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

(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.

Amendment of regulation 49 (application for grant of UK marketing authorisation or parallel import licence)

48

• (1) Regulation 49 is amended as follows.

• (2) In paragraph (1), after “regulation 58,” insert “ 58C, 58E, 58F and 58G, ”.

• (3) After paragraph (1) insert—

(1A) The licensing authority may 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.

• (4) For paragraph (3) substitute—

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

• (5) After paragraph (3) insert—

(3A) An application for a parallel import licence may not be made by— (a) the holder of the marketing authorisation, within the meaning of the 2001 Directive, or the EU marketing authorisation, in respect of the relevant medicinal product to be imported; or (b) a company which is in the same group as the holder of that marketing authorisation.

• (6) At the end insert—

(9) 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).

Amendment of regulation 50 (accompanying material)

49

• (1) Regulation 50 is amended as follows.

• (1A) After paragraph (1) insert—

(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.

• (1B) After paragraph (3) insert—

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

• (2) For paragraph (4) substitute—

(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.

• (3) After paragraph (5) insert—

(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 .

• (4) In paragraph (6), before sub-paragraph (a), insert—

(za) regulation 50A (requirement for certain applications to include results of paediatric investigation plan); (zb) regulation 50E (application for paediatric use marketing authorisation); (zc) regulation 50F (other applications including paediatric indications); (zd) regulation 50G (applications relating to orphan medicinal products); (ze) regulation 50H (applications relating to advanced therapy medicinal products); (zf) regulation 50I (applications relating to conditional marketing authorisations); (zg) regulation 50J (applications relating to medicinal products containing or consisting of genetically modified organisms);

• (4A) In paragraph (6)—

• (a) for sub-paragraph (a), substitute—

(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);

• (b) for sub-paragraph (b), substitute—

(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);

• (c) for sub-paragraph (c), substitute—

(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);

• (5) After paragraph (6), insert—

(7) The licensing authority may make appropriate arrangements with any EEA State or the EMA in order to obtain the information it considers necessary to satisfy itself that a product to be imported under a parallel import licence is essentially similar to a product that has been granted a UK marketing authorisation. (8) If the licensing authority makes arrangements under paragraph (7), it must publish a list of the EEA States or the organisation with which it has made such arrangements.

Amendment of Schedule 8 (material to accompany an application for a UK marketing authorisation)

50

• (1) Schedule 8 is amended as follows.

• (2) In paragraph 12—

• (a) in sub-paragraph (a), after “pharmacovigilance” insert “ who is ordinarily resident, and operates, in the United Kingdom or a member State”;

• (b) for sub-paragraph (b) substitute—

(b) the country (which must be either the United Kingdom or a member State) in which the appropriately qualified person resides and carries out his or her tasks;

• (c) for paragraph (e) substitute—

(e) a reference to the physical location where the pharmacovigilance system master file for the medicinal product can be accessed electronically, which must be in the United Kingdom.

• (3) For paragraph 18 substitute—

(18) Where— (a) in the case of a UKMA(NI) or a UKMA(UK), an application for authorisation for the medicinal product to be placed on the market is under consideration in one or more member States— (i) a list of the member State or States concerned, and (ii) in relation to each such application, a copy of the summary of the product characteristics, and the package leaflet, proposed by the applicant; (b) in the case of a medicinal product for sale or supply in Great Britain, an application for authorisation for the medicinal product to be placed on the market is under consideration in a country other than the United Kingdom, or by the EMA, notification of that fact.

• (4) In paragraph 19, for “a member State or by a third country” substitute “, in the case of a medicinal product for sale or supply in Northern Ireland, a member State or by a country other than an EEA State, or in the case of a medicinal product for sale or supply in Great Britain, by a country other than the United Kingdom or by the European Commission”.

• (5) In paragraph 20, after “Where” insert “, in the case of a medicinal product for sale or supply in Northern Ireland,”.

