
(a)decide to have regard to the opinions and assessments described in sub-paragraphs (a) and (b) in relation to certain types of medicinal products only; and
(b)determine and publish a list of the countries other than the United Kingdom whose assessments of applications for a marketing authorisation are relevant for the purposes of paragraph (4A)(b).”.
(3) Omit paragraphs (6) and (7).
63.—(1) Schedule 11 is amended as follows.
(2) In paragraph 1 (application of Part 1)—
(a)in sub-paragraph (1)—
(i)in sub-paragraph (b) omit “and”, and
(ii)at the end insert—
“(d)a proposal to agree, or to refuse to agree, a paediatric investigation plan;
(e)a proposal to grant, or to refuse to grant, or to revoke, a waiver or deferral of the initiation or completion of some or all of the measures set out in a paediatric investigation plan; and
(f)a proposal to decide that the orphan criteria are not met in relation to a medicinal product which is the subject of an application for the grant of a UK marketing authorisation.”;
(b)after sub-paragraph (1) insert—
“(1A) Paragraphs 12 and 13 of this Part also apply to—
(a)an application for the grant of a parallel import licence;
(b)an application to renew a parallel import licence;
(c)a proposal to revoke, vary or suspend a parallel import licence (including variation by the variation or removal of a condition to which a parallel import licence is subject) other than a proposal to vary the licence on the application of or by agreement with its holder; and
(d)a refusal to vary a parallel import licence following an application for a variation by the holder.”; and
(c)omit sub-paragraph (2).
(3) In paragraph 12 (licensing authority decision in other cases), in sub-paragraphs (1), (2) and (5)—
(a)insert “, parallel import licence” after “UK marketing authorisation” in each place it appears; and
(b)insert “, licence” after “the authorisation” in each place it appears.
(4) In paragraph 14(a) (application of Part 2), for the words from “Article 2(3)” to the end, substitute “paragraph 1 of Schedule 10A; and”.
(5) In paragraph 15(2) and (3)(b), insert “UK” before “marketing authorisation”.
(6) In paragraph 16—
(a)in sub-paragraph (2)(b), insert “UK” before “marketing authorisation”; and
(b)in sub-paragraph (5), omit the words from “or in any Directive” to the end.
(7) Omit paragraph 17.
(8) In Part 3 (referral to the Committee for Herbal Medicinal Products)—
(a)in the heading to Part 3, for “Committee for Herbal Medicinal Products” substitute “appropriate committee for traditional herbal registrations”;
(b)in paragraph 24—
(i)in sub-paragraph (1), for the words from “Committee” to the end substitute “appropriate committee in accordance with regulation 130A(1)”; and
(ii)omit sub-paragraph (2); and
(c)in paragraph 29(1), for “proceed with its proposal” substitute “grant or refuse the application”.
(9) Omit Part 4 (exceptions to Schedule).
64. After regulation 58, insert—
58A.—(1) Paragraph (2) applies if—
(a)an application to which regulation 50A (requirement for certain applications to include the results of a paediatric investigation plan) applies, and in relation to which there is an agreed paediatric investigation plan, is granted by the licensing authority; and
(b)the licensing authority is satisfied that the material provided by the applicant pursuant to regulation 50A(3) demonstrates compliance with the agreed paediatric investigation plan.
(2) Where this paragraph applies, the licensing authority must—
(a)include in the UK marketing authorisation a statement to the effect that it is satisfied as set out in paragraph (1)(b); and
(b)ensure that the results of all studies referred to in the paediatric investigation plan are included in the summary of product characteristics and, if the licensing authority considers that the information would be useful to patients, in the package leaflet.
(3) Where paragraph (2) applies, the holder of a patent or supplementary protection certificate covering the medicinal product to which the application relates is entitled to a six month extension of the period referred to in Articles 13(1) and 13(3) of Regulation (EC) No 469/2009 of the European Parliament and of the Council of 6 May 2009 concerning the supplementary protection certificate for medicinal products (subject to paragraphs (4) and (5)).
(4) Paragraph (3) does not apply if the grant of the application referred to in paragraph (1)(a)—
(a)relates to a new paediatric indication; and
(b)the holder of the UK marketing authorisation—
(i)is entitled to a one year extension of the ten year period referred to in regulation 51(8), under regulation 51(12),
(ii)is entitled to an extension of that ten year period of less than one year by virtue of the application of regulation 51(13), or
(iii)would have been entitled to a one year extension of that ten year period but for the application of regulation 51(14).
(5) If the UK marketing authorisation to which this regulation applies is an orphan marketing authorisation, paragraph (3) does not apply and regulation 58D(5) (orphan rewards) applies.
(6) Paragraphs (7) and (8) apply if the licensing authority grants a UK marketing authorisation in response to an application to which regulation 50E (paediatric use marketing authorisation) applies.
(7) Where this paragraph applies, the medicinal product to which the paediatric use marketing authorisation relates may retain the name of any medicinal product which contains the same active substance and in respect of which the holder of the paediatric use marketing authorisation has been granted a UK marketing authorisation for use in adults.
(8) Where this paragraph applies, the holder of the paediatric use marketing authorisation is entitled to benefit from the periods of data and marketing exclusivity referred to in regulation 51(1) and (8) in relation to the material supplied pursuant to regulation 50E(2).
58B.—(1) The licensing authority must publish a register of UK marketing authorisations—
(a)which include a paediatric indication following completion of an agreed investigation paediatric plan; and
(b)in relation to which the medicinal product was placed on the market for other indications before the holder obtained that paediatric indication.
(2) The register referred to in paragraph (1) must include the date by which the product must be placed on the market taking account of the paediatric indication in accordance with regulation 78A(4) (post-authorisation requirements in relation to UK marketing authorisations to which paediatric specific provisions apply).
(3) The licensing authority must publish a list of the marketing authorisation holders which have—
(a)benefitted from any of the rewards in regulation 58A; or
(b)failed to comply with any of the obligations in regulation 78A.
(4) The licensing authority must publish decisions made under—
(a)regulation 50B(5) or (7) (agreement and modification of paediatric investigation plan);
(b)regulation 50C(2) (deferral of the initiation or completion of measures in a paediatric investigation plan); and
(c)regulation 50D(2) (waiver of production of information in a paediatric investigation plan) in relation to a specific medicinal product.
(5) The decisions referred to in paragraph (4) must be published, with the omission of information of a commercially confidential nature, as soon as reasonably practicable after the decision has been made.
58C.—(1) If the licensing authority is satisfied in relation to an application for a UK marketing authorisation—
(a)the orphan criteria are met in relation to all of the therapeutic indications to which the application relates; and
(b)it is otherwise appropriate to grant a UK marketing authorisation in respect of the application under regulation 49(1)(a),
it may grant a UK marketing authorisation which is known as an orphan marketing authorisation.
(2) The licensing authority must publish and keep up to date a list of orphan marketing authorisations.
(3) Schedule 11 makes provision about advice and representations in relation to proposals to grant a UK marketing authorisation in respect of which the applicant intended to demonstrate that the orphan criteria were met, in cases where the licensing authority considers that those criteria are not met.
58D.—(1) Subject to the following provisions of this regulation, for the period of ten years beginning with the date on which the licensing authority grants an orphan marketing authorisation, the licensing authority must not—
(a)grant an application for a UK marketing authorisation; or
(b)grant an application to vary a UK marketing authorisation;
in relation to a medicinal product which is similar to the medicinal product to which the orphan marketing authorisation relates and in respect of the therapeutic indications which are covered by the orphan marketing authorisation.
(2) Paragraph (3) applies if—
(a)an EU marketing authorisation took effect in relation to the medicinal product to which an orphan marketing authorisation relates on or after exit day but before the licensing authority granted the orphan marketing authorisation; and
(b)the EU marketing authorisation was granted on the basis that the product was an orphan medicinal product within the meaning of the Orphan Regulation.
(3) Where this paragraph applies, the period of ten years referred to in paragraph (1) is reduced by the period of time—
(a)beginning on the date on which the EU marketing authorisation took effect; and
(b)ending immediately before the date on which the licensing authority granted the orphan marketing authorisation.
(4) The period of ten years referred to in paragraph (1) may be reduced to six years if, at the end of the fifth year beginning on the date referred to in paragraph (1), the licensing authority is satisfied that the orphan criteria are no longer met in relation to the medicinal product.
(5) The period of ten years referred to in paragraph (1) is extended to twelve years if regulation 58A(2) (paediatric rewards) applies to the orphan marketing authorisation.
(6) Paragraph (1) does not apply if—
(a)the holder of the orphan marketing authorisation consents to the grant or variation of a UK marketing authorisation in relation to a similar medicinal product;
(b)the licensing authority is satisfied that the holder of the orphan marketing authorisation is unable to supply sufficient quantities of the medicinal product to which the orphan marketing authorisation relates; or
(c)a subsequent applicant can establish to the satisfaction of the licensing authority that the medicinal product to which the application relates, although similar to the medicinal product to which the orphan marketing authorisation relates, is safer or more effective than, or clinically superior to, that product.
58E.—(1) When determining an application to which regulation 50H(3) (applications relating to combined advance therapy medicinal products) applies, the licensing authority must—
(a)assess the entire combined advanced therapy medicinal product in accordance with these Regulations; and
(b)recognise the results of the assessment of the notified body, if supplied.
(2) The licensing authority may request the notified body, if relevant, to provide it with information related to the results of the assessment.
(3) Paragraph (4) applies if an application to which regulation 50H(3) applies does not include the results of the assessment of a notified body, or if the notified body fails to supply information related to the results of the assessment when requested by the licensing authority.
(4) Where this paragraph applies, the licensing authority must seek an opinion on the conformity of the device part in accordance with the Medical Devices Regulations 2002(59) from a notified body identified in conjunction with the applicant, unless the licensing authority decides that the involvement of a notified body is not required.
58F.—(1) If the licensing authority is satisfied in relation to an application to which regulation 50I (applications relating to conditional marketing authorisations) applies that—
(a)the criteria in regulation 50I(3)(b) are met; and
(b)it is otherwise appropriate to grant a UK marketing authorisation in respect of the application in accordance with regulation 49(1)(a),
it may grant a UK marketing authorisation which is known as a conditional marketing authorisation.
(2) Where regulation 50I(2)(b) (applications relating to conditional marketing authorisations) applies, the licensing authority may grant a conditional marketing authorisation if, in addition to comprehensive clinical data, comprehensive pre-clinical or pharmaceutical data have not been supplied.
(3) The licensing authority may, of its own motion, propose that a conditional marketing authorisation be granted if, having consulted the applicant for a UK marketing authorisation, it considers that the criteria in regulation 50I(3)(b) are met.
