Part 4Amendment to Part 3 (Authorisation for Clinical Trials and Ethics Committee Opinion)

Substitution of regulation 11

regulation 10 + 10.  For regulation 11 (interpretation of Part 3) substitute—

Interpretation of Part 3

11.  In this Part—

“advanced therapy medicinal product” has the meaning given by regulation 2A of the 2012 Regulations(1);

“authorities” means the licensing authority and the ethics committee in collaboration with each other;

“modification of an important detail” means a modification to a clinical trial approval which—

“modification to a clinical trial approval” means a modification to—

“relevant committee” means—

“Route A substantial modification” means a modification to a clinical trial approval which is likely to have a substantial impact on the safety or rights of the participants or on the reliability or robustness of the data generated in the trial;

“Route B substantial modification” has the meaning given in regulation 11B;

“specialist group or committee” means a group or committee whose functions include the provision of advice on ethical or scientific issues in relation to—

“substantial modification” means—

“valid modification request” means a modification request which complies with the provisions of regulation 22;

“valid request for approval” means a request for approval which complies with the provisions of regulation 16.”.

Insertion of new regulations 11A and 11B

regulation 11 + 11.  After regulation 11 (interpretation of Part 3) insert—

Definition of notifiable trial

11A.—(1) In these Regulations, “notifiable trial” means a trial—

(a)where there are no significant safety concerns with any of the investigational medicinal products, as far as the sponsor is aware having made reasonable enquiries;

(b)which meets either Condition A, Condition B or Condition C; and

(c)which does not involve either—

(i)participants who are—

(aa)under the age of 18 years,

(bb)pregnant, or

(cc)breastfeeding, or

(ii)an investigational medicinal product that is—

(aa)an advanced therapy medicinal product, or

(bb)used for the first time in humans.

(2) Condition A is that 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 either—

(a)the product is used in accordance with that authorisation; or

(b)the use of the product in the trial is supported by established clinical practice.

(3) Condition B is that a trial relating to the investigational medicinal product or, if there is more than one, each of the investigational medicinal products, has been approved in the United Kingdom within the preceding 2 years of the date of request for approval whereby—

(a)the product was investigated at—

(i)the same or higher dose,

(ii)the same or higher frequency, and

(iii)the same or longer duration;

(b)the same manufacturing process was utilised for the product; and

(c)the approved trial—

(i)utilised the same route of administration for the product, and

(ii)investigated the product for the same indication.

(4) Condition C is that the trial has undergone assessment, and been approved, by the appropriate authority responsible for the licensing of clinical trials in one or more of the following—

(a)the European Union;

(b)an EEA State;

(c)the United States of America.

Definition of Route B substantial modification

11B.—(1) In these Regulations, “Route B substantial modification” means a modification to the approval of a clinical trial (“the relevant clinical trial”)—

(a)where there are no new significant safety concerns with any of the investigational medicinal products, as far as the sponsor is aware having made reasonable enquiries; and

(b)which meets either Condition A, Condition B or Condition C.

(2) Condition A is that—

(a)the relevant clinical trial does not involve an investigational medicinal product that is used for the first time in humans;

(b)the modification has been reviewed and approved by the appropriate authority responsible for the licensing of clinical trials in one or more of the following—

(i)the European Union;

(ii)an EEA State;

(iii)the United States of America; and

(c)the particulars and documents that have been reviewed in connection with the approval of the modification by the authority referred to in sub-paragraph (b)—

(i)are the same as those that accompany the modification request, and

(ii)do not include any particulars that are specific to the United Kingdom.

(3) Condition B is that the modification is limited to one or more of the following changes to the protocol for the relevant clinical trial—

(a)a change to the primary objective of the relevant clinical trial;

(b)an inclusion of new measurements for the primary endpoint;

(c)a change to the design of the relevant clinical trial, which has a significant impact on the statistical consideration;

(d)a change in the criteria by reference to which the relevant clinical trial ends;

(e)where the relevant clinical trial involves an investigational medicinal product that has been authorised for use in the United Kingdom, and which is used in accordance with the terms of that authorisation in the trial, a change to the number of planned interactions with the participants to assess their ongoing safety as a participant in the trial, which is not in response to a new safety concern;

(f)a change to the list of concomitant medication that a participant in the relevant clinical trial is or is not allowed to use;

(g)in relation to a clinical trial which is conducted in more than one country in accordance with a global protocol, a change to that protocol to include all requirements specific to the United Kingdom that were approved by the authorities in a separate protocol or addendum to the global protocol that is specific to the United Kingdom, where this change does not result in a change to the safety reporting requirements as set out in Part 5.

