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PART 5U.K.Marketing authorisations

Application of this PartU.K.

48.—(1) This Part applies to relevant medicinal products.

(2) In this Part—

[F1“EU reference medicinal product” means a medicinal product which falls within paragraph (b)(ii) or (iii) of the definition of “reference medicinal product;]

[F1“excluded reference product” means—

(a)

a medicinal product authorised on the basis that it was a generic medicinal product;

(b)

a medicinal product authorised on the basis that one or more of the circumstances listed in Article 10(3) of the 2001 Directive or regulation 52(1)(b) applied; or

(c)

a biological medicinal product authorised on the basis that it did not meet a condition for being a generic medicinal product for any of the reasons described in Article 10(4) of the 2001 Directive or regulation 53A(1);]

[F2“generic medicinal product”, in relation to a reference medicinal product for an application for—

(a)

a UKMA(NI) or UKMA(UK), has the meaning given in Article 10(2)(b) of the 2001 Directive;

(b)

a UKMA(GB), means a medicinal product—

(i)

that has the same qualitative and quantitative composition in active substances as the reference medicinal product;

(ii)

that has the same pharmaceutical form as the reference medicinal product; and

(iii)

whose bioequivalence with the reference medicinal product has been demonstrated by appropriate bioavailability studies;]

[F3“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—

(a)

has been granted an EU marketing authorisation or a marketing authorisation in an EEA State under the 2001 Directive; and

(b)

is essentially similar to a product that has been granted a UK marketing authorisation;]

“relevant medicinal product” means a medicinal product that is not—

(a)

a registrable homoeopathic medicinal product; or

(b)

a traditional herbal medicinal product; and

[F4“reference medicinal product” means—

(a)

in relation to an application for a UKMA(NI), a medicinal product—

(i)

authorised for sale or supply in Northern Ireland under regulation 49(1)(a), in accordance with the provisions of regulation 50; or

(ii)

in relation to which an EU marketing authorisation or a marketing authorisation granted by a member State pursuant to the 2001 Directive is or has been in force,

but which is not an excluded reference product;

(b)

in relation to an application for a UKMA(GB), a medicinal product—

(i)

authorised under regulation 49(1)(a), in accordance with the provisions of regulation 50;

(ii)

in relation to which an EU marketing authorisation was in force on IP completion 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; or

(iii)

in relation to which an EU marketing authorisation had ceased to be in force before IP completion day for reasons not related to safety, quality or efficacy,

but which is not an excluded reference product;

(c)

in relation to an application for a UKMA(UK), a medicinal product—

(i)

authorised under regulation 49(1)(a) for sale or supply in the whole of the United Kingdom, whether by virtue of one or more UK marketing authorisations, in accordance with the provisions of regulation 50; or

(ii)

in relation to which an EU marketing authorisation or a marketing authorisation granted by a member State pursuant to the 2001 Directive is or has been in force,

but which is not an excluded reference product;]

[F5(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 53B.

(7) Where this paragraph applies, the medicinal product is treated for the purposes of the application of regulation 51A(1) and (6) as if it 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 53B; 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 51A(1) and (6) 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.]

Textual Amendments

Application for UK marketing authorisationU.K.

Application for grant of UK marketing authorisation [F6or parallel import licence] U.K.

49.—[F7(1) The licensing authority may grant—

(a)subject to regulation 58, [F858C, 58E, 58F and 58G,] a UK marketing authorisation; or

(b)a parallel import licence,

for a relevant medicinal product in response to an application made in accordance with this Part.]

[F9(1A) The licensing authority may accept an application meeting reduced or alternative requirements specified in this Part (“under the unfettered access route”) and grant a UKMA(GB) only where—

(a)there is already in place, or will be at the time the UKMA(GB) is granted, a marketing authorisation in respect of the product authorising sale or supply in Northern Ireland,

(b)the applicant complies with the requirements in regulation 50(1A), and

(c)the medicinal product satisfies the definition of qualifying Northern Ireland goods.

(1B) 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.

(1C) A marketing authorisation or parallel import licence must state whether it is in force in—

(a)the whole United Kingdom;

(b)Great Britain only; or

(c)Northern Ireland only,

and in these Regulations the meaning of a reference to that authorisation or licence being “in force” is limited to that territory.]

(2) A marketing authorisation [F10or parallel import licence] granted under paragraph (1) shall contain terms approved by the licensing authority.

[F11(3) The applicant, where it is applying for—

[F12(a)a UKMA(UK) or UKMA(NI), must be established in the United Kingdom or an EEA State;]

(b)a UKMA(GB)—

(i)under the unfettered access route, must be established in Northern Ireland;

(ii)other than under the unfettered access route, must be established in the United Kingdom [F13or an EEA State];

(c)a [F14parallel import licence], must be established in the United Kingdom.]

[F15(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.]

(4) The application must be—

(a)made in writing;

(b)signed by or on behalf of the applicant; and

(c)unless the licensing authority directs otherwise, accompanied by any fee payable in connection with the application.

(5) An application is treated as signed for the purposes of paragraph (4)(b) if it is signed with an electronic signature.

(6) The application and any accompanying material must be in English.

(7) The application must include a statement indicating whether the product to which the application relates should be available—

(a)only on prescription;

(b)only from a pharmacy; or

(c)on general sale.

(8) The application must include a statement indicating—

(a)whether any terms of the authorisation are proposed relating to the method of sale or supply of the product (including, in particular, any proposed restrictions affecting the circumstances of the use or promotion of the product); and

(b)if so, what terms are proposed.

[F16( 9) The application must include a statement indicating whether the authorisation or licence sought is for sale or supply of the product in—

(a)the whole United Kingdom;

(b)Great Britain only; or

(c)Northern Ireland only.

(10) In this regulation “group” has the same meaning as in Part 15 of the Companies Act 2006 (see section 474(1) of that Act).]

Textual Amendments

F6Words in reg. 49 heading inserted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 4 and words in reg. 49 heading inserted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 4(2)(a)

F10Words in reg. 49(2) inserted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 4 and words in reg. 49(2) inserted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 4(2)(b)

Accompanying materialU.K.

50.—(1) An applicant for the grant of a UK marketing authorisation for a relevant medicinal product must provide the material specified in Schedule 8 in relation to the product.

[F17(1A) An applicant for the grant of a parallel import licence for a relevant medicinal product must provide the material specified in Schedule 8A in relation to the product.]

[F18(1A) An applicant for the grant of a UK marketing authorisation for a relevant medicinal product must provide—

(a)in the case of an application under the unfettered access route—

(i)the material specified in Schedule 8C, and

(ii)any material specified in Schedule 8 which is not included in the material specified in Schedule 8C, and

(b)in all other cases, the material specified in Schedule 8,

in relation to the product.]

(2) An applicant for the grant of a UK marketing authorisation [F19or parallel import licence] for a radionuclide generator must, in addition, provide—

(a)a general description of the system together with a detailed description of the components of the system which may affect the composition or quality of the daughter nucleid preparation; and

(b)qualitative and quantitative particulars of the eluate or the sublimate.

(3) The applicant must also, if requested by the licensing authority to do so, provide the licensing authority with material or information that the licensing authority reasonably considers necessary for dealing with the application.

[F20(3A) Paragraph (4) does not apply in respect of an application under the unfettered access route.]

[F21(4) If any of the medicinal products to which the application for a UK marketing authorisation relates—

(a)in the case of a UKMA(NI) or a UKMA(UK), is liable to be imported from a country other than an EEA State, or

(b)in the case of a UKMA(GB), is liable to be imported,

the material or information referred to in paragraph (3) may include an undertaking from the manufacturer of the product to comply with the matters set out in Schedule 9.]

(5) Material that is submitted under this regulation [F22for the purposes of a UK marketing authorisation] must be submitted in accordance with the applicable provisions of Annex I to the 2001 Directive.

[F23(5A) The Secretary of State may by regulations in respect of Great Britain amend Schedule 8B (modifications of Annex I) in relation to a UKMA(GB) 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 IP completion 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;

(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; 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.]

(6) [F24Unless the application is for a parallel import licence this] regulation is subject to—

[F25(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);]

[F26(a)regulation 51 (application for UKMA(NI) relating to generic medicinal products);

(aa)regulation 51A (application for UKMA(GB) relating to generic medicinal products);

(ab)regulation 51B (application for UKMA(UK) relating to generic medicinal products);]

[F27(b)regulation 52 (application for UKMA(NI) relating to certain medicinal products that do not qualify as generic etc);

(ba)regulation 52A (application for UKMA(GB) relating to certain medicinal products that do not qualify as generic etc);

(bb)regulation 52B (application for UKMA(UK) relating to certain medicinal products that do not qualify as generic etc);]

[F28(c)regulation 53 (application for UKMA(NI) relating to similar biological medicinal products);

(ca)regulation 53A (application for UKMA(GB) relating to similar biological medicinal products);

(cb)regulation 53B (application for UKMA(UK) relating to similar biological medicinal products);]

(d)regulation 54 (applications relating to products in well-established medicinal use);

(e)regulation 55 (applications relating to new combinations of active substances);

(f)regulation 56 (applications containing information supplied in relation to another medicinal product with consent); and

(g)Schedule 10 (applications relating to national homoeopathic products).

[F29(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.]

Textual Amendments

F18Reg. 50(1A) inserted after subparagraph (1) (31.12.2020) by virtue of S.I. 2019/775, regs. 1, 49(1A) (as inserted by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2020 (S.I. 2020/1488), reg. 1, Sch. 2 para. 37(a))

F19Words in reg. 50(2) inserted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 4 and words in reg. 50(2) inserted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 4(2)(c)

F22Words in reg. 50(5) inserted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 6(4) and words in reg. 50(5) inserted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 6(4)

F24Words in reg. 50(6) substituted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 6(5) and words in reg. 50(6) substituted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 6(5)

[F30Requirement for certain applications to include results of paediatric investigation planU.K.

50A.—(1) This regulation applies in relation to an application—

(a)under regulation 49 for a UKMA(GB) or UKMA(UK) 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 UKMA(GB) or UKMA(UK).

(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.

(7) In the case of an application for a UKMA(GB) under the unfettered access route, an agreed paediatric investigation plan in respect of the product’s marketing authorisation in Northern Ireland applies also to that application as regards the UK marketing authorisation.

(8) This regulation does not remove, in respect of an application for a UKMA(UK), the obligation also to comply with the requirements of the Paediatric Regulation in connection with the agreement of, and compliance with, an EU agreed paediatric investigation plan in relation to Northern Ireland.

Textual Amendments

Agreement and modification of paediatric investigation planU.K.

50B.—(1) Any person may prepare a paediatric investigation plan for the purposes of an application to which regulation 50A applies 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).

Textual Amendments

Deferral of initiation or completion of measures in paediatric investigation planU.K.

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).

Textual Amendments

Waiver of production of information in a paediatric investigation planU.K.

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).

Textual Amendments

Application for paediatric use marketing authorisationU.K.

50E.—(1) This regulation applies in relation to an application for a UKMA(GB) or UKMA(UK)—

(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.

(5) This regulation does not remove, in respect of an application for a UKMA(UK), the obligation also to comply with the requirements of the Paediatric Regulation in connection with the agreement of, and compliance with, an EU agreed paediatric investigation plan in relation to Northern Ireland.

Textual Amendments

Other applications including paediatric indicationsU.K.

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 UKMA(GB) for a relevant medicinal product which includes a paediatric indication; or

(b)an application to include a paediatric indication in an existing UKMA(GB).