(4) If the licensing authority grants a conditional marketing authorisation in relation to a medicinal product, it may at any time decide that it is appropriate to grant a UK marketing authorisation in relation to that product which is not a conditional marketing authorisation.
(5) If the licensing authority grants a conditional marketing authorisation, the product’s summary of product characteristics and package leaflet must include a statement to that effect, and the summary of product characteristics must include the date on which the conditional marketing authorisation is due for renewal.
58G.—(1) When determining an application for a UK marketing authorisation in relation to which regulation 50J (applications relating to medicinal products containing or consisting of genetically modified organisms) applies, the licensing authority must be satisfied that the application respects the environmental safety requirements laid down by Directive 2001/18/EC.
(2) In reaching its view under paragraph (1), the licensing authority must consult the bodies responsible for the giving of consent pursuant to the legislation referred to in regulation 50J(2)(a).”.
65.—(1) Regulation 59(60) is amended as follows.
(2) For paragraph (3) substitute—
“(3) An obligation to conduct such studies as are referred to in paragraph (2)(f) must—
(a)be based on the delegated acts adopted pursuant to Article 22b of the 2001 Directive; and
(b)take into account the scientific guidance that applies under regulation 205B in relation to post-authorisation efficacy studies.”.
(3) After paragraph (3), insert—
“(3A) The Ministers may by regulations make provision specifying the situations in which post-authorisation efficacy studies may be required by virtue of the condition referred to in paragraph (2)(f).
(3B) Paragraph (3)(a) ceases to apply on the coming into force of regulations made under paragraph (3A).”.
(4) In paragraph (4), insert “UK” before “marketing authorisation”.
(5) After paragraph (4), insert—
“(4A) Where the application is one to which regulation 50A, 50E or 50F (applications to which paediatric-specific provisions apply) applies, the licensing authority must, if it considers that there is a particular cause for concern, grant the UK marketing authorisation subject to a condition that—
(a)a risk management system be set up comprising a set of pharmacovigilance activities and interventions designed to identify, characterise, prevent or minimise risks relating to medicinal products, including the assessment of the effectiveness of those interventions; or
(b)specific post-marketing studies be performed and submitted for review.
(4B) The licensing authority may request the holder to submit, in addition to the assessment required to be submitted pursuant to Part 9 of Schedule 12A (post-authorisation safety studies), a report assessing the effectiveness of any risk management system, and the results of any studies performed, in compliance with a condition imposed under paragraph (4A).
(4C) If the licensing authority grants a conditional marketing authorisation—
(a)it must impose, as a condition of the conditional marketing authorisation, an obligation on the holder of the authorisation to complete ongoing studies, or to conduct new studies, with a view to confirming the that the positive therapeutic effects of the product outweigh the risks to the health of patients or the public associated with the product, and to provide the additional data referred to in regulation 50I(3)(a);
(b)it may impose, as a condition of the conditional marketing authorisation, an obligation on the holder of that authorisation in relation to collection of pharmacovigilance data.
(4D) If the licensing authority grants a UK marketing authorisation in relation to an advanced therapy medicinal product, it must, if it considers that there is a particular cause for concern, grant the UK marketing authorisation subject to a condition that—
(a)a risk management system be set up which is designed to identify, characterise, prevent or minimise risks related to advanced therapy medicinal products, including an evaluation of the effectiveness of that system; or
(b)that specific post-marketing studies be carried out and submitted for review by the licensing authority.
(4E) The licensing authority may request the holder to submit, in addition to the assessment required to be submitted pursuant to Part 9 of Schedule 12A, a report assessing the effectiveness of any risk management system, and the results of any studies performed, in compliance with a condition imposed under paragraph (4D).”.
(6) Omit paragraph (5).
66. In regulation 60, omit paragraph (9).
67. After regulation 60, insert—
60A.—(1) In this regulation—
“the appropriate authority” is to be construed in accordance with section 57(7) of the Health and Social Care Act 2012(61);
“appropriate documentation”, in relation to a sample of a batch submitted to the appropriate authority in accordance with the batch testing condition or pursuant to a notification under paragraph (12), means—
any certificate issued by a laboratory in an approved country for batch testing and certification of biological medicinal products that relates to the sample of the batch submitted to the appropriate authority with that certificate; and
such other documentation as the appropriate authority notifies the holder of the UK marketing authorisation to which the sample relates that it requires;
“approved country list for batch testing and certification of biological medicinal products” means the list described in paragraph (5), and “approved country for batch testing and certification of biological medicinal products” means a country included in that list;
“the batch testing condition”, in respect of a UK marketing authorisation, is a condition to the effect that, unless the batch testing exemption applies, the holder of the UK marketing authorisation—
must submit a sample from each batch of the medicinal product that is the subject of that authorisation to the appropriate authority, together with appropriate documentation; and
must not sell or supply, or offer to sell or supply, a medicinal product that forms part of that batch in the United Kingdom until the appropriate authority has examined—
the sample from that batch,
the appropriate documentation, or
both that sample and that documentation,
and confirmed that it is satisfied that the batch is in conformity with the approved specifications in the UK marketing authorisation; and
“the batch testing exemption” means that—
a certificate has been issued by a laboratory in a country other than the United Kingdom;
an agreement has been made between that country and the United Kingdom (whether or not the agreement is solely with that country, a group of countries or an organisation of which that country is a part); and
that agreement is to the effect that the appropriate authority will recognise that certificate in respect of the batch of the medicinal product, in place of the appropriate authority’s own examination of a sample from the batch, the appropriate documentation or both.
(2) The licensing authority may impose the batch testing condition in respect of a UK marketing authorisation for a medicinal product that is—
(a)a live vaccine;
(b)an immunological medicinal product used in the primary immunisation of infants or other groups at risk;
(c)an immunological product used in public health immunisation programmes;
(d)subject to paragraph (3), a new immunological product manufactured using new or altered kinds of technology or new for a particular manufacturer; or
(e)derived from human blood or human plasma.
(3) If the licensing authority imposes a condition in respect of a UK marketing authorisation for a medicinal product of a kind mentioned in paragraph (2)(d), it must, in imposing that condition, specify a period of time for the duration of the condition.
(4) The appropriate authority must complete its examination of the sample for testing, the appropriate documentation or both (as the case may be) within the period of 60 days, beginning with the date on which the appropriate authority is in receipt of both the sample for testing, and the appropriate documentation.
(5) The appropriate authority must publish a list, to be known as the approved country list for batch testing and certification of biological medicinal products, specifying the countries that are approved for the purposes of the appropriate authority’s assessment under paragraph (6).
(6) Where a holder of a UK marketing authorisation, in order to comply with the batch testing condition, submits appropriate documentation that includes a certificate issued by a laboratory in an approved country for batch testing and certification of biological medicinal products in respect of the batch, the appropriate authority must, in addition to any other factors it considers relevant, take that into account in determining whether the appropriate authority needs to undertake any further testing of the medicinal product submitted to it.
(7) In order to determine whether a country should be included in the approved country list for batch testing and certification of biological medicinal products, the appropriate authority may, in particular, take into account whether the relevant certification process in that country is based on testing performed under a quality assurance system that undergoes regular external assessment to ensure it meets an appropriate standard of competence for testing biological medicines.
(8) The appropriate authority must—
(a)review the countries it has included in the approved country list for batch testing and certification of biological medicinal products to determine if it is still satisfied that the country should remain on that list, and if it is not so satisfied, remove that country from the list; and
(b)undertake that review at least every three years beginning with the date on which that country is included in the list.
(9) The appropriate authority must—
(a)publish a list of countries, or organisations, with whom the United Kingdom has an agreement for the purposes of the application of the batch testing exemption;
(b)include in that list any conditions or restrictions in that agreement that affect the applicability of the batch testing exemption; and
(c)update that list as soon as reasonably practicable if—
(i)the United Kingdom no longer has an agreement with a country or organisation included in the list,
(ii)any such agreement is amended, or
(iii)the United Kingdom enters in to a new agreement with a country or organisation.
(10) Where a holder of a UK marketing authorisation relies on the batch testing exemption in relation to a batch of a medicinal product, that holder must submit the certificate in respect of that batch to the licensing authority and the appropriate authority, and such other documentation as those authorities may notify that holder they require, before it sells or supplies, or offers to sell or supply, a medicinal product that forms part of that batch in the United Kingdom.
(11) Paragraph (12) applies where the appropriate authority considers that there are public health concerns in respect of a batch of a medicinal product (“the relevant batch”) in relation to which the batch testing exemption would otherwise apply.
(12) Where this paragraph applies, the appropriate authority must, subject to paragraph (13), notify the holder of the UK marketing authorisation in respect of the relevant batch that it nevertheless requires that holder—
(a)to submit a sample from the relevant batch to the appropriate authority, together with appropriate documentation; and
(b)not to sell or supply, or to offer to sell or supply, a medicinal product that forms part of that batch in the United Kingdom until the appropriate authority has examined—
(i)the sample from that batch,
(ii)the appropriate documentation, or
(iii)both that sample and that documentation,
and confirmed that it is satisfied that the relevant batch is in conformity with the approved specifications in the UK marketing authorisation.
(13) The appropriate authority may only exercise its powers under paragraph (12) if the agreement made between the country in which the certificate was issued, and the United Kingdom (whether the agreement is solely with that country, a group of countries or an organisation of which that country is a part) provides for the relevant batch to be re-examined by the appropriate authority in the circumstances described in paragraph (11).”.
68.—(1) Regulation 61 is amended as follows.
(2) For paragraph (4), substitute—
“(4) The obligation in this paragraph is—
(a)to conduct a post-authorisation safety study; or
(b)to comply with such other conditions or restrictions as the licensing authority considers essential for the safe and effective use of the medicinal product.”.
(3) For paragraph (6) substitute—
“(6) If concerns as described in paragraph (2) apply to more than one medicinal product, the licensing authority—
(a)must, where the obligation is to conduct a post-authorisation safety study, encourage the UK marketing authorisation holders concerned to conduct a joint study; and
(b)may, where the obligation is to comply with any other conditions or restrictions, encourage the UK marketing authorisation holders concerned to take co-ordinated action to comply with the conditions or restrictions.”.
(4) For paragraph (7) substitute—
“(7) The obligation under paragraph (5) must—
(a)be based on the delegated acts adopted pursuant to Article 22b of the 2001 Directive; and
(b)take into account the scientific guidance that applies under regulation 205B in relation to post-authorisation efficacy studies
(7A) The Ministers may by regulations make provision specifying the situations in which post-authorisation efficacy studies may be required by virtue of the obligation under paragraph (5).
