Requirement for certain applications to include results of paediatric investigation plan50A

1

This regulation applies in relation to an application—

a

under regulation 49 for a F34UKMA(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 F34UKMA(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.

F357

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

8

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

Agreement and modification of paediatric investigation plan50B

1

Any person may prepare a paediatric investigation plan F36for the purposes of an application to which regulation 50A applies and submit it to the licensing authority with a request for agreement.

2

A paediatric investigation plan must—

a

specify the timing and measures proposed to assess the safety, quality and efficacy of a medicinal product in the paediatric population; and

b

describe any measures to adapt the formulation of the medicinal product so as to make its use more acceptable, easier, safer or more effective for different subsets of the paediatric population.

3

A person who requests the agreement of a paediatric investigation plan must submit it to the licensing authority not later than upon completion of the human pharmaco-kinetic studies in adults in relation to the medicinal product to which the plan relates, as specified in section 5.2.3 of Part I of Annex I to the 2001 Directive, unless the licensing authority agrees to accept a later request.

4

The licensing authority may request the person applying for agreement of a paediatric investigation plan to supply further information in relation to the plan or to submit proposed modifications to it.

5

The licensing authority must decide whether or not—

a

the proposed studies will ensure the generation of the necessary data determining the conditions in which the medicinal product may be used to treat the paediatric population or subsets of it; and

b

the expected therapeutic benefits of the medicinal product justify the studies proposed; and

in doing so must consider whether or not the measures proposed to adapt the formulation of the medicinal product for use in different subsets of the paediatric population are appropriate.

6

If, following a decision by the licensing authority to agree a paediatric investigation plan, the person carrying out the plan encounters such difficulties with its implementation as to render the plan unworkable or no longer appropriate, that person may propose changes or request a deferral or a waiver, by submitting a request to the licensing authority, explaining the grounds for the request.

7

Schedule 11 makes provision about advice and representations in relation to proposals to agree, or to refuse to agree, a paediatric investigation plan under paragraph (5) or to grant, or to refuse to grant, a deferral or waiver requested under paragraph (6).

Deferral of initiation or completion of measures in paediatric investigation plan50C

1

At the same time as the paediatric investigation plan is submitted under regulation 50B(1), the person requesting agreement of it may request the agreement of the licensing authority to a deferral of the initiation or completion of some or all of the measures set out in the plan.

2

If the licensing authority is satisfied that a deferral of the initiation or completion of some or all of the measures set out in a paediatric investigation plan can be justified on scientific and technical grounds, or on grounds related to public health, it may—

a

agree to a request by the applicant to grant a deferral; or

b

decide of its own motion to grant a deferral.

3

If the licensing authority is satisfied as set out in paragraph (2), it must decide to grant a deferral where it is satisfied that—

a

it is appropriate to conduct studies in adults prior to initiating studies in the paediatric population; or

b

studies in the paediatric population will take longer to conduct than studies in adults.

4

If the licensing authority grants an application to which regulation 50A applies, it must, if it also grants a deferral in accordance with this regulation—

a

record that fact in the product's summary of product characteristics, and, if it considers that it would be appropriate to do so, in the package leaflet; and

b

specify in the document notifying the applicant of the grant of the deferral the time limits for the initiation or completion of the measures to which the deferral relates.

5

Schedule 11 makes provision about advice and representations in relation to proposals to grant, or to refuse to grant, a deferral under paragraph (2) or (3).

Waiver of production of information in a paediatric investigation plan50D

1

The applicant making an application to which regulation 50A applies is exempt from the obligation to provide to the licensing authority the results of all studies performed, and details of all information collected, in compliance with an agreed paediatric investigation plan, if a waiver is granted in accordance with this regulation.

2

The licensing authority may grant a waiver in accordance with this regulation if it is satisfied that there is evidence showing that—

a

the medicinal product or class of medicinal products is likely to be ineffective or unsafe in all or part of the paediatric population;

b

the disease or condition for which the medicinal product or class of medicinal products is intended occurs only in adult populations; or

c

the medicinal product does not represent a significant therapeutic benefit over existing treatments for patients in the paediatric population.

3

The licensing authority may grant a waiver in accordance with this regulation—

a

in respect of the entire paediatric population, or a subset of it;

b

in respect of all of the therapeutic indications for the medicinal product concerned, or only some of them;

c

of its own motion, or at the request of the applicant; or

d

in respect of a specific product or a class of medicinal products.