(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.

Textual Amendments

Applications relating to orphan medicinal productsU.K.

50G.—(1) This regulation applies in relation to an application for a UK marketing authorisation for a relevant medicinal product—

(a)in relation to which the applicant intends to demonstrate that the orphan criteria are met, and

(b)which, in the case of an application for a UKMA(NI) or a UKMA(UK), is not a medicinal product designated as an orphan medicinal product in accordance with the Orphan Regulation.

(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 Great Britain; 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 Great Britain, 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.

Textual Amendments

Applications relating to advanced therapy medicinal productsU.K.

50H.—(1) This regulation applies in relation to an application for a UKMA(GB) 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 UKMA(GB) 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, including, where available, the results of the assessment of a notified body in accordance with those Regulations.

Textual Amendments

Applications relating to conditional marketing authorisations for sale or supply in Great Britain onlyU.K.

50I.—(1) This regulation applies in relation to an application for a UKMA(GB) 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.

Textual Amendments

Applications in relation to medicinal products containing or consisting of genetically modified organismsU.K.

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,

(ii)regulation 22 of the Genetically Modified Organisms (Deliberate Release) (Wales) Regulations 2002,

(iii)regulation 21 of the Genetically Modified Organisms (Deliberate Release) (Scotland) Regulations 2002, or

(iv)regulation 21 of the Genetically Modified Organisms (Deliberate Release) Regulations (Northern Ireland) 2003;

(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.]

Textual Amendments

[F31Application for UKMA(NI) relating to generic medicinal productsU.K.

51.—(1) An applicant for a UKMA(NI) for a relevant medicinal product that is a generic medicinal product may provide information in relation to the application in accordance with Article 10(1), (5) and (6) of the 2001 Directive.

(2) If the licensing authority grants a UKMA(NI) for the generic medicinal product in accordance with paragraph (1), it is a term of the authorisation that the product must not be sold or supplied, or offered for sale or supply, in Northern Ireland before the time at which it may be placed on the market in accordance with Article 10(1) of the 2001 Directive as modified by paragraph (3).

(3) The second subparagraph of Article 10(1) of the 2001 Directive has effect with the exception described in paragraph (4).

(4) Where—

(a)ten years have elapsed since a UK marketing authorisation was granted otherwise than under Chapter 4 of Title III to the 2001 Directive in relation to the reference medicinal product;

(b)in relation to that product there is—

(i)an EU marketing authorisation, or

(ii)a UKMA(NI) which was granted under that Chapter; and

(c)a period of ten years has not elapsed since the authorisation mentioned in sub-paragraph (b) for sale or supply of that product in the European Union,

the product may not be made available for sale or supply in Northern Ireland until the period mentioned in sub-paragraph (c) has elapsed.

Textual Amendments

Application for UKMA(GB) relating to generic medicinal productsU.K.

51A.—(1) An applicant for a UKMA(GB) 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 authorised for sale or supply in Great Britain which is or has been authorised for not less than eight years—

(a)under regulation 49(1)(a); or

(b)if the product is an EU reference medicinal product, under Regulation (EC) No 726/2004.

(2) 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.

(3) 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 (4).

(4) 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 (3).

(5) Until replaced by guidelines published under paragraph (4), the guidelines published by the EMA under Article 10(2)(b) of the 2001 Directive continue to apply on and after IP completion day as they applied immediately before IP completion day (subject to any amendments or variations published under paragraph (4)).

(6) If the licensing authority grants a UKMA(GB) 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 Great Britain before the expiry of ten years beginning with the date on which the marketing authorisation for the reference medicinal product entered into force.

(7) Paragraph (8) applies where an EU reference medicinal product which falls within paragraph (b)(ii) of the definition of “reference medicinal product” is used as a reference medicinal product for the purposes of this regulation.

(8) 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 IP completion day.

(9) Paragraph (10) applies if—

(a)during the first eight of the ten years referred to in paragraph (6) the marketing authorisation holder for the reference medicinal product obtained a UKMA(GB) or a UKMA(UK) 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.

(10) Where this paragraph applies, the period of ten years referred to in paragraph (6) is extended to eleven years.

(11) Paragraph (12) applies where—

(a)an application for the grant or variation of a UKMA(GB) 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.

(12) Where this paragraph applies, the applicant for a UKMA(GB) under paragraph (1) or regulation 52A or 53A may not refer in its application to the studies mentioned in paragraph (11)(b) for the period of one year beginning on the date on which the licensing authority grants or varies a UKMA(GB) in relation to the new indication.

Textual Amendments

Application for UKMA(UK) relating to generic medicinal productsU.K.

51B.—(1) This regulation applies in relation to an application for a UKMA(UK) for a generic medicinal product.

(2) Where the application relies on a reference medicinal product which is the subject of—

(a)a UKMA(UK), the provisions of regulation 51(1) and (2) apply in respect of the application;

(b)a separate UKMA(GB) and UKMA(NI), paragraphs (3) to (5) apply.

(3) The applicant 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 only after the expiry of both—

(a)the period referenced in the applicable Article referred to in regulation 51(1), in relation to the UKMA(NI) for the reference medicinal product; and

(b)the period specified in regulation 51A(1), in relation to the UKMA(GB) for the reference medicinal product.

(4) In the case of an application under paragraph (3) 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) If the licensing authority grants a UK marketing authorisation in relation to the generic medicinal product in accordance with paragraph (3), 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 both—

(a)the period specified in regulation 51(2), in relation to the UKMA(NI) for the reference medicinal product; and

(b)the period specified in regulation 51A(6) or (where applicable) 51A(10), in relation to the UKMA(GB) for the reference medicinal product.

(6) Paragraph (7) applies where—

(a)an application for the grant or variation of a UKMA(UK) 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.

(7) Where this paragraph applies, the applicant for a UKMA(UK) under paragraph (1) or regulation 52B or 53B may not refer in its application to the studies mentioned in paragraph (6)(b) for the period of one year beginning on the date on which the licensing authority grants or varies a UKMA(UK) in relation to the new indication.]

Textual Amendments

[F32Application for UKMA(NI) relating to certain medicinal products that do not qualify as generic etcU.K.

52.—(1) This regulation applies where—

(a)an application is made for a UKMA(NI) by reference to another medicinal product as reference medicinal product; and

(b)one or more of the circumstances listed in Article 10(3) of the 2001 Directive applies in respect of the application.

(2) The applicant must provide information in accordance with Article 10(3) and (6) of the 2001 Directive.

(3) Paragraphs (2) to (4) of regulation 51 apply to the application as they apply in relation to an application made in accordance with paragraph (1) of that regulation.

Textual Amendments

Application for UKMA(GB) relating to certain medicinal products that do not qualify as generic etcU.K.

52A.—(1) This regulation applies where—

(a)an application is made for a UKMA(GB) in respect of a product by reference to another medicinal product as reference medicinal product which is or has been authorised for sale or supply in Great Britain for not less than eight years—

(i)under regulation 49(1)(a); or

(ii)if the product is an EU reference medicinal product, under Regulation (EC) No 726/2004; and

(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.

(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).

(3) Paragraphs (2) to (10) of regulation 51A apply to the application as they apply in relation to an application made in accordance with paragraph (1) of that regulation.

Textual Amendments

Application for UKMA(UK) relating to certain medicinal products that do not qualify as generic etcU.K.

52B.—(1) This regulation applies in relation to an application for a UKMA(UK) in respect of a product by reference to another medicinal product as reference medicinal product.

(2) Where the application relies on a reference medicinal product which is the subject of—

(a)a UKMA(UK), the provisions of regulation 52(1) and (2) apply in respect of the application;

(b)a separate UKMA(GB) and UKMA(NI), paragraphs (3) to (5) apply.

(3) Subject to paragraph (4), the applicant 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 only after the expiry of both—

(a)the period referenced in the applicable Article referred to regulation 52(1), in relation to the UKMA(NI) for the reference medicinal product; and

(b)the period specified in regulation 52A(1), in relation to the UKMA(GB) for the reference medicinal product.

(4) Where one or more of the following circumstances applies in respect of the application—

(a)the medicinal product to which the application relates does not fall within the definition of generic medicinal product,

(b)bioequivalence with the reference medicinal product cannot be demonstrated through bioavailability studies, or

(c)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,

the applicant must provide the results of the appropriate pre-clinical tests or clinical trials relating to the applicable circumstance.

(5) Paragraphs (4) and (5) of regulation 51B apply to the application as they apply in relation to an application made in accordance with paragraph (3) of that regulation.]

Textual Amendments

[F33Application for UKMA(NI) relating to similar biological medicinal productsU.K.

53.—(1) This regulation applies if an applicant for a UKMA(NI) for a biological medicinal product is not able to show that product meets a condition for its being a generic version of a similar medicinal product because of any of the reasons described in Article 10(4) of the 2001 Directive.

(2) The applicant must provide information in accordance with Article 10(4) and (6) of the 2001 Directive.

(3) Paragraphs (2) to (4) of regulation 51 apply to the application as they apply in relation to an application made in accordance with paragraph (1) of that regulation.

Textual Amendments

Application for UKMA(GB) relating to similar biological medicinal productsU.K.

53A.—(1) This regulation applies if an applicant for a UKMA(GB) for a biological medicinal product is not able to show that product meets a condition for its being a generic version of a similar medicinal product because of differences relating to raw materials or differences in manufacturing processes of the biological medicinal product and the reference medicinal product.

(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 a reference medicinal product which is or has been authorised for not less than eight years—

(i)under regulation 49(1)(a), or

(ii)if the reference medicinal product is an EU reference medicinal product, under Regulation (EC) No 726/2004; but

(b)must provide the results of appropriate pre-clinical tests or clinical trials relating to the differences referred to in paragraph (1).

(3) 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 (4), or (as the case may be) as mentioned in paragraph (5).

(4) The licensing authority may publish guidelines concerning the type and quantity of supplementary data to be provided by an applicant under paragraph (2)(b).

(5) Unless replaced by guidelines published under paragraph (4), the guidelines published by the EMA under Article 10(4) of the 2001 Directive continue to apply on and after IP completion day as they applied immediately before IP completion day (subject to any amendments or variations published under that paragraph).

(6) Paragraphs (4) to (12) of regulation 51A apply to the application as they apply in relation to an application made in accordance with paragraph (1) of that regulation.

Textual Amendments

Application for UKMA(UK) relating to similar biological medicinal productsU.K.

53B.—(1) This regulation applies in relation to an application for a UKMA(UK) for a biological medicinal product.

(2) Where the application relies on a reference medicinal product which is the subject of—

(a)a UKMA(UK), the provisions of regulation 53 apply in respect of the application;

(b)a separate UKMA(GB) and UKMA(NI), paragraphs (3) to (5) apply.

(3) Subject to paragraph (4), the applicant 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 only after the expiry of both—

(a)the period referenced in the applicable Article referred to regulation 53(1), in relation to the UKMA(NI) for the reference medicinal product; and

(b)the period specified in regulation 53A(1), in relation to the UKMA(GB) for the reference medicinal product.

(4) Where the applicant for a biological medicinal product is not able to show that product meets a condition for its being a generic version of a similar medicinal product because of differences relating to raw materials or differences in manufacturing processes of the biological medicinal product and the reference medicinal product, the applicant must provide the results of the appropriate pre-clinical tests or clinical trials relating to the differences.