(7B) Paragraph (7)(a) ceases to apply on the coming into force of regulations made under paragraph (7A).”.
(5) Omit paragraph (13).
69. In regulation 64(4)(d), for “established in accordance with Articles 21a, 22 and 22a of the 2001 Directive” substitute “imposed under regulations 59 to 61”.
70. After regulation 64, insert—
64A.—(1) In this regulation, “classification”, in relation to a medicinal product, means the term of the product’s UK marketing authorisation which determines the way in which the product is to be made available, as described in regulation 62(1).
(2) This regulation applies where—
(a)the licensing authority grants or varies a UK marketing authorisation;
(b)the grant or variation of the UK marketing authorisation involves a change of the classification of the medicinal product to which the authorisation relates; and
(c)the application for the UK marketing authorisation or variation was supported by the results of significant pre-clinical tests or clinical trials relating to the proposed classification.
(3) Where this regulation applies, the licensing authority may not, for the period of one year beginning with the date on which the UK marketing authorisation was granted or varied, refer to the results of the tests or trials referred to in paragraph (2)(c) when examining an application by another applicant or UK marketing authorisation holder for a change of classification of the same kind as that to which the tests or trials relate.”.
71. In regulation 65(5) before sub-paragraph (a) insert—
“(za)regulation 65B;”.
72. After regulation 65A(62), insert—
65B.—(1) A conditional marketing authorisation remains in force—
(a)for an initial period of one year beginning with the date on which it is granted; and
(b)if it is renewed in accordance with regulation 66B, for further periods of one year beginning with the date on which the renewal is granted.
(2) If an application for the renewal or further renewal of a conditional marketing authorisation is made in accordance with regulation 66B the authorisation remains in force until the licensing authority notifies the applicant of its decision on the application.
65C.—(1) A UK marketing authorisation holder may apply to vary the authorisation.
(2) Any such application must be made in accordance with Schedule 10A.
(3) Schedule 10A does not apply to the transfer of a UK marketing authorisation from one person to another.
(4) The licensing authority may publish guidance on the details of the various categories of variations, on the operation of the procedures laid down in Schedule 10A, and on the documentation to be submitted pursuant to those procedures.
(5) Any guidance referred to in paragraph (4) must be regularly reviewed and, when necessary, updated.
(6) Unless replaced by guidelines published under paragraph (4), the guidelines published by the Commission under Article 4 of Regulation (EC) No 1234/2008(63) which applied immediately before exit day, insofar only as they concern applications under Chapter IIa of that Regulation, continue to apply to—
(a)applications made under regulation 65C on or after exit day; or
(b)applications made before exit day to which regulation 65C and Schedule 10A apply by virtue of Parts 3 and 5 of Schedule 33A.
(7) The Ministers may by regulations amend Schedule 10A.”.
73. Schedule 5 inserts a new Schedule 10A after Schedule 10.
74. In regulation 66(2), for “European Union” substitute “United Kingdom”.
75. In regulation 66A(2)(64), for “European Union” substitute “United Kingdom”.
76. After regulation 66A, insert—
66B.—(1) The licensing authority may renew a conditional marketing authorisation in relation to an application made to it by the holder of the authorisation.
(2) The application must be made at least six months before the date on which the conditional marketing authorisation is due to expire.
(3) The application must include an interim report on the fulfilment of the obligations to which the conditional marketing authorisation is subject.
(4) When considering an application under paragraph (1), the licensing authority must consider whether—
(a)the positive therapeutic effects of the product continue to outweigh the risks to the health of patients and the public associated with the product; and
(b)the obligations referred to in regulation 59(4C) and any time limits for their fulfilment remain appropriate, modifying or removing them if necessary.
(5) The provisions of regulation 66(2), (3), (4), (6) and (8) apply to an application for renewal of a conditional marketing authorisation.”.
77.—(1) Regulation 68(65) is amended as follows.
(2) In paragraph (5), after “exceptional circumstances)”, insert “, regulation 60A (conditions as to testing of samples by the appropriate authority)”.
(3) In paragraph (7)—
(a)after “authorisation” insert “or licence”; and
(b)for “European Union” substitute “United Kingdom”.
(4) In paragraph (8)(b), for “states other than EEA states” substitute “countries other than approved countries for import”.
(5) Omit paragraph (9).
(6) In paragraph (10)—
(a)in sub-paragraph (a) for “authorisation; or” substitute “authorisation or licence.”; and
(b)omit sub-paragraph (b).
(7) In paragraph (11)(a), after authorisation insert “or licence”.
(8) After paragraph (11A), insert—
“(11B) Condition L is that the licensing authority thinks that the term of the authorisation which specifies the way in which the product is to be made available, as described in regulation 62(1), is incorrect.
(11C) Condition M is that, in respect of a parallel import licence, the UK marketing authorisation in respect of the medicinal product that was specified in the application for that licence under paragraph 4 of Schedule 8A, has been varied, suspended or revoked by the licensing authority under this regulation.
(11D) Condition N is that, in respect of a parallel import licence, the licensing authority is no longer satisfied that the product is essentially similar to a product that has been granted a UK marketing authorisation.
(11E) The licensing authority may not exercise its powers under paragraph (1) by virtue of the condition in paragraph (11D)—
(a)before the end of the period of one year beginning with exit day; and
(b)in any event, in a way that prevents the import of any medicinal product in respect of which a qualified person undertook the certification referred to in Article 51(3) of the 2001 Directive before exit day.
(11F) Condition O is that the licensing authority thinks that a variation of a UK marketing authorisation is necessary as a result of the submission of the results of a study by the holder of that authorisation under regulation 78A(14).”.
(9) In paragraph (12)—
(a)after “UK marketing authorisation”, insert “or parallel import licence”; and
(b)after “an authorisation” insert “or licence”.
(10) Omit paragraph (13).
78. In regulation 69(66), omit paragraph (10).
79. Omit regulation 70.
80.—(1) Regulation 71(67) is amended as follows.
(2) In paragraph (1)—
(a)for sub-paragraph (a) substitute—
“(a)under regulation 68 the licensing authority revokes or suspends a UK marketing authorisation or parallel import licence; or”; and
(b)in sub-paragraph (b)—
(i)omit “or Article 20(4) of Regulation (EC) No 726/2004”; and
(ii)insert “UK” before “marketing authorisation”.
81. In regulation 72(1) omit “or 70(2) or Article 29(4) of Regulation (EC) No 726/2004”.
82.—(1) Regulation 73(68) is amended as follows.
(2) In paragraph (5A)(c), for “third country” substitute “country other than the United Kingdom”.
(3) Omit paragraph (5C).
83. In regulation 75(5)(69)—
(a)for sub-paragraph (a) substitute—
“(a)in a country other than the United Kingdom;” and
(b)in sub-paragraph (b), insert “UK” before “marketing authorisation”.
84. In regulation 76(2)(70) for the words from “European medicines web-portal” to the end, substitute “the UK web-portal established in accordance with regulation 203(1).”
85. In regulation 77, insert “UK” before “marketing authorisation”.
86. In regulation 78, insert “UK” before “marketing authorisation”.
87. After regulation 78, insert—
78A.—(1) Paragraph (2) applies where—
(a)a holder of a UK marketing authorisation intends to discontinue supply of the product to which that authorisation relates;
(b)the holder of the authorisation benefited from a reward or incentive under regulation 58A(3) or (8) or 58D(5) in relation to the product; and
(c)the period of protection provided pursuant to those regulations has expired.
(2) Where this paragraph applies, the holder of the UK marketing authorisation must—
(a)either—
(i)transfer the UK marketing authorisation to another person who has declared an intention to continue to supply the product; or
(ii)allow such a person to use the pharmaceutical, pre-clinical and clinical documentation contained in the file on that product in accordance with regulation 56; and
(b)notify the licensing authority of its intention to cease to supply the product before the beginning of the period of six months ending immediately before the day on which the holder does so.
(3) Paragraph (4) applies to the holder of a UK marketing authorisation if—
(a)that authorisation includes a paediatric indication following completion of an agreed paediatric investigation plan; and
(b)the product was placed on the market for other indications before that holder obtained that paediatric indication.
(4) Where this paragraph applies, the holder of the UK marketing authorisation must place the product on the market taking account of the paediatric indication before the end of the period of two years beginning immediately after the day on which the paediatric indication is authorised.
(5) Paragraph (6) applies if—
(a)a decision by the licensing authority in respect of a paediatric investigation plan is addressed to a person (“PIP sponsor”); and
(b)the plan refers to clinical trials carried out in a country other than the United Kingdom (“non-UK clinical trials”).
(6) Where this paragraph applies, the PIP sponsor must send to the licensing authority the details set out in Article 11 of the Clinical Trials Directive in relation to the non-UK clinical trials 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.
(7) Where paragraph (6) applies, the PIP sponsor must submit the results of those clinical trials to the licensing authority within the period of twelve months beginning with the day on which the last of those trials ended, subject to paragraph (8).
(8) Paragraph (7) does not apply in the case of a clinical trial which forms part of a paediatric study to which paragraph (12) applies.
(9) Paragraph (10) applies in relation to the sponsor 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 the sponsor is not the holder of the authorisation; or
(b)the product does not have a UK marketing authorisation.
(10) Where this paragraph applies, the sponsor of the clinical trial must submit the results of the trial to the licensing authority within the period of twelve months beginning with the day on which the trial ended.
(11) Paragraph (12) applies in relation to the holder of a UK marketing authorisation who sponsors a paediatric clinical trial in respect of the medicinal product to which that authorisation relates.
(12) Where this paragraph applies, the holder of the UK marketing authorisation must submit the results of the trial to the licensing authority within the period of six months beginning with the day on which the trial ended.
(13) Paragraph (14) applies in relation to the holder of a UK marketing authorisation who sponsors a study which involves the use in the paediatric population of a medicinal product to which that UK marketing authorisation relates, irrespective of whether or not—
(a)the studies are conducted in accordance with an agreed paediatric investigation plan; or
(b)the marketing authorisation holder intends to apply for a marketing authorisation for a paediatric indication in relation to the product.
(14) Where this paragraph applies, the holder of the UK marketing authorisation must submit the results of the study to the licensing authority within the period of six months beginning with the day on which the study ended.
(15) Where the licensing authority has granted a deferral of the initiation or completion of some or all of the measures set out in a paediatric investigation plan, in accordance with regulation 50C, the person to whom that decision was addressed must submit to the licensing authority an annual report providing an update on progress with the paediatric studies to which the deferral relates.
