The Medicines for Human Use (Clinical Trials) Regulations 2004

• Citation: S.I. 2004/1031
• Sections: 290

Section 1 Citation and commencement

These Regulations may be cited as the Medicines for Human Use (Clinical Trials) Regulations 2004 and shall come into force on 1st May 2004.

Section 2 Interpretation

(1) In these Regulations—

“ the 2012 Regulations ” means the Human Medicines Regulations 2012;

“ the Act ” means the Medicines Act 1968 ;

“ adult ” means a person who has attained the age of 16 years;

“ adverse event ” means any untoward medical occurrence in a subject to whom a medicinal product has been administered, including occurrences which are not necessarily caused by or related to that product;

“ adverse reaction ” means any untoward and unintended response in a subject to an investigational medicinal product which is related to any dose administered to that subject;

“ authorised health professional ” means—

a doctor,

a dentist,

a nurse, or

a pharmacist;

“ appropriate committee ” for the purposes of any provision of these Regulations under which a function falls to be performed means whichever the licensing authority considers to be appropriate of—

the Commission on Human Medicines; or

an expert committee appointed by the licensing authority;

“ assemble ”, in relation to an investigational medicinal product, means—

enclosing the product (with or without other medicinal products of the same description) in a container which is labelled before the product is sold or supplied, or used in a clinical trial, or

where the product (with or without other medicinal products of the same description) is already contained in the container in which it is to be sold or supplied, or used in a clinical trial, labelling the container before the product is sold or supplied, or used in a clinical trial, in that container,

and “assembly” has a corresponding meaning;

“business”, except in Schedule 2, includes a professional practice and includes any activity carried on by a body of persons, whether corporate or unincorporate;

“ chief investigator ” means—

in relation to a clinical trial conducted at a single trial site, the investigator for that site, or

in relation to a clinical trial conducted at more than one trial site, the authorised health ... professional, whether or not he is an investigator at any particular site, who takes primary responsibility for the conduct of the trial;

“ clinical trial ” means any investigation in human subjects, other than a non-interventional trial, intended—

to discover or verify the clinical, pharmacological or other pharmacodynamic effects of one or more medicinal products,

to identify any adverse reactions to one or more such products, or

to study absorption, distribution, metabolism and excretion of one or more such products,

with the object of ascertaining the safety or efficacy of those products;

“ Commission Directive 2003/94/EC ” , other than in Parts 2 and 3 of Schedule 7, means—

in the case of an investigational medicinal product manufactured or assembled in, or imported into, Great Britain—

Commission Directive 2003/94/EC laying down the principles and guidelines of good manufacturing practice for medicinal products for human use and for investigational medicinal products for human use, as modified by Schedule 2A to the 2012 Regulations, or

if Regulations have been made under the powers in regulation B17(1) of the 2012 Regulations, and have come into force, those Regulations;

in the case of an investigational medicinal product manufactured or assembled in, or imported into, Northern Ireland, Commission Directive 2003/94/EC laying down the principles and guidelines of good manufacturing practice for medicinal products for human use and for investigational medicinal products for human use;

“ the Commission on Human Medicines ” means the Commission on Human Medicines within the meaning of regulation 9 of the 2012 Regulations;

“ conditions and principles of good clinical practice ” means the conditions and principles specified in Schedule 1;

“ conducting a clinical trial ” includes—

administering, or giving directions for the administration of, an investigational medicinal product to a subject for the purposes of that trial,

giving a prescription for an investigational medicinal product for the purposes of that trial,

carrying out any other medical or nursing procedure in relation to that trial, and

carrying out any test or analysis—

to discover or verify the clinical, pharmacological or other pharmacodynamic effects of the investigational medicinal products administered in the course of the trial,

to identify any adverse reactions to those products, or

to study absorption, distribution, metabolism and excretion of those products,

but does not include any activity undertaken prior to the commencement of the trial which consists of making such preparations for the trial as are necessary or expedient;

“ container ”, in relation to an investigational medicinal product, means the bottle, jar, box, packet or other receptacle which contains or is to contain it, not being a capsule, cachet or other article in which the product is or is to be administered, and where any such receptacle is or is to be contained in another such receptacle, includes the former but does not include the latter receptacle;

“ country ” means a country or territory;

“ dentist ” means a person registered in the dentists register under the Dentists Act 1984 ...;

“the Directive” means Directive 2001/20/ EC of the European Parliament and of the Council 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 for human use;

“Directive 2001/83/ EC ” means Directive 2001/83/ EC of the European Parliament and of the Council on the Community code relating to medicinal products for human use;

“ doctor ” means a registered medical practitioner ;

“ EAMS medicinal product ” means a medicinal product that—

has been included in the Early Access to Medicines Scheme by means of the licensing authority issuing an EAMS scientific opinion in respect of it; and

remains in the scheme by virtue of the EAMS scientific opinion not ceasing to have effect in respect of it by virtue of regulation 167D of the 2012 Regulations;

“ EAMS scientific opinion ” is to be construed in accordance with regulation 167C(2)(b) of the 2012 Regulations;

“ Early Access to Medicines Scheme ” means the scheme of that name established and operated under regulation 167C(1) of the 2012 Regulations;

“ EEA State” means a Member State, Norway, Iceland or Liechtenstein;

...

“ electronic signature ” means data in electronic form which is attached to or logically associated with other data in electronic form and which is used by the signatory to sign;

“ European Economic Area ” means the European Economic Area created by the EEA Agreement;

“the European Medicines Agency” means the European Medicines Agency established by Regulation ( EC ) No. 726/2004 of the European Parliament and of the Council laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency;

“ ethics committee ” means—

a committee established or recognised in accordance with Part 2,

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

the Gene Therapy Advisory Committee;

“ export ” means export to another country from the United Kingdom , whether by land, sea or air;

...

