The Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2025

(A32) (1) A sponsor shall keep detailed records of all serious adverse events and serious adverse reactions, including suspected unexpected serious adverse reactions, which occur during the course of a clinical trial— (a) in the United Kingdom; (b) conducted outside of the United Kingdom where— (i) the sponsor of both the trial in the United Kingdom and the trial outside of the United Kingdom is the same or, where the sponsor is a company, in the same group, and (ii) the investigational medicinal product being tested or used in the trial conducted outside of the United Kingdom is the same as the investigational medicinal product being tested or used in the clinical trial mentioned in sub-paragraph (a). (2) A sponsor shall evaluate the events and reactions mentioned in paragraph (1), with a view to— (a) minimising and preventing any risk presented by the use of the investigational medicinal product to which those events and reactions relate; and (b) taking appropriate measures as soon as reasonably practicable to investigate the risks presented and implement actions for minimising and preventing those risks. (3) For purposes of paragraph (1)(b)(i), “group” has the same meaning as in Part 15 of the Companies Act 2006 (see section 474(1) of that Act).

Amendment to regulation 32

24

In regulation 32 (notification of adverse events), for “subject”, in each place where it occurs, substitute “participant”.

Amendment to regulation 33

25

• (1) Regulation 33 (notification of suspected unexpected serious adverse reactions) is amended as follows.

• (2) For paragraph (1)²⁴ substitute—

(1) A sponsor shall ensure that all relevant information about a suspected unexpected serious adverse reaction which occurs during the course of a clinical trial in the United Kingdom and is fatal or life-threatening is reported as soon as possible to the licensing authority, and in any event no later than 7 days after the sponsor was first aware of the reaction.

• (3) In paragraph (2)—

• (a) for “paragraph (1)(b)” substitute “paragraph (1)”;

• (b) for “persons or bodies listed in that paragraph” substitute “licensing authority”.

• (4) For paragraph (3)²⁵ substitute—

(3) A sponsor shall ensure that a suspected unexpected serious adverse reaction which occurs during the course of a clinical trial in the United Kingdom, other than those referred to in paragraph (1), is reported as soon as possible to the licensing authority, and in any event no later than 15 days after the sponsor is first aware of the reaction.

• (5) Before paragraph (5) insert—

(4A) Paragraphs (1) to (3) do not apply to suspected unexpected serious adverse reactions specified in the protocol as not requiring immediate reporting. (4B) The sponsor shall report suspected unexpected serious adverse reactions to which paragraph (4A) applies to the licensing authority in accordance with the reporting requirements, including the time periods for such reporting, that are specified in the protocol.

• (6) Omit paragraph (5).

Amendment to regulation 35

26

• (1) Regulation 35 (annual list of suspected serious adverse reactions and safety report) is amended as follows.

• (2) In the heading, omit “list of suspected serious adverse reactions and”.

• (3) For paragraph (1) substitute—

(1) Within the period of 60 days beginning with the day after the day on which the reporting year ends, a sponsor shall, in relation to each investigational medicinal product tested in clinical trials referred to in regulation A32(1), provide the licensing authority with a report on the safety of the participants of those trials.

• (4) After paragraph (1) insert—

(1A) A report under paragraph (1) shall include— (a) the records of, and evaluation relating to, any serious adverse reactions and serious adverse events which have occurred during the reporting year, including suspected unexpected serious adverse reactions, kept or conducted under regulation A32; (b) the record of the taking of any measures referred to in regulation A32(2)(b); (c) a description of how any safety concerns in the clinical trial have been assessed and managed; and (d) a description of the overall safety profile of each investigational medicinal product being tested or used in the trials referred to in regulation A32(1), as well as a summary description of the processes adopted by the sponsor to monitor the overall safety profile of those products. (1B) The records of serious adverse reactions and serious adverse events referred to in paragraph (1A)(a) may take the form of a list. (1C) The licensing authority may request that the sponsor provide a list of serious adverse reactions and serious adverse events, including suspected unexpected serious adverse reactions, which have occurred at any time during the reporting year, in relation to a clinical trial referred to in regulation A32(1), where it considers it necessary to do so to investigate specific safety issues— (a) which emerge from the report under paragraph (1); or (b) which have otherwise come its attention, and raise concerns about the safety of the trial or the participants. (1D) The sponsor shall provide the list requested under paragraph (1C) within the period of 30 days beginning with the day of receiving the request, or within such shorter period as the licensing authority may specify in the request.

• (5) In paragraph (2), at the beginning, for “paragraph (1)” substitute “this regulation”.