• (6) For paragraph 21 substitute—

(21) Where an authorisation for the medicinal product to be placed on the market has been refused— (a) in the case of a medicinal product for sale or supply in Northern Ireland, by a member State or by a country other than an EEA State, or (b) in the case of a medicinal product for sale or supply in Great Britain, by a country other than the United Kingdom, details of that decision and of the reasons for it.

• (7) In paragraph 22 for “A copy of any” substitute “In the case of a medicinal product for sale or supply in Northern Ireland, a copy of any”.

• (8) For paragraph 23 substitute—

(23) For medicinal products included on the list referred to— (a) in the case of a medicinal product for sale or supply in Northern Ireland, in Article 23 of Regulation (EC) No 726/2004, the symbol and statement “▼ This medicinal product is subject to additional monitoring”, or (b) in the case of a medicinal product for sale or supply in Great Britain, in regulation 202A, the symbol and statement “▼ This medicinal product is subject to additional monitoring”.

• (9) After paragraph 25, insert—

(25A) In the case of an advanced therapy medicinal product for sale or supply in Great Britain which contains cells or tissues, a detailed description of those cells or tissues and of their specific origin, including the species of animal in cases of non-human origin.

• (10) After paragraph 35, insert—

(36) In the case of an advanced therapy medicinal product for sale or supply in Great Britain— (a) references in this Part of this Schedule to administration of a product include references to the advanced therapy medicinal product's use, application or implantation; and (b) descriptions, instructions and warnings must include explanatory drawings and pictures where necessary.

Amendment of Schedule 8A (material to accompany an application for a parallel import licence)

51

Paragraph 6 of Schedule 8A is amended as follows—

• (a) in sub-paragraph (a), after “pharmacovigilance” insert “ who resides and operates in the United Kingdom ”;

• (b) omit sub-paragraph (b); and

• (c) in paragraph (e) at the end inset “or, if kept in electronic form, from which it can be accessed, which in either case, must be in the United Kingdom”.

Amendment of Schedule 9 (undertakings by non-United Kingdom manufacturers)

52

• (1) Schedule 9 is amended as follows.

• (2) In the heading, for “EEA” substitute “ United Kingdom ”.

• (3) In each place where it occurs, insert “ UK ” before “marketing authorisation”.