“ the Gene Therapy Advisory Committee ” means the Gene Therapy Advisory Committee appointed by the Secretary of State ...;

“ Health and Social Services Board ” means a Health and Social Services Board established under the Health and Personal Social Services (Northern Ireland) Order 1972 ;

“ Health Board ” means a Health Board established under the National Health Service (Scotland) Act 1978 ;

“ health care ” means services for or in connection with the prevention, diagnosis or treatment of illness;

“ health care professional ” means—

a doctor,

a dentist,

a nurse,

a pharmacist,

a person registered in the register of optometrists maintained under section 7(a) of the Opticians Act 1989, ...

a person registered in a register established and maintained under article 5 of Health Professions Order 2001 ,

a registered osteopath as defined by section 41 of the Osteopaths Act 1993 , ...

a registered chiropractor as defined by section 43 of the Chiropractors Act 1994 , or

a person registered under the Anaesthesia Associates and Physician Associates Order 2024 ;

“ health centre ” means a health centre maintained under section 2 or 3 of the National Health Service Act 1977, section 36 of the National Health Service (Scotland) Act 1978 or Article 5 of the Health and Personal Social Services (Northern Ireland) Order 1972;

“ health service body ” means—

a ... Health Board or Health and Social Services Board,

a Special Health Authority, ... integrated care board or Local Health Board established under the National Health Service Act 1977,

NHS England ,

a Special Health Board established under the National Health Service (Scotland) Act 1978,

Healthcare Improvement Scotland established under the National Health Service (Scotland) Act 1978,

a special health and social services agency established under the Health and Personal Social Services (Special Agencies) (Northern Ireland) Order 1990 ,

...

the Scottish Dental Practice Board or the Common Services Agency for the Scottish Health Service established under the National Health Service (Scotland) Act 1978,

the Northern Ireland Central Services Agency for the Health and Social Services established under the Health and Personal Social Services (Northern Ireland) Order 1972,

a National Health Service trust established under the National Health Service and Community Care Act 1990 or the National Health Service (Scotland) Act 1978,

an NHS foundation trust within the meaning of section 1(1) of the Health and Social Care (Community Health and Standards) Act 2003 , or

a Health and Social Services trust established under the Health and Personal Social Services (Northern Ireland) Order 1991 ;

“ hospital ” includes a clinic, nursing home or similar institution;

“import”, except in regulation 13 and Schedule 13, means import, or attempt to import—

into Great Britain other than from Northern Ireland, or

into Northern Ireland from a country other than an EEA State,

whether by land, sea or air and “ imported ” is to be construed accordingly;

“ informed consent ” shall be construed in accordance with paragraph 3 of Part 1 of Schedule 1;

“ insurance or indemnity ” includes provision for meeting losses or liabilities—

under a scheme established under—

section 21 of the National Health Service and Community Care Act 1990 (schemes for meeting losses and liabilities etc. of certain health service bodies in England and Wales) ,

section 85B of the National Health Service (Scotland) Act 1978 (schemes for meeting losses and liabilities etc. of certain health service bodies in Scotland) , or

Article 24 of the Health and Personal Social Services (Northern Ireland) Order 1991 (schemes for meeting losses and liabilities etc. of certain health service bodies in Northern Ireland) , or

in accordance with guidance issued by—

the Secretary of State,

the Scottish Ministers,

the National Assembly for Wales, or

the Department for Health, Social Services and Public Safety,

as to the arrangements to be adopted by health service bodies for meeting the costs arising from clinical negligence (known as NHS Indemnity);

“ investigational medicinal product ” means a pharmaceutical form of an active substance or placebo being tested, or to be tested, or used, or to be used, as a reference in a clinical trial, and includes a medicinal product which has a marketing authorization but is, for the purposes of the trial—

used or assembled (formulated or packaged) in a way different from the form of the product authorised under the authorization,

used for an indication not included in the summary of product characteristics under the authorization for that product, or

used to gain further information about the form of that product as authorised under the authorization;

“ investigational medicinal product dossier ” means, in relation to an investigational medicinal product, the dossier relating to that product which accompanies a request for authorisation to conduct a trial in which that product is or is to be used, in accordance with paragraph 11 of Schedule 3;

“ investigator ” means, in relation to a clinical trial, the authorised health professional responsible for the conduct of that trial at a trial site, and if the trial is conducted by a team of authorised health professionals at a trial site, the investigator is the leader responsible for that team;

“ investigator’s brochure ” means a document containing a summary of the clinical and non-clinical data relating to an investigational medicinal product which are relevant to the study of the product in human subjects;

“ labelling ”, in relation to an investigational medicinal product, means affixing to or otherwise displaying on it a notice describing or otherwise relating to the contents, and “label” has a corresponding meaning;

“legal representative”, other than in regulation 3 and Parts 2 to 4 of Schedule 3, has the meaning given by Part 1 of Schedule 1;

“ licensing authority ” shall be construed in accordance with regulation 6 of the 2012 Regulations ;

“ manufacture ”, in relation to an investigational medicinal product, includes any process carried out in the course of making the product, but does not include dissolving or dispersing the product in, or diluting it or mixing it with, some other substance used as a vehicle for the purposes of administering it;

“ manufacturer’s licence (MM) ” has the meaning given in regulation 8(1) of the 2012 Regulations;

“ manufacturer’s licence (POC) ” has the meaning given in regulation 8(1) of the 2012 Regulations;

“ manufacturing authorisation ” has the meaning given by regulation 36(1);

“ manufacturing authorisation (MM) ” means a manufacturing authorisation that authorises the manufacture or assembly of MM investigational medicinal products;

“ manufacturing authorisation (POC) ” means a manufacturing authorisation that authorises the manufacture or assembly of POC investigational medicinal products;

“ marketing authorization ” means—

a UK marketing authorization,

an EU marketing authorisation (as defined in the 2012 Regulations), or

an authorization granted by a regulatory body responsible for licensing medicinal products in a country that is included in the list referred to in regulation 2A(1);

“ medicinal product ” means a medicinal product within the meaning of regulation 2(1) of the 2012 Regulations.

“ minor ” means a person under the age of 16 years;

“ MM ” means modular manufacture;

“ MM (IMP) control site ” means the premises at which the holder of a manufacturing authorisation (MM) supervises and controls the manufacture or assembly of MM investigational medicinal products;

“ MM (IMP) master file ” means a detailed description of the arrangements for manufacture or assembly of an MM investigational medicinal product;

“ MM investigational medicinal product ” means an investigational medicinal product that, for reasons relating to deployment, the licensing authority determines it necessary or expedient to be manufactured or assembled in a modular unit;

“ modular unit ” means a relocatable manufacturing unit;

“ non-interventional trial ” means a study of one or more medicinal products which have a marketing authorization, where the following conditions are met—

the products are prescribed in the usual manner in accordance with the terms of that authorization,

the assignment of any patient involved in the study to a particular therapeutic strategy is not decided in advance by a protocol but falls within current practice,

the decision to prescribe a particular medicinal product is clearly separated from the decision to include the patient in the study,

no diagnostic or monitoring procedures are applied to the patients included in the study, other than those which are ordinarily applied in the course of the particular therapeutic strategy in question, and

epidemiological methods are to be used for the analysis of the data arising from the study;

“ nurse ” means a registered nurse or registered midwife;

“ pharmaceutical form of an active substance ” includes any substance or article to which these Regulations have effect by virtue of an order under section 104 or 105 of the Act (which relate to the application of Act to certain articles and substances which are not medicinal products);