(4) Condition C is that the modification is limited to one or more of the following changes to the investigator’s brochure or the summary of product characteristics for the relevant clinical trial—

(a)an inclusion of new toxicological or pharmacological data related to the investigational medicinal product, where there are no changes to the protocol of the relevant clinical trial as a result of safety concerns with the data;

(b)a change to the reference safety information which involves an increase in the frequency of adverse reactions, where there are no new expected adverse reactions;

(c)a change to the investigator’s brochure which is not a change to—

(i)the assessment of the risks and benefits of the relevant clinical trial as approved by the authorities, or

(ii)the safety profile of any of the investigational medicinal products used in the relevant clinical trial;

(d)an update to the section of the summary of product characteristics which deals with undesirable effects of the investigational medicinal product.

(5) In this regulation—

“concomitant medication”, in relation to a clinical trial, means any medicinal product that is not used for the purposes of the trial;

“primary endpoint” means the variable or measure capable of providing the most clinically relevant and convincing evidence directly related to the primary objective of the trial, for example, the period between the first receipt of treatment or a placebo by a participant and the occurrence of a pre-defined event;

“reference safety information” means information in the product information relating to expected serious adverse reactions associated with an investigational medicinal product, which is used to determine the adverse reactions that are to be treated as suspected unexpected serious adverse reactions in relation to that investigational medicinal product.”.

Amendment to regulation 12

regulation 12 + 12.—(1) Regulation 12 (requirement for authorisation and ethics committee opinion) is amended as follows.

(2) In paragraph (2)—

regulation 12 2 a + (a)in sub-paragraph (a), for “subject” substitute “participant”;

regulation 12 2 b + (b)in sub-paragraph (b), for “subjects” substitute “participants”.

(3) For paragraph (3)(2) substitute—

“(3) The conditions referred to in paragraphs (1) and (2) are—

(a)an ethics committee has given a favourable opinion in relation to the clinical trial; and

(b)the clinical trial has been authorised by the licensing authority,

in accordance with these Regulations.”.

(4) Omit paragraph (4).

Amendment to regulation 13

regulation 13 + 13.—(1) Regulation 13 (supply of investigational medicinal products for the purpose of clinical trials) is amended as follows.

(2) In paragraph (1)(d), for “subject” substitute “participant”.

(3) In paragraph (2)(b)(ii)(3)—

regulation 13 3 a + (a)in sub-paragraph (aa), for “Article 13 of the Directive” substitute “Article 62 of the EU Regulation”;

regulation 13 3 b + (b)in sub-paragraph (bb), for “Article 13(3) and (4) of the Directive” substitute “Article 62 of the EU Regulation”.

Substitution of regulations 14 to 26

regulation 14 + 14.  For regulations 14 to 26 substitute—

Request for authorisation to conduct a clinical trial

14.—(1) The sponsor must make a request for authorisation to conduct a clinical trial to the licensing authority in accordance with the procedure set out in regulation 16.

(2) Where the trial is a notifiable trial, the sponsor must indicate that it is a notifiable trial in accordance with regulation 16(2)(b).

Application for ethics committee opinion

15.—(1) The sponsor must make an application for an ethics committee opinion in relation to a clinical trial in accordance with the procedure set out in regulation 16.

(2) The application must be made to one ethics committee only, regardless of the number of trial locations at which the trial is to be conducted.

(3) Subject to paragraph (4), the application must be made to an ethics committee established or recognised—

(a)for the entire United Kingdom; and

(b)in relation to a description or class of clinical trial into which the proposed trial falls.

(4) If—

(a)a clinical trial is conducted at one or more trial locations in Scotland;

(b)the trial involves adults unable by virtue of physical or mental incapacity to give informed consent; and

(c)the chief investigator is professionally based at a hospital, health centre, surgery or other establishment or facility in Scotland,

the application for an ethics committee opinion in relation to that trial must be made to an Ethics Committee constituted by regulations made by the Scottish Ministers under section 51(6) of the Adults with Incapacity (Scotland) Act 2000.

(5) For the purposes of paragraph (4), a chief investigator is professionally based at the hospital, health centre, surgery or other establishment or facility at or from which the chief investigator’s professional practice is primarily conducted.

Request for approval and combined procedure

16.—(1) Subject to paragraph (5), the request for authorisation under regulation 14 and the application for an ethics committee opinion under regulation 15 must be made by way of a single application dossier (a “request for approval”).