4

A person who requests a waiver in accordance with this regulation must submit the request to the licensing authority not later than upon completion of the human pharmaco-kinetic studies in adults in relation to the medicinal product concerned, as specified in section 5.2.3 of Part I of Annex I to the 2001 Directive, unless the licensing authority agrees to accept a later application.

5

The licensing authority must maintain and publish a list of waivers which are granted under this regulation in respect of a class of medicinal products.

6

The licensing authority may review a waiver which it has granted under this regulation and may revoke it if it considers it appropriate, having regard to the matters specified in paragraph (2).

7

If the licensing authority revokes a waiver granted under this regulation, the holder of the UK marketing authorisation to which the waiver relates must, at the end of the period of 36 months beginning with the date of publication of the decision to revoke the waiver, submit the information referred to in regulation 50A(3) to the licensing authority.

8

If the licensing authority grants an application to which regulation 50A applies, it must, if it also grants a waiver in accordance with this regulation, record that fact in the product's summary of product characteristics, and, if it considers that it would be appropriate to do so, in the package leaflet.

9

Schedule 11 makes provision about advice and representations in relation to proposals to grant, or to refuse to grant, a waiver in response to a request made in accordance with paragraph (4) and to revoke a waiver under paragraph (6).

Application for paediatric use marketing authorisation50E

1

This regulation applies in relation to an application for a F37UKMA(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.

F385

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

Other applications including paediatric indications50F

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 F39UKMA(GB) for a relevant medicinal product which includes a paediatric indication; or

b

an application to include a paediatric indication in an existing F39UKMA(GB).

2

The applicant making an application to which this regulation applies must include in the application details of the measures intended to ensure the follow up of efficacy and of possible adverse reactions to the paediatric use of the medicinal product.

Applications relating to orphan medicinal products50G

F401

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 F41Great 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 F41Great Britain, or if such method exists, the medicinal product will be of significant benefit to those affected by the condition.

3

The applicant for a UK marketing authorisation to which this regulation applies must, in addition to the material specified in regulation 50, provide to the licensing authority material that demonstrates that the orphan criteria are met.

4

Schedule 9A makes further provision about the orphan criteria and terms used in regulation 58D.

5

The Ministers may by regulations amend Schedule 9A.

Applications relating to advanced therapy medicinal products50H

1

This regulation applies in relation to an application for a F42UKMA(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 F42UKMA(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 M10, including, where available, the results of the assessment of a notified body in accordance with those Regulations.

Applications relating to conditional marketing authorisations F43for sale or supply in Great Britain only50I

1

This regulation applies in relation to an application for a F44UKMA(GB) for a relevant medicinal product which falls within paragraph (2).

2

A relevant medicinal product falls within this paragraph if it is—

a

aimed at the treatment, prevention or diagnosis of seriously debilitating or life-threatening diseases; or

b

to be used in emergency situations, in response to public health threats.

3

The applicant for a UK marketing authorisation to which this regulation applies may request that the licensing authority grant a conditional marketing authorisation if—

a

comprehensive clinical data referring to the safety and efficacy of the medicinal product have not been supplied; and

b

the applicant can demonstrate that—

i

the positive therapeutic effects of the product outweigh the risks to the health of patients or of the public associated with the product,

ii

it is likely that the applicant will be in a position to provide the comprehensive clinical data,

iii

unmet medical needs will be fulfilled, and

iv

the benefit to the public health of the immediate availability on the market of the medicinal product concerned outweighs the risk inherent in the fact that additional data are still required.

4

In this regulation, “unmet medical needs” means medical needs in relation to a condition for which there exists no satisfactory method of diagnosis, prevention or treatment authorised in the United Kingdom, or, even if such method exists, in relation to which the medicinal product concerned will be of major therapeutic advantage to those affected.

5

The applicant for a UK marketing authorisation to which this regulation applies must include in the application material which demonstrates that the criteria in paragraph (3)(b) are met.

Applications in relation to medicinal products containing or consisting of genetically modified organisms50J

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 M11,

ii

regulation 22 of the Genetically Modified Organisms (Deliberate Release) (Wales) Regulations 2002 M12,

iii

regulation 21 of the Genetically Modified Organisms (Deliberate Release) (Scotland) Regulations 2002 M13, or

iv

regulation 21 of the Genetically Modified Organisms (Deliberate Release) Regulations (Northern Ireland) 2003 M14;

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.