“ Pharmaceutical Society ” in relation to Great Britain means the Royal Pharmaceutical Society of Great Britain, and in relation to Northern Ireland means the Pharmaceutical Society of Northern Ireland;

“ pharmacist ” means—

in relation to Great Britain, a person registered as a pharmacist in Part 1 ... of the register maintained under article 19 of the Pharmacy Order 2010, and

in relation to Northern Ireland, a person registered in the register of pharmaceutical chemists for Northern Ireland made out and maintained under Articles 6 and 9 of the Pharmacy (Northern Ireland) Order 1976;

“ Phase I trial ” means a clinical trial to study the pharmacology of an investigational medicinal product when administered to humans, where the sponsor and investigator have no knowledge of any evidence that the product has effects likely to be beneficial to the subjects of the trial;

“ POC ” means point of care;

“ POC (IMP) control site ” means the premises at which the holder of a manufacturing authorisation (POC) supervises and controls the manufacture or assembly of POC investigational medicinal products;

“ POC (IMP) master file ” means a detailed description of the arrangements for the manufacture or assembly of a POC investigational medicinal product;

“ POC (IMP) site ” means a site at which the manufacture or assembly of a POC investigational medicinal product takes place;

“ POC investigational medicinal product ” means an investigational medicinal product that, for reasons relating to method of manufacture, shelf life, constituents or method or route of administration, can only be manufactured at or near the place where the product is to be used or administered;

“ the principles and guidelines of good manufacturing practice ” means the principles and guidelines of good manufacturing practice set out in Commission Directive 2003/94/EC ;

“ protocol ” means a document that describes the objectives, design, methodology, statistical considerations and organisation of a clinical trial;

“ qualified person ” means—

a person who as respects qualifications and experience satisfies the requirements of Article 49 or 50 of Directive 2001/83/EC , or

a person who, without satisfying the requirements referred to in paragraph (a)—

has been engaged in activities equivalent to those to be performed in accordance with regulation 43(2) in respect of investigational medicinal products for a period of at least 6 months prior to 1st May 2004,

has, in accordance with paragraph 6(1) of Schedule 6, been named as a qualified person in a valid application for a manufacturing authorisation made prior to 1st May 2006, and

is—

a member of the Institute of Biology, the Pharmaceutical Society, the Royal Society of Chemistry, or such other body as may appear to the licensing authority to be an appropriate body for the purpose of this paragraph, or

the holder of a diploma, certificate or other evidence of formal qualifications awarded on completion of a university or other higher education course of study in pharmacy, chemistry, medicine, biology or a related life science, which the licensing authority have stated in a notice in writing to that person to be qualifications sufficient for the purpose of performing the functions of a qualified person;

“ relevant ethics committee ”, in relation to a clinical trial, means—

in a case where an ethics committee has given a favourable opinion in relation to that trial and paragraph 13 of Schedule 2 applies, the ethics committee which is the relevant ethics committee for that trial by virtue of sub-paragraph (5) of that paragraph;

in a case where an ethics committee has given an unfavourable opinion in relation to that trial but a favourable opinion has been given by an appeal panel in accordance with paragraph 4(4) of Schedule 4, that committee, or

in any other case, the ethics committee which has given a favourable opinion in relation to that trial in accordance with regulation 15;

“serious adverse event”, “serious adverse reaction” or “ unexpected serious adverse reaction ” means any adverse event, adverse reaction or unexpected adverse reaction, respectively, that—

results in death,

is life-threatening,

requires hospitalisation or prolongation of existing hospitalisation,

results in persistent or significant disability or incapacity, or

consists of a congenital anomaly or birth defect;

“ signatory ” means a natural person who creates an electronic signature;

“ sponsor ” shall be construed in accordance with regulation 3;

“ Strategic Health Authority ” means a Strategic Health Authority established under the National Health Service Act 1977 ;

“ subject ” means, in relation to a clinical trial, an individual, whether a patient or not, who participates in a clinical trial—

as a recipient of an investigational medicinal product or of some other treatment or product, or

without receiving any treatment or product, as a control;

...

“ trial site ” means a hospital, health centre, surgery or other establishment or facility at or from which a clinical trial, or any part of such a trial, is conducted;

“ UK marketing authorization ” —

has the same meaning as “UK marketing authorisation” in the 2012 Regulations (and references to “UKMA(UK)”, “UKMA(GB)” and “UKMA(NI)” in these Regulations should be construed in accordance with that definition); and

includes a product licence granted by the licensing authority for the purposes of section 7 of the Medicines Act 1968;

“ unexpected adverse reaction ” means an adverse reaction the nature and severity of which is not consistent with the information about the medicinal product in question set out—

in the case of a product with a marketing authorization, in the summary of product characteristics , or equivalent document, for that product,

in the case of any other investigational medicinal product, in the investigator’s brochure relating to the trial in question.

(2) Any reference in these Regulations to the holder of a manufacturing authorisation shall be construed as a reference to the holder of such an authorisation which is for the time being in force.

(3) Any reference in these Regulations to an application, request or other document that is signed includes a reference to an application, request of other document that is signed with an electronic signature.

Section 2A List of countries for the purpose of the definition of “marketing authorization”

(1) The licensing authority must publish a list of countries for the purpose of the definition of “marketing authorization”.

(2) In order to determine whether a country should be included in the list referred to in paragraph (1), the licensing authority may, in particular, take into account the regulatory equivalence of that country to the United Kingdom in assessing the safety, quality and efficacy of medicinal products.

(3) The licensing authority must—

(a) review the countries it has included in the list referred to in paragraph (1) to determine if it is still satisfied that the country should remain on that list, and if it is not so satisfied, remove that country from the list; and

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

Section 3 Sponsor of a clinical trial

(1) In these Regulations, subject to the following paragraphs, “ sponsor ” means, in relation to a clinical trial, the person who takes responsibility for the initiation, management and financing (or arranging the financing) of that trial.

(2) If two or more persons take responsibility for the matters specified in paragraph (1) in relation to a clinical trial, those persons may—

(a) take joint responsibility for carrying out the functions of the sponsor of that trial under these Regulations; or

(b) allocate responsibility for carrying out the functions of the sponsor of that trial in accordance with paragraphs (4) to (10).

(3) If two or more persons take joint responsibility in accordance with paragraph (2)(a)—

(a) any reference to the sponsor in these Regulations shall, in relation to that trial, be construed as a reference to those persons; and

(b) paragraphs (4) to (10) shall not apply.

(4) One of the persons referred to in paragraph (2) shall be responsible for carrying out the functions of a sponsor under Part 3 (authorisation for clinical trials and ethics committee opinion) and shall make the request for authorisation to conduct the trial in accordance with regulation 17.