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

53

After regulation 50, insert—

(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. (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). (50C) (1) At the same time as the paediatric investigation plan is submitted under regulation 50B(1), the person requesting agreement of it may request the agreement of the licensing authority to a deferral of the initiation or completion of some or all of the measures set out in the plan. (2) If the licensing authority is satisfied that a deferral of the initiation or completion of some or all of the measures set out in a paediatric investigation plan can be justified on scientific and technical grounds, or on grounds related to public health, it may— (a) agree to a request by the applicant to grant a deferral; or (b) decide of its own motion to grant a deferral. (3) If the licensing authority is satisfied as set out in paragraph (2), it must decide to grant a deferral where it is satisfied that— (a) it is appropriate to conduct studies in adults prior to initiating studies in the paediatric population; or (b) studies in the paediatric population will take longer to conduct than studies in adults. (4) If the licensing authority grants an application to which regulation 50A applies, it must, if it also grants a deferral in accordance with this regulation— (a) record that fact in the product's summary of product characteristics, and, if it considers that it would be appropriate to do so, in the package leaflet; and (b) specify in the document notifying the applicant of the grant of the deferral the time limits for the initiation or completion of the measures to which the deferral relates. (5) Schedule 11 makes provision about advice and representations in relation to proposals to grant, or to refuse to grant, a deferral under paragraph (2) or (3). (50D) (1) The applicant making an application to which regulation 50A applies is exempt from the obligation to provide to the licensing authority the results of all studies performed, and details of all information collected, in compliance with an agreed paediatric investigation plan, if a waiver is granted in accordance with this regulation. (2) The licensing authority may grant a waiver in accordance with this regulation if it is satisfied that there is evidence showing that— (a) the medicinal product or class of medicinal products is likely to be ineffective or unsafe in all or part of the paediatric population; (b) the disease or condition for which the medicinal product or class of medicinal products is intended occurs only in adult populations; or (c) the medicinal product does not represent a significant therapeutic benefit over existing treatments for patients in the paediatric population. (3) The licensing authority may grant a waiver in accordance with this regulation— (a) in respect of the entire paediatric population, or a subset of it; (b) in respect of all of the therapeutic indications for the medicinal product concerned, or only some of them; (c) of its own motion, or at the request of the applicant; or (d) in respect of a specific product or a class of medicinal products. (4) A person who requests a waiver in accordance with this regulation must submit the request to the licensing authority not later than upon completion of the human pharmaco-kinetic studies in adults in relation to the medicinal product concerned, as specified in section 5.2.3 of Part I of Annex I to the 2001 Directive, unless the licensing authority agrees to accept a later application. (5) The licensing authority must maintain and publish a list of waivers which are granted under this regulation in respect of a class of medicinal products. (6) The licensing authority may review a waiver which it has granted under this regulation and may revoke it if it considers it appropriate, having regard to the matters specified in paragraph (2). (7) If the licensing authority revokes a waiver granted under this regulation, the holder of the UK marketing authorisation to which the waiver relates must, at the end of the period of 36 months beginning with the date of publication of the decision to revoke the waiver, submit the information referred to in regulation 50A(3) to the licensing authority. (8) If the licensing authority grants an application to which regulation 50A applies, it must, if it also grants a waiver in accordance with this regulation, record that fact in the product's summary of product characteristics, and, if it considers that it would be appropriate to do so, in the package leaflet. (9) Schedule 11 makes provision about advice and representations in relation to proposals to grant, or to refuse to grant, a waiver in response to a request made in accordance with paragraph (4) and to revoke a waiver under paragraph (6). (50E) (1) This regulation applies in relation to an application for a 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. (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. (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. (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. (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. (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.

Insertion of new Schedule in relation to orphan provisions

54

Schedule 4 inserts a new Schedule 9A after Schedule 9.

Amendment of Schedule 10 (national homoeopathic products)

55

In paragraph 4(4)(a) of Schedule 10 (exceptions to requirement to submit safety data) insert “ UK ” before “marketing authorisation”.

Substitution of regulation 51 (applications relating to generic medicinal products)

56

For regulation 51 substitute—

(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. (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. (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.

Amendment of regulation 52 (applications relating to certain medicinal products that do not qualify as generic etc)

57

For regulation 52 substitute—

(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. (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. (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.

Amendment of regulation 53 (applications relating to similar biological medicinal products)

58

For regulation 53 substitute—

(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. (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. (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.

Amendment of regulation 54 (applications relating to products in well-established medicinal use)

59

• (1) Regulation 54 is amended as follows.

• (2) In paragraph (1) before “European Union”, insert “ United Kingdom or the ”.

• (3) For paragraph (2), substitute—

(2) The applicant may, by way of derogation from paragraph 10 of Schedule 8, replace the results of pre-clinical tests or clinical trials with appropriate scientific literature.

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

60

For regulation 55 substitute—

(55) (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.

Amendment of regulation 56 (applications containing information supplied in relation to another product with consent)

61

In regulation 56(2), omit “in accordance with Article 10c of the 2001 Directive”.

Amendment of regulation 58 (consideration of application)

62

• (1) Regulation 58 is amended as follows.

• (2) After paragraph (4), insert—

(4A) When considering an application for a UK marketing authorisation, the licensing authority may, if it considers it appropriate, have regard to— (a) an opinion of the Committee for Medicinal Products for Human Use; or (b) the results of an assessment of an application for a marketing authorisation by the appropriate authority for the licensing of medicinal products of a country other than the United Kingdom, in respect of the medicinal product to which the application relates. (4B) The licensing authority may under paragraph (4A)— (a) decide to have regard to the opinions and assessments described in 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.