(5) The type and quantity of supplementary data to be provided by the applicant under paragraph (4) 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 (6), or (as the case may be) as mentioned in paragraph (7).

(6) The licensing authority may publish guidelines concerning the type and quantity of supplementary data to be provided by an applicant under paragraph (4).

(7) Unless replaced by guidelines published under paragraph (6), the guidelines published by the EMA under Article 10(4) of the 2001 Directive continue to apply on and after IP completion day as they applied immediately before IP completion day (subject to any amendments or variations published under that paragraph).

(8) Paragraphs (4) and (5) of regulation 51B apply to the application as they apply in relation to an application made in accordance with paragraph (1) of that regulation.]

Textual Amendments

Applications relating to products in well-established medicinal useU.K.

54.—(1) This regulation applies if an applicant for a UK marketing authorisation for a relevant medicinal product is able to demonstrate that the active substances of the product have been in well-established medicinal use within the [F34United Kingdom or the] European Union for at least 10 years, with recognised efficacy and an acceptable level of safety in terms of the conditions set out in Annex I to the 2001 Directive.

[F35(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.]

Textual Amendments

Applications relating to new combinations of active substancesU.K.

[F3655.—(1) This regulation applies to an application for a UK marketing authorisation for a relevant medicinal product that contains active substances, provided those active substances—

(a)have not been used in that combination for therapeutic purposes; and

(b)where the application is for—

(i)a UKMA(NI), have been used in medicinal products that have been the subject of a marketing authorisation under these Regulations, the 2001 Directive or Regulation (EC) No 726/2004;

(ii)a UKMA(GB), have been used in medicinal products that have been the subject of a marketing authorisation under these Regulations; or

(iii)a UKMA(UK), have been used in medicinal products that have been the subject of—

(aa)a UKMA(UK) under these Regulations; or

(bb)a relevant Northern Ireland authorisation.

(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.

(3) In paragraph (1), “relevant Northern Ireland authorisation” means—

(a)a UKMA(NI) under these Regulations;

(b)a marketing authorisation under the 2001 Directive; or

(c)an EU marketing authorisation,

which authorises the sale or supply of a medicinal product in Northern Ireland.]

Textual Amendments

Applications containing information supplied in relation to another product with consentU.K.

56.—(1) This regulation applies to an application for a UK marketing authorisation for a relevant medicinal product where—

(a)the product that is the subject of the application (“product A”) has the same qualitative and quantitative composition in terms of active substances and the same pharmaceutical form as a product (“product B”);

(b)product B is the subject of a UK marketing authorisation; and

(c)the holder of the marketing authorisation for product B has allowed use to be made of the pharmaceutical, pre-clinical and clinical documentation contained in the file on product B with a view to examining subsequent applications relating to other medicinal products possessing the same qualitative and quantitative composition in terms of active substances and the same pharmaceutical form.

(2) The documentation referred to in paragraph (1)(c) in relation to product B may be used in relation to the application in relation to product A F37...

Textual Amendments

Obligation to update information supplied in connection with applicationU.K.

57.—(1) The applicant for a UK marketing authorisation must update information supplied in accordance with paragraphs 18 to 21 of Schedule 8 (material to accompany an application for a UK marketing authorisation) in connection with the application.

(2) The applicant must update information supplied in connection with the application to include any further information that is relevant to the evaluation of the safety, quality or efficacy of the product concerned.

(3) Updated information within paragraphs (1) or (2) must be provided as soon as is reasonably practicable after the applicant becomes aware of it.

[F38Obligation to update information supplied in connection with parallel import licence applicationU.K.

57A.—(1) The applicant for a parallel import licence must update information supplied in accordance with Schedule 8A (material to accompany an application for a parallel import licence) in connection with the application.

(2) The applicant must update information supplied in connection with the application to include any further information that is relevant to the evaluation of the safety, quality or efficacy of the product concerned.

(3) Updated information within paragraphs (1) or (2) must be provided as soon as is reasonably practicable after the applicant becomes aware of it.]

Textual Amendments

Consideration of applicationU.K.

Consideration of applicationU.K.

58.—(1) The licensing authority must take all reasonable steps to ensure that it makes a decision to grant or refuse a UK marketing authorisation before the end of 210 days beginning immediately after the day on which the application for the authorisation is submitted in accordance with regulations 49 to 55.

(2) If the licensing authority requests the applicant to provide any further information or material, the period referred to in paragraph (1) is suspended for the period—

(a)beginning with the date on which the request is made; and

(b)ending with the date on which the information or material is provided.

(3) If the licensing authority requests the applicant to give an oral or written explanation of the application, the period referred to in paragraph (1) is suspended for the period—

(a)beginning with the date on which the request is made; and

(b)ending with the date on which the explanation is provided.

(4) The licensing authority may grant the application only if, having considered the application and the accompanying material, the authority thinks that—

(a)the applicant has established the therapeutic efficacy of the product to which the application relates;

(b)the positive therapeutic effects of the product outweigh the risks to the health of patients or of the public associated with the product;

(c)the application and the accompanying material complies with regulations 49 to 55; and

(d)the product's qualitative and quantitative composition is as described in the application and the accompanying material.

[F39(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 that paragraph in relation to certain types of medicinal products only;

(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); and

(c)decide to have regard to the assessments described in paragraph (4A)(b) in relation to medicinal products that have been authorised by way of certain procedures only.

(4C) When considering an application for a UK marketing authorisation (other than an application under the unfettered access route), the licensing authority may, if it considers it appropriate and without undertaking further consideration, rely on a decision by the European Commission to authorise the medicinal product to which the application relates to establish that any or all of the conditions in paragraph (4)(a), (b) or (d) have been met.]

(5) Schedule 11 makes provision about advice and representations in relation to an application for the grant of a UK marketing authorisation.

F40(6) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

F41(7) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

[F42(8) In the case of an application under the unfettered access route, the licensing authority may grant a UKMA(GB) (notwithstanding paragraph (4)) where the licensing authority—

(a)has considered the application under the unfettered access route and the accompanying material,

(b)is satisfied that the applicant has complied with the application requirements, and

(c)is satisfied that the conditions in regulation 50 will continue to be met.

(9) The licencing authority may refuse to grant an application under the unfettered access route where it is of the opinion that it would represent a risk to public health to do so.]

Textual Amendments

[F43Paediatric rewardsU.K.

58A.—( 1) Paragraph (2) applies if—

(a)an application—

(i)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; or

(ii)to which Article 7 or 8 of the Paediatric Regulation applies, and in relation to which there is an EU 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—

(i)regulation 50A(3), where paragraph (1)(a)(i) applies; or

(ii)Article 7 or 8 of the Paediatric Regulation, where paragraph (1)(a)(ii) applies,

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—

(a)paragraph (2) applies; or

(b)an application to which Article 7 or 8 of the Paediatric Regulation applies—

(i)includes the results of all studies conducted in compliance with an EU agreed paediatric investigation plan; or

(ii)confirms completion of an EU agreed paediatric investigation plan which failed to lead to the authorisation of a paediatric indication, but the results of the studies conducted are reflected in the summary of product characteristics and, if appropriate, the package leaflet of the medicinal product,

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) to (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 is entitled to a one year extension of the ten year period referred to in regulation 51A(6), under regulation 51A(12).

(4A) Paragraph (3) does not apply where—

(a)the territorial protection conferred by the supplementary protection certificate referred to in paragraph (3) does not cover the whole of the United Kingdom; and

(b)the UK marketing authorisation in which the statement of compliance is included is not in force in the same part of the United Kingdom as the supplementary protection certificate.

(4B) Where—

(a)the territorial protection conferred by the supplementary protection certificate referred to in paragraph (3) does cover the whole of the United Kingdom; and

(b)the UK marketing authorisation in which the statement of compliance is included is in force in in Great Britain only or in Northern Ireland only,

the extension provided for in paragraph (3) only applies in relation to Great Britain only or Northern Ireland only (as appropriate).

(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 51A(1) and (6) in relation to the material supplied pursuant to regulation 50E(2).

Textual Amendments

Publication of information relating to paediatric marketing authorisationsU.K.

58B.—(1) The licensing authority must publish a register of UK marketing authorisations—

(a)which include a paediatric indication following completion of an agreed paediatric investigation 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.

Textual Amendments

Consideration of applications relating to orphan medicinal productsU.K.

58C.—(1) If the licensing authority is satisfied in relation to an application for a UK marketing authorisation (including an application under the unfettered access route)—

(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.

Textual Amendments

Orphan rewardsU.K.

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.

(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.

Textual Amendments

Consideration of applications relating to combined advanced therapy medicinal productsU.K.

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 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.

Textual Amendments

Consideration of applications relating to conditional marketing authorisationsU.K.

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 UKMA(GB) 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.

Textual Amendments

Consideration of applications in relation to medicinal products containing or consisting of genetically modified organismsU.K.

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).]

Textual Amendments

Conditions of UK marketing authorisation [F44or parallel import licence]: generalU.K.

59.—(1) [F45Unless paragraph (1A) applies the licensing authority] may—

(a)grant a UK marketing authorisation subject to one or more of the conditions in paragraph (2); or

(b)vary or remove a condition in paragraph (2) to which the UK marketing authorisation is subject.

[F46(1A) Where the application concerns a parallel import licence, the licensing authority may—

(a)grant a parallel import licence subject to one or more of the conditions in paragraph (2)(a), (c), (d) or (e); or

(b)vary or remove a condition in paragraph (2)(a), (c), (d) or (e) to which the parallel import licence is subject.]

(2) Those conditions are—

(a)to take certain measures for ensuring the safe use of the medicinal product and include them in the risk management plan;

(b)to conduct post-authorisation safety studies;

(c)to comply with obligations on the recording or reporting of suspected adverse reactions which are stricter than those referred to in Part 11;

(d)any other conditions or restrictions with regard to the safe and effective use of the medicinal product;

(e)the existence of an adequate pharmacovigilance system; and

(f)to conduct post-authorisation efficacy studies where concerns relating to some aspects of the efficacy of the medicinal product are identified and can be resolved only after the medicinal product has been marketed.

(3) [F47In relation to a UKMA(NI) or UKMA(UK), an obligation] to conduct such studies as are referred to in paragraph (2)(f) must be based on the delegated acts adopted pursuant to Article 22b of the 2001 Directive, while taking into account the scientific guidance referred to in Article 108a of the 2001 Directive.

[F48(3A) In relation to a UKMA(GB), 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.

(3B) The Secretary of State may by regulations make provision in respect of Great Britain specifying the situations in which post-authorisation efficacy studies may be required by virtue of the condition referred to in paragraph (2)(f).

(3C) Paragraph (3A)(a) ceases to apply on the coming into force of regulations made under paragraph (3B).]

(4) The [F49UK] marketing authorisation [F50or parallel import licence] must lay down deadlines for the fulfilment of the conditions in paragraph (2) [F51where relevant and necessary].

[F52(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).]

(5) The licensing authority must notify the EMA of any [F53UKMA(NI) or UKMA(UK)] that it has granted subject to a condition included in accordance with this regulation.

(6) The holder of the authorisation must incorporate any condition included in a marketing authorisation [F54or parallel import licence] in accordance with this regulation into the risk management system for the product.

(7) Schedule 11 makes provision about advice and representations in relation to proposals to vary or remove a condition to which a UK marketing authorisation is subject.