(16) The first report referred to in paragraph (15) must be submitted within the period of twelve months beginning with the date on which the licensing authority granted the deferral.
78B.—(1) The holder of a UK marketing authorisation in respect of an advanced therapy medicinal product must—
(a)establish and maintain a system ensuring that the individual product and its starting raw materials, including all substances coming into contact with the cells or tissues it may contain, can be traced through the sourcing, manufacturing, packaging, storage, transport and delivery to the hospital, institution or private practice where the product is used;
(b)where the product contains human tissues or cells, ensure that the traceability system is complementary to and compatible with requirements imposed pursuant to—
(i)as regards gametes and embryos, sections 12(3), and 33A to 33D of, and paragraph 1 of Schedule 3A to, the Human Fertilisation and Embryology Act 1990(71),
(ii)as regards blood cells, regulations 8, 9(e) and 14 of the Blood Safety and Quality Regulations 2005(72), and
(iii)as regards other cells and tissues, regulations 13 and 16 of, and paragraph 1 of Schedule 2 to, the Human Tissue (Quality and Safety for Human Application) Regulations 2007(73);
(c)keep the data referred to in paragraph (a) for a minimum of 30 years after the expiry of the date of the product, or longer if required by the licensing authority as a term of the UK marketing authorisation; and
(d)in the event of the UK marketing authorisation holder’s bankruptcy or liquidation occurring within the period of time for which that holder is required to keep the data referred to in paragraph (a), transfer that data to another person or the licensing authority.
(2) The holder of a UK marketing authorisation who is subject to the obligations in paragraph (1) remains subject to them even if the UK marketing authorisation is suspended or revoked.”.
88. Omit regulation 79.
89.—(1) Regulation 80 is amended as follows.
(2) In the introductory words, insert “UK” before “marketing authorisation”.
(3) In sub-paragraph (a) for “or the European Commission in accordance with Article 22(1) of Regulation (EC) No 1234/2008”substitute “in accordance with paragraph 14(1) of Schedule 10A”.
(4) In sub-paragraph (b) from “or the European Commission” to the end substitute “in accordance with paragraph 14(3) of Schedule 10A; or”.
(5) For sub-paragraph (c) substitute—
“(c)fails to submit an application for variation of the UK marketing authorisation to the licensing authority in accordance with paragraph 14(4) of Schedule 10A before the end of the period of fifteen days beginning with the day after—
(i)the taking under paragraph 14(1) of Schedule 10A or, as the case may be,
(ii)the imposition under paragraph 14(3) of that Schedule,
of an urgent safety restriction.”.
90. Omit regulations 81 to 94(74).
91. Omit regulation 94A(75).
92.—(1) Regulation 95 is amended as follows.
(2) In the introductory words, insert “UK” before “marketing authorisation”.
(3) Omit sub-paragraphs (c) and (d).
93.—(1) Regulation 96(76) is amended as follows.
(2) In paragraph (1)—
(a)insert “UK” before “marketing authorisation”; and
(b)omit sub-paragraphs (b) and (c).
(3) In paragraph (2), for “these Regulations; or” to the end substitute “these Regulations.”.
94.—(1) Regulation 97(77), is amended as follows.
(2) In each place where it occurs—
(a)for “a marketing authorisation” substitute “a UK marketing authorisation”; and
(b)for “the marketing authorisation” substitute “the UK marketing authorisation”.
(3) In paragraph (2), after “exceptional circumstances)” insert “, regulation 60A (condition as to the testing of samples by the appropriate authority)”.
95. In regulation 98(2)(a), insert “UK” before “marketing authorisation”.
96.—(1) Regulation 99 is amended as follows.
(2) In paragraph (1), omit “other than a breach of regulation 79 (failure to provide information on marketing authorisation to EMA)”.
(3) Omit paragraph (2).
97.—(1) Regulation 101(78) is amended as follows.
(2) In paragraph (1), insert “UK” before “marketing authorisation”.
(3) In paragraph (3), for “any of regulations 88 to 93,” substitute “either of regulations”.
98. In regulation 102 (application of Part 6), at the end insert—
“(7) The Ministers may by regulations amend paragraphs (4) to (6).
(8) The Ministers may only exercise the power in paragraph (7) if they consider that it is necessary to do so because of new scientific evidence.”.
99.—(1) Regulation 103 is amended as follows.
(2) In paragraph (4), for “European Union” substitute “United Kingdom”.
(3) In paragraph (8)—
(a)in sub-paragraph (e)—
(i)omit “or another EEA State”, and
(ii)for “that EEA State” substitute “a country other than the United Kingdom”; and
(b)in sub-paragraph (f), for “another member state” substitute “a country other than the United Kingdom”.
100. Omit regulation 104(5) and (6).
101. In regulation 108(2), for “European Union” substitute “United Kingdom”.
102.—(1) Regulation 110(79) is amended as follows.
(2) In paragraph (7), for “European Union” substitute “United Kingdom”.
(3) Omit paragraph (10).
103. Omit regulation 111.
104. In regulation 112(1), omit “or regulation 111(2)”.
105. In regulation 113(3A)(80), omit “in accordance with article 123(2) of the 2001 Directive”.
106. In regulation 115(5)(a) for “which is not an EEA State” substitute “other than the United Kingdom”.
107. In regulation 116(2) for “European” to the end substitute “UK web-portal established in accordance with regulation 203(1).”
108. For the italic heading “Application of Part”, substitute “Interpretation and application of Part”.
109. Before regulation 125 (traditional herbal medicinal products), insert—
124A. In this Part, “relevant list” means—
(a)the list referred to in Article 16f(1) of the 2001 Directive, as that list may be amended from time to time; or
(b)if the licensing authority publishes a list under regulation 126A(1), that list.”.
110. In regulation 125(5)(b), for “European Union” substitute “United Kingdom or a country included in the list published under regulation 125A(1)”.
111. After regulation 125 insert—
125A.—(1) The licensing authority may publish a list of countries for the purposes of regulation 125(5)(b) (condition D).
(2) In establishing the list under paragraph (1), the licensing authority may only include a country in that list if it is satisfied that—
(a)continuous use evidence in respect of that country can be sufficiently validated by the licensing authority; and
(b)the country has a level of pharmacovigilance that is equivalent to that in the United Kingdom to ensure that any safety issues in respect of the herbal medicinal product have been properly identified.
(3) The licensing authority must—
(a)review any list it publishes under paragraph (1) to determine if a country still satisfies the criteria for inclusion in the list specified in paragraph (2), and if it is not so satisfied, remove that country from the list; and
(b)undertake such a review at least every three years beginning with the date on which the country is included in that list.”.
112. After regulation 126 (addition of vitamins or minerals) insert—
126A.—(1) The licensing authority may establish, and publish a list of, herbal substances, preparations and combinations thereof for use in traditional herbal medicinal products.
(2) A list established under paragraph (1) must contain, with regard to each herbal substance—
(a)the indication;
(b)the specified strength and posology;
(c)the route of administration; and
(d)any other information necessary for the safe use of the herbal substance as a traditional medicinal product.
(3) The licensing authority may review and amend any list it publishes under paragraph (1) at such intervals as it considers appropriate.”.
113. In regulation 127(3), for “European Union” substitute “United Kingdom”.
114. In regulation 128(3), for “list referred to in Article 16f(1) of the 2001 Directive” substitute “relevant list”.
115.—(1) Schedule 12 is amended as follows.
(2) In paragraphs 16 and 17, for “another member State or a third country” substitute “a country other than the United Kingdom”.
(3) In paragraph 21—
(a)for “Article 23 of Regulation (EC) No 726/2004” substitute “regulation 202A”;
(b)before “statement”, insert “symbol and”; and
(c)before “This”, insert “▼”.
116.—(1) Regulation 130 is amended as follows.
(2) In paragraph (6), insert “UK” before “marketing authorisation”.
(3) In paragraph (7), for “Article” to the end substitute “regulation 130A.”.
(4) In paragraph (8), for “list referred to in Article 16f(1) of the 2001 Directive” substitute “relevant list”.
(5) Omit paragraph (9).
(6) In paragraph (10)(a) for “Article 16h(3) of the 2001 Directive” substitute “regulation 143A”.
(7) Omit paragraphs (12) and (13).
117. After regulation 130 (consideration of application) insert—
130A.—(1) Where an application for a traditional herbal registration has been made and the licensing authority considers that—
(a)the traditional herbal medicinal product does not satisfy regulation 125(5)(b) (Condition D); but
(b)otherwise satisfies the conditions in regulation 125,
the licensing authority may refer the matter to the appropriate committee for relevant advice, and the procedure in Part 3 of Schedule 11 applies (referral to the appropriate committee for traditional herbal registrations).
(2) In this regulation—
“appropriate committee” has the same meaning as in paragraph 2(4) of Schedule 11;
“relevant advice” means advice as to whether—
the conditions in regulation 125, other than condition D, are met in relation to the application; and
the licensing authority should exercise its powers under regulation 143A to establish a herbal monograph.”.
118. In regulation 133(2), for “European Union” substitute “United Kingdom”.
119.—(1) Regulation 135(81) is amended as follows.
(2) In paragraph (7)(b), for “from states other than EEA States” substitute “countries other than approved countries for import”.
(3) Omit paragraph (8).
(4) In paragraph (9), omit sub-paragraph (b) (and the “and” immediately preceding it).
(5) Omit paragraph (11).
120.—(1) Regulation 136 is amended as follows.
(2) In paragraph (1)(a), for “list referred to in article 16f(1) of the 2001 Directive” substitute “relevant list”.
(3) Omit paragraph (3).
121. Omit regulation 138(10).
122. Omit regulation 139.
123. In regulation 140(1)(a), for “regulation 135, 136, 139(2) or Article 34(3) of the 2001 Directive” substitute “regulation 135 or 136”.
124. In regulation 141(1), omit “or 139(2)”.
125. Omit regulation 142(5C)(82).
126. After regulation 143 (obligation to take account of scientific or technical progress) insert—
143A.—(1) The licensing authority may establish herbal monographs for herbal medicinal products and traditional herbal medicinal products.
(2) Subject to paragraph (3), the licensing authority must—
(a)consult the appropriate committee, within the meaning of paragraph 2(4) of Schedule 11, on a proposal to establish herbal monographs under paragraph (1); and
(b)take the advice of the appropriate committee into account in determining whether to proceed with that proposal.
(3) Where an application for a traditional herbal registration has been referred to the appropriate committee by the licensing authority under regulation 130A, the licensing authority must consider whether to exercise its powers under paragraph (1), taking into account any relevant advice of the appropriate committee given under Part 3 of Schedule 11 in relation to that application.