(2) The request for approval must—

(a)be submitted to an online portal made available for this purpose;

(b)where the trial is a notifiable trial, include a statement confirming that the trial is a notifiable trial;

(c)be accompanied by—

(i)the particulars and documents specified in Part A1 of Schedule 3, and

(ii)subject to paragraph (3), any fee which may be payable in connection with that application under the Medicines (Products for Human Use) (Fees) Regulations 2016.

(3) Paragraph (2)(c)(ii) does not apply where arrangements have been made with the licensing authority or the ethics committee for payment of the fee referred to in that paragraph other than at the time of the request.

(4) The request for approval and accompanying material must be supplied in English.

(5) In exceptional circumstances (for example, in an urgent situation where it would be beneficial to progress one request or application while preparing the other), and if agreed in advance by the licensing authority or the ethics committee, a request for authorisation under regulation 14 and an application for an ethics committee opinion under regulation 15 may be made separately.

(6) Where an agreement has been reached under paragraph (5), the licensing authority or the ethics committee (as the case may be) must confirm—

(a)which of the particulars and documents specified in Part A1 of Schedule 3 must accompany—

(i)the request for authorisation, and

(ii)the application for an ethics committee opinion; and

(b)the arrangements for the payment of the fee specified in paragraph (2)(c)(ii).

(7) Where an agreement has been reached under paragraph (5), the submission of both the request for authorisation and the application of an ethics committee constitutes a “request for approval”.

(8) The authorities must confirm whether the request for approval is valid within the period of 7 days beginning with the date of the submission of the request and notify the sponsor accordingly.

Assessment of request for approval

17.—(1) Where the licensing authority and an ethics committee receive a valid request for approval—

(a)the licensing authority must assess the request for authorisation in relation to the clinical trial to which the request for approval relates;

(b)the ethics committee must assess the application for an ethics committee opinion in relation to the clinical trial to which the request for approval relates.

(2) The licensing authority—

(a)must consider the safety of the clinical trial and the safeguarding of clinical trial participants; and

(b)may have regard to whether the sponsor has failed to comply with regulation 25(1) or 25(2)(a) in relation to another clinical trial, and not rectified that failure.

(3) The ethics committee must consider—

(a)whether the anticipated benefits to participants and other individuals or groups affected by the medical condition under investigation outweigh the anticipated risks and inconveniences, taking account of—

(i)the risks to the health of any of the participants posed by the medical condition for which the product is being investigated, and

(ii)the nature of the intervention compared to normal clinical care; and

(b)the measures used to—

(i)seek and obtain informed consent for participation in the trial, and

(ii)protect and promote the interests of participants and the general public (including by promoting transparency in research).

(4) Where the request for approval contains a statement under regulation 16(2)(b) confirming that the trial is a notifiable trial, the licensing authority may, if it considers appropriate and without undertaking further assessment, rely on that statement to provide an authorisation of the clinical trial to which the request for approval relates.

(5) The ethics committee may consider, and give an opinion on, any other issue relating to the clinical trial, if—

(a)the committee has been asked by the sponsor to consider the issue;

(b)it is, in the committee’s opinion, relevant to the other matters considered by the committee in accordance with paragraph (3).

(6) The ethics committee may, before giving its opinion, obtain expert advice on any field which relates to the clinical trial.

(7) If the licensing authority or the ethics committee considers it appropriate to do so, they may consult either or both of the following—

(a)a relevant committee;

(b)a specialist group or committee.

(8) The authorities must not approve a clinical trial involving products for gene therapy if the use of those products in that trial would result in modifications to any participant’s germ line genetic identity.

Approval procedure for clinical trials

18.—(1) Having carried out the assessments required by regulation 17—

(a)the licensing authority must provide its decision in relation to the request for authorisation to conduct the clinical trial in accordance with this regulation; and

(b)the ethics committee must give an opinion in relation to the clinical trial in accordance with this regulation.

(2) The authorities must notify the sponsor of the decision in paragraph (1)(a) and the opinion in paragraph (1)(b).

(3) A notice under paragraph (2) must—

(a)be in writing; and

(b)state that the authorities—

(i)approve the request for approval,

(ii)approve the request for approval, subject to conditions specified in the notice, or

(iii)do not approve the request for approval, setting out the grounds for this decision.

(4) Subject to paragraphs (7) and (8) and regulation 18C, the authorities must take all reasonable steps to ensure that the notice is given within the period of 30 days beginning with the date on which the authorities notified the sponsor that the request for approval was valid in accordance with regulation 16(8).