(5) The request for authorisation referred to in regulation 17 shall specify—

(a) who, in accordance with paragraph (4), is responsible for carrying out the functions of the sponsor under Part 3;

(b) who is to be responsible for carrying out the functions of the sponsor under Part 4 (good clinical practice and the conduct of clinical trials); and

(c) who is to be responsible for carrying out the functions of the sponsor under Part 5 (pharmacovigilance).

(6) After the clinical trial has been authorised by the licensing authority in accordance with regulation 18, 19 or 20, a different person may be specified as responsible for carrying out the functions of the sponsor under Part 3, 4 or 5 by making a substantial amendment to the terms of a clinical trial authorisation in accordance with regulations 24 to 26.

(7) Where a person is responsible for carrying out the functions of the sponsor under Part 3 by virtue of paragraph (5), or is specified in accordance with paragraph (6) as responsible for those functions, any reference to the sponsor in—

(a) that Part, except regulation 15,

(b) Parts 2 to 4 of Schedule 3,

(c) Schedule 5, in so far as it relates to decisions of the licensing authority under Part 3, and

(d) Schedule 12,

shall, in relation to the trial, be construed as a reference to that person.

(8) Where a person is specified in accordance with paragraph (5) or (6) as responsible for carrying out the functions of the sponsor under Part 4, any reference to the sponsor in—

(a) that Part, except regulation 28(1), or

(b) Schedule 5, in so far as it relates to notices under regulation 31(1),

shall, in relation to the trial, be construed as a reference to that person.

(9) Where a person is specified in accordance with paragraph (5) or (6) as responsible for carrying out the functions of the sponsor under Part 5, any reference to the sponsor in that Part shall, in relation to the trial, be construed as a reference to that person.

(10) Any reference to the sponsor in—

(a) regulations 15 and 28(1),

(b) Parts 2 and 6 to 9, and

(c) Schedules 1 and 7, and Part 1 of Schedule 3,

shall, in relation to the trial, include a reference to a person specified in accordance with paragraph (5) or (6).

(11) A person who is a sponsor of a clinical trial in accordance with this regulation must—

(a) be established in the United Kingdom or a country that is included in the list referred to in paragraph (11A) , or

(b) have a legal representative who is so established.

(12) A person who is a sponsor of a clinical trial in accordance with this regulation may delegate any or all of his functions under these Regulations to any person but any such arrangement shall not affect the responsibility of the sponsor.

(11A) The licensing authority must publish a list of countries where a sponsor of a clinical trial, or their legal representative, may be established for the purpose of paragraph (11).

(11B) In order to determine whether a country should be included in the list referred to in paragraph (11A), the licensing authority may, in particular, take into account—

(a) the mechanisms that the country has in place to assist the licensing authority in contacting, or obtaining information in respect of, a sponsor or legal representative that is established there; and

(b) the country's ability to assist the licensing authority in any action it may need to take in respect of a sponsor or legal representative that is established there.

(11C) The licensing authority must—

(a) review the countries it has included in the list referred to in paragraph (11A) to determine if it is still satisfied that the country should remain on that list, and if it is not so satisfied, remove that country from the list; and

(b) undertake such a review at least every three years beginning on the date on which that country is included in that list.

Section 3A Sponsor’s responsibility for the investigator’s brochure

The sponsor of a clinical trial shall—

(a) ensure that the investigator’s brochure for that trial, and any update of that brochure, presents the information it contains in a concise, simple, objective, balanced and non-promotional form that enables a clinician or potential investigator to understand it and make an unbiased risk-benefit assessment of the appropriateness of the proposed clinical trial; and

(b) validate and update the investigator’s brochure at least once a year.

Section 4 Responsibility for functions under the Directive

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Section 5 United Kingdom Ethics Committees Authority

(1) The body responsible for establishing, recognising and monitoring ethics committees in the United Kingdom in accordance with these Regulations is the United Kingdom Ethics Committees Authority, which is a body consisting of—

(a) the Health Research Authority ;

(b) the National Assembly for Wales;

(c) the Scottish Ministers; and

(d) the Department for Health, Social Services and Public Safety for Northern Ireland.

(2) The functions of the Authority—

(a) may, by agreement between them, be performed by any one of the Health Research Authority , the National Assembly for Wales, the Scottish Ministers and the Department for Health, Social Services and Public Safety for Northern Ireland acting alone, or any two or more of them acting jointly; and

(b) may be performed by any one of the Health Research Authority , the National Assembly for Wales, the Scottish Ministers and the Department for Health, Social Services and Public Safety for Northern Ireland acting alone solely in relation to a part of the United Kingdom with respect to which the Health Research Authority , the Assembly, the Ministers or the Department, as the case may be, have responsibilities.

(3) In accordance with the preceding provisions of this regulation, in these Regulations “ the United Kingdom Ethics Committees Authority ” (“ the Authority ”) means any one or more of the Health Research Authority , the National Assembly for Wales, the Scottish Ministers and the Department for Health, Social Services and Public Safety for Northern Ireland, and, in the case of anything falling to be done by the Authority, means any one or more of them acting as mentioned in paragraph (2).

(4) The Authority may appoint such persons as they think necessary for the proper discharge by them of their functions, and those persons shall be appointed on such terms and conditions (including conditions as to remuneration, benefits, allowances and reimbursement for expenses) as the Authority think fit.

(5) Arrangements may be made between the Authority and any relevant authority for—

(a) any functions of the Authority to be exercised by, or by members of staff of, the relevant authority; or

(b) the provision of staff, premises or administrative services by the relevant authority to the Authority.

(6) Any arrangements under paragraph (5) for the exercise of any functions of the Authority shall not affect the responsibility of the Authority.

(7) In this regulation, “ relevant authority ” means any government department, local or public authority or holder of public office.

Section 6 Establishment of ethics committees

(1) The Authority may establish ethics committees to act—

(a) for the entire United Kingdom or for such areas of the United Kingdom; and

(b) in relation to such descriptions or classes of clinical trials,

as the Authority consider appropriate.

(2) The Authority may—

(a) vary the area for which any committee they have established acts or, as the case may be, the descriptions or classes of clinical trials in relation to which such a committee acts; and

(b) abolish any such committee.

Section 7 Recognition of ethics committees

(1) Subject to paragraph (3), the Authority may, by a notice in writing, recognise a committee as an ethics committee for the purposes of these Regulations if—

(a) an application in relation to that committee has been made in accordance with paragraph (2); and

(b) they are satisfied that the proposed arrangements for the membership and operation of that ethics committee would—

(i) enable that committee to perform the functions of an ethics committee adequately; and

(ii) comply with the provisions of Schedule 2.