Textual Amendments

F44Words in reg. 59 heading inserted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 4 and words in reg. 59 heading inserted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 4(2)(d)

F45Words in reg. 59(1) substituted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 8(2) and words in reg. 59(1) substituted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 8(2)

F50Words in reg. 59(4) inserted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 4 and words in reg. 59(4) inserted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 4(2)(e)

F51Words in reg. 59(4) substituted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 8(4) and words in reg. 59(4) substituted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 8(4)

F54Words in reg. 59(6) inserted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 4 and words in reg. 59(6) inserted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 4(2)(e)

Conditions of UK marketing authorisation [F55or parallel import licence]: exceptional circumstancesU.K.

60.—(1) The licensing authority may—

(a)grant a UK marketing authorisation [F55or parallel import licence] subject to conditions in accordance with the following paragraphs of this regulation; or

(b)vary or remove such a condition to which the UK marketing authorisation [F55or parallel import licence] is subject.

(2) The powers in paragraph (1) may be exercised only after consultation with the applicant for the authorisation [F56or licence] or (as the case may be) its holder.

(3) The power in paragraph (1)(a) to grant an authorisation [F57or licence] subject to conditions may be exercised only—

(a)in exceptional circumstances; and

(b)when the applicant can show that the applicant is unable to provide comprehensive data on the efficacy and safety of the medicinal product under normal conditions of use.

(4) The conditions must relate to a matter addressed by Annex I to the 2001 Directive.

(5) The conditions may, in particular, relate to the safety of the product to which the authorisation [F56or licence] relates.

(6) The conditions may, in particular, require that, where there is a serious adverse reaction relating to the use of the product—

(a)the reaction must be reported to the licensing authority; and

(b)such other action as may be specified in the conditions must be taken.

(7) The licensing authority must keep under review—

(a)the conditions under this regulation to which a UK marketing authorisation [F55or parallel import licence] is subject; and

(b)the holder's compliance with those conditions.

(8) The licensing authority must consider those matters no less frequently than—

(a)at the end of the period of one year beginning with the date on which the authorisation [F56or licence] was granted; and

(b)at the end of each subsequent period of one year.

[F58(9) The licensing authority must notify the EMA of any UKMA(NI) or UKMA(UK) that it has granted subject to a condition included in accordance with this regulation.]

(10) The holder of the authorisation [F56or licence] must incorporate any condition included in a marketing authorisation [F59or licence] in accordance with this regulation into the risk management system for the product.

(11) Schedule 11 makes provision about advice and representations in relation to proposals to vary or remove a condition to which a UK marketing authorisation [F55or parallel import licence] is subject.

Textual Amendments

[F60Condition as to the submitting of samples and other information to the appropriate authority U.K.

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;

“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—

(a)

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

(b)

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—

(a)

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

(b)

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—

(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 batch is in conformity with the approved specifications in the UK marketing authorisation; and

“the batch testing exemption” means that—

(a)

in the case of a medicinal product for sale or supply in Northern Ireland only—

(i)

a certificate has been issued by a laboratory in an EEA State, and

(ii)

in relation to a product of a kind listed in Article 114(1) of the 2001 Directive, the certificate was issued in the same EEA State as that in which the batch was manufactured, or

(i)

a certificate has been issued by a laboratory in a country other than the United Kingdom,

(ii)

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

(iii)

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 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) and regulation 60B(5).

(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 under this regulation or regulation 60B;

(b)include in that list any conditions or restrictions in that agreement that affect the applicability of the batch testing exemption under this regulation or regulation 60B; 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).

(14) The appropriate authority may, in any particular case, apply this regulation to a medicinal product imported into the United Kingdom pursuant to a parallel import licence and accordingly any reference in this regulation to—

(a)a UK marketing authorisation should be read as a reference to a parallel import licence for a medicinal product,

(b)the holder of a UK marketing authorisation should be read as a reference to the holder of a parallel import licence, and

(c)the approved specifications in a UK marketing authorisation should be read as a reference to the approved specifications in the UK reference product specified for the purposes of the parallel import licence in accordance with paragraph 4 of Schedule 8A.

(15) Where, pursuant to paragraph (14), this regulation is applied to a medicinal product imported into the United Kingdom pursuant to a parallel import licence, sub-paragraph (a) of the definition of “the batch testing exemption” does not apply.

(16) In the application of this regulation to a medicinal product for sale or supply in Northern Ireland only to which Article 114 of the 2001 Directive applies, a reference in this regulation to a laboratory is to an Official Medicines Control Laboratory or a laboratory referred to in that Article.]

Textual Amendments

[F60Submitting of samples and other information: EU marketing authorisationsU.K.

60B.—(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;

“appropriate documentation”, in relation to a sample of a batch submitted to the appropriate authority in accordance with the batch testing requirement or pursuant to a notification under paragraph (8), means such documentation as the appropriate authority notifies the holder of the EU 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 regulation 60A(5), and “approved country for batch testing and certification of biological medicinal products” means a country included in that list;

“the batch testing exemption” means that—

(i)

a certificate has been issued by a laboratory in an EEA State, and

(ii)

in relation to a product of a kind listed in Article 114(1) of the 2001 Directive, the certificate was issued in the same EEA State as that in which the batch was manufactured, or

(i)

a certificate has been issued by a laboratory in a country other than the United Kingdom,

(ii)

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

(iii)

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;

“the batch testing requirement”, in respect of an EU marketing authorisation, is a requirement that, unless the batch testing exemption applies, the holder of the EU marketing authorisation—

(a)

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

(b)

must not sell or supply, or offer to sell or supply, a medicinal product that forms part of that batch in Northern Ireland 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 batch is in conformity with the approved specifications in the EU marketing authorisation.

(2) The licensing authority may impose the batch testing requirement on the holder of an EU marketing authorisation for a medicinal product—

(a)that is—

(i)a live vaccine;

(ii)an immunological product used in the primary immunisation of infants or other groups at risk;

(iii)an immunological product used in public health immunisation programmes;

(iv)subject to paragraph (3), a new immunological product manufactured using new or altered kinds of technology or new for a particular manufacturer; or

(v)derived from human blood or human plasma, and

(b)which is intended for sale or supply in Northern Ireland.

(3) If the licensing authority imposes the batch testing requirement in respect of an EU marketing authorisation for a medicinal product of a kind mentioned in paragraph (2)(a)(iv), it must, in imposing that requirement, specify a period of time for the duration of the requirement.

(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) Where a holder of an EU marketing authorisation, in order to comply with the batch testing requirement, 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.

(6) Where a holder of an EU 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 Northern Ireland.

(7) Paragraph (8) 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.

(8) Where this paragraph applies, the appropriate authority must, subject to paragraph (9), notify the holder of the EU 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 Northern Ireland 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 EU marketing authorisation.

(9) The appropriate authority may only exercise its powers under paragraph (8) 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 (7).

(10) A reference in this regulation to a laboratory (other than in paragraph (b) of the definition of “the batch testing exemption” in paragraph (1)) is to an Official Medicines Control Laboratory or a laboratory referred to in Article 114 of the 2001 Directive.]

Textual Amendments

Conditions of UK marketing authorisation: new obligations post-authorisationU.K.

61.—(1) After the granting of a UK marketing authorisation, the licensing authority may impose an obligation on the holder of the authorisation in accordance with either or both of —

(a)paragraph (4), in a case where paragraph (2) applies; or

(b)paragraph (5), in a case where paragraph (3) applies.

(2) This paragraph applies if there are concerns about the risks of a medicinal product that is the subject of a marketing authorisation.

(3) This paragraph applies if the understanding of the disease or the clinical methodology indicate that previous efficacy evaluations might have to be revised significantly.

[F61(4) The obligation in this paragraph is—

(a)to conduct a post-authorisation safety study; or

(b) in relation to a UKMA(GB), to comply with such other conditions or restrictions as the licensing authority considers essential for the safe and effective use of the medicinal product.]

(5) The obligation in this paragraph is to conduct a post-authorisation efficacy study.

(6) If concerns as described in paragraph (2) apply to more than one medicinal product [F62authorised by a UKMA(NI) or UKMA(UK)], the licensing authority shall, following consultation with the Pharmacovigilance Risk Assessment Committee, encourage the marketing authorisation holders concerned to conduct a joint post-authorisation safety study.

[F63(6A) If concerns as described in paragraph (2) apply to more than one medicinal product authorised by a UKMA(GB), 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.]

(7) [F64In relation to a UKMA(NI) or UKMA(UK), the obligation under paragraph (5) must] be based on the delegated acts adopted pursuant to Article 22b of the 2001 Directive while taking account of the scientific guidance referred to in Article 108a of the 2001 Directive.

[F65(7A) In relation to a UKMA(GB), 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.

(7B) The Secretary of State may by regulations make provision in respect of Great Britain specifying the situations in which post-authorisation efficacy studies may be required by virtue of the obligation under paragraph (5).

(7C) Paragraph (7A)(a) ceases to apply on the coming into force of regulations made under paragraph (7B).]

(8) Where the licensing authority imposes an obligation under paragraph (4) or (5), it must without delay give written notice to the holder of —

(a)the imposition of the obligation;

(b)the justification for the imposition;

(c)the objectives and timeframe for submission and conduct of the study; and

(d)the opportunity to present written observations in accordance with paragraph (9) and the time limit specified for doing so.

(9) Where the holder so requests within the period of thirty days beginning on the day after the receipt by the holder of the notice referred to in paragraph (8), the licensing authority must provide the holder of the authorisation with an opportunity to present written observations in response to the imposition of the obligation within the time limit specified by the licensing authority in the notice.

(10) Where the holder presents written observations under paragraph (9), the licensing authority must withdraw or confirm the imposition of the obligation under paragraph (4) or (5) on the basis of the written observations as soon as is reasonably practicable.

(11) Paragraph (12) applies where the licensing authority—

(a)imposes an obligation under paragraph (4) or (5) and the holder does not present written representations under paragraph (9); or

(b)confirms the imposition of an obligation under paragraph (10).

(12) Where this paragraph applies, the licensing authority must vary the marketing authorisation to include the obligation as a condition of the marketing authorisation as if it were a condition imposed under regulation 59 (conditions of UK marketing authorisations: general).

(13) The licensing authority must notify the EMA [F66, in relation to a UKMA(NI) or UKMA(UK),] that the marketing authorisation is subject to a condition included in accordance with paragraph (12).

(14) The holder of the authorisation must incorporate any condition included in a marketing authorisation in accordance with paragraph (12) into the risk management system for the product.

(15) Schedule 11, which makes provision about advice and representations in relation to proposals to vary or remove a condition to which a UK marketing authorisation is subject, shall apply in relation to the variation or removal of a condition included in a marketing authorisation in accordance with paragraph (12).

Textual Amendments

Classification of UK marketing authorisation [F67or parallel import licence] U.K.

62.—(1) A UK marketing authorisation [F68or parallel import licence] must include a term that the product to which the authorisation relates is to be available—

(a)only on prescription;

(b)only from a pharmacy; or

(c)on general sale.

(2) In making a determination under paragraph (1), the licensing authority must have regard to the following in relation to the product—

(a)the maximum single dose;

(b)the maximum daily dose;

(c)the strength of the product;

(d)its pharmaceutical form;

(e)its packaging; and

(f)such other circumstances relating to its use as the licensing authority considers relevant.