Part 7 — Amendment to Part 6 (Manufacture and Importation of Investigational Medicinal Products)

Amendment to regulation 36

27

In regulation 36 (requirement for authorisation to manufacture or import investigational medicinal products), in paragraph (1), for “regulation 37” substitute “regulations 37 and 37A”.

Insertion of new regulation 37A

28

After regulation 37 (exemption for hospitals and health centres) insert—

(37A) (1) The restriction imposed by regulation 36(1) does not apply to the manufacture or assembly of a radiopharmaceutical used for diagnostic purposes where the conditions in paragraph (2) are satisfied. (2) The conditions referred to in paragraph (1) are that— (a) the manufacture or assembly is carried out by the holder of a manufacturer’s licence, as defined in regulation 8(1) of the 2012 Regulations, which does not relate to the manufacture of investigational medicinal products; and (b) the radiopharmaceutical is exclusively for use in a hospital or health centre which is— (i) a trial location for the clinical trial in which the product is to be used, or (ii) taking part in the clinical trial.

Amendment to regulation 40

29

In regulation 40 (grant or refusal of manufacturing authorisation), in paragraph (1)(a)(ii)²⁶, after “Commission Directive 2003/94/EC” insert “in respect of Great Britain, or of Commission Delegated Regulation 2017/1569 in respect of Northern Ireland”.

Amendment to regulation 43

30

• (1) Regulation 43 (qualified persons) is amended as follows.

• (2) In paragraph (2A)(b)²⁷, for “Article 13 of the Directive” substitute “Article 62 of the EU Regulation”.

• (3) In paragraph (2C)(b), after “Commission Directive 2003/94/EC” insert “in respect of Great Britain or Commission Delegated Regulation 2017/1569 in respect of Northern Ireland”.

• (4) In paragraph (5)²⁸, for “the said Article 49 or 50” substitute “Schedule 7 to the 2012 Regulations”.

• (5) In paragraph (6)(a)(i), for “the said Articles 49 or 50 of Directive 2001/83/EC” substitute “Schedule 7 to the 2012 Regulations”.

Part 8 — Insertion of new Part 6A (Non-Investigational Medicinal and Non-Medicinal Products)

Insertion of new Part 6A

31

After Part 6, insert—

(45A) (1) A non-investigational medicinal product shall be manufactured or assembled in accordance with the principles and guidelines for good manufacturing practice which apply under these Regulations or the 2012 Regulations. (2) A product which is not a medicinal product but which is used or to be used in a clinical trial, as described in the protocol, must— (a) comply with safety standards applicable to that product; and (b) be listed in the investigational medicinal product dossier with information about its properties, labelling, manufacture and safety controls, appropriate to the product.

Part 9 — Substitution of Part 7 (Labelling of Investigational Medicinal Products)