(5) If a notice is given in accordance with paragraph (3)(b)(ii)—

(a)the notice must specify whether the conditions relate to either or both of the following—

(i)the licensing authority’s decision on the clinical trial authorisation;

(ii)the ethics committee opinion;

(b)the clinical trial is to be treated as approved only if the conditions specified in the notice are satisfied.

(6) If a notice is given in accordance with paragraph (3)(b)(iii), regulations 18A and 18B apply.

(7) The time period referred to in paragraph (4) is extended by 90 days where the licensing authority or the ethics committee consults either or both of the following—

(a)a relevant committee;

(b)a specialist group or committee.

(8) If the clinical trial involves a medicinal product for xenogenic cell therapy, the time periods set out in paragraphs (4) and (7) do not apply and the authorities may give written notice under this regulation at any time after the date on which the authorities notified the sponsor that the request for approval was valid in accordance with regulation 16(8).

(9) Where an ethics committee gives an opinion in accordance with this regulation, it must publish the conclusion of that opinion, whether favourable or unfavourable.

(10) Where a request for authorisation under regulation 14 and an application for an ethics committee opinion under regulation 15 are made separately in accordance with regulation 16(5)—

(a)the time periods mentioned in this regulation, regulation 18A and 18B applies separately to the request for authorisation and the application for an ethics committee opinion;

(b)the clinical trial is to be treated as approved upon receiving both the authorisation from the licensing authority and a favourable opinion from the ethics committee.

Request for further information regarding a request for approval

18A.—(1) A notice given in accordance with regulation 18(3)(b)(iii) must—

(a)request further information required to reconsider the approval of the request; and

(b)specify whether the request for further information relates to either or both of the following—

(i)the licensing authority’s decision on the clinical trial authorisation;

(ii)the ethics committee opinion.

(2) If the sponsor is given a notice which contains a request for further information in accordance with paragraph (1), the sponsor may send an amended request for approval for further consideration within—

(a)the period of 60 days beginning with the day on which the notice is given; or

(b)any such extended period as the appropriate authority may in any particular case allow.

(3) An amended request for approval can be a response to the request for further information or an amendment to the request for approval.

(4) In this regulation, “appropriate authority” has the meaning given in regulation 18B(1).

Approval procedure for amended requests for approval

18B.—(1) An amended request for approval must be reviewed by the appropriate authority, which, for the purposes of this regulation, is either or both of the following—

(a)the licensing authority, if the request for further information relates to the licensing authority’s decision on the clinical trial authorisation;

(b)the ethics committee, if the request for further information relates to the ethics committee opinion.

(2) The appropriate authority must notify the sponsor of its decision or its opinion, or both its decision and opinion.

(3) A notice under paragraph (2) must—

(a)be in writing; and

(b)state that the appropriate authority—

(i)approves the amended request,

(ii)approves the amended request, subject to conditions specified in the notice, or

(iii)does not approve the amended request, setting out the grounds for this decision.

(4) Subject to paragraphs (6) and (7) and regulation 18C, the appropriate authority must take all reasonable steps to ensure that the notice is given within the period of 10 days beginning with the date of receipt of an amended request for approval.

(5) If a notice is given in accordance with paragraph (3)(b)(ii)—

(a)the notice must specify whether the conditions relate to either or both of the following—

(i)the licensing authority’s decision on the clinical trial authorisation;

(ii)the ethics committee opinion;

(b)the clinical trial is to be treated as approved only if the conditions specified in the notice are satisfied.

(6) The period of 10 days referred to in paragraph (4) is extended by a further—

(a)30 days, where the licensing authority or the ethics committee consults either or both of the following—

(i)a relevant committee;

(ii)a specialist group or committee;

(b)60 days, where—

(i)the investigational medicinal product is an advanced therapy medicinal product, and

(ii)the licensing authority or the ethics committee consults either or both of the groups or committees mentioned in sub-paragraph (a).

(7) If the clinical trial involves a medicinal product for xenogenic cell therapy, the time periods set out in paragraphs (4) and (6) do not apply and the appropriate authority may give written notice under this regulation at any time after receipt of an amended request for approval.

(8) The request for approval is to be treated as rejected and the authorities may not consider any further amendments to the request if—

(a)the authorities give written notice to the sponsor which contains a request for further information in accordance with regulation 18A(1) and the sponsor does not submit an amended request in accordance with regulation 18A(2); or

(b)the sponsor has submitted an amended request in accordance with regulation 18A(2), but the appropriate authority gives written notice to the sponsor in accordance with paragraph (3)(b)(iii).

