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

(a) if— (i) in the case of a product for sale or supply in Great Britain, the product has a UK marketing authorisation, certificate of registration or traditional herbal registration, or (ii) in the case of a product for sale or supply in Northern Ireland, the product has a marketing authorisation, Article 126a authorisation, certificate of registration or traditional herbal registration, and

• (3) In paragraph (3), omit “from a state other than an EEA State”.

Amendment of Schedule 7A (information to be provided for registration as an importer, manufacturer or distributor of active substances)

43

• (1) Schedule 7A is amended as follows.

• (2) In paragraph 13(b), omit “from third countries”.

• (3) In paragraph 15(c), omit “to a third country”.

Amendment of regulation 45O (requirements for registration as an importer, manufacturer or distributor of an active substance)

44

• (1) Regulation 45O is amended as follows.

• (2) For paragraph (1) substitute—

(1) Where principles and guidelines of good manufacturing practice have been published under, or apply by virtue of, regulation C17, which apply to an active substance manufactured in Great Britain, a manufacturer in Great Britain must comply with the principles and guidelines of good manufacturing practice for active substances. (1A) Where the Commission has adopted principles and guidelines of good manufacturing practice under the third paragraph of Article 47 of the 2001 Directive which applies to an active substance manufactured in Northern Ireland, a manufacturer in Northern Ireland must comply with the principles and guidelines of good manufacturing practice for active substances.

• (3) For paragraph (2) substitute—

(2) Where principles and guidelines of good distribution practice have been published under, or apply by virtue of, regulation C17, which apply to an active substance distributed in Great Britain, a distributor in Great Britain must comply with the principles and guidelines of good distribution practice for active substances. (2A) Where the Commission has adopted principles and guidelines of good distribution practice under the fourth paragraph of Article 47 of the 2001 Directive which applies to an active substance distributed in the Northern Ireland, a distributor in Northern Ireland must comply with the principles and guidelines of good distribution practice for active substances.

• (4) In paragraph (3)—

• (a) for “the UK” substitute “Northern Ireland”;

• (b) for “from a third country” substitute “into Northern Ireland from a country other than an EEA State”;

• (c) for “exporting third country” in both places it occurs substitute “exporting country”;

• (d) in sub-paragraph (c)(ii), for “the Union” substitute “Northern Ireland”.

• (4A) After paragraph (3) insert—

(3A) Without prejudice to regulation 37(4) and paragraph 9A of Schedule 8, where principles and guidelines of good manufacturing practice have been published under, or apply by virtue of, regulation C17, which apply to an active substance imported into Great Britain other than from Northern Ireland and where an active substance is so imported— (a) the importer must comply with good manufacturing practice and good distribution practice in relation to the active substance, (b) the active substances must have been manufactured in accordance with standards which are at least equivalent to good manufacturing practice, and (c) the active substances must be accompanied by a written confirmation from the competent authority of the exporting country of the following— (i) the standards of manufacturing practice applicable to the plant manufacturing the exported active substance are at least equivalent to good manufacturing practice, (ii) the manufacturing plant concerned is subject to regular, strict and transparent controls and to the effective enforcement of standards of manufacturing practice at least equivalent to good manufacturing practice, including repeated and unannounced inspections, so as to ensure a protection of public health at least equivalent to that in Great Britain, and (iii) in the event of findings relating to non-compliance, information on such findings is supplied by the exporting country to the licensing authority without any delay.

• (5) In paragraph (4)—

• (a) for “(3)(c) does” substitute “(3)(c) and (3A)(c) do”;

• (b) in sub-paragraph (a), after “Article 111b of the 2001 Directive” insert “(in the case of an import into Northern Ireland) or paragraph (6) (in the case of an import into Great Britain)”;

• (c) in sub-paragraph (b)(i), after “competent authority of a member State” insert “or licensing authority (in the case of an import into Northern Ireland) or licensing authority or an appropriate authority responsible for the licensing of medicinal products in a country included in a list under paragraph (6) (in the case of an import into Great Britain)”.

• (6) At the end insert—

(6) The licensing authority may publish a list of countries which it is satisfied have a regulatory framework applicable to active substances exported to Great Britain that is equivalent to the regulatory framework in Great Britain, in that the respective control and enforcement activities in those countries ensures an equivalent level of protection of public health. (7) Before including a country in the list under paragraph (6), the licensing authority must assess the equivalence referred to in that paragraph by— (a) reviewing relevant documentation; and (b) unless the country is included in the approved country for batch testing list, carrying out— (i) an on-site review of the country's regulatory system, and (ii) if the licensing authority considers it necessary, an inspection of one or more of that country's manufacturing sites for active substances. (8) In carrying out an assessment under paragraph (7) the licensing authority must in particular take account of the— (a) country's rules for good manufacturing practice; (b) regularity of inspections to verify compliance with good manufacturing practice; (c) effectiveness of enforcement of good manufacturing practice; and (d) regularity and rapidity of information provided by that country relating to non-compliant producers of active substances. (9) The licensing authority must— (a) review the list under paragraph (6) to determine if a country included in it still satisfies the requirements for inclusion in the list, and if it is not so satisfied, remove that country; and (b) undertake such a review at least every three years, beginning with the date on which a country is included in the list .

PART 4 — Amendment of Part 4 (requirement for authorisation)

Amendment of regulation 46 (requirement for authorisation)

45

• (1) Regulation 46 is amended as follows.