(4) The licensing authority must publish a list of any herbal monographs established under this regulation.
(5) Until the licensing authority exercises the power under paragraph (1), the Community herbal monographs published from time to time under Article 16h(3) of the 2001 Directive continue to apply, and holders of a traditional herbal registration and the licensing authority must continue to take them into account in exercising any function or in relation to any obligation to which they are relevant under this Part.”.
127. In regulation 144, for “Article 16h(3) of the 2001 Directive” substitute “regulation 143A”.
128. In regulation 145(5)(a), for “which is not an EEA State” substitute “other than the United Kingdom”.
129. In regulation 146(2), for “European” to the end substitute “the UK web-portal established in accordance with regulation 203(1).”
130. After regulation 148 (obligation to ensure appropriate and continued supplies) insert—
148A.—(1) Where, in the event of a risk to public health, the holder of a traditional herbal registration takes urgent safety restrictions on its own initiative, it must inform the licensing authority immediately.
(2) If the licensing authority has not raised objections within 24 hours following receipt of that information, the urgent safety restrictions are deemed to be accepted by the licensing authority.
(3) In the event of a risk to public health, the licensing authority may impose urgent safety restrictions.
(4) Where an urgent safety restriction is taken by the holder of a traditional herbal registration, or imposed by the licensing authority, the holder must submit an application for variation of that registration in relation to that restriction within 15 days beginning with the date of the initiation of that restriction.”.
131.—(1) Regulation 149 is amended as follows.
(2) In the heading to regulation 149, at the end insert “: offences”.
(3) In sub-paragraph (a), for “or the European Commission in accordance with Article 22(1) of Regulation (EC) No 1234/2008” substitute “in accordance with regulation 148A(1)”.
(4) In sub-paragraph (b), for “or the European Commission under Article 22(2) of that Regulation” substitute “in accordance with regulation 148A(2)”.
(5) For sub-paragraph (c), substitute—
“(c)fails to submit an application for variation of the traditional herbal registration to the licensing authority in accordance with regulation 148A(4) before the end of the period of 15 days beginning with the day after—
(i)the taking under regulation 148A(1), or
(ii)the imposition under regulation 148A(2),
of an urgent safety restriction.”.
132. Omit Part 8.
133. In regulation 159(1)—
(a)insert “UK” before “marketing authorisation”; and
(b)for “, certificate of registration or Article 126a authorisation” substitute “or certificate of registration”.
134. In regulation 164(2)(a) and (b)—
(a)insert “UK” before “marketing authorisation”; and
(b)for “, certificate of registration or Article 126a authorisation” substitute “or certificate of registration”.
135. In regulation 168, in paragraph (8)—
(a)in sub-paragraph (a), for “EEA State” substitute “approved country for import”; and
(b)for sub-paragraph (b) substitute—
“(b)imported from an approved country for import—
(i)it is manufactured or assembled in that country by a person who is the holder of an authorisation in that country in relation to its manufacture or assembly, and
(ii)it is imported by the holder of a wholesale dealer’s licence under Part 3 that includes the import of a medicinal product from such a country.”.
136. In regulation 169(9)(a), insert “UK” before “marketing authorisation”.
137. In paragraph regulation 171(2)(c) for “Regulation (EC) No 726/2004” substitute “regulation 49(1)”.
138. In regulation 173(c), insert “UK” before “marketing authorisation”.
139.—(1) Regulation 177(83) is amended as follows.
(2) In paragraph (1)—
(a)for “Schedule 33”, substitute “Schedules 12A and 33”;
(b)omit “, except to the extent set out in paragraph (4)(b),”;
(c)in sub-paragraph (a), at the end insert “or”;
(d)omit sub-paragraph (c) (and “or” immediately preceding it).
(3) In paragraph (2)—
(a)after “this Part” insert “and Schedule 12A”;
(b)in sub-paragraph (a), insert “or” at the end;
(c)omit sub-paragraph (c) (and “or” immediately preceding it).
(4) In paragraph (3)—
(a)for “Schedule 33” substitute “Schedules 12A and 33”;
(b)in sub-paragraph (a), at the end insert “or”;
(c)omit sub-paragraph (c) (and “or” immediately preceding it).
(5) Omit paragraph (4).
(6) In paragraph (5), omit the definitions of “co-ordination group”, “Eudravigilance database”, “Implementing Regulation” and “relevant competent authorities”.
140.—(1) Regulation 180 is amended as follows.
(2) In paragraph (1), omit “and report the results of that audit to the European Commission”.
(3) In paragraph (2)—
(a)omit “results of the”; and
(b)for “reported to the European Commission” substitute “performed”.
141. Omit regulation 181.
142.—(1) Regulation 182(84) is amended as follows.
(2) In paragraph (2)(a), for “resides and operates in the EU” substitute “is ordinarily resident, and operates, in the United Kingdom”.
(3) In paragraph (3), insert at the beginning “Without prejudice to the requirements set out in regulation 65C and Schedule 10A (variations to a UK marketing authorisation)”.
(4) Omit paragraph (6).
143. In regulation 184, after paragraph (2) insert—
“(3) The holder must also comply with the requirements of paragraph 13 of Schedule 12A in relation to auditing the pharmacovigilance system.”.
144. In regulation 185(b), after “by” insert “a holder,”.
145. In regulation 186(1)—
(a)at the end of sub-paragraph (a) insert “and”; and
(b)omit sub-paragraphs (c) to (e).
146. After regulation 186 insert—
“186A. The licensing authority must collaborate with the World Health Organisation in matters of pharmacovigilance, and must in particular—
(a)take the necessary steps to promptly submit to the World Health Organisation appropriate and adequate information regarding the measures taken in the United Kingdom which may have a bearing on public health protection in other countries; and
(b)make available promptly all suspected adverse reaction reports occurring in the United Kingdom to the World Health Organisation.”.
147.—(1) Regulation 187 is amended as follows.
(2) In paragraph (1), for “in the EEA or in third countries” substitute “in the United Kingdom or another country”.
(3) In paragraph (4), for “EEA” substitute “United Kingdom”.
148.—(1) Regulation 188 is amended as follows.
(2) In each place where it occurs, for “Eudravigilance database” substitute “licensing authority”.
(3) In paragraph (1)—
(a)in sub-paragraph (a)—
(i)for “EEA” substitute “United Kingdom”, and
(ii)for “third countries” substitute “countries other than the United Kingdom”;
(b)in sub-paragraph (b), for “EEA” substitute “United Kingdom”;
(c)in sub-paragraph (e), for “EMA and the competent authorities of the EEA States” substitute “licensing authority”.
(4) Omit paragraphs (2) and (3).
(5) In paragraph (4)(a), omit “other than monitored publications”.
(6) In paragraph (5), omit the definitions of “monitored active substance” and “monitored publication”.
(7) Omit paragraph (6).
149.—(1) Regulation 189 is amended as follows.
(2) In paragraph (1)—
(a)in sub-paragraph (a), for “in the Eudravigilance database” substitute “that it collects by virtue of operating its pharmacovigilance system under this Part”; and
(b)in sub-paragraph (d), for “regulations 59 to 61” substitute “regulations 59, 60 and 61”.
(3) Omit paragraphs (2) to (4).
150. In regulation 190(1), omit “the EMA and”.
151.—(1) Regulation 191 is amended as follows.
(2) In paragraphs (1) and (7), for “EMA” substitute “licensing authority”.
(3) In paragraph (2), insert “UK” before “marketing authorisation”.
(4) In paragraph (3), omit—
(a)“or an Article 126a authorisation” in both places it appears; and
(b)“or Article 126a authorisation”.
(5) After paragraph (4) insert—
“(4A) A PSUR must also include the content, and be submitted in the format, specified in Part 8 of Schedule 12A.”.
(6) After paragraph (8), insert—
“(8A) In the case of a conditional marketing authorisation, the holder must submit PSURs immediately upon the request of the licensing authority and at least every six months beginning with the date on which the authorisation for the medicinal product is granted or renewed by the licensing authority.”.
(7) In paragraph (10), for “within the EEA” in each place it appears substitute “in the United Kingdom”.
(8) Omit paragraph (11).
152.—(1) Regulation 192 is amended as follows.
(2) In paragraph (1)(a), insert “UK” before “marketing authorisation”.
(3) In paragraph (3), for “EMA” substitute “licensing authority”.
(4) Omit paragraphs (9) to (11).
153.—(1) Regulation 193 is amended as follows.
(2) Omit paragraph (1)(a).
(3) For paragraph (2) substitute—
“(2) Where one or more of the grounds in paragraph (3) is met, the holder may submit a request in writing to the licensing authority, or the licensing authority may in any event decide, to—
(a)determine a UK reference date from which submission dates are calculated in respect of products that fall under paragraph (1); or
(b)change the frequency and date of submission of the PSUR.”.
(4) For paragraph (4) substitute—
“(4) Where the licensing authority makes a decision under paragraph (2) following a written request from a holder, it must notify that holder in writing of its decision to approve or refuse the request.”.
(5) In paragraph (5)—
(a)for “Article 107c(4) or Article 107c(6) of the 2001 Directive” substitute “paragraph (2)”; and
(b)for “EMA” substitute “licensing authority”.
(6) For paragraph (6) substitute—
“(6) Subject to paragraph (6A), in this regulation, “UK reference date” means a date determined by the licensing authority under paragraph (2)(a) in respect of medicinal products containing the same active substance or the same combination of active substances.
(6A) Until the licensing authority makes a decision under paragraph (2), any—
(a)Union reference date in respect of medicinal products containing the same active substance or the same combination of active substances; or
(b)date of submission and frequency of periodic safety reports in respect of such products,
published by the EMA under Article 107c(7) of the 2001 Directive, is deemed to be the UK reference date or, as the case may be, the required date or frequency of PSUR submission, in respect of those medicinal products.”.
(7) After paragraph (6A) insert—
“(7) The licensing authority must publish a list of—
(a)UK reference dates it determines under paragraph (2); and
(b)the required date of submission and frequency for PSURs in respect of medicinal products containing the same active substance or the same combination of active substances.
(8) Any change to the date of submission and frequency of PSURs as a result of the application of this regulation is to take effect after a 6 month period, such period beginning with the day after the licensing authority publishes that change under paragraph (7).”.
154. Omit regulation 194.
155.—(1) Regulation 195(85) is amended as follows.
(2) In the heading, omit “where EU single assessment procedure does not apply”.
(3) For paragraph (1) substitute—
“(1) This regulation applies where PSURs relating to a medicinal product have been submitted to the licensing authority under regulations 191 to 192.”.