Substitution of Part 7

32

For Part 7 (labelling of investigational medicinal products) substitute—

(46) (1) Subject to paragraph (4), where the investigational medicinal product is not an authorised medicinal product, it must be labelled with the following information— (a) the words “for clinical trial use only”; (b) a warning that the product must be stored out of the reach and sight of children (unless the product is to be exclusively administered in a hospital or health centre taking part in the clinical trial); (c) information to identify the sponsor and contact persons involved in the clinical trial; (d) information to allow identification of the clinical trial, for example the clinical trial reference code; (e) information linking the product to the participant, for example, the participant identification number; (f) information to allow identification of the medicinal product, including— (i) the common name of the active substance, (ii) the strength and pharmaceutical form, (iii) the contents by weight, volume or number of doses, and (iv) the batch or code number; (g) information related to the use of the medicinal product, including— (i) instructions for use (which may be by reference to a patient information leaflet), (ii) method or route of administration, (iii) expiry date, and (iv) any special storage precautions; and (h) in the case of trials in which blinding occurs, the name of any comparator or placebo product used alongside the investigational medicinal product. (2) Subject to paragraph (4), where the investigational medicinal product is an authorised medicinal product, it must be labelled either— (a) in accordance with paragraph (1); or (b) in accordance with Part 13 of the 2012 Regulations. (3) Paragraph (4) applies to an investigational medicinal product which is— (a) an authorised medicinal product to be exclusively administered in a hospital or health centre taking part in the clinical trial; or (b) a radiopharmaceutical used for diagnostic purposes. (4) Where paragraph (3) applies, the investigational medicinal product must be labelled with at least the following information— (a) the words “for clinical trial use only”, or equivalent wording; (b) information linking the product to the participant, for example, the participant identification number; (c) information to allow identification of the medicinal product, including— (i) the common name of the active substance, (ii) the strength and pharmaceutical form, (iii) the contents by weight, by volume or by number of doses, and (iv) the batch or code number; (d) information related to the use of the medicinal product (which may be by reference to a patient information leaflet); (e) the expiry date; and (f) any other information relating to the clinical trial or the product that the authorities, as defined in regulation 11 (interpretation of Part 3), may require by guidelines published under paragraph (8). (5) The sponsor may request to disapply or vary any of the requirements of this regulation at the time of the application under regulation 16. (6) If a request under paragraph (5) is agreed— (a) the licensing authority must inform the sponsor by a notice in writing at the time of approval under regulation 18 or 18B; and (b) the sponsor must record that decision and any conditions in the investigational medicinal product dossier. (7) Where— (a) the trial is a notifiable trial; and (b) the request concerns an authorised medicinal product which is to be exclusively administered in a hospital or health centre taking part in the trial, the request is to be treated as agreed if no notice is given in accordance with paragraph (6)(a). (8) The licensing authority may publish guidance on labelling of investigational medicinal products, which may include guidance on how the labelling requirements are to be met in relation to products that are— (a) radiopharmaceuticals used for diagnostic purposes; (b) used exclusively in a hospital or health centre; (c) provided in differently sized or differently assembled packs, for example blister packs and small packages. (9) For the purposes of this regulation, a medicinal product is authorised if there is a UK marketing authorisation or Article 126a authorisation, each as defined in regulation 8(1) of the 2012 Regulations, in force for the product. (10) This regulation is subject to regulation 46B (labelling of certain POC investigational medicinal products). (46A) (1) Subject to paragraph (2), a non-investigational medicinal product must be labelled in accordance with the requirements set out in regulation 46, and any reference in that regulation to “investigational medicinal product” is to be construed as a reference to “non-investigational medicinal product” accordingly. (2) Regulation 46(4) does not apply to a non-investigational medicinal product which falls within sub-paragraph (a) of regulation 46(3). (46B) Regulation 46 does not apply to a POC investigational medicinal product that is to be administered in its entirety immediately after manufacture.

Part 10 — Amendment to Part 8 (Enforcement and Related Provisions)

Amendment to regulation 48

33

In regulation 48 (infringement notices), for paragraph (4)²⁹ substitute—

(4) This regulation applies to regulations 3A, 12(1) and (2), 13(1), 22(2) to (5), 25(1) and (2)(a), 27, 28(1) to (3), 29, 29A, 30(2), 31A to 35, 36(1), 36A, 36B, 42, 43(1) and (6), 45A, 46 and 46A.

Amendment to regulation 49

34

• (1) Regulation 49 (offences) is amended as follows.

• (2) In paragraph (1)³⁰—

• (a) after sub-paragraph (b) insert—

(ba) regulation 22(2) to (5); (bb) regulation 25(1) and (2)(a); (bc) regulation 26(7)(a);

• (b) after sub-paragraph (ff) insert—

(fg) regulation A32;

• (c) in sub-paragraph (l), at the end, omit “and”;

• (d) in sub-paragraph (m), for “(6),” substitute “(6); and”;

• (e) after sub-paragraph (m), insert—

(n) regulation 45A,

• (3) In paragraphs (6) and (7), in each place where it occurs, for “subject” substitute “participant”.

• (4) After paragraph (7) insert—

(8) Any sponsor who sells or supplies, or procures the sale or supply of, a non- investigational medicinal product— (a) to a participant for the purposes of a clinical trial; or (b) to a person for the purpose of administering the product to such a participant, the labelling of which does not comply with regulation 46A, shall be guilty of an offence. (9) Any person who sells or supplies, or procures the sale or supply of, a non-investigational medicinal product— (a) to a participant for the purposes of a clinical trial; or (b) to a person for the purpose of administering the product to such a participant, the labelling of which does not comply with regulation 46A, knowing, or having reasonable cause to believe, that the labelling does not so comply, shall be guilty of an offence.

Amendment to regulation 50

35

In regulation 50 (false or misleading information), in paragraph (1)—

• (a) in sub-paragraph (b), at the end, omit “or”;

• (b) after sub-paragraph (c) insert—

(d) notifying a modification of an important detail; or (e) making a modification request,

Part 11 — Amendment to Part 9 (Miscellaneous Provisions)

Amendment to regulation 58

36

In regulation 58 (detailed guidance), in paragraph (c), for “substantial amendment to the clinical trial authorisation” substitute “substantial modification, as defined in regulation 11 (interpretation of Part 3),”.