(3) A UK marketing authorisation [F69or parallel import licence] must be granted subject to a condition that the product to which the authorisation relates is to be available only on prescription if the licensing authority considers that the product—

(a)is likely to present a direct or indirect danger to human health, even when used correctly, if used without the supervision of a doctor or dentist;

(b)is frequently and to a very wide extent used incorrectly, and as a result is likely to present a direct or indirect danger to human health;

(c)contains substances, or preparations of substances, of which the activity requires, or the side effects require, further investigation; or

(d)is normally prescribed by a doctor or dentist for parenteral administration.

(4) In deciding whether paragraph (3) applies to a product, the licensing authority must take into account whether the product—

(a)contains a substance listed in any of Schedules I, II or IV to the Narcotics Drugs Convention (where the product is not a preparation listed in Schedule III to that Convention);

(b)contains a substance listed in any of Schedules I to IV of the Psychotropic Substances Convention (where the product is not a preparation which may be exempted from measures of control in accordance with paragraphs 2 and 3 of article 3 of that Convention);

(c)is likely, if incorrectly used—

(i)to present a substantial risk of medicinal abuse,

(ii)to lead to addiction, or

(iii)to be used for illegal purposes;

(d)contains a substance that, by reason of its novelty or properties, might fall within paragraph (c), but as to which there is insufficient information available to determine whether it does so fall;

(e)by reason of its pharmaceutical characteristics or novelty, or in the interests of public health, is reserved for treatments that can only be followed in a hospital;

(f)is used in the treatment of conditions that must be diagnosed in a hospital or in an institution with special diagnostic facilities (although administration and subsequent supervision may be carried out elsewhere); or

(g)is intended for outpatients but may produce very serious side effects which would require a prescription drawn up as required by a specialist and special supervision throughout the treatment.

(5) A UK marketing authorisation [F70or parallel import licence] may include a term that the product to which the authorisation relates is to be available on general sale only if the licensing authority considers that the product can with reasonable safety be sold or supplied otherwise than by, or under the supervision of, a pharmacist.

Textual Amendments

F67Words in reg. 62 heading inserted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 4 and words in reg. 62 heading inserted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 4(2)(f)

F68Words in reg. 62(1) inserted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 4 and words in reg. 62(1) inserted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 4(2)(g)

F69Words in reg. 62(3) inserted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 4 and words in reg. 62(3) inserted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 4(2)(g)

F70Words in reg. 62(5) inserted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 4 and words in reg. 62(5) inserted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 4(2)(g)

Frequency of periodic safety update reportsU.K.

63.—(1) The licensing authority must, if paragraph (2) applies, include in a UK marketing authorisation a term that specifies the frequency, calculated from the date on which the authorisation is granted, with which the holder of the authorisation must submit periodic safety update reports in accordance with regulation 191(8) (obligation on holder to submit periodic safety update reports: general requirements).

(2) This paragraph applies in the case of a medicinal product in relation to which regulation 191(8) applies by virtue of regulation 191(1).

Duties of licensing authority in connection with determinationU.K.

64.—(1) This regulation applies if the licensing authority grants a UK marketing authorisation.

(2) The licensing authority must inform the holder of the authorisation of the summary of the product characteristics as approved by the authority.

(3) The licensing authority must ensure that the summary of the product characteristics continues to match the version it has approved, subject to any changes it approves.

(4) As soon as is reasonably practicable after granting the marketing authorisation, the licensing authority must make available publicly—

(a)the marketing authorisation;

(b)the package leaflet;

(c)the summary of the product characteristics;

[F71(d)any conditions—

(i)in the case of a UKMA(NI) or UKMA(UK), established in accordance with Articles 21a, 22 and 22a of the 2001 Directive;

(ii)in the case of UKMA(GB), imposed under regulations 59 to 61; and]

(e)any deadlines for the fulfilment of those conditions.

(5) The licensing authority must draw up an assessment report and make comments on the file as regards—

(a)the results of the pharmaceutical and pre-clinical tests, the clinical trials, the risk management system and the pharmacovigilance system of the product to which the authorisation relates; or

(b)in the case of a national homoeopathic medicinal product within the meaning of Schedule 10, the information submitted under paragraphs 3 to 5 of that Schedule.

(6) The licensing authority must—

(a)revise the assessment report whenever new information becomes available that is of importance for the evaluation of the quality, safety or efficacy of the medicinal product;

(b)make the assessment report publicly available (with the omission of information of a commercially confidential nature) as soon as is reasonably practicable after it has been prepared or revised; and

(c)include in the assessment report a summary, written in a manner that is understandable to the public, that contains, in particular, a section relating to the conditions of use of the medicinal product.

(7) The assessment must be provided separately for each indication that is authorised.

Textual Amendments

[F72Obligation of licensing authority in case of change of classificationU.K.

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—

(i)a UK marketing authorisation;

(ii)an Article 126a authorisation;

(iii)a traditional herbal registration; or

(iv)a certificate of registration of a homoeopathic medicinal product;

(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.]

Textual Amendments

Validity of UK marketing authorisationU.K.

Validity of UK marketing authorisationU.K.

65.—(1) Subject to the following paragraphs, a UK marketing authorisation remains in force—

(a)for an initial period of five years beginning with the date on which it is granted; and

(b)if the authorisation is renewed in accordance with regulation 66, for an unlimited period after its renewal.

(2) The licensing authority may, on the first application for renewal of an authorisation, determine on grounds relating to pharmacovigilance, including exposure of an insufficient number of patients to the medicinal product concerned, that it should be necessary for the holder to make one further application for renewal.

(3) In that event the authorisation remains in force—

(a)for a further period of five years beginning with the date on which it is first renewed; and

(b)if the authorisation is further renewed under regulation 66, for an unlimited period after its further renewal.

(4) If an application for the renewal or further renewal of an authorisation is made in accordance with regulation 66 the authorisation remains in force until the licensing authority notifies the applicant of its decision on the application.

(5) This regulation is subject to—

[F73(za)regulation 65B;]

(a)regulation 67 (failure to place on the market etc); and

(b)regulation 68 (revocation etc of marketing authorisations).

Textual Amendments

[F74Validity of parallel import licenceU.K.

65A.—(1) Unless paragraph (2) applies, a parallel import licence remains in force for a period of 5 years from the date it is granted or renewed.

(2) A parallel import licence will cease to be valid if—

(a)the information supplied in the application for a licence no longer matches the information currently approved for the reference product by the licensing authority;

(b)details about the product imported under the licence are not consistent with the details supplied in the application; or

(c)the patient information leaflet supplied with the product is not consistent with latest version of the leaflet that is required to be issued with the product by the licensing authority, and

an application to vary the licence to update any details in relation to sub-paragraph (a) to (c) has not been granted by the licensing authority because the condition in regulation 68(11) has not been met.]

Textual Amendments

[F75Validity of conditional marketing authorisationU.K.

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.

Textual Amendments

Variation of a UKMA(GB)U.K.

65C.—(1) A UKMA(GB) 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 UKMA(GB) 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 which applied immediately before IP completion 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 IP completion day; or

(b)applications made before IP completion 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.]

Textual Amendments

Application for renewal of authorisationU.K.

66.—(1) The licensing authority may renew a UK marketing authorisation in response to an application made in accordance with this regulation.

[F76(2) The applicant, where it is applying for renewal of—

(a)a UKMA(NI)—

(i)in accordance with Chapter 4 of Title III of the 2001 Directive, must be established in the European Union;

(ii)on any other basis, must be established in the United Kingdom;

(b)a UKMA(GB)—

(i)under the unfettered access route, must be established in Northern Ireland;

(ii)other than under the unfettered access route, must be established in the United Kingdom;

(c)a UKMA(UK), must be established in the United Kingdom.]

(3) The application must be—

(a)made in writing;

(b)signed by or on behalf of the applicant; and

(c)unless the licensing authority directs otherwise, accompanied by any fee payable in connection with the application.

(4) An application is treated as signed for the purposes of paragraph (3)(b) if it is signed with an electronic signature.

(5) The application must be made so that it is received by the licensing authority before the beginning of the period of nine months ending with the expiry of the period mentioned in paragraph (1)(a) or (as the case may be) (3)(a) of regulation 65 (initial and further period of validity).

(6) The holder must provide a consolidated version of the file in respect of quality, safety and efficacy, including—

(a)the evaluation of data contained in suspected adverse reaction reports and periodic safety update reports submitted in accordance with Part 11; and

(b)all amendments made since the authorisation was granted.

(7) The licensing authority may renew a UK marketing authorisation only if, having considered the application and the material accompanying it, the authority thinks that the positive therapeutic effects of the product to which the authorisation relates outweigh the risks of the product to the health of patients or of the public.

(8) Schedule 11 makes provision about advice and representations in relation to an application for the renewal of a UK marketing authorisation.

Textual Amendments

F76Reg. 66(2) substituted (31.12.2020) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 (S.I. 2019/775), reg. 74 (as amended by (S.I. 2020/1488), reg. 1, Sch. 2 para. 55); 2020 c. 1, Sch. 5 para. 1(1)

[F77Application for renewal of a parallel import licenceU.K.

66A.—(1) The licensing authority may renew a parallel import licence in response to an application made in accordance with this regulation.

(2) The applicant must be established in the [F78United Kingdom].

(3) The application must be—

(a)made in writing;

(b)signed by or on behalf of the applicant; and

(c)unless the licensing authority directs otherwise, accompanied by any fee payable in connection with the application.

(4) An application is treated as signed for the purposes of paragraph (3)(b) if it is signed with an electronic signature.

(5) The application must be made so that it is received by the licensing authority within three months of the end of a period expiring 5 years after the date of grant or (as the case may be) latest renewal of the licence.]

Textual Amendments

[F79Renewal of conditional marketing authorisationU.K.

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.]

Textual Amendments

Failure to place on the market etcU.K.

67.—(1) A UK marketing authorisation ceases to be in force if the product to which it relates is not placed on the market in the United Kingdom [F80(or, in the case of a UKMA(GB) granted after an application under the unfettered access route, in Great Britain)] during the period of three years beginning immediately after the day on which it was granted.

(2) A UK marketing authorisation for a product which has been placed on the market ceases to be in force if the product to which it relates is not sold or supplied in the United Kingdom [F81(or, in the case of a UKMA(GB) granted after an application under the unfettered access route, in Great Britain)] for a period of three years.

(3) This regulation does not apply if the licensing authority grants an exemption from its operation.

(4) An exemption may be granted—

(a)in response to an application in writing by the holder of the UK marketing authorisation; or

(b)by the licensing authority of its own motion.

(5) An exemption may be granted only—

(a)in exceptional circumstances; and

(b)on public health grounds.

(6) An exemption—

(a)has effect for the period determined by the licensing authority, which may not exceed three years beginning with the day on which it is granted; and

(b)may be renewed or further renewed.

Textual Amendments

Revocation, variation and suspension of marketing authorisationU.K.

Revocation, variation and suspension of UK marketing authorisation [F82or parallel import licence] U.K.

68.—(1) The licensing authority may revoke, vary or suspend a UK marketing authorisation [F83or parallel import licence] if any of the following conditions is met.

(2) Condition A is that the licensing authority thinks that—

(a)the product to which the authorisation relates is harmful;

(b)the positive therapeutic effects of the product do not outweigh the risks of the product to the health of patients or of the public;

(c)the product lacks therapeutic efficacy, in that therapeutic results cannot be obtained from the product; or

(d)the product's qualitative or quantitative composition is not as described in the application for the authorisation or the material supplied with it.

(3) Condition B is that the licensing authority thinks that the application or the material supplied with it is incorrect.