Application for UKMA(NI) relating to generic medicinal products51

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.

Application for UKMA(GB) relating to generic medicinal products51A

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.

Application for UKMA(UK) relating to generic medicinal products51B

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.

Application for UKMA(NI) relating to certain medicinal products that do not qualify as generic etc52

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.

Application for UKMA(GB) relating to certain medicinal products that do not qualify as generic etc52A

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.

Application for UKMA(UK) relating to certain medicinal products that do not qualify as generic etc52B

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.

Application for UKMA(NI) relating to similar biological medicinal products53

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.

Application for UKMA(GB) relating to similar biological medicinal products53A

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.

Application for UKMA(UK) relating to similar biological medicinal products53B

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.

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.

Paediatric rewards58A

F591

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.

F603

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

F61b

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).

F624A

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 F63regulation 51A(1) and (6) in relation to the material supplied pursuant to regulation 50E(2).

Publication of information relating to paediatric marketing authorisations58B

1

The licensing authority must publish a register of UK marketing authorisations—

a

which include a paediatric indication following completion of an F64agreed 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.

Consideration of applications relating to orphan medicinal products58C

1

If the licensing authority is satisfied in relation to an application for a UK marketing authorisation F65(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.

Orphan rewards58D

1

Subject to the following provisions of this regulation, for the period of ten years beginning with the date on which the licensing authority grants an orphan marketing authorisation, the licensing authority must not—

a

grant an application for a UK marketing authorisation; or

b

grant an application to vary a UK marketing authorisation;

in relation to a medicinal product which is similar to the medicinal product to which the orphan marketing authorisation relates and in respect of the therapeutic indications which are covered by the orphan marketing authorisation.

F662

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

F663

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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.

Consideration of applications relating to combined advanced therapy medicinal products58E

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 M15 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.

Consideration of applications relating to conditional marketing authorisations58F

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 F67UKMA(GB) in respect of the application in accordance with regulation 49(1)(a),

it may grant a UK marketing authorisation which is known as a conditional marketing authorisation.

2

Where regulation 50I(2)(b) (applications relating to conditional marketing authorisations) applies, the licensing authority may grant a conditional marketing authorisation if, in addition to comprehensive clinical data, comprehensive pre-clinical or pharmaceutical data have not been supplied.

3

The licensing authority may, of its own motion, propose that a conditional marketing authorisation be granted if, having consulted the applicant for a UK marketing authorisation, it considers that the criteria in regulation 50I(3)(b) are met.

4

If the licensing authority grants a conditional marketing authorisation in relation to a medicinal product, it may at any time decide that it is appropriate to grant a UK marketing authorisation in relation to that product which is not a conditional marketing authorisation.

5

If the licensing authority grants a conditional marketing authorisation, the product's summary of product characteristics and package leaflet must include a statement to that effect, and the summary of product characteristics must include the date on which the conditional marketing authorisation is due for renewal.

Consideration of applications in relation to medicinal products containing or consisting of genetically modified organisms58G

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).

Condition as to the submitting of samples and other information to the appropriate authority 60A

1

In this regulation—

• “the appropriate authority” is to be construed in accordance with section 57(7) of the Health and Social Care Act 2012 M17;

• “appropriate documentation”, in relation to a sample of a batch submitted to the appropriate authority in accordance with the batch testing condition or pursuant to a notification under paragraph (12), means—

  1. a

     any certificate issued by a laboratory in an approved country for batch testing and certification of biological medicinal products that relates to the sample of the batch submitted to the appropriate authority with that certificate; and

  2. b

     such other documentation as the appropriate authority notifies the holder of the UK marketing authorisation to which the sample relates that it requires;

• “approved country list for batch testing and certification of biological medicinal products” means the list described in paragraph (5), and “approved country for batch testing and certification of biological medicinal products” means a country included in that list;

• “the batch testing condition”, in respect of a UK marketing authorisation, is a condition to the effect that, unless the batch testing exemption applies, the holder of the UK marketing authorisation—

  1. a

     must submit a sample from each batch of the medicinal product that is the subject of that authorisation to the appropriate authority, together with appropriate documentation; and

  2. b

     must not sell or supply, or offer to sell or supply, a medicinal product that forms part of that batch in the United Kingdom until the appropriate authority has examined—

     1. i

        the sample from that batch,

     2. ii

        the appropriate documentation, or

     3. iii

        both that sample and that documentation,

  and confirmed that it is satisfied that the batch is in conformity with the approved specifications in the UK marketing authorisation; and

• F74“the batch testing exemption” means that—

  1. a

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

     1. i

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

     2. ii

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

  2. b
     1. i

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

     2. ii

        an agreement has been made between that country and the United Kingdom (whether or not the agreement is solely with that country, a group of countries or an organisation of which that country is a part), and

     3. iii

        that agreement is to the effect that the appropriate authority will recognise that certificate in respect of the batch of the medicinal product, in place of the appropriate authority’s own examination of a sample from the batch, the appropriate documentation or both.