(4) After paragraph (3) insert—
“(3A) If the licensing authority considers under paragraph (3)(b) that an authorisation or registration needs to be varied, it may require the holder to submit to the licensing authority, within a time period that the licensing authority specifies, an application for a variation, including—
(a)an updated summary of the product characteristics; and
(b)an updated package leaflet.”.
(5) In paragraph (4), omit the definitions of “EU reference date” and “EU single assessment procedure”.
156. For regulation 196(86) and the italic heading immediately preceding it substitute—
196.—(1) The licensing authority may conduct a major safety review where—
(a)on the basis of concerns resulting from the evaluation of data from pharmacovigilance activities it considers—
(i)suspending or revoking a UK marketing authorisation or traditional herbal registration of a medicinal product or in respect of a class of medicinal products,
(ii)prohibiting the supply of a medicinal product or a class of medicinal products,
(iii)refusing the renewal of a UK marketing authorisation or traditional herbal registration, or
(iv)action is necessary to vary a UK marketing authorisation or traditional herbal registration or a class of such authorisations or registrations, including to impose new conditions; or
(b)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 to which a UK marketing authorisation or traditional herbal registration relates,
(ii)taken action to have that product’s authorisation or registration cancelled or intends to do so, or
(iii)not applied for the renewal of that product’s authorisation or registration.
(2) If the licensing authority conducts a review under paragraph (1), it must—
(a)announce the initiation of that review on the UK web-portal as soon as reasonably practicable;
(b)include in that announcement—
(i)an outline of its reasons for conducting a major safety review, the medicinal products concerned and, where applicable, the active substances concerned, and
(ii)the proposed structure and time-scale of the review;
(c)notify a holder if the product to which that holder’s authorisation or registration relates is within the scope of the review; and
(d)publish the outcome of that review, including any recommendations it is making, or action it is proposing to take, as soon as reasonably practicable after the conclusion of that review.
(3) A holder who is notified under paragraph (2)(c)—
(a)must provide to the licensing authority such information as the licensing authority notifies that holder it requires, within such time period as the licensing authority specifies; and
(b)may, where such information contains confidential data relevant to the subject matter of the review, because the data relates to a manufacturing process or trade secret, notify the licensing authority that that data is provided in confidence.
(4) Where the licensing authority proposes that action should be taken in respect of any UK marketing authorisation or traditional herbal registration—
(a)during the conduct of the major safety review, because urgent action is necessary to protect public health; or
(b)upon the conclusion of such a review,
it may exercise its powers under Part 5 or 7 (as the case may be) in relation to that authorisation or registration.”.
157. Omit regulation 197.
158.—(1) Regulation 198 is amended as follows.
(2) In paragraph (2), for “competent authorities of the EEA States in which the study is conducted” substitute “licensing authority”.
(3) In paragraph (3)—
(a)in sub-paragraph (c), for “relevant competent authorities” substitute “licensing authority”;
(b)in sub-paragraph (d), for “competent authorities of the EEA States in which the study was conducted” substitute “the licensing authority if the study is conducted in the United Kingdom”.
159.—(1) Regulation 199 is amended as follows.
(2) In paragraph (2), for “body specified in paragraph (3)” substitute “licensing authority”.
(3) Omit paragraphs (3) and (4).
(4) In paragraph (5), omit “Where this paragraph applies”.
(5) In paragraph (6), omit sub-paragraph (b) (and “or” immediately preceding it).
(6) Omit paragraphs (7) and (8).
160.—(1) Regulation 200 is amended as follows.
(2) In paragraph (2), for “body specified in paragraph (3)” substitute “licensing authority”.
(3) Omit paragraphs (3) and (4).
(4) In paragraph (5), omit “Where this paragraph applies”.
(5) Omit paragraphs (6) and (7).
161.—(1) Regulation 201 is amended as follows.
(2) In paragraph (2), for “body specified in paragraph (3)” substitute “licensing authority”.
(3) Omit paragraph (3).
(4) In paragraph (4), omit from “for reports” where it first appears to the end.
162. Omit regulation 202.
163. After regulation 202 insert—
202A.—(1) The licensing authority may establish a list of medicinal products that are subject to additional monitoring.
(2) The list referred to in paragraph (1) is to include the names and active substances of—
(a)medicinal products authorised in the United Kingdom that contain a new active substance which, on 1st January 2011, was not contained in any medicinal product authorised in the United Kingdom;
(b)any biological medicinal product not covered by sub-paragraph (a) that was authorised in the United Kingdom after 1st January 2011;
(c)medicinal products that are authorised pursuant to these Regulations, subject to the conditions referred to in regulation 50I, 59(2)(b) or (c), 60 or 61(4).
(3) If the licensing authority considers it appropriate, medicinal products that are authorised pursuant to these Regulations, subject to the conditions referred to in regulation 59(2)(a), (d), (e) or (f), 61(5) or 183(2), may also be included in the list referred to in paragraph (1).
(4) For medicinal products included in the list referred to in paragraph (1)—
(a)the summary of product characteristics and the package leaflet must include a symbol and statement as follows: “▼ This medicinal product is subject to additional monitoring”; and
(b)that symbol must be proportional to the font of the subsequent standardised text, and each side of the triangle must have a minimum length of 5 millimetres.
(5) In the cases referred to in paragraph (2)(a) and (b), the licensing authority must, unless paragraph (6) applies, remove a medicinal product from the list after five years, beginning with the day after the UK reference date referred to in regulation 193.
(6) In the cases referred to in paragraph (2)(c) and (3), the licensing authority must remove a medicinal product from the list once the condition or obligation under a provision specified in those paragraphs has been fulfilled.
(7) Until the licensing authority publishes a list of medicinal products under paragraph (1), the reference to that list is instead to be read as a reference to the list referred to in Article 23 of Regulation (EC) No 726/2004, as that list may be amended from time to time.”.
164.—(1) Regulation 203 is amended as follows.
(2) In paragraph (1), omit from “linked” to the end.
(3) In paragraph (2)—
(a)in sub-paragraph (e) for “Article 23 of Regulation (EC) No 726/2004” substitute “the list published by the licensing authority under, or which applies by virtue of, regulation 202A”; and
(b)in sub-paragraph (f), omit “(including by way of the web-based forms referred to in Article 25 of Regulation (EC) No 725/2004”.
165. Omit regulation 204.
166.—(1) Regulation 205 is amended as follows.
(2) In paragraph (2), for “bodies listed in paragraph (3)” substitute “licensing authority”.
(3) Omit paragraph (3).
167. After regulation 205 insert—
205A.—(1) Schedule 12A makes further provision as to the obligations of a holder and the licensing authority in respect of the performance of pharmacovigilance activities under this Part.
(2) The Ministers may by regulations amend Schedule 12A.
(3) Regulations under paragraph (2) may make provision regarding the performance of pharmacovigilance activities under this Part as to—
(a)the content and maintenance of the pharmacovigilance system master file kept by the holder;
(b)the minimum requirements for the quality system for the performance of pharmacovigilance activities by the holder and the licensing authority;
(c)the use of internationally agreed terminology, formats and standards for the performance of pharmacovigilance activities;
(d)the minimum requirements for the monitoring of data recorded by the licensing authority pursuant to regulation 185 (recording obligations on the licensing authority) to determine whether there are new risks or whether risks have changed;
(e)the format and content of electronic transmission of suspected adverse reactions by a holder;
(f)the format and content of electronic periodic safety reports and risk management plans; and
(g)the format of protocols, abstracts and final study reports for the post-authorisation safety studies.”.
168. Schedule 6 inserts a new Schedule 12A after Schedule 12 to the 2012 Regulations.
169. After new regulation 205A insert—
205B.—(1) The licensing authority may publish—
(a)guidance on good pharmacovigilance practices for both the licensing authority and UK marketing authorisation holders;
(b)scientific guidance on post authorisation efficacy studies.
(2) Subject to paragraph (3), the guidance issued by the Commission under Article 108a of the 2001 Directive on the matters specified in paragraph (1)(a) and (b) continues to apply until the date on which the licensing authority publishes guidance under paragraph (1).
(3) The licensing authority—
(a)may determine that provisions of the guidance specified in paragraph (2) no longer apply, or apply subject to specified modifications, from a date that it specifies; and
(b)must, if it so determines, publish its determination.
(4) Guidance published under paragraph (1), or which applies by virtue of paragraph (2) (as modified by any determination under paragraph (3), as the case may be), is to be taken into account in consideration of whether there has been any failure to comply with a provision in this Part, or Schedule 12A, to which the guidance is relevant.”.
170.—(1) Regulation 206(87) is amended as follows.
(2) In paragraph (1)—
(a)omit “relevant”; and
(b)after “provision” insert “of this Part or Schedule 12A (“relevant provision”).
(3) Omit paragraphs (3) and (4).
171. In regulation 207(1), after “other than” insert “Schedule 12A (further requirements in respect of pharmacovigilance activities) and”.
172. In regulation 208, omit “or the EMA”.
173. In regulation 209(3), omit sub-paragraphs (h) and (i).
174. Omit regulation 210(88).
175.—(1) Regulation 210A(89) is amended as follows.
(2) In the heading, for “the Implementing Regulation” substitute “Schedule 12A”.
(3) In paragraph (1)—
(a)in sub-paragraph (a) for “the Implementing Regulation” substitute “Schedule 12A”; and
(b)in sub-paragraph (b)—
(i)for “the Implementing Regulation” substitute “Schedule 12A”, and
(ii)omit “or the EMA”.
(4) For paragraph (2) substitute—
“(2) The provisions of Schedule 12A mentioned in paragraph (1)(a) are—
(a)Part 1 (pharmacovigilance system master file);
(b)Parts 2 and 3 (minimum requirements for the quality systems in the performance of pharmacovigilance activities);
(c)Part 6 (transmission of reports of suspected adverse reactions);
(d)paragraph 24 (update of risk management plans);
(e)Part 8 (periodic safety update reports); and
(f)Part 9 (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 paragraph 26(8) or 29(1) of Schedule 12A 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.”.
176. In regulation 211, omit from first “or” to “No 726/2004)”.
177. In regulation 212, for “182, 186, 188, 191, 192, 198, 199, 200, 201, 202 and 210” substitute “198, 199, 200, 201 and 202”.
178. In Schedule 33, omit paragraphs 1, 2 and 4 to 10.
179. In regulation 213(1)(90)—
(a)insert at the appropriate place—
““approved country health professional” means a person who is practising in a profession included in the list published under regulation 214(6A) in a country that is included in that list in relation to that profession;”;
(b)omit the definition of “EEA health professional”(91); and
(c)in the definition of “relevant prescriber”, for “EEA health professional” substitute “approved country health professional”.