Approval procedure time periods in special circumstances

18C.—(1) For the purposes of regulations 18(4) and 18B(4)—

(a)where the sponsor selects a date other than the next available ethics committee meeting, then the time periods referred to in those regulations will begin from the date that is 7 days before the chosen ethics committee meeting date; and

(b)where the clinical trial involves a medical device, then the time periods referred to in those regulations may begin from the date of formal acceptance under regulation 16(4) of the Medical Devices Regulations 2002(4).

(2) Where the valid request for approval or amended request for approval falls under both paragraphs (1)(a) and (1)(b), the time periods referred to in regulations 18(4) and 18B(4) will begin from the later of the dates mentioned in paragraphs (1)(a) and (1)(b).

Clinical trials conducted in countries other than the United Kingdom

19.—(1) If the licensing authority receives a request for authorisation which complies with regulations 14 and 16, relating to a clinical trial which is or is to be conducted in another country as well as the United Kingdom, the licensing authority may, if it thinks fit, require the production by the sponsor of either or both of the following—

(a)an undertaking, given by the sponsor, to permit their premises in that country to be inspected by or on behalf of the licensing authority for the purpose of establishing whether the conditions and principles of good clinical practice in accordance with Schedule 1 are satisfied or adhered to in relation to that trial; or

(b)an undertaking, given by the owner or occupier of any premises in that country at which the clinical trial is or is to be conducted, to permit those premises to be inspected by or on behalf of the licensing authority for the purpose of establishing whether the conditions and principles of good clinical practice are satisfied or adhered to in relation to that trial.

(2) If a sponsor fails to produce an undertaking required by the licensing authority in accordance with paragraph (1), that failure constitutes a ground for not approving the request for authorisation.

Modifications to clinical trial approval

20.  A modification to a clinical trial approval may be made—

(a)by the licensing authority or the ethics committee, in accordance with regulation 21; or

(b)by the sponsor, in accordance with regulations 22, 22A and 22B.

Modifications by the licensing authority or the ethics committee

21.—(1) The appropriate authority may require the sponsor to make modifications to a clinical trial approval if it appears to the authority to be necessary to ensure—

(a)the safety or scientific validity of the clinical trial; or

(b)that the conditions and principles of good clinical practice are satisfied or adhered to in relation to the clinical trial.

(2) Where the appropriate authority proposes a modification in accordance with paragraph (1), that authority must, at least 7 days before the date on which it is proposed that the modification should take effect, serve a notice on the sponsor stating their proposal and the reasons for it.

(3) If, within the period of 7 days beginning with the date on which notice is served in accordance with paragraph (2), the sponsor makes representations in writing to the appropriate authority, that authority—

(a)must take those representations into account before deciding whether to require the sponsor to make the modification; and

(b)may delay the date the proposed modification is to take effect, in order to allow time for them to consider those representations.

(4) In this regulation, the “appropriate authority” means either or both of the following—

(a)the licensing authority;

(b)the ethics committee.

Modifications by the sponsor

22.—(1) A sponsor may make a modification to a clinical trial approval, other than a substantial modification, at any time and without the need for submitting a request under this regulation.

(2) A sponsor must—

(a)keep records of the modifications made in accordance with paragraph (1); and

(b)send those records to the licensing authority or the ethics committee, where the authority or committee (as the case may be) gives written notice requiring the sponsor to provide those records.

(3) If a sponsor makes a modification of an important detail, the sponsor must notify the authorities of the modification through an online portal made available for this purpose.

(4) If the sponsor proposes to make a substantial modification to a clinical trial approval which consists of, or includes, a substantial modification to—

(a)the terms of the request for approval of the clinical trial; or

(b)the particulars or documents that accompanied that request for approval,

the sponsor must submit a modification request to the authorities in accordance with paragraphs (6) and (7).

(5) Where the request for approval of the clinical trial was made under regulation 16(5), then a valid modification request must be submitted pursuant to paragraph (4) if the sponsor proposes to make a substantial modification to the clinical trial approval which consists of, or includes, a substantial modification to—

(a)the terms of the request for authorisation of the clinical trial;

(b)the application for an ethics committee opinion in relation to the trial; or

(c)the particulars or documents that accompanied—

(i)the request for authorisation, or

(ii)the application for an ethics committee opinion.