[F84(4) Condition C is that the licensing authority thinks that there has been a breach of—

(a)a term of the authorisation or licence;

(b)in the case of a UK marketing authorisation, a requirement imposed by Part 13 (packaging and leaflets); or

(c)in the case of a parallel import licence, a requirement in relation to packaging and leaflets imposed by the licensing authority.]

[F85(5) Condition D is that the licensing authority thinks that a condition to which—

(a)the UK marketing authorisation or parallel import licence is subject by virtue of regulation 59 (conditions of UK marketing authorisations or parallel import licence: general); or

(b)the UK marketing authorisation is subject by virtue of regulations 60 (conditions of UK marketing authorisations: exceptional circumstances) [F86, regulation 60A (conditions as to testing of samples by the appropriate authority)] or 61 (conditions of UK marketing authorisations: new obligations post-authorisation),

has not been fulfilled.]

(6) Condition E is that the licensing authority thinks that the holder of the authorisation has not complied with regulation 75(1) to (3) (requirements to provide information).

(7) Condition F is that the holder of the authorisation [F87or licence] has ceased to be [F88established in—

(a)the United Kingdom; or

(b)in relation to a UKMA(NI), either the United Kingdom or the European Union,

in accordance with the requirements of these Regulations.]

(8) Condition G is that—

(a)the product to which the authorisation relates is manufactured in the United Kingdom; and

(b)the licensing authority thinks that the holder of the manufacturer's licence for the product has failed to comply in relation to the product with regulations 37 (manufacturing and assembly), 38 (imports from [F89countries other than approved countries for import]), 39 (further requirements for manufacturer's licence), 40 (obligation to provide information relating to control methods) or 41 (requirements as to qualified persons).

(9) Condition H is that—

(a)the product to which the authorisation relates is manufactured in a member State F90...; and

(b)the licensing authority thinks that the licensee under the manufacturer's licence for the product has failed to comply in relation to the product with provision giving effect to Article 41 of the 2001 Directive (requirements relating to manufacturing authorisations) in that member State.

(10) Condition I is that the licensing authority thinks that urgent action to protect public health is necessary, in which case it—

(a)may suspend the [F91authorisation or licence.]

F92(b). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

(11) Condition J is that—

(a)the holder applies to vary the authorisation [F93or licence]; and

(b)the licensing authority thinks that the application should be granted.

[F94(11A) Condition K is that the manufacture of the product to which the authorisation relates is not carried out in compliance with the particulars provided under paragraphs 5 and 9 of Schedule 8.]

[F95(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 IP completion 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 IP completion 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).

(11G) Condition P is that the licensing authority thinks that the revocation, variation or suspension is necessary or expedient in light of the Protocol on Ireland/Northern Ireland in the withdrawal agreement.]

(12) Schedule 11 makes provision about advice and representations in relation to a proposal to revoke, vary or suspend a UK marketing authorisation [F96or parallel import licence], other than a proposal to vary an authorisation [F97or licence] on the application of its holder.

F98(13) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Textual Amendments

F82Words in reg. 68 heading inserted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 4 and words in reg. 68 heading inserted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 4(2)(h)

F83Words in reg. 68(1) inserted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 4 and words in reg. 68(1) inserted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 4(2)(i)

F88Reg. 68(7)(a)(b) and words substituted for words (31.12.2020) by S.I. 2019/775, reg. 77(3)(b) (as substituted by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2020 (S.I. 2020/1488), reg. 1, Sch. 2 para. 57(a))

Suspension of use etc of relevant medicinal productU.K.

69.—(1) The licensing authority may, if any of the following conditions are met, suspend the use, sale, supply or offer for sale or supply within the United Kingdom of a product to which a UK marketing authorisation [F99or parallel import licence] relates.

(2) Condition A is that the licensing authority thinks that—

(a)the product to which the authorisation relates is harmful;

(b)the positive therapeutic effects of the product do not outweigh the risks of the product to the health of patients or of the public;

(c)the product lacks therapeutic efficacy, in that therapeutic results cannot be obtained from the product; or

(d)the product's qualitative or quantitative composition is not as described in the application for the authorisation or the material supplied with it.

(3) Condition B is that the licensing authority thinks that the holder of the authorisation has not complied with regulation 75(7) (requirements to provide proof of controls on manufacturing process).

(4) Condition C is that the licensing authority thinks that there has been a breach of—

(a)a term of the authorisation; or

(b)a requirement imposed by Part 13 (packaging and leaflets).

(5) Condition D is that the licensing authority thinks that paragraph (4) or (5) of regulation 26 (power to revoke, suspend or vary manufacturers' licences) applies in relation to the manufacturer's licence for the product to which the authorisation relates.

(6) A suspension under this regulation may relate to batches of the product.

(7) The licensing authority must give notice in writing of a suspension under this regulation to the holder of the UK marketing authorisation [F100or parallel import licence].

(8) The licensing authority must provide in the notice that the suspension—

(a)is to take effect immediately or from a date specified in the notice; and

(b)is to apply for the period specified in the notice.

(9) Where a medicinal product is the subject of a suspension under this regulation, the licensing authority may—

(a)in exceptional circumstances; and

(b)for such a transitional period as the licensing authority may determine,

allow the supply of the medicinal product to patients who are already being treated with the medicinal product.

F101(10) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Textual Amendments

F99Words in reg. 69(1) inserted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 4 and words in reg. 69(1)(7) inserted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 4(2)(j)

F100Words in reg. 69(7) inserted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 4 and words in reg. 69(1)(7) inserted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 4(2)(j)

Authorisations granted under Chapter 4 of Title III of the 2001 DirectiveU.K.

F10270.  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Textual Amendments

Withdrawal of medicinal product from the marketU.K.

71.—(1) This regulation applies if—

[F103(a)under regulation 68 the licensing authority revokes or suspends a UK marketing authorisation or parallel import licence; or]

[F104(b)under—

(i)regulation 69 the licensing authority suspends the use, sale, supply or offer for sale or supply within Great Britain of a product to which a UKMA(GB) relates; or

(ii)regulation 69 or Article 20(4) of Regulation (EC) No 726/2004 the licensing authority suspends the use, sale, supply or offer for sale or supply within Northern Ireland of a product to which a UKMA(NI) or UKMA(UK) relates.]

(2) The licensing authority may give written notice to the person who is, or immediately before its revocation was, the holder of the authorisation [F105or related parallel import licence] requiring that person to comply with both of the following requirements.

(3) Requirement A is to take all reasonably practicable steps to inform wholesalers, retailers, medical practitioners, patients and others who may be in possession of the product to which the authorisation relates of—

(a)the revocation or suspension;

(b)the reasons for the revocation or suspension; and

(c)any action to be taken to restrict or prevent further use, sale, supply or offer for sale or supply of the product.

(4) Requirement B is to take all reasonably practicable steps to withdraw from the market in the United Kingdom and recover possession of—

(a)the product; or

(b)the batches of the product specified in the notice,

within the time and for the period specified in the notice.

Textual Amendments

F105Words in reg. 71(2) inserted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 13 and words in reg. 71(2) inserted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 13

Sale etc of suspended medicinal productU.K.

72.—(1) This regulation applies if the use, sale, supply or offer for sale or supply of a medicinal product is suspended in accordance with

[F106(a)in the case of a medicinal product authorised for sale or supply by a UKMA(GB), regulation 69;

(b)in the case of a medicinal product authorised for sale or supply by a UKMA(NI) or UKMA(UK), regulation 69 or Article 20(4) of Regulation (EC) No 726/2004].

(2) A person must not—

(a)sell, supply or offer to sell or supply the product; or

(b)procure the sale, supply or offer for sale or supply of the product,

knowing, or having reasonable cause to believe, that such use, sale, supply or offer for sale or supply is suspended.

Textual Amendments

F106Reg. 72(1)(a)(b) substituted for words in reg. 72(1) (31.12.2020) by S.I. 2019/775, reg. 81 (as substituted by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2020 (S.I. 2020/1488), reg. 1, Sch. 2 para. 59)

Obligations of holder of marketing authorisationU.K.

Obligation to notify placing on the market etcU.K.

73.—(1) The holder of a UK marketing authorisation must notify the licensing authority of the date on which the product to which the authorisation relates is placed on the market in the United Kingdom, taking account of the various presentations authorised.

(2) A notification under paragraph (1) must be given before the end of the period of two months beginning with the date on which the product is placed on the market.

(3) The holder of a UK marketing authorisation must notify the licensing authority if the product to which the authorisation relates is to be withdrawn from the market in the United Kingdom (whether temporarily or permanently).

(4) A notification under paragraph (3) must be given before the beginning of the period of two months ending with the date on which the product is to be withdrawn from the market unless it is not reasonably practicable to do so.

(5) In that event, the notification must be given as far as is reasonably practicable in advance of the date on which the product is withdrawn from the market.

[F107(5A) The holder of a UK marketing authorisation must notify the licensing authority forthwith if the holder takes action to—

(a)request the cancellation of the authorisation;

(b)not apply for the renewal of the authorisation; or

(c)withdraw the product to which the authorisation relates from the market in a [F108country other than the United Kingdom] (whether temporarily or permanently) and the action is based on any of the grounds set out in Article 116 or 117(1) of the 2001 Directive.

(5B) A notification under paragraph (3) or (5A) must include the reasons for the action, in particular declaring if the action is based on any of the grounds set out in Article 116 or 117(1) of the 2001 Directive.

(5C) The holder of a [F109UKMA(NI) or UKMA(UK)] must also notify the EMA forthwith where the action which is the subject of a notification by the holder under paragraph (3) or (5A) is based on any of the grounds set out in Article 116 or 117(1) of the 2001 Directive.]

(6) The licensing authority may require the holder of a UK marketing authorisation to provide—

(a)information relating to the volume of sales in the United Kingdom of the product to which the authorisation relates; or

(b)information of which the holder is aware relating to the volume of prescriptions in the United Kingdom for the product.

(7) The holder of a UK marketing authorisation must provide the licensing authority with information that it requires under paragraph (6)—

(a)where the period within which the information must be provided is specified in a written notice given to the holder by the licensing authority, before the end of that period; or

(b)otherwise, as soon as is reasonably practicable after receipt of the request.

Textual Amendments

F109Words in reg. 73(5C) substituted (31.12.2020) by virtue of S.I. 2019/775, reg. 82(3) (as substituted by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2020 (S.I. 2020/1488), reg. 1, Sch. 2 para. 60)

Obligation to take account of scientific and technical progressU.K.

74.—(1) The holder of a UK marketing authorisation must keep under review the methods of manufacture and control of the product to which the authorisation relates, taking account of scientific and technical progress.

(2) As soon as is reasonably practicable after becoming aware of the need to do so, the holder must apply to vary the marketing authorisation to make any changes to those methods that are required to ensure they are generally accepted scientific methods.

Obligation to provide information relating to safety etcU.K.

75.—(1) The holder of a UK marketing authorisation [F110or parallel import licence] must provide the licensing authority with any new information that might entail the variation of the authorisation.

(2) The holder [F111of a UK marketing authorisation] must, in particular, provide the licensing authority with the following information—

(a)information about any prohibition or restriction imposed in relation to the product to which the authorisation relates by the competent authority of any country in which the product is on the market;

(b)positive and negative results of clinical trials or other studies in all indications and populations, whether or not included in the marketing authorisation;

(c)data on the use of the medicinal product where such use is outside the terms of the marketing authorisation; and

(d)any other information that the holder considers might influence the evaluation of the benefits and risks of the product.

