The Human Medicines (Amendment etc.) (EU Exit) Regulations 2019

New regulation 50A to 50J (applications in relation to particular medicinal products) U.K.

53.  After regulation 50, insert—

“Requirement for certain applications to include results of paediatric investigation plan

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

(a) under regulation 49 for a [F1 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 [F1 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.

[F2 (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.]

Agreement and modification of paediatric investigation plan

50B.— (1) Any person may prepare a paediatric investigation plan [F3 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).

Deferral of initiation or completion of measures in paediatric investigation plan

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).

Waiver of production of information in a paediatric investigation plan

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).

Application for paediatric use marketing authorisation

50E.— (1) This regulation applies in relation to an application for a [F4 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.

[F5 (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.]

Other applications including paediatric indications

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 [F6 UKMA(GB)] for a relevant medicinal product which includes a paediatric indication; or

(b) an application to include a paediatric indication in an existing [F6 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.

Applications relating to orphan medicinal products

50G.— [F7 (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 [F8 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 [F8 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.

Applications relating to advanced therapy medicinal products

50H.— (1) This regulation applies in relation to an application for a [F9 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 [F9 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 M1 , including, where available, the results of the assessment of a notified body in accordance with those Regulations.

Applications relating to conditional marketing authorisations [F10 for sale or supply in Great Britain only]

50I.— (1) This regulation applies in relation to an application for a [F11 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.

Applications in relation to medicinal products containing or consisting of genetically modified organisms

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 M2 ,

(ii) regulation 22 of the Genetically Modified Organisms (Deliberate Release) (Wales) Regulations 2002 M3 ,

(iii) regulation 21 of the Genetically Modified Organisms (Deliberate Release) (Scotland) Regulations 2002 M4 , or

(iv) regulation 21 of the Genetically Modified Organisms (Deliberate Release) Regulations (Northern Ireland) 2003 M5 ;

(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

F1 Words in reg. 53 substituted (31.12.2020 immediately before IP completion day) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2020 (S.I. 2020/1488), reg. 1, Sch. 2 para. 40(a)(i)

F2 Words in reg. 53 inserted (31.12.2020 immediately before IP completion day) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2020 (S.I. 2020/1488), reg. 1, Sch. 2 para. 40(a)(ii)

F3 Words in reg. 53 inserted (31.12.2020 immediately before IP completion day) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2020 (S.I. 2020/1488), reg. 1, Sch. 2 para. 40(b)

F4 Words in reg. 53 substituted (31.12.2020 immediately before IP completion day) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2020 (S.I. 2020/1488), reg. 1, Sch. 2 para. 40(c)(i)

F5 Words in reg. 53 inserted (31.12.2020 immediately before IP completion day) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2020 (S.I. 2020/1488), reg. 1, Sch. 2 para. 40(c)(ii)

F6 Word in reg. 53 substituted (31.12.2020 immediately before IP completion day) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2020 (S.I. 2020/1488), reg. 1, Sch. 2 para. 40(d)

F7 Words in reg. 53 substituted (31.12.2020 immediately before IP completion day) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2020 (S.I. 2020/1488), reg. 1, Sch. 2 para. 40(e)(i)

F8 Words in reg. 53 substituted (31.12.2020 immediately before IP completion day) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2020 (S.I. 2020/1488), reg. 1, Sch. 2 para. 40(e)(ii)

F9 Word in reg. 53 substituted (31.12.2020 immediately before IP completion day) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2020 (S.I. 2020/1488), reg. 1, Sch. 2 para. 40(f)

F10 Words in reg. 53 inserted (31.12.2020 immediately before IP completion day) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2020 (S.I. 2020/1488), reg. 1, Sch. 2 para. 40(g)(i)

F11 Word in reg. 53 substituted (31.12.2020 immediately before IP completion day) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2020 (S.I. 2020/1488), reg. 1, Sch. 2 para. 40(g)(ii)

Commencement Information

I1 Reg. 53 in force at 31.12.2020 on IP completion day (in accordance with 2020 c. 1, Sch. 5 para. 1(1)), see reg. 1

Marginal Citations

M1 S.I. 2002/618, as amended by the Medical Devices (Amendment etc.) (EU Exit) Regulations 2019.

M2 S.I. 2002/2443, as amended by S.I. 2004/2411.

M3 S.I. 2002/3188, as amended by S.I. 2005/1913.

M4 S.S.I. 2002/541, as amended by S.S.I. 2004/439.

M5 S.R. 2003/167, as amended by S.R. 2005/272.