(6) A modification request must—

(a)be submitted to an online portal made available for this purpose;

(b)clearly identify the proposed substantial modification and whether it relates to the authorisation by the licensing authority or the ethics committee opinion;

(c)where the proposed substantial modification is a Route B substantial modification, include a statement confirming that it is a Route B substantial modification;

(d)be accompanied by—

(i)the particulars and documents specified in Part 3 of Schedule 3, and

(ii)any fee which may be payable in connection with that application under the Medicines (Products for Human Use) (Fees) Regulations 2016.

(7) The modification request and accompanying material in paragraph (6) must be supplied in English.

(8) The authorities must confirm whether the modification request is valid within the period of 7 days beginning with the date of the submission of the request and notify the sponsor accordingly.

Approval procedure for substantial modifications

22A.—(1) Where the licensing authority and an ethics committee receive a valid modification request in relation to a substantial modification to a clinical trial approval—

(a)the licensing authority must—

(i)review the request in relation to the authorisation to conduct the clinical trial, and

(ii)provide its decision in accordance with this regulation;

(b)the ethics committee must—

(i)review the request in relation to the ethics committee opinion for the clinical trial, and

(ii)provide an opinion in accordance with this regulation.

(2) Where the modification request contains a statement under regulation 22(6)(c) confirming that the modification is a Route B substantial modification, the licensing authority may, if it considers appropriate and without undertaking further assessment, rely on that statement to provide its decision on the modification request.

(3) The authorities must notify the sponsor of the decision in paragraph (1)(a)(ii) or the opinion in paragraph (1)(b)(ii), or both the decision and the opinion.

(4) A notice under paragraph (3) must—

(a)be in writing; and

(b)state that the authorities—

(i)approve the proposed modification,

(ii)approve the proposed modification, subject to conditions specified in the notice, or

(iii)do not approve the proposed modification, setting out the grounds for this decision.

(5) The authorities must take all reasonable steps to ensure that the notice is given within the period of 35 days beginning with the date on which the authorities notified the sponsor that the modification request was valid in accordance with regulation 22(8).

(6) If a notice is given in accordance with paragraph (4)(b)(ii)—

(a)the notice must specify whether the conditions relate to either or both of the following—

(i)the licensing authority’s decision on the clinical trial authorisation;

(ii)the ethics committee opinion;

(b)the modification is to be treated as approved only if the conditions specified in the notice are satisfied.

(7) If a notice is given in accordance with paragraph (4)(b)(iii), regulations 22B and 22C apply.

Request for further information regarding proposed substantial modifications

22B.—(1) A notice given in accordance with regulation 22A(4)(b)(iii) may request further information required to reconsider the approval of the request.

(2) If the notice contains a request for further information in accordance with paragraph (1), then the notice must specify whether the request for further information relates to either or both of the following—

(a)the licensing authority’s decision;

(b)the ethics committee opinion.

(3) If the sponsor is given a notice in accordance with regulation 22A(4)(b)(iii) which contains a request for further information in accordance with paragraph (1), the sponsor may send an amended modification request for further consideration within—

(a)the period of 60 days beginning with the day on which the notice is given; or

(b)such extended period as the appropriate authority may in any particular case allow.

(4) An amended modification request can be a response to the request for further information or an amendment to the modification request.

(5) In this regulation, “appropriate authority” has the meaning given in regulation 22C(1).

Approval procedure for amended requests regarding substantial modifications

22C.—(1) An amended modification request must be reviewed by the appropriate authority, which, for the purposes of this regulation, is either or both of the following—

(a)the licensing authority, if the request for further information relates to the licensing authority’s decision;

(b)the ethics committee, if the request for further information relates to the ethics committee opinion.

(2) The appropriate authority must notify the sponsor of its decision or its opinion, or both its decision and opinion.

(3) A notice under paragraph (2) must—

(a)be in writing; and

(b)state that the appropriate authority—

(i)approves the amended request,

(ii)approves the amended request, subject to conditions specified in the notice, or

(iii)does not approve the amended request, setting out the grounds for this decision.

(4) The appropriate authority must take all reasonable steps to ensure that the notice is given within the period of 10 days beginning with the date of receipt of an amended modification request.

(5) If a notice is given in accordance with paragraph (3)(b)(ii)—

(a)the notice must specify whether the conditions relate to either or both of the following—

(i)the licensing authority’s decision;

(ii)the ethics committee opinion;

(b)the modification is to be treated as approved only if the conditions specified in the notice are satisfied.