(2) An application for recognition of an ethics committee shall be—

(a) made in writing to the Authority; and

(b) accompanied by such information, documents and particulars as are necessary to enable the Authority to determine the application.

(3) If any committee—

(a) was established or recognised by—

(i) the Secretary of State,

(ii) the Scottish Ministers,

(iii) the National Assembly for Wales,

(iv) the Department of Health, Social Services and Public Safety, or

(v) a Strategic Health Authority, Health Board or Health and Social Services Board,

for the purpose of advising on the ethics of research investigations on human beings, and

(b) was in existence on 30th April 2004,

the Authority may recognise that committee in accordance with paragraph (1) without an application for recognition being submitted.

(4) When recognising a committee the Authority shall specify—

(a) whether the committee may act for the entire United Kingdom or only for a particular area of the United Kingdom;

(b) the description or class of clinical trial in relation to which it may act as an ethics committee; and

(c) any other conditions or limitations that apply to that committee.

(5) The Authority may—

(a) vary the area for which a committee recognised under this regulation acts,

(b) vary the description or class of clinical trial in relation to which it may act as an ethics committee, or

(c) vary or revoke any conditions or limitations imposed under paragraph (4) ,

where it considers it necessary or appropriate to do so.

Section 8 Revocation of recognition

The Authority may revoke a recognition of an ethics committee if they are satisfied that—

(a) the provisions of Schedule 2 are not complied with in relation to that committee;

(b) the committee is failing to perform its functions under these Regulations adequately or at all; or

(c) it is otherwise necessary or expedient to do so.

Section 9 Constitution and operation of ethics committees

The provisions of Schedule 2 have effect in relation to ethics committees.

Section 10 Other functions of the Authority

(1) The Authority shall monitor the extent to which ethics committees adequately perform their functions under these Regulations.

(2) The Authority may provide advice and assistance to ethics committees with respect to the performance of their functions.

Section 11 Interpretation of Part 3

In this Part—

“ amendment to the clinical trial authorisation ” means an amendment to—

the terms of the request for authorisation to conduct that trial or the application for an ethics committee opinion in relation to that trial,

the protocol for that trial, or

the other particulars or documents accompanying that request for authorisation or application for ethics committee approval;

“ substantial amendment to the clinical trial authorisation ” means an amendment to the clinical trial authorisation which is likely to affect to a significant degree—

the safety or physical or mental integrity of the subjects of the trial,

the scientific value of the trial,

the conduct or management of the trial, or

the quality or safety of any investigational medicinal product used in the trial;

“ valid application ” means an application for an ethics committee opinion which complies with the provisions of regulation 14; and

“ valid request for authorisation ” means a request to the licensing authority for authorisation to conduct a clinical trial which complies with the provisions of regulation 17, and “ valid amended request ” shall be construed accordingly.

Section 12 Requirement for authorisation and ethics committee opinion

(1) No person shall—

(a) start a clinical trial or cause a clinical trial to be started; or

(b) conduct a clinical trial,

unless the conditions specified in paragraph (3) are satisfied.

(2) No person shall—

(a) recruit an individual to be a subject in a trial;

(b) issue an advertisement for the purpose of recruiting individuals to be subjects in a trial,

unless the condition specified in paragraph (3)(a) has been satisfied.

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

(a) an ethics committee to which an application in relation to the trial may be made in accordance with regulation 14 or an appeal panel appointed under Schedule 4 has given a favourable opinion in relation to the clinical trial; and

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

(4) For the purposes of these Regulations, a clinical trial has been authorised by the licensing authority if—

(a) in the case of a trial to which regulation 18 relates—

(i) the trial is to be treated as authorised by virtue of regulation 18, or

(ii) the authority has accepted the request for authorisation in accordance with the procedure specified in Schedule 5; or

(b) in the case of a clinical trial to which regulation 19 or 20 applies—

(i) the authority has given a notice of authorisation in accordance with those regulations, or

(ii) the authority has accepted the request for authorisation in accordance with the procedure specified in Schedule 5.

Section 13 Supply of investigational medicinal products for the purpose of clinical trials

(1) Subject to paragraphs (3) and (4), no person shall, in the course of a business carried on by him, sell or supply any investigational medicinal product to—

(a) an investigator,

(b) a health care professional who is a member of an investigator’s team,

(c) a person who provides or is to provide health care under the direction or control of a person referred to in sub-paragraphs (a) and (b), or

(d) a subject,

for the purpose of administering that product in a clinical trial, unless the conditions specified in paragraph (2) are satisfied.

(2) The conditions referred to in paragraph (1) are—

(a) the licensing authority has authorised the clinical trial for the purposes of which the product is sold or supplied;

(b) in the case of—

(i) an investigational medicinal product manufactured or assembled in the United Kingdom except for an MM investigational medicinal product or a POC investigational medicinal product , the product has been manufactured or assembled—

(aa) in accordance with the terms of a manufacturing authorisation, or

(bb) in the case of assembly only, under the exemption in regulation 37;

(ia) an MM investigational medicinal product manufactured or assembled in the United Kingdom, the product has been manufactured or assembled in accordance with the terms of a manufacturing authorisation (MM) or assembled under the exemption in regulation 37;

(ib) a POC investigational medicinal product manufactured or assembled in the United Kingdom, the product has been manufactured or assembled in accordance with the terms of a manufacturing authorisation (POC) or assembled under the exemption in regulation 37;

(ii) an investigational medicinal product imported into Northern Ireland from an EEA State—

(aa) the product has been manufactured, assembled or imported into an EEA State in accordance with the terms of an authorisation referred to in Article 13 of the Directive granted by a competent authority of an EEA State, and

(bb) the production batch of investigational medicinal products of which the product is a part has been checked and certified by a qualified person pursuant to Article 13(3) and (4) of the Directive;

(iii) an investigational medicinal product imported into Northern Ireland from a country other than an EEA State, the product has been imported into Northern Ireland in accordance with the terms of a manufacturing authorisation;

(iv) an investigational medicinal product imported into Great Britain other than from Northern Ireland, the product has been imported in accordance with the terms of a manufacturing authorisation.

(2A) The condition specified in paragraph (2)(b) does not apply to an investigational medicinal product that has been manufactured or assembled in accordance with the terms of a ... marketing authorization or marketing authorisation issued by the competent authority of an EEA State in accordance with Directive 2001/83/EC relating to that product.

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

(4) The restriction in paragraph (1) shall not apply to—

(a) the sale or supply of a medicinal product in Great Britain in accordance with the terms of a UKMA(GB) or UKMA(UK), and

(b) the sale or supply of a medicinal product in Northern Ireland in accordance with—

(i) the terms of a UKMA(NI) or UKMA(UK), or

(ii) an EU marketing authorisation (as defined in the 2012 Regulations).