Part 12 — Amendment to the Schedules

Amendment to Schedule 1

37

• (1) Schedule 1 (conditions and principles of good clinical practice and for the protection of clinical trial subjects) is amended as follows.

• (2) In the heading, for “subjects” substitute “participants”.

• (3) In Part 1 (application and interpretation)—

• (a) for “any subject”, in each place where it occurs, substitute “any participant”;

• (b) for “that subject”, in each place where it occurs, substitute “that participant”;

• (c) for “a subject”, in each place where it occurs, substitute “a participant”;

• (d) in paragraph 1(7)³¹—

• (i) for “the subject” substitute “the participant”;

• (ii) omit “or by an appeal panel appointed under Schedule 4”;

• (e) in paragraph 2, in the definition of “Declaration of Helsinki” omit “, as amended by the General Assembly of the Association in October 1975, October 1983, September 1989 and October 1996”;

• (f) in paragraph 3—

• (i) in sub-paragraph (1)—

• (aa) at the beginning, insert “Subject to sub-paragraph (3),”;

• (bb) in paragraph (b)(ii), for “given orally” substitute “communicated (whether by talking, using sign language or any other means);

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

(3) Where sub-paragraph (4) applies, the protocol for the clinical trial for which consent is given may make provision for simplified arrangements for obtaining and evidencing consent, which shall include— (a) the reason for obtaining consent using simplified arrangements; (b) the information to be provided to the participant, and the means of providing that information; and (c) the means by which consent shall be evidenced. (4) This sub-paragraph applies where— (a) the investigational medicinal product or, if there is more than one, each of the investigational medicinal products, is authorised for use in the United Kingdom and is used in accordance with that authorisation; (b) the investigational medicinal product or, if there is more than one, each of the investigational medicinal products, is given to the participant in the course of that participant’s routine health care; and (c) the participant receives no additional medication and undergoes no additional intervention or diagnostic procedure, solely for the purposes of the clinical trial. (5) For the purposes of sub-paragraph (4)— - “intervention” includes complementary or alternative therapies, the taking of tissue samples, and requirements in relation to imaging and radiotherapy; and - “medication” includes nutritional products and alternative remedies.

• (4) For Part 2 (conditions and principles which apply to all clinical trials) substitute³²—

(1) Clinical trials must be conducted in accordance with the principles of good clinical practice set out in the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Guideline for Good Clinical Practice, as amended from time to time³³. (2) Except where it would be a contravention of these Regulations, clinical trials must be conducted in accordance with the principles of the Declaration of Helsinki. (3) The investigator and sponsor must have regard to all relevant guidance with respect to commencing and conducting a clinical trial. (4) Provision must be made for insurance or indemnity to cover all liabilities of the investigator and sponsor which may arise in relation to the clinical trial.

• (5) In Part 3 (conditions which apply in relation to an adult able to consent or who has given consent prior to the onset of incapacity), for “the subject”, in each place where it occurs, substitute “the participant”.

• (6) In Part 5 (conditions and principles which apply in relation to an incapacitated adult)—

• (a) for “the subject”, in each place where it occurs, substitute “the participant”;

• (b) in paragraph 1, for “the subject’s” substitute “the participant’s”;

• (c) in paragraph 7, for “a subject” substitute “a participant”.

Omission of Schedule 2

38

Omit Schedule 2 (additional provisions relating to ethics committees).

Amendment to Schedule 3

39

• (1) Schedule 3 (particulars and documents that must accompany an application for an ethics committee opinion, a request for authorisation, a notice of amendment and a notification of the conclusion of a trial) is amended as follows.

• (2) In the heading, for “an application for an ethics committee opinion, a request for authorisation, a notice of amendment” substitute “a request for approval, a modification request”.

• (3) At the beginning of the Schedule insert—

(1) A completed application. (2) A statement or cover letter drawing attention to any features which are particular to the clinical trial, if required. (3) The protocol for the proposed trial describing the objective, design, methodology, statistical considerations, purpose and organisation of the clinical trial. (4) The investigator’s brochure or equivalent document. (5) The following documents or, in each case, an explanation of why that document is not being provided— (a) documentation relating to compliance with the principles and guidelines of good manufacturing practice, where applicable; (b) a dossier providing the following information or cross-referring to the document in paragraph 4 if it contains such information— (i) details of the quality of any investigational medicinal product or non-investigational medicinal product, (ii) details of the manufacture and control of the investigational medicinal product, and (iii) data from non-clinical studies and from clinical use of the product; (c) a copy of the scientific advice of the licensing authority, or of any third country, with regard to the clinical trial; (d) a description of the content of the labelling; (e) all information given to the participants, or their legal representatives, before their decision to participate or abstain from participation in the clinical trial; (f) proof of insurance, a guarantee, or any other similar arrangement, where applicable; (g) responses to areas for discussion raised by the Commission on Human Medicines, where applicable.