2

The licensing authority may impose the batch testing condition in respect of a UK marketing authorisation for a medicinal product that is—

a

a live vaccine;

b

an immunological F75... product used in the primary immunisation of infants or other groups at risk;

c

an immunological product used in public health immunisation programmes;

d

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

e

derived from human blood or human plasma.

3

If the licensing authority imposes a condition in respect of a UK marketing authorisation for a medicinal product of a kind mentioned in paragraph (2)(d), it must, in imposing that condition, specify a period of time for the duration of the condition.

4

The appropriate authority must complete its examination of the sample for testing, the appropriate documentation or both (as the case may be) within the period of 60 days, beginning with the date on which the appropriate authority is in receipt of both the sample for testing, and the appropriate documentation.

5

The appropriate authority must publish a list, to be known as the approved country list for batch testing and certification of biological medicinal products, specifying the countries that are approved for the purposes of the appropriate authority's assessment under paragraph (6) F76and regulation 60B(5).

6

Where a holder of a UK marketing authorisation, in order to comply with the batch testing condition, submits appropriate documentation that includes a certificate issued by a laboratory in an approved country for batch testing and certification of biological medicinal products in respect of the batch, the appropriate authority must, in addition to any other factors it considers relevant, take that into account in determining whether the appropriate authority needs to undertake any further testing of the medicinal product submitted to it.

7

In order to determine whether a country should be included in the approved country list for batch testing and certification of biological medicinal products, the appropriate authority may, in particular, take into account whether the relevant certification process in that country is based on testing performed under a quality assurance system that undergoes regular external assessment to ensure it meets an appropriate standard of competence for testing biological medicines.

8

The appropriate authority must—

a

review the countries it has included in the approved country list for batch testing and certification of biological medicinal products to determine if it is still satisfied that the country should remain on that list, and if it is not so satisfied, remove that country from the list; and

b

undertake that review at least every three years beginning with the date on which that country is included in the list.

9

The appropriate authority must—

a

publish a list of countries, or organisations, with whom the United Kingdom has an agreement for the purposes of the application of the batch testing exemption F77under this regulation or regulation 60B;

b

include in that list any conditions or restrictions in that agreement that affect the applicability of the batch testing exemption F77under this regulation or regulation 60B; and

c

update that list as soon as reasonably practicable if—

i

the United Kingdom no longer has an agreement with a country or organisation included in the list,

ii

any such agreement is amended, or

iii

the United Kingdom enters in to a new agreement with a country or organisation.

10

Where a holder of a UK marketing authorisation relies on the batch testing exemption in relation to a batch of a medicinal product, that holder must submit the certificate in respect of that batch to the licensing authority and the appropriate authority, and such other documentation as those authorities may notify that holder they require, before it sells or supplies, or offers to sell or supply, a medicinal product that forms part of that batch in the United Kingdom.

11

Paragraph (12) applies where the appropriate authority considers that there are public health concerns in respect of a batch of a medicinal product (“the relevant batch”) in relation to which the batch testing exemption would otherwise apply.

12

Where this paragraph applies, the appropriate authority must, subject to paragraph (13), notify the holder of the UK marketing authorisation in respect of the relevant batch that it nevertheless requires that holder—

a

to submit a sample from the relevant batch to the appropriate authority, together with appropriate documentation; and

b

not to sell or supply, or to offer to sell or supply, a medicinal product that forms part of that batch in the United Kingdom until the appropriate authority has examined—

i

the sample from that batch,

ii

the appropriate documentation, or

iii

both that sample and that documentation,

and confirmed that it is satisfied that the relevant batch is in conformity with the approved specifications in the UK marketing authorisation.

13

The appropriate authority may only exercise its powers under paragraph (12) if the agreement made between the country in which the certificate was issued, and the United Kingdom (whether the agreement is solely with that country, a group of countries or an organisation of which that country is a part) provides for the relevant batch to be re-examined by the appropriate authority in the circumstances described in paragraph (11).