• (3) Omit paragraphs (6) and (7).

• (4) After paragraph (7) insert—

(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.

Amendment of Schedule 11 (advice and representations)

63

• (1) Schedule 11 is amended as follows.

• (2) In paragraph 1 (application of Part 1)—

• (a) in sub-paragraph (1)—

• (i) in sub-paragraph (b) omit “and”, and

• (ii) at the end insert—

and; (d) a proposal to decide that the orphan criteria are not met in relation to a medicinal product which is the subject of an application for the grant of a UK marketing authorisation.

• (b) after sub-paragraph (1) insert—

(1A) Paragraphs 12 and 13 of this Part also apply to— (a) an application for the grant of a parallel import licence; (b) an application to renew a parallel import licence; (c) a proposal to revoke, vary or suspend a parallel import licence (including variation by the variation or removal of a condition to which a parallel import licence is subject) other than a proposal to vary the licence on the application of or by agreement with its holder; and (d) a refusal to vary a parallel import licence following an application for a variation by the holder.

; and

• (c) for sub-paragraph (2) substitute—

(2) In relation to an application for a UKMA(NI) or THR(NI), this Part is subject to Part 4 of this Schedule.

• (2A) In paragraph 2 (requirement to consult the appropriate committee), after sub-paragraph (2), insert—

(2A) The licensing authority must consult the appropriate committee if the authority proposes to decide that the orphan criteria are not met in relation to a medicinal product which is the subject of an application for the grant of a UK marketing authorisation.

• (2B) In paragraph 3 (exceptions to requirement to consult)—

• (a) in sub-paragraph (1), after “traditional herbal registration” insert “ , or to a proposal to decide that the orphan criteria are not met in relation to a medicinal product which is the subject of an application for the grant of a UK marketing authorisation, ”; and

• (b) in sub-paragraph (1)(a), after “determined”, insert “ or the decision to be made ”.

• (2C) In paragraph 5 (provisional opinion against authorisation)—

• (a) after sub-paragraph (2), insert—

(2A) If the appropriate committee is consulted under paragraph 2(2A), it may give a provisional opinion that it may be unable to advise the licensing authority to decide that the orphan criteria are met in relation to a medicinal product which is the subject of an application for the grant of a UK marketing authorisation.

; and

• (b) in sub-paragraph (3), after “grant or renewal”, insert “ , the applicant intending to demonstrate that the orphan criteria are met in relation to a medicinal product, ”.

• (2D) In paragraph 10 (decision of licensing authority)—

• (a) omit the “or” at the end of sub-paragraph (1)(b); and

• (b) at the end of sub-paragraph (1)(c) insert—

; or (d) decide whether to proceed with its proposal to decide that the orphan criteria are not met in relation to a medicinal product which is the subject of an application for the grant of a UK marketing authorisation,

• (3) In paragraph 12 (licensing authority decisions in other cases)—

• (a) in sub-paragraph (1), insert “ , parallel import licence ” after “ UK marketing authorisation ” in each place it appears;

• (b) in sub-paragraph (5), insert “ , licence ” after “ the authorisation ”; and

• (c) after sub-paragraph (4), insert—

(4A) This paragraph also applies if, having been consulted under paragraph 2(2A), the appropriate committee has not given a provisional opinion in the terms described in paragraph 5(2A) and the licensing authority proposes to decide, against that committee's advice, that the orphan criteria are not met in relation to a medicinal product which is the subject of an application for the grant of a UK marketing authorisation.