• (4) Omit Parts 1 (application for ethics committee opinion) and 2 (request for authorisation).

• (5) In Part 3 (notice of amendment)—

• (a) in the heading to Part 3, for “notice of amendment” substitute “modification request”;

• (b) omit paragraph 1;

• (c) in paragraph 2(b)³⁴, for “on the European database referred to in Article 11 of the Directive” substitute “by the authorities”;

• (d) in paragraph 3, for “amendment” substitute “modification”;

• (e) in paragraph 4, for “amendment” substitute “modification, and if more than one modification, a statement for each modification”;

• (f) in paragraph 5(b), for “authorisation or the application for an ethics committee opinion” substitute “approval”;

• (g) in paragraph 6—

• (i) in sub-paragraph (a), for “amendment” substitute “modification or modifications”;

• (ii) in sub-paragraph (b), for “assessment referred to in paragraph 11(2) of Part 2” substitute “summary assessment of the potential risks and benefits of using the product in the proposed trial”.

• (6) In Part 4 (notification of conclusion of a clinical trial)—

• (a) omit paragraph 1;

• (b) in paragraph 2(b)³⁵, for “on the European database referred to in Article 11 of the Directive” substitute “by the authorities”;

• (c) in paragraph 4—

• (i) in sub-paragraph (2)—

• (aa) for “site” substitute “location”;

• (bb) for “sites” substitute “locations”;

• (ii) for sub-paragraph (3), substitute—

(3) If the trial was conducted at any trial locations outside the United Kingdom, a statement as to whether the trial has ended at any of those locations and— (a) if ended, the date on which the trial ended; or (b) if not ended, the anticipated end date of the trial.

Amendment to Schedule 4

40

• (1) Schedule 4 (appeal against unfavourable ethics committee opinion) is amended as follows.

• (2) In paragraph 1—

• (a) in sub-paragraph (1)³⁶—

• (i) for “regulation 16(3), 4(b) or (7)” substitute “regulation 24(3)”;

• (ii) for “chief investigator” substitute “sponsor”;

• (iii) omit paragraph (b) and the “or” preceding it;

• (b) in sub-paragraph (2) omit—

• (i) “Subject to sub-paragraph (4),”;

• (ii) “or appoint a panel”;

• (c) in sub-paragraph (3)—

• (i) omit “or appoint a panel”;

• (ii) for “chief investigator” substitute “sponsor”;

• (d) omit sub-paragraph (4).

• (3) In paragraph 2—

• (a) in sub-paragraph (a)—

• (i) for “ethics committee which gave the unfavourable opinion” substitute “Authority”;

• (ii) for “chief investigator” substitute “sponsor”;

• (iii) at the end, omit “and”;

• (b) in sub-paragraph (b), for “regulation 15,” substitute “regulation 17; and”;

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

(c) that committee shall within 30 days beginning with the day on which the application is sent to the committee under paragraph (a), or such extended period as the Authority may in any particular case allow, either confirm the opinion or give a favourable opinion.

• (4) Omit paragraphs 3 to 6.

Amendment to Schedule 5

41

• (1) Schedule 5 (procedural provisions relating to the refusal or amendment of, or imposition of conditions relating to, clinical trial authorisations and the suspension or termination of clinical trials) is amended as follows.

• (2) In paragraph 1³⁷, for “regulation 26(1)” substitute “regulation 23(2)”.

• (3) In paragraph 2—

• (a) in sub-paragraph (1)—

• (i) in the opening words, for “an amendment to the clinical trial authorisation” substitute “a substantial modification”;

• (ii) in paragraph (a), for “amendment” substitute “modification”;

• (iii) in paragraph (b), for “amendment to the clinical trial authorisation” substitute “modification”;

• (b) in sub-paragraph (2), for “notice of amendment to a clinical trial authorisation” substitute “valid modification request”.

Amendment to Schedule 7

42

• (1) Schedule 7 (standard provisions for manufacturing authorisations) is amended as follows.