180.—(1) Regulation 214(92) is amended as follows.
(2) In paragraph (2)(a), for “EEA health professional” substitute “approved country health professional”.
(3) In paragraph (6), for “EEA health professional” substitute “approved country health professional”.
(4) After paragraph (6) insert—
“(6A) The licensing authority must publish a list of approved countries and professions for the purposes of the definition of “approved county health professional”.
(6B) In order to determine whether a country or profession should be included in the list published under paragraph (6A), the licensing authority may, in particular, take into account—
(a)the country’s standards of professional qualification;
(b)the country’s system for ensuring that qualified professionals have undergone training which meets the requirements that apply in that country;
(c)the effectiveness of enforcement of professional standards;
(d)the mechanisms the country has in place to assist members of the public in obtaining information in respect of a qualified professional who is established there; and
(e)the regularity and rapidity of information provided by that country relating to non-compliant professionals.
(6C) The licensing authority must—
(a)review a country or profession it has included in the list published under paragraph (6A) to determine if it is still satisfied that they should remain on the list, and if it is not so satisfied, remove it from that list; and
(b)undertake such a review at least every 3 years beginning with the date on which that country or profession was included in that list.”.
181. In regulation 216(2), for “EEA health professional” substitute “approved country health professional”.
182. In regulation 217(8)(a)(93), for “EEA health professional” substitute “approved country health professional”.
183.—(1) Regulation 217A(94) is amended as follows.
(2) In the heading, omit “other than the UK”.
(3) In paragraph (2)(a), omit “other than the UK”.
184.—(1) Regulation 218(95) is amended as follows.
(2) In the heading, and each place where it subsequently occurs, for “EEA health professional” substitute “approved country health professional”.
(3) In paragraph (5)(c) and (d)(ii)(bb), for “EEA health professional’s” substitute “approved country health professional’s”.
(4) In paragraph (2)(a), for “relevant European State except the United Kingdom” substitute “country included in the list published under regulation 214(6A)”.
185. In regulation 219(2)(96), for “EEA health professional” substitute “approved country health professional”.
186.—(1) Regulation 219A(97) is amended as follows.
(2) In the heading, for “EEA health professionals” substitute “approved country health professionals”.
(3) In paragraph (2), for “EEA health professional” substitute “approved country health professional”.
187. In regulation 229(3)(f)(98), for “marketing authorisation, Article 126a authorisation” substitute “UK marketing authorisation”.
188. In regulation 230(8)(99), for “marketing authorisation, Article 126a authorisation” substitute “UK marketing authorisation”.
189. In regulation 231(8), for “marketing authorisation, Article 126a authorisation” substitute “UK marketing authorisation”.
190. In regulation 232(8), for “marketing authorisation, Article 126a authorisation” substitute “UK marketing authorisation”.
191. In regulation 233(7)(100), for “marketing authorisation, Article 126a authorisation” substitute “UK marketing authorisation”.
192. In regulation 234(9)(101), for “marketing authorisation, Article 126a authorisation” substitute “UK marketing authorisation”.
193.—(1) Schedule 17(102) is amended as follows.
(2) In the table in Part 1, in column 1 in entry 10, insert “UK” before “marketing authorisations”.
(3) In the table in Part 4, in columns 1 and 2 in entry 9, insert “UK” before “marketing authorisation”.
194. In regulation 249(2)—
(a)in sub-paragraph (a), insert “UK” before “marketing authorisation”;
(b)in sub-paragraph (b), insert “and” at the end; and
(c)omit sub-paragraph (d) (and “and” immediately preceding it).
195. In regulation 254(2)(a), for the words from “laid down in” to the end, substitute—
“imposed pursuant to—
(a)as regards gametes and embryos, sections 12(3), and 33A to 33D of, and paragraph 1 of Schedule 3A to, the Human Fertilisation and Embryology Act 1990(103);
(b)as regards blood cells, regulations 8, 9(e) and 14 of the Blood Safety and Quality Regulations 2005(104); and
(c)as regards other cells and tissues, regulations 13 and 16 of, and paragraph 1 of Schedule 2 to, the Human Tissue (Quality and Safety for Human Application) Regulations 2007(105);”.
196. Omit regulations 255A to 255C(106).
197. Part 12A(107) is omitted.
198.—(1) Regulation 257 is amended as follows.
(2) In paragraph (6), after “this regulation,” insert “regulation 257C,”.
(3) After paragraph (7) insert—
“(8) Nothing in this regulation applies to the outer or immediate packaging of an advanced therapy medicinal product.”.
199. Omit regulations 257A and 257B(108).
200. After regulation 257, insert—
257C.—(1) The information specified in Part 4 of Schedule 24 must appear—
(a)on the outer packaging of an advanced therapy medicinal product (other than an exempt advanced therapy medicinal product); and
(b)on the immediate packaging of the product, unless paragraph (2) or (3) applies to the packaging.
(2) This paragraph applies to the immediate packaging if the packaging is in the form of a blister pack and is placed in outer packaging which complies with the requirements of Part 4 of Schedule 24.
(3) This paragraph applies to immediate packaging if the packaging is too small to display the information required by Part 4 of Schedule 24.
(4) The information specified in Part 5 of Schedule 24 must appear on immediate packaging to which paragraph (2) or (3) applies.
257D.—(1) The licensing authority may publish guidance on packaging and package leaflets which may, in particular, include—
(a)the wording of certain special warnings for certain categories of medicinal products;
(b)the particular information needs relating to products that are a pharmacy medicine;
(c)the legibility of particulars on the labelling and package leaflet;
(d)the methods of identification and authentication of medicinal products;
(e)the list of excipients which must feature on the labelling of medicinal products and the way in which these excipients must be indicated.
(2) Until such time as the licensing authority publishes guidance under paragraph (1), any guidance published by the Commission under Article 65 of the 2001 Directive, insofar as that guidance was in force immediately before exit day(109), continues to apply as if it had been published by the licensing authority under paragraph (1).
257E. The Ministers may by regulations require the use of certain forms of labelling of a medicinal product in order to make it possible to ascertain—
(a)the price of the medicinal product;
(b)any reimbursement conditions of the National Health Service;
(c)the legal status for supply to the patient in accordance with regulation 5 (classification), insofar as not already provided for in Schedule 25;
(d)authenticity and identification of the medicinal product in accordance with Article 54a(5) of the 2001 Directive.”.
201.—(1) Schedule 24 is amended as follows.
(2) In paragraph 7(b), for “published pursuant to Article 65 of the 2001 Directive” substitute “published under regulation 257D”.
(3) In paragraphs 15, 16 and 23, for “marketing authorisation, Article 126a authorisation” substitute “UK marketing authorisation”.
(4) Omit paragraph 18A(110).
(5) After Part 3 insert—
34. The name of the advanced therapy medicinal product which is the international non-proprietary name, or if none, the common name.
35. Where appropriate, whether the product is intended for babies, children or adults.
36. The expiry date in clear terms including the year and month and, if applicable, day.
37. A description of the active substance, expressed qualitatively and quantitatively.
38. Where the product contains tissues and cells of human or animal origin—
(a)a statement that the product contains such cells or tissues; and
(b)a short description of the cells or tissues and of their specific origin, including the species of animal in cases on non-human origin.
39. The pharmaceutical form and the contents by weight, volume or number of doses of the product.
40. A list of excipients, including preservative systems.
41. The method of use, application, administration or implantation and, if appropriate, the route of administration, with space provided for the prescribed dose to be indicated.
42. A special warning that the product is to be stored out of the sight and reach and children.
43. Any special warning necessary for the particular product.
44. Any special storage precautions.
45. Specific precautions relating to the disposal of the unused product or of waste derived from the product and, where appropriate, reference to any appropriate collection system.
46. The name and address of the holder of the UK marketing authorisation and, where applicable, the name of the representative appointed by the holder to represent him.
47. The UK marketing authorisation number.
48. The manufacturer’s batch number.
49. The unique donation code assigned by a tissue establishment pursuant to—
(a)paragraph 1 of Schedule 3A to the Human Fertilisation and Embryology Act 1990(111), as regards human gametes and embryos; and
(b)paragraph 1 of Schedule 2 to the Human Tissue (Quality and Safety for Human Application) Regulations 2007(112), as regards other human tissues and cells.
50. Where the exempt advanced therapy medicinal product is for autologous use, the unique patient identifier and the words “for autologous use only”.
51. The information specified in Part 2.
52. The unique donation code assigned by a tissue establishment pursuant to—
(a)paragraph 1 of Schedule 3A to the Human Fertilisation and Embryology Act 1990, as regards human gametes and embryos; and
(b)paragraph 1 of Schedule 2 to the Human Tissue (Quality and Safety for Human Application) Regulations 2007, as regards other human tissues and cells.
53. Where the exempt advanced therapy medicinal product is for autologous use, the unique patient identifier and the words “for autologous use only”.”
202. In regulation 259(2), for “marketing authorisation, Article 126a authorisation” substitute “UK marketing authorisation”.
203.—(1) Regulation 260 is amended as follows.
(2) After paragraph (1) insert—
“(1A) If the medicinal product is an advanced therapy medicinal product (other than an exempt advanced therapy medicinal product), the package leaflet must contain the information specified in Part 3 of Schedule 27 in the order specified in that Part.”.
(3) In paragraph (2), after “Part 2 of that Schedule)” insert “, or where the product is an advanced therapy medicinal product, the information specified in Part 3 of that Schedule,”.
(4) In paragraph (3), for “marketing authorisation, Article 126a authorisation” substitute “UK marketing authorisation”.
204.—(1) Schedule 27(113) is amended as follows.
(2) In paragraph 8(c)(ii), for “Article 65 of the 2001 Directive”, substitute “published under regulation 257D”.
(3) In paragraph 11(f), for “marketing authorisation, Article 126a authorisation” substitute “UK marketing authorisation”.
(4) Omit paragraph 12.
(5) In paragraph 13—
(a)for “Article 23 of Regulation (EC) No 726/2004” substitute “regulation 202A”;
(b)before “statement”, insert “symbol and”; and
(c)before “This”, insert “▼”.
(6) At the end insert—
18. The name of the advanced therapy medicinal product.
19. Where appropriate, whether the product is intended for babies, children or adults.
20. The common name of the advanced therapy medicinal product.
21. The therapeutic group, or type of activity, of the product, in terms easily comprehensible for the patient.
22. Where the product contains cells or tissues, a description of those cells or tissues and of their specific origin, including the species of animal in cases of non-human origin.