F7814

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

a

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

b

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

c

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

15

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

16

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

F79Submitting of samples and other information: EU marketing authorisations60B

1

In this regulation—

• “the appropriate authority” is to be construed in accordance with section 57(7) of the Health and Social Care Act 2012;

• “appropriate documentation”, in relation to a sample of a batch submitted to the appropriate authority in accordance with the batch testing requirement or pursuant to a notification under paragraph (8), means such documentation as the appropriate authority notifies the holder of the EU marketing authorisation to which the sample relates that it requires;

• “approved country list for batch testing and certification of biological medicinal products” means the list described in regulation 60A(5), and “approved country for batch testing and certification of biological medicinal products” means a country included in that list;

• “the batch testing exemption” means that—

  1. a
     1. i

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

     2. ii

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

  2. b
     1. i

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

     2. ii

        an agreement has been made between that country and the United Kingdom (whether or not the agreement is solely with that country, a group of countries or an organisation of which that country is a part), and

     3. iii

        that agreement is to the effect that the appropriate authority will recognise that certificate in respect of the batch of the medicinal product, in place of the appropriate authority’s own examination of a sample from the batch, the appropriate documentation or both;

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

  1. a

     must submit a sample from each batch of the medicinal product that is the subject of that authorisation to the appropriate authority, together with appropriate documentation; and

  2. b

     must not sell or supply, or offer to sell or supply, a medicinal product that forms part of that batch in Northern Ireland until the appropriate authority has examined—

     1. i

        the sample from that batch,

     2. ii

        the appropriate documentation, or

     3. iii

        both that sample and that documentation,

  and confirmed that it is satisfied that the batch is in conformity with the approved specifications in the EU marketing authorisation.

2

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

a

that is—

i

a live vaccine;

ii

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

iii

an immunological product used in public health immunisation programmes;

iv

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

v

derived from human blood or human plasma, and

b

which is intended for sale or supply in Northern Ireland.

3

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

4

The appropriate authority must complete its examination of the sample for testing, the appropriate documentation or both (as the case may be) within the period of 60 days, beginning with the date on which the appropriate authority is in receipt of both the sample for testing, and the appropriate documentation.

5

Where a holder of an EU marketing authorisation, in order to comply with the batch testing requirement, submits appropriate documentation that includes a certificate issued by a laboratory in an approved country for batch testing and certification of biological medicinal products in respect of the batch, the appropriate authority must, in addition to any other factors it considers relevant, take that into account in determining whether the appropriate authority needs to undertake any further testing of the medicinal product submitted to it.

6

Where a holder of an EU marketing authorisation relies on the batch testing exemption in relation to a batch of a medicinal product, that holder must submit the certificate in respect of that batch to the licensing authority and the appropriate authority, and such other documentation as those authorities may notify that holder they require, before it sells or supplies, or offers to sell or supply, a medicinal product that forms part of that batch in Northern Ireland.

7

Paragraph (8) applies where the appropriate authority considers that there are public health concerns in respect of a batch of a medicinal product (“the relevant batch”) in relation to which the batch testing exemption would otherwise apply.

8

Where this paragraph applies, the appropriate authority must, subject to paragraph (9), notify the holder of the EU marketing authorisation in respect of the relevant batch that it nevertheless requires that holder—

a

to submit a sample from the relevant batch to the appropriate authority, together with appropriate documentation; and

b

not to sell or supply, or to offer to sell or supply, a medicinal product that forms part of that batch in Northern Ireland until the appropriate authority has examined—

i

the sample from that batch,

ii

the appropriate documentation, or

iii

both that sample and that documentation,

and confirmed that it is satisfied that the relevant batch is in conformity with the approved specifications in the EU marketing authorisation.

9

The appropriate authority may only exercise its powers under paragraph (8) if the agreement made between the country in which the certificate was issued, and the United Kingdom (whether the agreement is solely with that country, a group of countries or an organisation of which that country is a part) provides for the relevant batch to be re-examined by the appropriate authority in the circumstances described in paragraph (7).

10

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

d

any conditions—

i

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

ii

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

Obligation of licensing authority in case of change of classification64A

1

In this regulation, “classification”, in relation to a medicinal product, means the term of the product's UK marketing authorisation which determines the way in which the product is to be made available, as described in regulation 62(1).