• (2) In Part 1 (interpretation)—

• (a) before the definition of “Commission Directive 2003/94/EC” insert—

• “Commission Delegated Regulation 2017/1569”, in relation to the holder of an authorisation in Northern Ireland, means Commission Delegated Regulation (EU) 2017/1569 of 23 May 2017 supplementing Regulation (EU) No 536/2014 of the European Parliament and of the Council by specifying principles of and the guidelines for good manufacturing practice for investigational medicinal products for human use and arrangements for inspections, as that Regulation has effect in EU law³⁸;

• (b) in the definition of “Commission Directive 2003/94/EC”³⁹ omit paragraph (b).

• (3) In Part 2 (provisions which may be incorporated in an authorisation relating to the manufacture or assembly of investigational medicinal products)—

• (a) in paragraph 3, after “Commission Directive 2003/94/EC” insert “in respect of Great Britain, or Article 10(1) of Commission Delegated Regulation 2017/1569 in respect of Northern Ireland,”;

• (b) in paragraph 4, after “Commission Directive 2003/94/EC” insert “in respect of Great Britain, or Article 10(2) of Commission Delegated Regulation 2017/1569 in respect of Northern Ireland,”;

• (c) in paragraph 7(a), after “Commission Directive 2003/94/EC” insert “in respect of Great Britain or Article 8 of Commission Delegated Regulation 2017/1569 in respect of Northern Ireland”;

• (d) in paragraph 8, after “Commission Directive 2003/94/EC” insert “in respect of Great Britain or Article 11 of Commission Delegated Regulation 2017/1569 in respect of Northern Ireland”.

• (4) In Part 3 (provisions which may be incorporated in an authorisation relating to the importation of investigational medicinal products)—

• (a) in paragraph 2, after “Commission Directive 2003/94/EC” insert “in respect of Great Britain, or Article 10(2) of Commission Delegated Regulation 2017/1569 in respect of Northern Ireland,”;

• (b) in paragraph 5(a), after “Commission Directive 2003/94/EC” insert “in respect of Great Britain or Article 8 of Commission Delegated Regulation 2017/1569 in respect of Northern Ireland”.

Part 13 — Consequential provisions

Amendment of the Medicines (Products for Human Use) (Fees) Regulations 2016

43

• (1) The Medicines (Products for Human Use) (Fees) Regulations 2016⁴⁰ are amended as follows.

• (2) In regulation 20—

• (a) in the heading, for “amendments” substitute “modifications”;

• (b) in paragraph (1)—

• (i) for “valid notice of amendment under regulation 24 (amendments” substitute “modification request under regulation 22 (modifications”;

• (ii) for “paragraphs 10 or 11 of Part 2 of Schedule 3 (request for authorisation)” substitute “paragraphs 2 or 5(a) of Part A1 of Schedule 3 (request for approval)”.

• (3) In Schedule 2, in Part 4, in paragraph 49, for “notice of amendment relating to an amendment” substitute “modification request relating to a modification”.

Part 14 — Transitional provisions

Amendment to regulation 56

44

In regulation 56 (transitional provisions), for “Schedules 12 and 13” substitute “Schedules 12, 13 and 14”.