Section 14 Application for ethics committee opinion

(1) An application for an ethics committee opinion in relation to a clinical trial shall be made by the chief investigator for that trial.

(2) A chief investigator for a trial shall make an application for an ethics committee opinion in relation to that trial to one ethics committee only, regardless of the number of trial sites at which the trial is to be conducted.

(3) Subject to paragraphs (4) and (5), the application for an ethics committee opinion in relation to a clinical trial shall be made to an ethics committee established or recognised—

(a) for—

(i) the entire United Kingdom, or

(ii) in relation to an area of the United Kingdom in which the chief investigator is professionally based; and

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

(4) If a clinical trial—

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

(b) 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 shall be made to the Ethics Committee constituted by regulations made by the Scottish Ministers under section 51(6) of the Adults with Incapacity (Scotland) Act 2000 .

(5) An application for an ethics committee opinion in relation to a clinical trial involving medicinal products for gene therapy, other than a trial falling within paragraph (4), shall be made to the Gene Therapy Advisory Committee.

(6) An application shall be—

(a) in writing;

(b) signed by the chief investigator making the application; and

(c) accompanied by the particulars and documents specified in Part 1 of Schedule 3.

(7) The application and any accompanying material shall be supplied in the English language.

(8) For the purposes of this regulation, a chief investigator is professionally based at the hospital, health centre, surgery or other establishment or facility at or from which he primarily conducts his professional practice.

Section 15 Ethics committee opinion

(1) Except as provided for in paragraph (4A) (which removes the requirement on the Gene Therapy Advisory Committee to give an opinion) and subject to paragraphs (3) and (4) (which suspend and disapply time limits respectively), an ethics committee shall give an opinion in relation to the clinical trial to which a valid application relates within the specified period beginning with the date of receipt of the valid application.

(2) Where following receipt of a valid application it appears to the committee that further information is required in order to give an opinion on a trial, the committee may, within the specified period and before giving its opinion, send a notice in writing to the applicant requesting that he furnishes the committee with that information.

(3) Where the committee sends a request in accordance with paragraph (2), the specified period shall be suspended pending receipt of the information requested.

(3A) An ethics committee may give a favourable opinion subject to conditions specified in writing in relation to a clinical trial.

(3B) If an ethics committee gives a favourable opinion subject to conditions, the ethics committee is to be treated as having given a favourable opinion in relation to the clinical trial only if the specified conditions are satisfied.

(4) If the clinical trial involves a medicinal product for xenogenic cell therapy, the time limits referred to in paragraphs (1) to (3) shall not apply and the ethics committee may give an opinion in relation to that trial or send a notice under paragraph (2) at any time after receipt of the valid application.

(4A) Where a notification under paragraph (4B) is received by the Authority—

(a) the Gene Therapy Advisory Committee shall not give an opinion in relation to the clinical trial to which the application subject to that notification relates;

(b) the Authority shall direct that the application be considered by another ethics committee specified in the direction;

(c) the Gene Therapy Advisory Committee shall send the application to the ethics committee specified in the direction immediately following the direction being given; and

(d) the ethics committee specified in the direction shall, subject to the application being valid, give an opinion in relation to the clinical trial to which that application relates within the specified period beginning with the date of the Gene Therapy Advisory Committee’s receipt of the application.

(4B) The Chairman, vice-chairman or alternate vice-chairman of the Gene Therapy Advisory Committee may notify the Authority (instead of giving an opinion) within the specified period beginning with the date of the Committee’s receipt of an application that the clinical trial to which that application relates does not merit an opinion from the Gene Therapy Advisory Committee.

(5) In preparing its opinion, the committee shall consider, in particular, the following matters—

(a) the relevance of the clinical trial and its design;

(b) whether the evaluation of the anticipated benefits and risks as required under paragraph 10 of Part 2 of Schedule 1 is satisfactory and whether the conclusions are justified;

(c) the protocol;

(d) the suitability of the investigator and supporting staff;

(e) the investigator’s brochure or, where the investigational medicinal product has a marketing authorization and the product is to be used in accordance with the terms of that authorization, the summary of product characteristics , or equivalent document, relating to that product ;

(f) the quality of the facilities for the trial;

(g) the adequacy and completeness of the written information to be given, and the procedure to be followed, for the purpose of obtaining informed consent to the subjects' participation in the trial;

(h) if the subjects are to include minors or persons incapable of giving informed consent, whether the research is justified having regard to the conditions and principles specified in Part 4 or Part 5 respectively of Schedule 1;

(i) provision for indemnity or compensation in the event of injury or death attributable to the clinical trial;

(j) any insurance or indemnity to cover the liability of the investigator or sponsor;

(k) the amounts, and, where appropriate, the arrangements, for rewarding or compensating investigators and subjects;

(l) the terms of any agreement between the sponsor and the owner or occupier of the trial site which are relevant to the arrangements referred to in sub-paragraph (k); and

(m) the arrangements for the recruitment of subjects.

(6) If—

(a) any subject of the clinical trial is to be a minor; and

(b) the committee does not have a member with professional expertise in paediatric care,

it shall, before giving its opinion, obtain advice on the clinical, ethical and psychosocial problems in the field of paediatric care which may arise in relation to that trial.

(7) If—

(a) any subject to the clinical trial is to be an adult incapable by reason of physical and mental incapacity to give informed consent to participation in the trial; and

(b) the committee does not have a member with professional expertise in the treatment of—

(i) the disease to which the trial relates, and

(ii) the patient population suffering that disease,

it shall, before giving its opinion, obtain advice on the clinical, ethical and psychosocial problems in the field of that disease and patient population which may arise in relation to that trial.

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

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

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

(9) Where an ethics committee gives an opinion in accordance with this regulation, it shall publish a summary of that opinion.

(10) In this regulation—

“ the specified period ” means—

in the case of a clinical trial involving a medicinal product for gene therapy or somatic cell therapy or a medicinal product containing a genetically modified organism or a tissue engineered product —

where a specialist group or committee is consulted, 180 days, or

where there is no such consultation, 90 days; or

in any other case, 60 days;

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

tissue engineered products;

in the case of medicinal products for gene therapy or somatic cell therapy, the use of such therapies in the treatment of humans; or

in the case of medicinal products containing genetically modified organisms, the administration of such products to humans.

Section 16 Review and appeal relating to ethics committee opinion

(1) This regulation applies where a chief investigator for a trial has been notified by the ethics committee to which he made an application in accordance with regulation 14 that the committee’s opinion in relation to that trial is not favourable.