• (2) In paragraph (2)—

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

• (b) after sub-paragraph (a) insert—

(aa) an EU marketing authorisation;

• (3) In paragraph (3), before “European Economic Area” insert “ United Kingdom or the ”.

• (4) In paragraph (6)—

• (a) after “in force for the product” insert “in the country in which the product is intended to be sold or supplied, or offered for sale or supply”;

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

• (c) after sub-paragraph (a) insert—

(aa) an EU marketing authorisation;

• (5) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

• (6) In paragraph (9), before “European Economic Area” insert “ United Kingdom or the ”.

• (7) In paragraph (11)(a), before “European Economic Area” insert “ United Kingdom or the ”.

Amendment of regulation 47 (breach of requirement)

46

• (1) Regulation 47 is amended as follows.

• (2) In paragraphs (3) and (4), before “European Economic Area”, insert “ United Kingdom or the ”.

• (3) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

PART 5 — Amendment of Part 5 (marketing authorisations)

Amendment of regulation 48 (application of Part 5)

47

• (1) Regulation 48 is amended as follows.

• (2) In paragraph (2)—

• (a) at the appropriate place insert—

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

“excluded reference product” means— (a) a medicinal product authorised on the basis that it was a generic medicinal product; (b) a medicinal product authorised on the basis that one or more of the circumstances listed in Article 10(3) of the 2001 Directive or regulation 52(1)(b) applied; or (c) a biological medicinal product authorised on the basis that it did not meet a condition for being a generic medicinal product for any of the reasons described in Article 10(4) of the 2001 Directive or regulation 53A(1);

• (b) for the definition of “generic medicinal product”, substitute—

“generic medicinal product”, in relation to a reference medicinal product for an application for— (a) a UKMA(NI) or UKMA(UK), has the meaning given in Article 10(2)(b) of the 2001 Directive; (b) a UKMA(GB), means a medicinal product— (i) that has the same qualitative and quantitative composition in active substances as the reference medicinal product; (ii) that has the same pharmaceutical form as the reference medicinal product; and (iii) whose bioequivalence with the reference medicinal product has been demonstrated by appropriate bioavailability studies;

• (c) for the definition of “parallel import licence” substitute—

“parallel import licence” means a licence that is granted by the licensing authority under this Part authorising the holder to place on the market a medicinal product imported in to the United Kingdom from an EEA State where that product— (a) has been granted an EU marketing authorisation or a marketing authorisation in an EEA State under the 2001 Directive; and (b) is essentially similar to a product that has been granted a UK marketing authorisation;

; and

• (d) for the definition of “reference medicinal product”, substitute—

“reference medicinal product” means— (a) in relation to an application for a UKMA(NI), a medicinal product— (i) authorised for sale or supply in Northern Ireland under regulation 49(1)(a), in accordance with the provisions of regulation 50; or (ii) in relation to which an EU marketing authorisation or a marketing authorisation granted by a member State pursuant to the 2001 Directive is or has been in force, but which is not an excluded reference product; (b) in relation to an application for a UKMA(GB), a medicinal product— (i) authorised under regulation 49(1)(a), in accordance with the provisions of regulation 50; (ii) in relation to which an EU marketing authorisation was in force on IP completion day, but in relation to which no UK marketing authorisation is in force because the holder of the EU marketing authorisation notified the licensing authority in accordance with paragraph 6(3) of Schedule 33A that it did not wish to be the holder of a converted EU marketing authorisation; or (iii) in relation to which an EU marketing authorisation had ceased to be in force before IP completion day for reasons not related to safety, quality or efficacy, but which is not an excluded reference product; (c) in relation to an application for a UKMA(UK), a medicinal product— (i) authorised under regulation 49(1)(a) for sale or supply in the whole of the United Kingdom, whether by virtue of one or more UK marketing authorisations, in accordance with the provisions of regulation 50; or (ii) in relation to which an EU marketing authorisation or a marketing authorisation granted by a member State pursuant to the 2001 Directive is or has been in force, but which is not an excluded reference product;

• (3) After paragraph (2) insert—

(3) In this Part, references to a medicinal product to be imported that is “essentially similar to a product that has been granted a UK marketing authorisation” are to be read as references to a medicinal product to be imported that— (a) has been manufactured to the same formulation as a product that has been granted a UK marketing authorisation (“the UK product”); (b) contains the same active ingredients as the UK product; (c) has the same therapeutic effect as the UK product, and for the purposes of sub-paragraph (a), any differences in a product's formulation are to be ignored in so far as they are considered to be immaterial by the licensing authority. (4) For the purposes of the definition of generic medicinal product— (a) the different salts, esters, ethers, isomers, mixtures of isomers, complexes or derivatives of an active substance are considered to be the same active substance, unless they differ significantly in properties with regard to safety or efficacy; and (b) the various immediate-release oral pharmaceutical forms are considered to be the same pharmaceutical form. (5) When a medicinal product has been granted a UK marketing authorisation under regulation 49(1)(a) in accordance with the provisions of regulation 50 (“initial marketing authorisation”), any additional strengths, pharmaceutical forms, administration routes, presentations, variations and extensions in relation to which a UK marketing authorisation is granted under regulation 49(1)(a), or which are included in the initial UK marketing authorisation, belong to the same “global marketing authorisation”. (6) Paragraph (7) applies if a medicinal product— (a) belongs to a global marketing authorisation but is not the initial marketing authorisation; and (b) is used as a reference medicinal product in accordance with regulations 51 to 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—