Insertion of Schedule 14

45

After Schedule 13 (transitional provisions relating to EU Exit) insert—

Schedule 14 (1) (1) In this Schedule— - “end of trial date” is the date of the conclusion of the trial that is specified in the protocol of a clinical trial and which, in the case of a clinical trial conducted in other countries as well as the United Kingdom, is the end of the date of the trial in all the participating countries; - “the new rules” means these Regulations as in force on and after the relevant day; - “new rules clinical trial” means a clinical trial which is not an old rules clinical trial; - “old committee” means an ethics committee recognised under the old rules that has been abolished or has ceased to operate as an ethics committee for the purposes of these Regulations; - “the old rules” means these Regulations as in force immediately before the relevant day; - “old rules clinical trial” is to be construed in accordance with paragraph 2(1)(a); - “the relevant day” means the day on which this Schedule comes into force. (2) Where, by virtue of this Schedule, the old rules continue to apply, regulation 2 of the old rules applies to the interpretation of the old rules, except in so far as it is necessary for regulation 2 of the new rules to apply to their interpretation in order to give effect to a provision of this Schedule (for example, because a new committee is performing functions of an old committee). (3) For purposes of this Schedule, “sponsor”, in the context of the old rules, has the meaning given in regulation 3 of the old rules. (4) Regulation 53 of the new rules applies to both the new rules and the old rules. (2) (1) If a request for authorisation to conduct a clinical trial has been received by the licensing authority before the relevant day, or an application for an ethics committee opinion in relation to a clinical trial has been received before the relevant day, Part 3 of the old rules including its related Schedules, rather than Part 3 of the new rules including its related Schedules, applies in respect of— (a) that trial (an “old rules clinical trial”), including— (i) the authorisation of that trial and any amended requests for authorisation, (ii) the giving of an ethics committee opinion in relation to that trial, or a review or appeal relating to such an opinion, and (iii) information sharing and the publication of information; and (b) the supply of any investigational medicinal product for a purpose related to that trial, subject to the following sub-paragraphs. (2) An ethics committee established under regulation 6(1) of the new rules (“a new committee”) may, with the agreement of the Authority, take over and perform any function under the old rules of an ethics committee recognised under the old rules. (3) Where a new committee performs functions of an ethics committee under the old rules pursuant to this Schedule, the new committee may, with the agreement of the Authority, regulate its proceedings and business in relation to old rules clinical trials in a manner that is consistent, subject to any necessary modifications, with how it regulates its proceedings and business in relation to new rules clinical trials, provided that there is no detriment to— (a) the sponsor of an old rules clinical trial; or (b) achieving the outcome of performing the functions of an old committee under the old rules. (4) Any recognition of an ethics committee under regulation 7 of the old rules may, with the agreement of the Authority, continue in effect notwithstanding the repeal of regulation 7, but— (a) solely for the purposes of that committee performing the functions under the old rules of an ethics committee, and Part 2 of the old rules and its related Schedules continue to apply for that purpose; and (b) subject to any conditions or limitations imposed by the Authority. (5) In a case where the licensing authority or ethics committee receives a valid notice of amendment to a clinical trials authorisation from a sponsor before the relevant day, Part 3 of the old rules including its related Schedules, rather than Part 3 of the new rules including its related Schedules, applies in respect of that notice of amendment, including— (a) the giving of a written notice by the licensing authority, and the review of any amended notice of amendment or any appeal relating to such written notice; and (b) the giving of an opinion by an ethics committee, and the review of any amended notice of amendment, but no notice of amendment received on or after the relevant day pursuant to the old rules is to be treated as valid. (6) In a case where the licensing authority serves a notice on a sponsor pursuant to regulation 23 of the old rules before the relevant day, the old rules continue to apply for the purposes of the consideration of representations relating to, and any making of an amendment as a consequence of, that notice. (7) As regards the modifications to an old rules clinical trial authorisation on and after the relevant day, except in a case to which sub-paragraph (5) or (6) applies, that modification (including a modification that would have been an amendment by the sponsor under regulation 24 of the old rules) is to be made in accordance with and subject to the requirements of the new rules. (8) Regulation 25 of the new rules applies to old rules clinical trials as it does to new rules clinical trials (including automatic deferrals in regulation 25(10)), except that— (a) it does not apply to an old rules clinical trial that has an end of trial date that is before the relevant day; and (b) in the case of an old rules trial that has been approved but its end of trial date is on or after the relevant day— (i) where, before the relevant day the first individual has not yet been recruited to be a participant in that trial, regulation 25(1) applies as if the reference to approval of the trial were a reference to the relevant day, (ii) where, before the relevant day the first individual has been recruited to be a participant in that trial, regulation 25(1) applies as if the reference to approval of the trial were a reference to the relevant day and sub-paragraph (a) were omitted, and (iii) regulation 25(2)(b) does not apply. (3) (1) Part 4 of the new rules applies in respect of old rules clinical trials as it does in respect of new rules clinical trials, subject to the following sub-paragraph. (2) Regulation 31A(7) of the old rules, rather than regulation 31A(7) of the new rules, applies in respect of old rules clinical trials. (4) (1) Part 5 of the new rules applies in respect of old rules clinical trials as it does in respect of new rules clinical trials, subject to the following sub-paragraphs. (2) The sponsor of an old rules clinical trial may elect that Part 5 of the old rules is to apply, temporarily, in respect of the clinical trial, rather than Part 5 of the new rules, provided that the licensing authority has received notification of that election— (a) unless paragraph (b) applies, within the period of 60 days beginning with the day after the relevant day; (b) where, in order to comply with the old rules, a reporting or notification obligation under the old rules needs to be discharged before that 60 day period expires, when or before that reporting or notification obligation is discharged (which must be on or before the latest day on which that reporting notification needs to be discharged in order to comply with the old rules). (3) Where a sponsor of an old rules clinical trial has made a valid election pursuant to sub-paragraph (2), once the sponsor has discharged their obligations under regulation 35(1) of the old rules, or the period during which the sponsor is required to do so has expired, whichever is the sooner, the election ceases to have effect. (5) (1) Part 6 of the new rules, including its related Schedules, applies in respect of the manufacture and importation of investigational medicinal products used in old rules clinical trials as it does in respect of the manufacture and importation of investigational medicinal products used in new rules clinical trials, subject to the following sub-paragraph. (2) Regulation 37A does not apply to radiopharmaceuticals used for diagnostic purposes. (6) Part 7 of the old rules applies in respect of investigational medicinal products used in old rules clinical trials, if those products are manufactured before the relevant day, and in these circumstances investigational medicinal products— (a) manufactured before the relevant day; and (b) labelled in accordance with regulation 46 of the old rules, may continue to be used in a clinical trial for which they are for use, subject to complying with Part 7 of the old rules. (7) (1) Where the old rules continue to apply by virtue of this Schedule, with or without modifications, Part 8 of the old rules applies to the enforcement of those old rules, subject to the following sub-paragraph. (2) Where, by virtue of this Schedule, a provision (whether of the old rules or the new rules) applies with modifications, for the purposes of securing the effective enforcement of that provision as so modified, an enforcement authority may include those modifications in an infringement notice.

