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

• (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)[^f00034], 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)[^f00035], 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)[^f00036]—

• (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 1[^f00037], 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 law[^f00038];

• (b) in the definition of “Commission Directive 2003/94/EC”[^f00039] 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 2016[^f00040] 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

[^f00001]: 2021 c. 3. The powers in section 2(1) of the Medicines and Medical Devices Act 2021, and the provisions that relate to it, are exercisable by the “appropriate authority”. As defined in section 2(6)(a) of the Act, the appropriate authority for England and Wales and Scotland is the Secretary of State. In relation to Northern Ireland, as defined in section 2(6)(b)(ii), the appropriate authority can mean the Secretary of State and the Department of Health in Northern Ireland acting jointly.

[^f00002]: S.I. 2004/1031.

[^f00003]: The definition of “chief investigator” was amended by S.I. 2006/1928.

[^f00004]: OJ No. L 238, 16.09.17, p. 12-21.

[^f00005]: The definition of “Commission Directive 2003/94/EC” was amended by S.I. 2019/744.

[^f00006]: The definition of “the Directive” was substituted by S.I. 2008/941.

[^f00007]: OJ No. L 158, 27.05.14, p. 1-76.

[^f00008]: The definition of “the Gene Therapy Advisory Committee” was amended by S.I. 2008/941.

[^f00009]: Paragraph (f) of the definition of “health care professional” was amended by S.I. 2012/1479 and 2019/1094.

[^f00010]: 2006 c. 41; section 2 was substituted by the Health and Care Act 2022 (c. 31), Schedule 5, paragraph 10; section 3 was substituted by the Health and Care Act 2022 (c. 31), section 21.

[^f00011]: 2006 c. 42.

[^f00012]: Paragraph (a) of the definition of “health service body” was amended by S.I. 2013/235.

[^f00013]: Regulation 7 was amended by S.I. 2006/1928.

[^f00014]: S.I. 2012/1916; this definition was inserted by S.I. 2019/775.

[^f00015]: Regulation 12(3) was amended by S.I. 2006/1928.

[^f00016]: Paragraph (2) was inserted by S.I. 2019/744.

[^f00017]: S.I. 2002/618, amended by S.I. 2019/791; there are other amending instruments but none is relevant.

[^f00018]: Regulation 27A was inserted by S.I. 2006/1928.

[^f00019]: The Guideline can be found at https://ich.org/page/efficacy-guidelines. A printed version of the document can be made available on request by the Department of Health and Social Care, 39 Victoria Street, London SW1H 0EU.

[^f00020]: Regulation 29(c) was amended by S.I. 2006/1928.

[^f00021]: Regulation 29A was inserted by S.I. 2006/1928.

[^f00022]: Regulation 30(2) was substituted by S.I. 2009/1164.

[^f00023]: Regulation 31(1)(a)(ii) was amended by S.I. 2006/1928.

[^f00024]: Regulation 33(1) was amended by S.I. 2019/744.

[^f00025]: Regulation 33(3) was amended by S.I. 2019/744.

[^f00026]: Regulation 40(1)(a)(ii) was substituted by S.I. 2006/1928.

[^f00027]: Paragraph (2A) was inserted by S.I. 2019/744.

[^f00028]: Paragraph (5) was substituted by S.I. 2019/744.

[^f00029]: Regulation 48(4) was amended by S.I. 2006/1928.

[^f00030]: Regulation 49(1) was amended by S.I. 2006/1928.

[^f00031]: Paragraph 1(7) of Schedule 1 was inserted by S.I. 2006/2984.

[^f00032]: Part 2 of Schedule 1 was substituted by S.I. 2006/1928.

[^f00033]: The Guideline can be found at https://ich.org/page/efficacy-guidelines. A printed version of the document can be made available on request by the Department of Health and Social Care, 39 Victoria Street, London SW1H 0EU.

[^f00034]: Paragraph 2 was amended by S.I. 2006/1928.

[^f00035]: Paragraph 2 was amended by S.I. 2006/1928.

[^f00036]: Paragraph 1(1) was amended by S.I. 2006/1928.

[^f00037]: Paragraph 1 was substituted by S.I. 2005/2754.

[^f00038]: OJ No. L 238, 16.09.17, p. 12-21.

[^f00039]: The definition of “Commission Directive 2003/94/EC” was inserted by S.I. 2019/744.

[^f00040]: S.I. 2016/190.