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

(a) the 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 the opinion was given by an ethics committee other than the Gene Therapy Advisory Committee, the chief investigator may within 90 days of being notified that the committee’s opinion is not favourable, give a notice to the United Kingdom Ethics Committees Authority—

(a) stating his wish to appeal against the opinion; and

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

(4) Where the opinion was given by the Gene Therapy Advisory Committee, the chief investigator may, within 14 days of being notified of that opinion—

(a) give a notice in writing to the Committee requiring the Committee to review its opinion; or

(b) give a notice in writing to the United Kingdom Ethics Committee Authority—

(i) stating his wish to appeal against the opinion; and

(ii) setting out his representations with respect to that opinion.

(5) Where the Gene Therapy Advisory Committee is required by a notice under paragraph (4) to review its opinion, it must do so within 60 days of receipt of the notice.

(6) On a review pursuant to paragraph (5), the Gene Therapy Advisory Committee may vary or confirm their opinion and shall give notice in writing to the chief investigator of the variation or confirmation.

(7) If the Gene Therapy Advisory Committee confirm their opinion pursuant to paragraph (6), a chief investigator may within the 14 days of being notified of the confirmation give notice in writing to the United Kingdom Ethics Committees Authority—

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

(b) setting out his representations with respect to that opinion

(8) Schedule 4 shall have effect to regulate the procedure where the Authority receives a notice in accordance with paragraph (3), (4) or (7).

Section 17 Request for authorisation to conduct a clinical trial

(1) A request for authorisation to conduct a clinical trial shall be made to the licensing authority by the sponsor of the trial.

(2) Subject to paragraph (2A), a request shall—

(a) be in writing and signed by or on behalf of the sponsor; and

(b) be accompanied by—

(i) the particulars and documents specified in Part 2 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 .

(2A) No fee need accompany a request where arrangements have been made with the licensing authority for payment of the fee referred to in paragraph (2)(b)(ii) other than at the time of request.

(3) The request and any accompanying material shall be supplied in the English language.

Section 18 Authorisation procedure for clinical trials involving general medicinal products

(1) This regulation applies to clinical trials involving medicinal products other than those to which regulations 19 and 20 apply.

(2) The licensing authority may, within the period of 30 days from the date of receipt of a valid request for authorisation of a clinical trial to which this regulation applies, give written notice to the sponsor—

(a) setting out the licensing authority’s grounds for not accepting the request;

(b) stating that the licensing authority accepts the request for authorisation; or

(c) stating that the licensing authority accepts the request for authorisation, subject to the conditions specified in the notice.

(3) Subject to paragraph (4), if—

(a) a notice is given in accordance with paragraph (2)(b); or

(b) no notice is given in accordance with paragraph (2),

the clinical trial is to be treated as authorised.

(4) If a notice is given in accordance with paragraph (2)(c), the clinical trial is to be treated as authorised only if the conditions specified in the notice are satisfied.

(5) If the sponsor is given a notice in accordance with paragraph (2)(a) or (c), he may, within the period of 14 days, or such extended period as the licensing authority may in any particular case allow, from the date on which the notice was received, send an amended request to the licensing authority for further consideration.

(6) The licensing authority shall consider a valid amended request and may, within the period of 60 days from the date on which the original request was received give a written notice to the sponsor—

(a) setting out the licensing authority’s grounds for not accepting the amended request;

(b) stating that the licensing authority accepts the amended request; or

(c) stating that the licensing authority accepts the amended request, subject to the conditions specified in the notice.

(7) Subject to paragraph (8), if a valid amended request has been received and—

(a) a notice is given in accordance with paragraph (6)(b); or

(b) no notice is given in accordance with paragraph (6),

the clinical trial is to be treated as authorised.

(8) If a valid amended request has been received and a notice is given in accordance with paragraph (6)(c), the clinical trial is to be treated as authorised only if the conditions specified in the notice are satisfied.

(9) If—

(a) the licensing authority gives written notice to the sponsor of grounds for non-acceptance in accordance with paragraph (2)(a) and the sponsor does not submit an amended request in accordance with paragraph (5), or

(b) the sponsor has submitted an amended request in accordance with paragraph (5), but the licensing authority gives written notice to the sponsor of grounds for non-acceptance in accordance with paragraph (6)(a),

the request is to be treated as rejected and the authority shall not consider any further amendments to the request.

Section 19 Authorisation procedure for clinical trials involving medicinal products for gene therapy etc.

(1) This regulation applies to clinical trials involving—

(a) medicinal products for gene therapy and somatic cell therapy, including xenogenic cell therapy;

(b) medicinal products containing genetically modified organisms; or

(c) tissue engineered products.

(2) Subject to the following provisions of this regulation, the licensing authority may, within the period of 30 days from the date of receipt of a valid request for authorisation of a clinical trial to which this regulation applies—

(a) issue a written authorisation to the sponsor; or

(b) give a notice in writing to the sponsor setting out the grounds for not accepting the request.

(3) The licensing authority shall not authorise a clinical trial involving products for gene therapy if the use of those products in that trial would result in modifications to any subject’s germ line genetic identity.

(4) If the licensing authority considers that it is appropriate to do so, they may consult the relevant committee before deciding whether to authorise a clinical trial.

(5) Where the authority consults the relevant committee in accordance with paragraph (4), the period specified in paragraph (2) shall be extended by a further 90 days.

(6) Where a sponsor is given a notice in accordance with paragraph (2)(b), he may, within the period of 30 days, or such extended period as the licensing authority may in any particular case allow, from the date on which the notice was received, send an amended request to the licensing authority for further consideration.

(7) The licensing authority shall consider a valid amended request and, not later than 90 days, or, in a case falling within paragraph (5), 180 days, from the date on which the original request was received—

(a) issue a written authorisation to the sponsor; or

(b) give a notice in writing to the sponsor setting out the grounds for not accepting the request.

(8) A written authorisation issued under this regulation may contain such conditions as the licensing authority consider appropriate.

(9) If the clinical trial involves a medicinal product for xenogenic cell therapy, the time limits set out in paragraphs (2), (5) and (7) shall not apply and the authority may issue an authorisation or notice under those paragraphs at any time after receipt of the request.

(10) In this regulation, “ the relevant committee ” means—

(a) the Commission on Human Medicines ... ; or

(b) such other body or committee as the licensing authority may consider appropriate in relation to the application under consideration.