23. Where the product contains medical devices or active implantable medical devices, a description of those devices and their specific origin.
24. The product’s therapeutic indications.
25. A list of information which is necessary before the medicinal product is taken or used, including—
(a)contra-indications;
(b)appropriate precautions for use;
(c)interactions with other medicinal products which may affect the action of the product;
(d)interactions with other substances, including alcohol, tobacco and foodstuffs which may affect the action of the product;
(e)special warnings; if any, relating to the product.
26. The list mentioned in paragraph 25 must—
(a)take into account the special requirements of particular categories of users (including, in particular, children, pregnant or breastfeeding women, the elderly and persons with specific pathological conditions);
(b)mention, if appropriate, possible effects on the ability to drive vehicles or operate machinery; and
(c)list any excipients—
(i)if knowledge of the excipients is important for the safe and effective use of the product; and
(ii)the excipients are included in the guidance published under regulation 257D.
27. Instructions for proper use of the product including in particular—
(a)the dosage;
(b)the method of use, application, administration or implantation and, if necessary, the route of administration;
(c)the frequency of administration (including, if necessary, specifying the times at which the product may or must be administered);
(d)the duration of treatment if this is to be time limited;
(e)symptoms of an overdose and the action, if any, to be taken in the case of an overdose;
(f)what to do if one or more doses have not been taken;
(g)a specific recommendation to consult a doctor or pharmacist, as appropriate, for further explanation of the use of the product.
28. A description of the adverse reactions which may occur in normal use of the medicinal product and, if necessary, the action to be taken in such a case.
29. A reference to the expiry date printed on the packaging of the product with—
(a)a warning against using the product after that date;
(b)if appropriate, details of special storage precautions to be taken;
(c)if necessary, a warning concerning visible signs of deterioration;
(d)the full qualitative and quantitative composition;
(e)the name and address of the UK marketing authorisation holder and, if applicable, the name of the holder’s appointed representative; and
(f)the name and address of the manufacturer.
30. The date on which the package leaflet was last revised.”.
205.—(1) Regulation 266 is amended as follows.
(2) In paragraph (1), omit “unless either or both of paragraphs (2) and (3) applies”.
(3) Omit paragraphs (2) and (3).
206. In regulation 267, in each place where it occurs, for “marketing authorisation, Article 126a authorisation” substitute “UK marketing authorisation”.
207.—(1) Regulation 268(114) is amended as follows.
(2) In paragraph (1), for “marketing authorisation, Article 126a authorisation” substitute “UK marketing authorisation”.
(3) In paragraph (2)(a)—
(a)for “Article 28 or 32 of the Paediatric Regulation” substitute “regulation 50C(4), 50D(8) or 58A(2)(b)”; and
(b)omit “, Article 9 of Commission Regulation 2016/161”.
208.—(1) Regulation 269(115) is amended as follows.
(2) In paragraph (1), for “marketing authorisation, Article 126a authorisation” substitute “UK marketing authorisation”.
(3) In paragraph (2)(a)—
(a)for “Article 28 or 32 of the Paediatric Regulation” substitute “regulation 50C(4), 50D(8) or 58A(2)(b)”; and
(b)omit “, Article 9 of Commission Regulation 2016/161”.
209. In regulation 270(1) and (2), for “marketing authorisation, Article 126a authorisation” substitute “UK marketing authorisation”.
210.—(1) Regulation 273 is amended as follows.
(2) In paragraph (2), for sub-paragraph (b) substitute—
“(b)any specification for non-reclosable child resistant packaging that the licensing authority is satisfied is of an equivalent or higher technical specification to that specified in sub-paragraph (a).”.
(3) In paragraph (3), for sub-paragraph (b) substitute—
“(b)any specification for reclosable child resistant packaging that the licensing authority is satisfied is of an equivalent or higher technical specification to that specified in sub-paragraph (a).”.
211. In regulation 279—
(a)in sub-paragraph (a), insert “UK” before “marketing authorisation”;
(b)at the end of sub-paragraph (b), insert “or”; and
(c)omit sub-paragraph (d) (and “or” immediately preceding it).
212. In regulation 280(1)—
(a)for “marketing authorisation,” substitute “UK marketing authorisation or”; and
(b)omit “or Article 126a authorisation”.
213. In regulation 281(1)—
(a)in sub-paragraph (a), insert “UK” before “marketing authorisation”;
(b)at the end of sub-paragraph (b) insert “or”; and
(c)omit sub-paragraph (d) (and “or” immediately preceding it).
214. In regulation 293(1)—
(a)insert “UK” before “marketing authorisation”;
(b)for “certificate of registration,” substitute “certificate of registration or”; and
(c)omit “or Article 126a authorisation”.
215. In regulation 295(2)(d)—
(a)insert “UK” before “marketing authorisation”;
(b)for “certificate of registration,” substitute “certificate of registration or”; and
(c)omit “or Article 126a authorisation”.
216. In paragraphs 1, 2 and 6 of Schedule 30(116), for “marketing authorisation, certificate of registration, traditional herbal registration or Article 126a authorisation”, substitute “UK marketing authorisation, certificate of registration or traditional herbal registration”.
217. In regulation 299(3), for “marketing authorisation, certificate of registration, traditional herbal registration or Article 126a authorisation”, substitute “UK marketing authorisation, certificate of registration or traditional herbal registration”.
218. In regulation 321(5)—
(a)in sub-paragraph (c), insert “UK” before “marketing authorisation”;
(b)omit sub-paragraph (d).
219. In regulation 322(1)—
(a)for “, 7” substitute “or 7”; and
(b)omit “or 8 (Article 126a authorisations)”.
220.—(1) Regulation 323(117) is amended as follows.
(2) In paragraph (1) omit “and the relevant EU provisions”.
(3) In paragraph (3)—
(a)at the end of sub-paragraph (b) insert “and”; and
(b)omit sub-paragraph (d).
(4) Omit paragraph (4A).
221.—(1) Regulation 327(118) is amended as follows.
(2) In paragraph (1)(c)—
(a)in paragraph (v), insert “UK” before “marketing authorisation”;
(b)insert “or” at the end of paragraph (vi);
(c)omit paragraph (viii) (and “or” immediately preceding it).
(3) In paragraph (2)—
(a)in sub-paragraph (g)—
(i)in paragraph (ii), after “Part 11” insert “or Schedule 12A” and insert “and” at the end, and
(ii)omit paragraphs (iii), (iv) and (v); and
(b)omit sub-paragraph (h).
(4) Omit paragraph (4A).
(5) In paragraph (5)—
(a)in sub-paragraph (a) for “, (g) or (h)” substitute “or (g)”; and
(b)in sub-paragraph (b) omit “ or (4A)”.
222.—(1) Regulation 331 is amended as follows.
(2) In paragraph (1)—
(a)insert “UK” before “marketing authorisation”; and
(b)omit sub-paragraph (c) (and “and” immediately preceding it).
(3) In paragraph (4) for sub-paragraph (c) substitute—
“(c)in the case of a holder of a UK marketing authorisation or traditional herbal registration, Part 11 (pharmacovigilance).”.
223. After regulation 331 (finding and reports of inspections) insert—
331A.—(1) The licensing authority may publish guidelines specifying the principles applicable to inspections referred to in this Part.
(2) Guidelines under paragraph (1) may include the form and content of reports under regulation 331 and of certificates of good manufacturing practice or good distribution practice.
(3) Until the licensing authority exercises its power under paragraph (1), the guidelines adopted by the European Commission under Article 111a of the 2001 Directive, as they had effect immediately before exit day(119), are to continue to apply.”.
224. In regulation 341(4)(a), insert “UK” before “marketing authorisation”.
225. After regulation 344 insert—
344A.—(1) The Ministers may by regulations modify the application of any of the specified provisions in circumstances where the United Kingdom, or any part of the United Kingdom, is experiencing or may experience a serious shortage of medicinal products, or of medicinal products of a specified description, arising from the withdrawal of the United Kingdom from the European Union.
(2) Regulations may only be made under paragraph (1) for the purposes of preventing, remedying or mitigating the serious shortage that is being or may be experienced.
(3) For the purposes of paragraph (1), the “specified provisions” are the provisions of Parts 1, 3 to 5, 10 to 13 and 16, and of the associated Schedules.
(4) The reference in paragraph (1) to a serious shortage arising from the withdrawal of the United Kingdom from the European Union includes reference to a serious shortage where the withdrawal of the United Kingdom from the European Union is one but not the only significant factor contributing to the shortage.
(5) No regulations under paragraph (1) may be made, or have effect, after the end of the period of two years beginning with exit day.
344B.—(1) Regulations made under a power in the regulations listed in paragraph (2)—
(a)are to be made by statutory instrument;
(b)may make different provision for different purposes and different areas; and
(c)may include incidental, supplemental, consequential, transitional, transitory or saving provisions, including consequential amendments to these Regulations.
(2) The regulations referred to in paragraph (1) are—
(a)regulation B17(1) and (4) (good manufacturing practice);
(b)regulation 50(5A) (Annex I to the 2001 Directive);
(c)regulation 50G(5) (orphan criteria etc);
(d)regulations 59(3A) and 61(7A) (post-authorisation efficacy studies);
(e)regulation 65C(7) (variations of UK marketing authorisations);
(f)regulation 102(7) (homoeopathic medicinal products);
(g)regulation 205A(2) (further obligations in respect of pharmacovigilance activities);
(h)regulation 257E (certain forms of labelling); and
(i)regulation 344A (modifications to deal with serious shortages).
(3) A statutory instrument containing regulations made under the powers listed in paragraph (2) is subject to annulment in pursuance of a resolution of either House of Parliament.”.
226. In regulation 345(5)—
(a)insert “UK” before “marketing authorisation”;
(b)insert “or” after “certificate of registration”; and
(c)omit “or Article 126a authorisation”.
227. In regulation 346(120)—
(a)in sub-paragraph (c), omit paragraphs (iia), (iiia), (iva), (xixa), (xxviiii) and (xxviiij); and
(b)in sub-paragraph (d), omit paragraphs (ia) and (ivab).
228.—(1) After regulation 347 insert—
347A. Schedule 33A contains transitional provision in relation to the EU Exit Regulations.”.
(2) Schedule 7 inserts a new Schedule 33A after Schedule 33.
229. Schedule 8 contains consequential amendments.
230. Schedule 9 contains revocations of retained direct EU law.
Signed by the authority of the Secretary of State for Health and Social Care
Name
Minister of State
Department of Health and Social Care
Name
Two of the Lords Commissioners of Her Majesty’s Treasury
Her Majesty’s Treasury
Address
Date