2

This regulation applies where—

F87a

the licensing authority grants or varies—

i

a UK marketing authorisation;

ii

an Article 126a authorisation;

iii

a traditional herbal registration; or

iv

a certificate of registration of a homoeopathic medicinal product;

b

the grant or variation of the UK marketing authorisation involves a change of the classification of the medicinal product to which the authorisation relates; and

c

the application for the UK marketing authorisation or variation was supported by the results of significant pre-clinical tests or clinical trials relating to the proposed classification.

3

Where this regulation applies, the licensing authority may not, for the period of one year beginning with the date on which the UK marketing authorisation was granted or varied, refer to the results of the tests or trials referred to in paragraph (2)(c) when examining an application by another applicant or UK marketing authorisation holder for a change of classification of the same kind as that to which the tests or trials relate.

za

regulation 65B;

Validity of conditional marketing authorisation65B

1

A conditional marketing authorisation remains in force—

a

for an initial period of one year beginning with the date on which it is granted; and

b

if it is renewed in accordance with regulation 66B, for further periods of one year beginning with the date on which the renewal is granted.

2

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

Variation of a F88UKMA(GB)65C

1

A F89UKMA(GB) holder may apply to vary the authorisation.

2

Any such application must be made in accordance with Schedule 10A.

3

Schedule 10A does not apply to the transfer of a F89UKMA(GB) from one person to another.

4

The licensing authority may publish guidance on the details of the various categories of variations, on the operation of the procedures laid down in Schedule 10A, and on the documentation to be submitted pursuant to those procedures.

5

Any guidance referred to in paragraph (4) must be regularly reviewed and, when necessary, updated.

6

Unless replaced by guidelines published under paragraph (4), the guidelines published by the Commission under Article 4 of Regulation (EC) No 1234/2008M19 which applied immediately before F90IP completion day, insofar only as they concern applications under Chapter IIa of that Regulation, continue to apply to—

a

applications made under regulation 65C on or after F90IP completion day; or

b

applications made before F90IP completion day to which regulation 65C and Schedule 10A apply by virtue of Parts 3 and 5 of Schedule 33A.

7

The Ministers may by regulations amend Schedule 10A.

2

The applicant, where it is applying for renewal of—

a

a UKMA(NI)—

i

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

ii

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

b

a UKMA(GB)—

i

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

ii

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

c

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

Renewal of conditional marketing authorisation66B

1

The licensing authority may renew a conditional marketing authorisation in relation to an application made to it by the holder of the authorisation.

2

The application must be made at least six months before the date on which the conditional marketing authorisation is due to expire.

3

The application must include an interim report on the fulfilment of the obligations to which the conditional marketing authorisation is subject.

4

When considering an application under paragraph (1), the licensing authority must consider whether—

a

the positive therapeutic effects of the product continue to outweigh the risks to the health of patients and the public associated with the product; and

b

the obligations referred to in regulation 59(4C) and any time limits for their fulfilment remain appropriate, modifying or removing them if necessary.

5

The provisions of regulation 66(2), (3), (4), (6) and (8) apply to an application for renewal of a conditional marketing authorisation.

—

a

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

b

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

2

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

a

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

i

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

ii

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

b

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

Post authorisation requirements in relation to UK marketing authorisations to which paediatric specific provisions apply78A

1

Paragraph (2) applies where—

a

a holder of a UK marketing authorisation intends to discontinue supply of the product to which that authorisation relates;

b

the holder of the authorisation benefited from a reward or incentive under regulation 58A(3) or (8) or 58D(5) in relation to the product; and

c

the period of protection provided pursuant to those regulations has expired.

2

Where this paragraph applies, the holder of the UK marketing authorisation must—

a

either—

i

transfer the UK marketing authorisation to another person who has declared an intention to continue to supply the product; or

ii

allow such a person to use the pharmaceutical, pre-clinical and clinical documentation contained in the file on that product in accordance with regulation 56; and

b

notify the licensing authority of its intention to cease to supply the product before the beginning of the period of six months ending immediately before the day on which the holder does so.

3

Paragraph (4) applies to the holder of a UK marketing authorisation if—

a

that authorisation includes a paediatric indication following completion of an agreed paediatric investigation plan; and

b

the product was placed on the market for other indications before that holder obtained that paediatric indication.

4

Where this paragraph applies, the holder of the UK marketing authorisation must place the product on the market taking account of the paediatric indication before the end of the period of two years beginning immediately after the day on which the paediatric indication is authorised.