[F112(2A) The holder of a parallel import licence must, in particular, provide the licensing authority with—

(a)information about any prohibition or restriction imposed in relation to the product to which the licence relates by the competent authority of any country in which the product is on the market; and

(b)other information that the holder considers might influence the evaluation of the benefits and risks of the product.]

(3) Information within paragraph (1) [F113to (2A)] must be provided as soon as is reasonably practicable after the holder becomes aware of it.

(4) The licensing authority may require the holder of a UK marketing authorisation to provide the authority with information that—

(a)is specified by the licensing authority; and

(b)demonstrates that the positive therapeutic effects of the product to which the authorisation relates continue to outweigh the risks of the product to the health of patients or of the public.

[F114(4A) The licensing authority may require the holder of a parallel import licence to provide further information specified by the licensing authority.]

(5) The information that may be required under paragraph (4) [F115or (4A)] includes information arising from use of the product—

[F116(a)in a country other than the United Kingdom;]

(b)outside the terms of the [F117UK] marketing authorisation,

including use in clinical trials.

(6) If the information supplied under paragraph (1), (2)[F118, (4) or (4A)] entails the variation of the UK marketing authorisation [F119or parallel import licence], the holder must make an application to the licensing authority to that effect as soon as is reasonably practicable after becoming aware of the information.

(7) The licensing authority may require the holder of a UK marketing authorisation to provide the authority with proof of the control methods employed by the manufacturer of the product to which the authorisation relates.

(8) The holder of a UK marketing authorisation [F120or parallel import licence] must provide the licensing authority with information it requests under paragraphs [F121(4), (4A) or] (7)—

(a)where the period within which the information must be provided is specified in a written notice given to the holder by the licensing authority, before the end of that period; or

(b)otherwise, as soon as is reasonably practicable after receipt of the request.

Textual Amendments

F110Words in reg. 75(1) inserted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 4 and words in reg. 75(1) inserted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 4(2)(l)

F113Words in reg. 75(3) substituted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 14(4) and words in reg. 75(3) substituted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 14(4)

F118Words in reg. 75(6) substituted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 14(7) and words in reg. 75(6) substituted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 14(7)

F119Words in reg. 75(6) inserted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 4 and words in reg. 75(6) inserted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 4(2)(l)

F120Words in reg. 75(8) inserted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 4 and words in reg. 75(8) inserted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 4(2)(l)

F121Words in reg. 75(8) substituted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 14(8) and words in reg. 75(8) substituted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 14(8)

Obligation in relation to product informationU.K.

76.—(1) The holder of a UK marketing authorisation [F122or parallel import licence] for a medicinal product must ensure that the product information relating to the product is kept up to date with current scientific knowledge.

[F123(2) In this regulation “current scientific knowledge” includes the conclusions of the assessment and recommendations made public by means of—

(a)in the case of a medicinal product authorised for sale or supply by a UKMA(NI) or a UKMA(UK)—

(i)the European medicines web-portal established in accordance with Article 26 of Regulation (EC) No 726/2004, and

(ii)the UK web-portal established in accordance with regulation 203(1);

(b)in the case of a medicinal product authorised for sale or supply by a UKMA(GB), the UK web-portal established in accordance with regulation 203(1).]

Textual Amendments

F122Words in reg. 76(1) inserted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 4 and words in reg. 76(1) inserted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 4(2)(m)

Record-keeping obligationsU.K.

77.  The holder of a marketing authorisation [F124or parallel import licence] must keep any documents or information that will facilitate the withdrawal or recall from sale or supply of any product to which the authorisation relates.

Textual Amendments

Obligation to ensure appropriate and continued suppliesU.K.

78.  The holder of a marketing authorisation must take all reasonable steps to ensure appropriate and continued supplies of the product to which the authorisation relates to pharmacies and persons authorised to supply the product so that the needs of patients in the United Kingdom are met.

[F125Post authorisation requirements in relation to UK marketing authorisations to which paediatric specific provisions applyU.K.

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.

Textual Amendments

Post authorisation requirements in relation to UKMA(GB) for advanced therapy medicinal productsU.K.

78B.—(1) The holder of a UKMA(GB) 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,

(ii)as regards blood cells, regulations 8, 9(e) and 14 of the Blood Safety and Quality Regulations 2005, 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;

(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 UKMA(GB); and

(d)in the event of the UKMA(GB) 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 UKMA(GB) who is subject to the obligations in paragraph (1) remains subject to them even if the UKMA(GB) is suspended or revoked.]

Textual Amendments

Offences relating to specific requirementsU.K.

Failure to provide information on marketing authorisations to EMAU.K.

79.—(1) The holder of [F126a UKMA(NI) or UKMA(UK)] is guilty of an offence if the holder—

(a)has not submitted information to the EMA as required by Article 57(2)(b) of Regulation (EC) No 726/2004 (information on all existing medicinal products for human use authorised or registered in the EU) in relation to any medicinal product that is the subject of a marketing authorisation granted before 2nd July 2012; and

(b)fails to do so as soon as is reasonably practicable after the coming into force of these Regulations.

(2) The holder of [F127UKMA(NI) or UKMA(UK)] is guilty of an offence if the holder fails to submit information to the EMA as required by Article 57(2)(c) of Regulation (EC) No 726/2004 (information on any new or varied authorisations granted in the EU) in relation to any medicinal product that is the subject of a marketing authorisation granted on or after 2nd July 2012 as soon as is reasonably practicable after the grant of the authorisation.

Textual Amendments

Urgent safety restrictionsU.K.

80.  The holder of a [F128UK] marketing authorisation is guilty of an offence if the holder —

[F129(a)fails—

(i)in respect of a UKMA(GB) or UKMA(UK), to inform the licensing authority in accordance with paragraph 14(1) of Schedule 10A, or

(ii)in respect of a UKMA(NI), UKMA(UK) or EU marketing authorisation, to inform the European Commission in accordance with Article 22(1) of Regulation (EC) No 1234/2008,

that the holder has taken urgent safety restrictions on the holder’s own initiative;]

[F130(b)fails—

(i)in respect of a UKMA(GB), to implement an urgent safety restriction imposed on the holder by the licensing authority in accordance with paragraph 14(3) of Schedule 10A, or

(ii)in respect of a UKMA(NI) or UKMA(UK), to implement an urgent safety restriction imposed on the holder by the European Commission under Article 22(2) of Regulation (EC) No 1234/2008; or]

(c)fails [F131in respect of a UKMA(NI)] to submit an application for variation of the marketing authorisation to the licensing authority or the European Commission in accordance with Article 22(3) of that Regulation before the end of a period of fifteen days beginning on the day after—

(i)the taking under Article 22(1) or, as the case may be,

(ii)the imposition under Article 22(2),

of that Regulation of an urgent safety restriction.

[F132(d)fails in respect of a UKMA(GB) 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.]

Textual Amendments

[F133Urgent safety restrictions: parallel import licencesU.K.

80A.  The holder of a parallel import licence is guilty of an offence if the holder—

(a)fails to inform the licensing authority that the holder has taken urgent safety restrictions on the holder’s own initiative;

(b)fails to implement an urgent safety restriction imposed on the holder by the licensing authority; or

(c)fails to submit an application for variation of the parallel import licence to the licensing authority before the end of a period of fifteen days beginning on the day after—

(i)the taking of urgent safety restrictions under paragraph (a) or, as the case may be,

(ii)the imposition of urgent safety restrictions under paragraph (b).]

Textual Amendments

Offences relating to EU marketing authorisationsU.K.

[F134Application of regulations 81 to 94U.K.

A81.  Regulations 81 to 94 apply in relation to medicinal products for sale or supply in Northern Ireland [F135(that are not in Northern Ireland by virtue of regulation 167A)].]

Textual Amendments

Obligation to update information supplied in connection with EU applicationU.K.

81.  An applicant for an EU marketing authorisation is guilty of an offence if that person fails to supply updated information to the EMA in accordance with Article 8(3) of the 2001 Directive as applied by Article 6(1) of Regulation (EC) No 726/2004.

EU marketing authorisations: failure to notify placing on market etcU.K.

82.—(1) The holder of an EU marketing authorisation is guilty of an offence if the holder fails to notify the EMA in accordance with—

(a)the first paragraph of Article 13(4) of Regulation (EC) No 726/2004 (requirement to notify date of placing of product on the market); F136...

(b)the second paragraph of Article 13(4) of Regulation (EC) No 726/2004 (requirement to notify that product is to be withdrawn from the [F137market); or]

[F138(c)Article 14b of Regulation (EC) No 726/2004 (requirement to notify suspending of marketing of the product etc).]

(2) The holder of an EU marketing authorisation is guilty of an offence if the holder fails to provide the EMA with information that it requires under the third paragraph of Article 13(4) of Regulation (EC) No 726/2004 (information as to sales and prescriptions)—

(a)where the period within which the information must be provided is specified in a written notice given to the holder by the EMA, before the end of that period; or

(b)otherwise, as soon as is reasonably practicable after receipt of the request.

Textual Amendments

EU marketing authorisations: failure to take account of technical and scientific progressU.K.

83.  The holder of an EU marketing authorisation is guilty of an offence if the holder fails to apply to vary the marketing authorisation as required by Article 16(1) of Regulation (EC) No 726/2004 (obligation to take account of scientific and technical progress).

EU marketing authorisations: failure to provide information as to safety etcU.K.

84.—(1) The holder of an EU marketing authorisation is guilty of an offence if the holder fails to provide information to the EMA, the Commission or the licensing authority as required by Article 16(2) of Regulation (EC) No 726/2004 (new information which might entail amendment of particulars or documents) as soon as is reasonably practicable after becoming aware of the information.

(2) The holder of an EU marketing authorisation is guilty of an offence if the holder fails to provide the EMA with information that it requests as required by the first paragraph of Article [F13916(3a)] of Regulation (EC) No 726/2004 (data on risk-benefit balance).

Textual Amendments

EU marketing authorisations: failure to update product informationU.K.

85.—(1) The holder of an EU marketing authorisation for a medicinal product is guilty of an offence if the holder fails to ensure that the product information relating to the product is kept up to date with current scientific knowledge, as required by Article 16(3) of Regulation (EC) No 726/2004.

(2) In this regulation “current scientific knowledge” includes the conclusions of the assessment and recommendations made public by means of the European medicines web-portal established in accordance with Article 26 of Regulation (EC) No 726/2004.

EU marketing authorisations: breach of pharmacovigilance condition etcU.K.

86.—(1) The holder of an EU marketing authorisation is guilty of an offence if the holder fails to comply with—

(a)any obligation to which the marketing authorisation is subject by virtue of Articles 10a(1) or 14(7); or

(b)any condition to which the authorisation is subject by virtue of Article 14(8),

of Regulation (EC) No 726/2004.

(2) The holder of an EU marketing authorisation is guilty of an offence if the holder fails to incorporate into the risk management system for the product as required by Article 14a of Regulation (EC) No 726/2004—

(a)any recommendation referred to in Article 9(4)(c), (ca), (cb) or (cc);

(b)any obligation to which the authorisation is subject by virtue of Articles 10a(1) or 14(7) ; or

(c)any condition to which the marketing authorisation is subject by virtue of Article 14(8),

of Regulation (EC) No 726/2004.

Offences relating to advanced therapy medicinal productsU.K.

Offences in connection with risk management systems and traceability systemsU.K.