• (3A) After Part 1 insert—

(13A) This Part applies to a proposed decision by the licensing authority— (a) to refuse to agree a paediatric investigation plan (including a waiver or deferral proposed to be included in that plan), or to agree such a plan otherwise than in accordance with the request for agreement; (b) to refuse to agree a modification to a paediatric investigation plan (including a waiver or deferral which is, or is proposed to be, included in that plan), or to agree such a modification otherwise than in accordance with the request for the modification; (c) to impose, revoke or refuse to grant a waiver of the obligation under regulation 50A(3) 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; or (d) to revoke a waiver which was agreed as part of an agreed paediatric investigation plan. (13B) (1) If the licensing authority proposes to make a decision to which this Part applies, the licensing authority must notify the person to whom the proposed decision would be addressed (“the applicant”). (2) The applicant may, by notice in writing to the licensing authority, request the opportunity to make written or oral representations to the appropriate committee. (3) The applicant must make the request before the end of the period of 28 days beginning with the day on which the notification is given or such longer period as the licensing authority may allow. (4) The licensing authority must inform the appropriate committee of the applicant's request. (13C) (1) If the applicant requests the opportunity to make written representations, the applicant must provide the appropriate committee with those representations and any documents on which the applicant wishes to rely in support of them— (a) before the end of the period of 28 days beginning with the date of the request; or (b) before the end of such shorter period as the licensing authority may specify in the notification under paragraph 13B. (2) The appropriate committee may at the request of the applicant extend the period mentioned in sub-paragraph (1) up to a maximum of 56 days beginning with the date of the request under paragraph 13B. (3) The applicant may submit additional representations or documents after the end of the period for doing so only with the permission of the appropriate committee. (4) The appropriate committee must— (a) take the representations made under this paragraph into account; and (b) report its findings and advice to the licensing authority together with the reasons for that advice. (13D) (1) If the applicant requests the opportunity to make oral representations, the applicant must provide the appropriate committee with a written summary of those representations and any documents on which the applicant wishes to rely in support of them— (a) before the end of the period of 28 days beginning with the date of the request; or (b) before the end of such shorter period as the licensing authority may specify in the notification under paragraph 13B. (2) The appropriate committee may, at the request of the applicant, extend the period mentioned in sub-paragraph (1) up to a maximum of 56 days beginning with the date of the request under paragraph 13B. (3) The applicant may submit additional representations or documents after the end of the period for doing so only with the permission of the appropriate committee. (4) After receiving the summary and any other documents provided under this paragraph, the appropriate committee must arrange for the applicant to make oral representations at a hearing before the committee. (5) The appropriate committee must— (a) take the representations made under this paragraph into account; and (b) report its findings and advice to the licensing authority together with the reasons for that advice. (13E) (1) This paragraph applies if the applicant— (a) requests the opportunity to make written representations, but fails to make those representations within the period for doing so; or (b) requests the opportunity to make oral representations, but— (i) fails to provide a summary of those representations or the documents in support of them within the period for doing so, or (ii) fails to make oral representations at a hearing before the appropriate committee. (2) The appropriate committee must notify the licensing authority of that fact. (13F) (1) The licensing authority must decide whether to proceed with its proposed decision— (a) if the applicant requested the opportunity to make written or oral representations, after receiving the appropriate committee's report under paragraph 13C or 13D or notification under paragraph 13E; or (b) if the applicant did not request the opportunity to make written or oral representations, after the expiry of the period of time for notifying a request for that opportunity. (2) If the appropriate committee gives a report under paragraph 13C or 13D, the licensing authority must take that into account in making its decision. (3) The licensing authority must notify the applicant of— (a) its decision; and (b) any advice given to it by the appropriate committee and the reasons for that advice. (13G) (1) This paragraph applies if the licensing authority notifies the applicant of its decision under paragraph 13F. (2) The applicant may notify the licensing authority in writing that the applicant wishes the licensing authority to submit the decision to review upon oral representations. (3) The applicant must give the notification before the end of the period of 28 days beginning with the day on which the notification is given to the applicant under paragraph 13F or such longer period as the licensing authority may allow. (4) The review must be conducted in accordance with Schedule 5. (5) This paragraph does not apply if the applicant has not made any representations in accordance with paragraph 13C or 13D.