(6) The modification request is to be treated as rejected and the authorities may not consider any further amendments to that request if—

(a)the authorities give written notice to the sponsor in accordance with regulation 22A(4)(b)(iii) and—

(i)the notice does not contain a request for further information in accordance with regulation 22B(1), or

(ii)the sponsor does not submit an amended request in accordance with regulation 22B(2); or

(b)the sponsor has submitted an amended request in accordance with regulation 22B(3), but the appropriate authority gives written notice to the sponsor in accordance with paragraph (3)(b)(iii).

Reference to the appropriate committee or the Medicines Commission

23.—(1) This regulation applies where—

(a)a sponsor has been notified under regulation 18(2) or 18B(2) that—

(i)the trial is not approved and the grounds for not approving the trial relate to the licensing authority’s decision on the clinical trial authorisation, or

(ii)the trial is approved subject to specified conditions and those conditions relate to the licensing authority’s decision;

(b)the licensing authority has modified a clinical trial approval under regulation 21; or

(c)the sponsor has been notified under regulation 22A(3) or 22C(2) that—

(i)a proposed substantial modification is not approved and the grounds for not approving the modification relate to the licensing authority’s decision, or

(ii)the proposed substantial modification is approved subject to conditions and those conditions relate to the licensing authority’s decision.

(2) Where this regulation applies, the sponsor may, within the period of 28 days beginning with the day on which notice is given or such extended period as the licensing authority may in any particular case allow, give notice in writing to the licensing authority of the sponsor’s wish to make written or oral representations to the appropriate committee.

(3) Schedule 5 has effect to regulate the procedure for reference to the appropriate committee following receipt of a notice in accordance with paragraph (1).

Review and appeal relating to ethics committee opinion

24.—(1) This regulation applies where—

(a)a sponsor has been notified under regulations 18(2) or 18B(2) that—

(i)the trial is not approved and the grounds for not approving the trial relate to the ethics committee opinion, or

(ii)the trial is approved subject to specified conditions and those conditions relate to the ethics committee opinion;

(b)the ethics committee has modified a clinical trial approval under regulation 21; or

(c)the sponsor has been notified under regulation 22A(3) or 22C(2) that—

(i)a proposed substantial modification is not approved and the grounds for not approving the modification relate to the ethics committee opinion, or

(ii)the proposed substantial modification is approved subject to conditions and those conditions relate to the ethics committee opinion.

(2) This regulation does not apply in relation to an opinion given by—

(a)an Ethics Committee constituted by regulations made by the Scottish Ministers under section 51(6) of the Adults with Incapacity (Scotland) Act 2000; or

(b)an ethics committee pursuant to paragraph 2 of Schedule 4.

(3) Where this regulation applies, the sponsor may, within the period of 28 days beginning with the day on which notice is given or such extended period as the Authority may in any particular case allow, give notice in writing to the Authority—

(a)stating the sponsor’s wish to appeal against the opinion; and

(b)setting out their representations with respect to that opinion.

(4) Schedule 4 has effect to regulate the procedure where the Authority receives a notice in accordance with paragraph (3).

Transparency requirements

25.—(1) Subject to paragraphs (5), (7) and (10), the sponsor must register a clinical trial in a public registry by the earlier of the following—

(a)the date on which the first individual is recruited to be a participant in that trial;

(b)90 days after the date of approval of the clinical trial.

(2) Subject to paragraphs (5), (7) and (10), within the period of 12 months beginning with the day after the conclusion of the clinical trial in accordance with regulation 27, the sponsor must—

(a)publish a summary of the results of the clinical trial in the same public registry or registries (if more than one) as the trial was registered in accordance with paragraph (1); and

(b)offer to all relevant persons a summary of the results written in a manner that is understandable to laypersons.

(3) The sponsor may apply for a deferral or waiver of the requirement to register a clinical trial in accordance with paragraph (1), stating why the deferral or waiver is needed—

(a)at the time of the request for approval under regulation 16; or

(b)at any time before the date specified in paragraph (1).

(4) The sponsor may apply for a deferral or waiver of either or both of the requirements in paragraph (2), stating why the deferral or waiver is needed—

(a)at the time of the request for approval under regulation 16; or

(b)at any time before the date specified in paragraph (2).

(5) Where the sponsor applies for a deferral or a waiver in accordance with paragraphs (3) or (4), the Authority may—

(a)where they consider appropriate, defer the requirement for up to a period of 30 months beginning with the day after the conclusion of the trial, for example, in order to protect commercially confidential information; or

(b)in exceptional circumstances, waive the requirement, for example, for reasons of national defence and security.

(6) The sponsor may apply for a further deferral, stating why the deferral is needed, at any time before the expiry of the previous deferral.