87.—(1) The holder of an EU marketing authorisation for an advanced therapy medicinal product is guilty of an offence if the holder fails to—

(a)submit an additional report evaluating the effectiveness of a risk management system and the results of studies within the period of 21 days beginning on the day following receipt of a request made under the second sub-paragraph of Article 14(2) of Regulation (EC) No 1394/2007, or such longer period as the EMA may specify; or

(b)include in any periodic safety update report referred to in Article 28(2) of Regulation (EC) No 726/2004 an evaluation of the effectiveness of a risk management system or of the results of any study performed pursuant to the first sub-paragraph of Article 14(2) of Regulation (EC) No 1394/2007, as required by the third sub-paragraph of Article 14(2).

(2) A person who is, or who immediately before its revocation or withdrawal was, the holder of an EU marketing authorisation for an advanced therapy medicinal product is guilty of an offence if the person fails to—

(a)establish and maintain a traceability system in accordance with the requirements set out in Article 15(1) of Regulation (EC) No 1394/2007;

(b)where the product contains human cells or tissues, to ensure that the traceability system is complementary to and compatible with the requirements laid down in Articles 8 and 14 of Directive 2004/23/EC, as regards human cells and tissues other than blood cells, and Articles 14 and 24 of Directive 2002/98/EC, as regards blood cells; or

(c)to keep the data to which the traceability system relates in accordance with the requirements of Article 15(4) of Regulation (EC) No 1394/2007.

Offence concerning data for advanced therapy medicinal productsU.K.

88.—(1) A person who is, or immediately before its revocation or suspension was, the holder of an EU marketing authorisation relating to an advanced therapy medicinal product is guilty of an offence if the person fails to—

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

(b)transfer the data referred to in Article 15(1) to the EMA in the event of that person's bankruptcy or liquidation in accordance with Article 15(5),

but this is subject to paragraph (2).

(2) Paragraph (1)(b) does not apply if—

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

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

Offences relating to the Paediatric RegulationU.K.

Offences in connection with withdrawal of product from the marketU.K.

89.—(1) This regulation applies to a person (“H”) if—

(a)H is the holder of a UK marketing authorisation;

(b)H has benefited from one or more rewards or incentives under [F140Article 37 or 38] of the Paediatric Regulation in relation to the product to which the authorisation relates, and

(c)all of the periods of protection provided pursuant to those Articles have expired in relation to H.

(2) H is guilty of an offence if H ceases to supply the product without previously in accordance with Article 35 of the Paediatric Regulation —

(a)transferring the UK marketing authorisation to another person who has declared an intention to continue to supply the product; or

(b)allowing such a person to use the pharmaceutical, pre-clinical and clinical documentation contained in the file on that product as provided for in regulation 56.

(3) H is guilty of an offence if H—

(a)ceases to supply the product; and

(b)does not in accordance with Article 35 of the Paediatric Regulation inform the EMA of H's intention to do so before the beginning of the period of six months ending immediately before the day on which H does so.

Textual Amendments

Failure to place on the market taking account of paediatric indicationU.K.

90.—(1) A person (“P”) is guilty of an offence if—

(a)P is the holder of a UK marketing authorisation;

(b)P obtains a paediatric indication in respect of the product to which the authorisation relates following completion of an agreed paediatric investigation plan;

(c)the product was placed on the market for other indications before P obtained that paediatric indication; and

(d)P fails to place the product on the market taking account of the paediatric indication in accordance with Article 33 of the Paediatric Regulation before the end of the period of two years beginning immediately after the day on which the paediatric indication is authorised.

(2) In this regulation “paediatric indication” means a term of the marketing authorisation enabling the product to which it relates to be used by or administered to persons under the age of 18 years.

Failure to notify results of third country clinical trialsU.K.

F14191.  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Textual Amendments

Failure of sponsor of UK paediatric clinical trial to notify results of trialU.K.

92.—(1) This regulation applies to the sponsor (“S”) of a paediatric clinical trial in the United Kingdom in respect of a medicinal product if—

(a)the product has a UK marketing authorisation but S is not the holder of the authorisation; or

(b)the product does not have a marketing authorisation.

(2) S is guilty of an offence if S does not submit the results of the clinical trial to the EMA in accordance with Article 41(2) of the Paediatric Regulation within the period of twelve months beginning with the day on which the trial ended.

Failure to notify results of paediatric studyU.K.

93.—(1) This regulation applies to a person (“H”) if—

(a)H is the holder of a UK marketing authorisation; and

(b)H sponsors a paediatric study in respect of the product to which the authorisation relates.

(2) H is guilty of an offence if H does not submit the results of the study to the licensing authority in accordance with Article 46(1) of the Paediatric Regulation within the period of six months beginning with the day on which the study ended.

(3) H is guilty of an offence if H does not submit the results of any clinical trial that forms part of that study to the EMA in accordance with Article 41(2) of the Paediatric Regulation within the period of six months beginning with the day on which the trial ended.

Failure to submit report to EMAU.K.

94.  The holder of a marketing authorisation is guilty of an offence if the holder fails to submit an annual report to the EMA as required by Article 34(4) of the Paediatric Regulation.

[F142Offences relating to the safety features appearing on the packaging of medicinal productsU.K.

Textual Amendments

F142Reg. 94A and cross-heading inserted (9.2.2019) by The Human Medicines (Amendment) Regulations 2019 (S.I. 2019/62), regs. 1, 8 and reg. 94A and cross-heading inserted (N.I.) (9.2.2019) by The Human Medicines (Amendment) Regulations 2019 (S.R. 2019/10), regs. 1, 8

Offences relating to Commission Regulation 2016/161U.K.

94A.—[F143(1) A person who is—

(a)the holder of a UKMA(NI), UKMA(UK) or parallel import licence, or

(b)a parallel distributor,

is guilty of an offence if the holder fails to comply with a requirement or obligation contained in a provision of Commission Regulation 2016/161 listed in paragraph (2).]

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

(a)Article 33 (uploading of information in the repositories system);

(b)Article 40 (products recalled, withdrawn or stolen);

(c)Article 41 (products to be supplied as free samples); and

(d)Article 42 (removal of unique identifiers from the repositories system).

[F144(3) In this regulation “parallel distributor” means a person who imports into Northern Ireland from an EEA state a product which has been granted a marketing authorisation under Regulation (EC) No 726/2004 and in relation to which that person is not the holder of a UKMA(NI), UKMA(UK), Article 126a authorisation, COR(NI), COR(UK), THR(NI) or THR(UK).]]

Textual Amendments

General provisions relating to offencesU.K.

Offences in connection with applicationU.K.

95.  A person is guilty of an offence if, in the course of an application for the grant, renewal or variation of a marketing authorisation for a relevant medicinal product, the person—

(a)fails to provide the licensing authority with any information that is relevant to the evaluation of the safety, quality or efficacy of the product;

(b)provides to the licensing authority any information that is relevant to the evaluation of the safety, quality or efficacy of the product but that is false or misleading in a material particular;

(c)[F145, in relation to an EU marketing authorisation for a product for sale or supply in Northern Ireland,] fails to provide the EMA with any information that is relevant to the evaluation of the safety, quality or efficacy of the product as required by paragraph (7) or (11) in the “Introduction and general principles” of Annex 1 to the 2001 Directive as applied by Article 6(1) of Regulation (EC) No 726/2004; or

(d)[F146, in relation to an EU marketing authorisation for a product for sale or supply in Northern Ireland,] provides to the EMA any information of the kind described in sub-paragraph (c) that is false or misleading in a material particular.

Textual Amendments

[F147Offences in connection with parallel import licence applicationU.K.

95A.  A person is guilty of an offence if, in the course of an application for the grant, renewal or variation of a parallel import licence for a relevant medicinal product, the person—

(a)fails to provide the licensing authority with any information that is relevant to the evaluation of the safety, quality or efficacy of the product; or

(b)provides to the licensing authority any information that is relevant to the evaluation of the safety, quality or efficacy of the product but that is false or misleading in a material particular.]

Textual Amendments

Provision of false or misleading informationU.K.

96.—(1) The holder of a marketing authorisation [F148or parallel import licence] is guilty of an offence if the holder provides any information to which paragraph (2) applies that is relevant to the evaluation of the safety, quality or efficacy of a medicinal product but that is false or misleading in a material particular to—

(a)the licensing authority;

(b)the EMA; or

(c)the competent authorities of other EEA States.

(2) This paragraph applies to information about the product that is supplied pursuant to the obligations in—

(a)these Regulations; or

(b)Regulation (EC) No 726/2004.

(3) This regulation is without prejudice to the operation of regulation 95.

Textual Amendments

F148Words in reg. 96(1) inserted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 4 and words in reg. 96(1) inserted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 4(2)(o)

Breach of pharmacovigilance conditionU.K.

[F14997.—(1) The holder of a marketing authorisation or a parallel import licence is guilty of an offence if the holder fails to comply with a condition to which the marketing authorisation or parallel import licence is subject by virtue of regulation 59 (conditions of a UK marketing authorisation or parallel import licence: general).

(2) The holder of a marketing authorisation is guilty of an offence if the holder fails to comply with a condition to which the marketing authorisation is subject by virtue of regulation 60 (conditions of a UK marketing authorisation: exceptional circumstances) [F150, regulation 60A (condition as to the testing of samples by the appropriate authority)] or 61 (conditions of a UK marketing authorisation: new obligations post-authorisation).]

Textual Amendments

General offence of breach of provision of this PartU.K.

98.—(1) A person is guilty of an offence if that person commits a breach of a provision in this Part.

(2) A breach of a provision in this Part includes any—

(a)failure by the holder of a marketing authorisation [F151or parallel import licence] to comply with any requirement or obligation in this Part:

(b)contravention by any person of any prohibition in this Part; or

(c)failure to comply with any requirement imposed on a person by the licensing authority pursuant to this Part.

(3) Paragraph (1) is without prejudice to any offence established by any other provision in this Part.

Textual Amendments

F151Words in reg. 98(2)(a) inserted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 4 and words in reg. 98(2)(a) inserted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 4(2)(p)

PenaltiesU.K.

99.—(1) A person guilty of an offence under this Part, other than a breach of regulation 79 (failure to provide information on marketing authorisations to EMA), is liable—

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

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

(2) A person guilty of a breach of regulation 79 is liable—

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

(b)on conviction on indictment, to a fine.

Persons liableU.K.

100.  If a breach of regulation 95 (offences in connection with application) is committed by a person acting as employee or agent, the employer or principal of that person is guilty of the same offence and is liable to be proceeded against and punished accordingly.

DefencesU.K.

101.—(1) Paragraph (2) applies if the holder of a marketing authorisation [F152or parallel import licence] is charged with an offence under this Part in respect of anything that—

(a)has been manufactured or assembled to the holder's order by another person; and

(b)has been so manufactured or assembled as not to comply with the terms of the authorisation.

(2) It is a defence for the holder to prove that—

(a)the holder communicated the terms of the authorisation to the other person; and

(b)the holder did not know and could not by the exercise of reasonable care have known that those terms had not been complied with.

(3) It is a defence for a person charged with an offence consisting of a breach of regulations 73(3) or 78, or an offence under any of regulations 88 to 93, 95 and 96, to prove that the person took all reasonable precautions and exercised all due diligence to avoid commission of that offence.

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

Textual Amendments

F152Words in reg. 101(1) inserted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 4 and words in reg. 101(1) inserted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 4(2)(q)