• (4) In paragraph 14(a) (application of Part 2), after “veterinary medicinal products” insert “or paragraph 1 of Schedule 10A”.

• (5) In paragraph 15(2) and (3)(b), insert “ UK ” before “marketing authorisation”.

• (6) In paragraph 16—

• (a) in sub-paragraph (2)(b), insert “ UK ” before “marketing authorisation”; and

• (b) in sub-paragraph (5), omit the words from “or in any Directive” to the end.

• (7) For paragraph 17 substitute—

(17) In relation to an application for a UKMA(NI) or THR(NI), this Part is subject to Part 4 of this Schedule.

• (8) In Part 3 (referral to the Committee for Herbal Medicinal Products)—

• (a) in the heading to Part 3, for “Committee for Herbal Medicinal Products” substitute “ appropriate committee for traditional herbal registrations ”;

• (b) in paragraph 24—

• (i) in sub-paragraph (1), for the words from “Committee” to the end substitute “ appropriate committee in accordance with regulation 130A(1) ”; and

• (ii) for sub-paragraph (2) substitute—

(2) In relation to an application for a UKMA(NI) or THR(NI), this Part is subject to Part 4 of this Schedule.

; and

• (c) in paragraph 29(1), for “proceed with its proposal” substitute “ grant or refuse the application ”.

• (9) In Part 4 (exceptions to Schedule) omit paragraphs 31, 34, 35, 37 and 38.

Insertion of provisions concerning consideration of certain applications for UK marketing authorisations

64

After regulation 58, insert—

(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). (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. (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. (58D) 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. (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; (2) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (3) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (4) The period of ten years referred to in paragraph (1) may be reduced to six years if, at the end of the fifth year beginning on the date referred to in paragraph (1), the licensing authority is satisfied that the orphan criteria are no longer met in relation to the medicinal product. (5) The period of ten years referred to in paragraph (1) is extended to twelve years if regulation 58A(2) (paediatric rewards) applies to the orphan marketing authorisation. (6) Paragraph (1) does not apply if— (a) the holder of the orphan marketing authorisation consents to the grant or variation of a UK marketing authorisation in relation to a similar medicinal product; (b) the licensing authority is satisfied that the holder of the orphan marketing authorisation is unable to supply sufficient quantities of the medicinal product to which the orphan marketing authorisation relates; or (c) a subsequent applicant can establish to the satisfaction of the licensing authority that the medicinal product to which the application relates, although similar to the medicinal product to which the orphan marketing authorisation relates, is safer or more effective than, or clinically superior to, that product. (58E) (1) When determining an application to which regulation 50H(3) (applications relating to combined advance therapy medicinal products) applies, the licensing authority must— (a) assess the entire combined advanced therapy medicinal product in accordance with these Regulations; and (b) recognise the results of the assessment of the notified body, if supplied. (2) The licensing authority may request the notified body, if relevant, to provide it with information related to the results of the assessment. (3) Paragraph (4) applies if an application to which regulation 50H(3) applies does not include the results of the assessment of a notified body, or if the notified body fails to supply information related to the results of the assessment when requested by the licensing authority. (4) Where this paragraph applies, the licensing authority must seek an opinion on the conformity of the device part in accordance with the Medical Devices Regulations 2002 from a notified body identified in conjunction with the applicant, unless the licensing authority decides that the involvement of a notified body is not required. (58F) it may grant a UK marketing authorisation which is known as a conditional marketing authorisation. (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), (2) Where regulation 50I(2)(b) (applications relating to conditional marketing authorisations) applies, the licensing authority may grant a conditional marketing authorisation if, in addition to comprehensive clinical data, comprehensive pre-clinical or pharmaceutical data have not been supplied. (3) The licensing authority may, of its own motion, propose that a conditional marketing authorisation be granted if, having consulted the applicant for a UK marketing authorisation, it considers that the criteria in regulation 50I(3)(b) are met. (4) If the licensing authority grants a conditional marketing authorisation in relation to a medicinal product, it may at any time decide that it is appropriate to grant a UK marketing authorisation in relation to that product which is not a conditional marketing authorisation. (5) If the licensing authority grants a conditional marketing authorisation, the product's summary of product characteristics and package leaflet must include a statement to that effect, and the summary of product characteristics must include the date on which the conditional marketing authorisation is due for renewal. (58G) (1) When determining an application for a UK marketing authorisation in relation to which regulation 50J (applications relating to medicinal products containing or consisting of genetically modified organisms) applies, the licensing authority must be satisfied that the application respects the environmental safety requirements laid down by Directive 2001/18/EC. (2) In reaching its view under paragraph (1), the licensing authority must consult the bodies responsible for the giving of consent pursuant to the legislation referred to in regulation 50J(2)(a).