5

Paragraph (6) applies if—

a

a decision by the licensing authority in respect of a paediatric investigation plan is addressed to a person (“PIP sponsor”); and

b

the plan refers to clinical trials carried out in a country other than the United Kingdom (“non-UK clinical trials”).

6

Where this paragraph applies, the PIP sponsor must send to the licensing authority the details set out in Article 11 of the Clinical Trials Directive in relation to the non-UK clinical trials within whichever is the later of—

a

the period of one month beginning after the day on which the decision was received; or

b

the period of one month beginning after the day on which the necessary permission to conduct the clinical trial was received from the competent authorities in the country where the clinical trial is to take place.

7

Where paragraph (6) applies, the PIP sponsor must submit the results of those clinical trials to the licensing authority within the period of twelve months beginning with the day on which the last of those trials ended, subject to paragraph (8).

8

Paragraph (7) does not apply in the case of a clinical trial which forms part of a paediatric study to which paragraph (12) applies.

9

Paragraph (10) applies in relation to the sponsor of a paediatric clinical trial in the United Kingdom in respect of a medicinal product if—

a

the product has a UK marketing authorisation but the sponsor is not the holder of the authorisation; or

b

the product does not have a UK marketing authorisation.

10

Where this paragraph applies, the sponsor of the clinical trial must submit the results of the trial to the licensing authority within the period of twelve months beginning with the day on which the trial ended.

11

Paragraph (12) applies in relation to the holder of a UK marketing authorisation who sponsors a paediatric clinical trial in respect of the medicinal product to which that authorisation relates.

12

Where this paragraph applies, the holder of the UK marketing authorisation must submit the results of the trial to the licensing authority within the period of six months beginning with the day on which the trial ended.

13

Paragraph (14) applies in relation to the holder of a UK marketing authorisation who sponsors a study which involves the use in the paediatric population of a medicinal product to which that UK marketing authorisation relates, irrespective of whether or not—

a

the studies are conducted in accordance with an agreed paediatric investigation plan; or

b

the marketing authorisation holder intends to apply for a marketing authorisation for a paediatric indication in relation to the product.

14

Where this paragraph applies, the holder of the UK marketing authorisation must submit the results of the study to the licensing authority within the period of six months beginning with the day on which the study ended.

15

Where the licensing authority has granted a deferral of the initiation or completion of some or all of the measures set out in a paediatric investigation plan, in accordance with regulation 50C, the person to whom that decision was addressed must submit to the licensing authority an annual report providing an update on progress with the paediatric studies to which the deferral relates.

16

The first report referred to in paragraph (15) must be submitted within the period of twelve months beginning with the date on which the licensing authority granted the deferral.

Post authorisation requirements in relation to F102UKMA(GB) for advanced therapy medicinal products78B

1

The holder of a F103UKMA(GB) in respect of an advanced therapy medicinal product must—

a

establish and maintain a system ensuring that the individual product and its starting raw materials, including all substances coming into contact with the cells or tissues it may contain, can be traced through the sourcing, manufacturing, packaging, storage, transport and delivery to the hospital, institution or private practice where the product is used;

b

where the product contains human tissues or cells, ensure that the traceability system is complementary to and compatible with requirements imposed pursuant to—

i

as regards gametes and embryos, sections 12(3), and 33A to 33D of, and paragraph 1 of Schedule 3A to, the Human Fertilisation and Embryology Act 1990 M26,

ii

as regards blood cells, regulations 8, 9(e) and 14 of the Blood Safety and Quality Regulations 2005 M27, and

iii

as regards other cells and tissues, regulations 13 and 16 of, and paragraph 1 of Schedule 2 to, the Human Tissue (Quality and Safety for Human Application) Regulations 2007 M28;

c

keep the data referred to in paragraph (a) for a minimum of 30 years after the expiry of the date of the product, or longer if required by the licensing authority as a term of the F103UKMA(GB); and

d

in the event of the F103UKMA(GB) holder's bankruptcy or liquidation occurring within the period of time for which that holder is required to keep the data referred to in paragraph (a), transfer that data to another person or the licensing authority.

2

The holder of a F103UKMA(GB) who is subject to the obligations in paragraph (1) remains subject to them even if the F103UKMA(GB) is suspended or revoked.

Application of regulations 81 to 94A81

Regulations 81 to 94 apply in relation to medicinal products for sale or supply in Northern Ireland.