(7) Where the sponsor applies for a further deferral in accordance with paragraph (6), the Authority may, where they consider appropriate, defer the requirement for up to a period of 30 months beginning with the day after the end of the previous deferral period, for example, in order to protect commercially confidential information.

(8) The Authority must give written notice of their decision to the sponsor—

(a)at the time the ethics committee provides a favourable opinion in accordance with regulation 18 or 18B, where the sponsor makes the application to defer or waive under paragraph (3)(a) or (4)(a); or

(b)subject to paragraph (9), within the period of 10 days beginning with the date of receipt of the application to defer or waive the requirement, where this application is made under paragraphs (3)(b), (4)(b) or (6).

(9) Where the sponsor makes an application under paragraph (3)(b) before the ethics committee provides a favourable opinion in accordance with regulation 18 or 18B, then the Authority may give written notice of their decision on the application for a deferral or waiver to the sponsor at the time the ethics committee provides a favourable opinion.

(10) Where the clinical trial is a Phase I trial, the Authority may provide an automatic deferral of—

(a)the requirement to register the trial in accordance with paragraph (1) for up to a period of 30 months beginning with the day after the conclusion of the trial, provided that the sponsor registers the required minimum information in a public registry before the date specified in paragraph (1);

(b)the requirements in paragraph (2) for up to a period of 30 months beginning with the day after the conclusion of the trial.

(11) The combined period of deferrals granted under paragraphs (5), (7) and (10) must not be more than the period of 10 years beginning with the day after the conclusion of the trial.

(12) In this regulation—

“public registry” means a a primary or partner registry of, or a data provider to, the WHO International Clinical Trials Registry Platform, provided that the registry, or the data provider, facilitates public access to information about the trial in the United Kingdom;

“relevant person” includes—

“required minimum information” includes the particulars identifying the trial and the details of the sponsor and investigator.

Lapse of clinical trial approval

26.—(1) Subject to the extension of the period in paragraphs (3) and (5), the clinical trial approval lapses at the end of the period of 24 months beginning with the date of approval of the trial if there are no participants recruited to take part in the trial.

(2) The sponsor may apply for an extension of the time period referred to in paragraph (1), stating why an extension is needed—

(a)at the time of the request for approval under regulation 16; or

(b)at any time before the expiry of the two-year period specified in paragraph (1).

(3) Where the sponsor applies for an extension in accordance with paragraph (2), the authorities may, where they consider appropriate, agree to extend the period for up to 36 months beginning with the day after the expiry of the period specified in paragraph (1), for example, where the trial involves the study of a rare disease or the trial is in anticipation of a disease causing a pandemic.

(4) The sponsor may apply for a further extension, stating why the extension is needed, at any time before the expiry of the previous extension.

(5) Where the sponsor applies for a further extension in accordance with paragraph (4), the authorities may, where they consider appropriate, agree to extend the period for up to 24 months beginning with the day after the end of the previous extension period, for example, where the trial involves the study of a rare disease or the trial is in anticipation of a disease causing a pandemic.

(6) The authorities must give written notice of their decision to the sponsor—

(a)at the time they approve the request for approval or amended request for approval in accordance with regulation 18 or 18B, where the sponsor makes the application to extend under paragraph (2)(a); or

(b)within the period of 30 days beginning with the date of receipt of the application to extend, where this application is made under paragraphs (2)(b) or (4).

(7) If the period has lapsed in accordance with paragraph (1)—

(a)the sponsor must notify the authorities in writing that the trial has ended; or

(b)the trial will be terminated in accordance with regulation 31.”.

Amendment to regulation 27A

regulation 15 + 15.  In regulation 27A (information sharing)(5), after “licensing authority” insert “, the Authority”.

Substitution of regulation 27B

regulation 16 + 16.  For regulation 27B (publication of information) substitute—

Publication of information

27B.—(1) Subject to paragraph (3), the Authority may make accessible to the public information contained in the items listed in paragraph (2) insofar as it relates to a clinical trial carried out, or being carried out, under these Regulations.

(2) The items listed in this paragraph are—

(a)the request for approval made under regulation 16;

(b)any amended request for approval made under regulation 18A;

(c)any substantial modification to the clinical trial approval made under regulation 21, 22, 22A or 22B;

(d)the favourable opinion of the ethics committee given in accordance with regulation 18(1)(b);

(e)the notification of the end of the clinical trial made under regulation 27.

(3) Prior to making information available to the public under paragraph (1), the Authority must, after consulting such persons as they consider appropriate, publish a list of the information which may be made accessible to the public under paragraph (1).”.