Amendment of regulation 59 (conditions of UK marketing authorisation or parallel import licence: general)

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• (1) Regulation 59 is amended as follows.

• (1A) In paragraph (3) for “An obligation” substitute “In relation to a UKMA(NI) or UKMA(UK), an obligation”.

• (2) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

• (3) After paragraph (3), insert—

(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) In paragraph (4), insert “ UK ” before “marketing authorisation”.

• (5) After paragraph (4), insert—

(4A) Where the application is one to which regulation 50A, 50E or 50F (applications to which paediatric-specific provisions apply) applies, the licensing authority must, if it considers that there is a particular cause for concern, grant the UK marketing authorisation subject to a condition that— (a) a risk management system be set up comprising a set of pharmacovigilance activities and interventions designed to identify, characterise, prevent or minimise risks relating to medicinal products, including the assessment of the effectiveness of those interventions; or (b) specific post-marketing studies be performed and submitted for review. (4B) The licensing authority may request the holder to submit, in addition to the assessment required to be submitted pursuant to Part 9 of Schedule 12A (post-authorisation safety studies), a report assessing the effectiveness of any risk management system, and the results of any studies performed, in compliance with a condition imposed under paragraph (4A). (4C) If the licensing authority grants a conditional marketing authorisation— (a) it must impose, as a condition of the conditional marketing authorisation, an obligation on the holder of the authorisation to complete ongoing studies, or to conduct new studies, with a view to confirming the that the positive therapeutic effects of the product outweigh the risks to the health of patients or the public associated with the product, and to provide the additional data referred to in regulation 50I(3)(a); (b) it may impose, as a condition of the conditional marketing authorisation, an obligation on the holder of that authorisation in relation to collection of pharmacovigilance data. (4D) If the licensing authority grants a UK marketing authorisation in relation to an advanced therapy medicinal product, it must, if it considers that there is a particular cause for concern, grant the UK marketing authorisation subject to a condition that— (a) a risk management system be set up which is designed to identify, characterise, prevent or minimise risks related to advanced therapy medicinal products, including an evaluation of the effectiveness of that system; or (b) that specific post-marketing studies be carried out and submitted for review by the licensing authority. (4E) The licensing authority may request the holder to submit, in addition to the assessment required to be submitted pursuant to Part 9 of Schedule 12A, a report assessing the effectiveness of any risk management system, and the results of any studies performed, in compliance with a condition imposed under paragraph (4D).

• (6) In paragraph (5) for “marketing authorisation” substitute “UKMA(NI) or UKMA(UK).

Amendment of regulation 60 (conditions of UK marketing authorisation: exceptional circumstances)

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In regulation 60—

• (a) after “UK marketing authorisation” in each place it occurs (including the heading to the regulation) insert “or parallel import licence”;

• (b) after “the authorisation” in each place it occurs insert “or licence”;

• (c) in paragraph (3), after “an authorisation” insert “or licence”;

• (d) for paragraph (9) substitute—

(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.

• (e) in paragraph (10), after “a marketing authorisation” insert “or licence”.

Insertion of new regulations 60A (condition as to the submitting of samples and other information to the appropriate authority)

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After regulation 60, insert—