Signed

Signed by authority of the Secretary of State for Health and Social Care

Merron — Parliamentary Under Secretary of State — Department of Health and Social Care — 28th April 2025

Sealed with the Official Seal of the Department of Health in Northern Ireland

Cathy Harrison — A senior officer of the Department of Health in Northern Ireland — 24th April 2025

Explanatory note

(This note is not part of the Regulations)

Explanatory Note

These Regulations amend the Medicines for Human Use (Clinical Trials) Regulations 2004 (“the 2004 Regulations”) which implement Directive 2001/20/EC on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products in humans.

Following withdrawal of the UK from the European Union, these Regulations are made in exercise of the powers conferred by sections 2(1), 5(1)(a) to (e), 6(1)(b) and 43 of the Medicines and Medical Devices Act 2021, in respect of clinical trials in the United Kingdom.

These Regulations make provision for the following matters:

• (a) Part 3 amends the provisions on the operation and constitution of the ethics committee, which are contained in Part 2 of the 2004 Regulations.

• (b) Part 4, which amends Part 3 of the 2004 Regulations, revises the approval procedure for clinical trials, combining the separate applications for regulatory authorisation and ethics committee opinion into one application route, leading to a co-ordinated review and a single UK decision. For trials considered lower risk, this will be notified and can be given automatic regulatory authorisation. The combined procedure is extended to substantial amendments to the trial approval, and references to amendments are replaced with references to modifications. This Part also introduces transparency requirements, which are to require registration of the trial in a public register, to publish a summary of the trial results, and to share those results with the participants.

• (c) Part 5 amends the provisions on the principles and conditions of good clinical practice by reference to the ICH guideline and makes clear, in applying those principles and conditions that the functions of the sponsor include those in relation to the development and maintenance of trial specific computerised systems.

• (d) Part 6 makes a number of changes to Part 5 of the 2004 Regulations, which concerns the pharmacovigilance requirements that apply to clinical trials under Part 5, in particular to allow aggregate reporting, and to impose specific requirements with respect to record keeping and the content of the annual report on the safety of trials.

• (e) Part 7 amends Part 6 of the 2004 Regulations on manufacturing and importation, and provides for an exemption from the need, in certain circumstances, for a manufacturing authorisation in respect of radiopharmaceuticals used for diagnostic purposes.

• (f) Part 8, which inserts a new Part 6A to the 2004 Regulations, makes a new provision concerning medicinal products which are used in the trial, but which are not being tested.

• (g) Part 9, which amends Part 7 of the 2004 Regulations, makes similar provision to the EU Clinical Trials Regulation in respect of labelling of investigational and non-investigational medicinal products.

• (h) Part 10 makes consequential changes to Part 8 of the 2004 Regulations relating to enforcement of the Regulations and extends the power of the licensing authority to issue infringement notices to facilitate compliance with the Regulations.

• (i) Part 11 amends all the Schedules that are related to the changes made to Parts 2 to 4 of the 2004 Regulations.

• (j) Part 12 inserts a new Schedule 14, which makes transitional provisions in relation to existing authorisations and applications.

References throughout the Regulations to a clinical trial subject are replaced with references to a participant; and similarly, references to a trial site, are replaced with references to a trial location.

A full impact assessment has not been produced for this instrument as no, or no significant, impact on the private, voluntary or public sector is foreseen. A de minimis assessment is available from the Department of Health and Social Care, 39 Victoria Street, London, SW1H 0EU and is published with the explanatory memorandum alongside this instrument at www.legislation.gov.uk.

Footnotes