Section 20 Authorisation procedure for clinical trials involving medicinal products with special characteristics

(1) This regulation applies to clinical trials—

(a) involving medicinal products—

(i) which do not have a marketing authorization and are developed by means of one of the following biotechnological processes—

(aa) recombinant DNA technology,

(bb) controlled expression of genes coding for biologically active proteins in prokaryotes and eukaryotes including transformed mammalian cells,

(cc) hybridoma and monoclonal antibody methods, or

(ii) which have an active ingredient—

(aa) that is a biological product of human or animal origin,

(bb) containing biological components of human or animal origin, or

(cc) the manufacturing of which requires such components,

other than products falling within regulation 19; or

(b) where the licensing authority, within 7 days from the date of receipt of a valid request for authorisation of the trial, issues a notice to the sponsor specifying that by virtue of the special characteristics of the medicinal product to which the trial relates, written authorisation for that trial is required.

(2) The licensing authority may, within the period of 30 days from the date of receipt of a valid request for authorisation of a clinical trial to which this regulation applies—

(a) issue a written authorisation to the sponsor; or

(b) give a notice in writing to the sponsor setting out the grounds for not authorising the trial.

(3) Where a sponsor is given a notice in accordance with paragraph (2)(b), he may, within the period of 14 days, or such extended period as the licensing authority may in any particular case allow, from the date on which the notice was received, send an amended request to the licensing authority for further consideration.

(4) The licensing authority shall consider a valid amended request and, not later than 60 days from the date on which the original request was received—

(a) issue a written authorisation to the sponsor; or

(b) give a notice in writing to the sponsor setting out the grounds for not accepting the request.

(5) A written authorisation issued under this regulation may contain such conditions as the licensing authority consider appropriate.

Section 21 Clinical trials conducted in countries other than the United Kingdom

(1) If the licensing authority receives a valid request for authorisation 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 they think fit, require the production by the sponsor of any one or more 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 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 accepting the request for authorisation, for the purposes of regulations 18 to 20.

Section 22 Amendments to clinical trial authorisation

Subject to regulation 30, an amendment to a clinical trial authorisation may be made—

(a) by the licensing authority, in accordance with regulation 23; or

(b) by the sponsor, in accordance with regulation 24 or 25.

Section 23 Amendments by the licensing authority

(1) Subject to paragraphs (2) and (3) , the licensing authority may make amendments to a clinical trial authorisation 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 licensing authority propose to make an amendment in accordance with paragraph (1), the authority shall, at least 14 days before the date on which it is proposed the amendment should take effect, serve a notice on the sponsor stating their proposal and the reasons for it.

(3) If, within 14 days of the date a notice is served in accordance with paragraph (2), the sponsor makes representations in writing to the licensing authority, the authority—

(a) shall take those representations into account before deciding whether to make the amendment; and

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

Section 24 Amendments by the sponsor

(1) A sponsor may make an amendment to a clinical trial authorisation, other than a substantial amendment, at any time.

(2) A sponsor shall—

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

(b) send those records, or copies of such records, to the licensing authority, where the authority send him a notice in writing requiring him to provide those records, or copies of such records.

(3) If the sponsor proposes to make a substantial amendment to a clinical trial authorisation which consists of, or includes, an amendment to—

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

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

he shall send a valid notice of amendment to the licensing authority, whether or not he is also required to send a notice in accordance with paragraph (4).

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

(a) the terms of the application for an ethics committee opinion in relation to the clinical trial; or

(b) the particulars or documents that accompanied that application,

he shall send a valid notice of amendment to the relevant ethics committee, whether or not he is also required to send a notice in accordance with paragraph (3).

(5) The licensing authority may, within the period of 35 days from the date of receipt of a valid notice of amendment, give written notice to the sponsor—

(a) setting out the licensing authority’s grounds for not accepting the proposed amendment; or

(b) stating that the licensing authority accepts the application for amendment, subject to any conditions which may be specified in the notice.

(6) A relevant ethics committee shall, within the period of 35 days from the date of receipt of a valid notice of amendment, give an opinion to the sponsor.

(7) Subject to paragraph (8), if the sponsor has sent a notice in accordance with paragraph (3), he may make the amendment only if—

(a) the licensing authority have given him a notice in accordance with paragraph (5)(b); or

(b) no notice has been given by the licensing authority in accordance with paragraph (5).

(8) If the sponsor has been given a notice in accordance with paragraph (5)(b), he may make the amendment subject to the conditions, if any, specified in the notice.

(9) If the sponsor has sent a notice in accordance with paragraph (4), he may make the amendment only if the relevant ethics committee has given a favourable opinion.

(10) In this regulation—

“any relevant fee” means, in relation to a notice of amendment, any fee which may be payable in connection with that notice under the Medicines (Products for Human Use) (Fees) Regulations 2016 ; and

“ valid notice of amendment ” means a notice that is—

in writing; and

accompanied by—

the particulars specified in Part 3 of Schedule 3, and

unless arrangements have been made with the licensing authority for the payment of any relevant fee other than at the time of the request, any such fee.

Section 25 Modifying or adapting rejected proposals for amendment

(1) Subject to the following provisions of this regulation, if—

(a) the ethics committee opinion on a proposed amendment to the protocol is not favourable; or

(b) the sponsor has been notified by the licensing authority of any grounds for non-acceptance of a proposed amendment to the protocol,

and it is possible to modify or adapt the proposed amendment in order to meet the concerns of ethics committee or the licensing authority as set out in the opinion or, as the case may be, the grounds for non-acceptance, the sponsor may amend the protocol accordingly.

(2) If a sponsor proposes to amend the protocol in accordance with paragraph (1), the sponsor shall, at least 14 days before the amendment is to be made, give a notice in writing to the licensing authority and the relevant ethics committee.

(3) The licensing authority may, within the period of 14 days from the date of receipt of a notice under paragraph (1), give written notice to the sponsor setting out the licensing authority’s further grounds for not accepting the modified or adapted amendment.

(4) The relevant ethics committee may, within the period of 14 days from the date of receipt of a notice under paragraph (1), give a written notice to the sponsor stating that its opinion of the modified or adapted amendment is unfavourable.

(5) If—

(a) the sponsor receives a written notice under paragraphs (3) or (4), he may not make the amendment; and

(b) if he receives no such notice, he may make the modified or adapted amendment.

Section 26 Reference to the appropriate committee or the Medicines Commission

(1) If—

(a) a sponsor has been notified by the licensing authority that—

(i) there are grounds for not accepting a request for authorisation, or

(ii) in accordance with regulation 18(2) or (6), 19(8) or 20(5), the trial is authorised subject to specified conditions;

(b) the licensing authority has amended a clinical trial authorisation under regulation 23; or

(c) the sponsor ... has been notified by the licensing authority in accordance with regulation 24(5) or 25(3) that—

(i) the authority does not accept a proposed, modified or adapted amendment to the clinical trial authorisation, or

(ii) the authority accepts such an amendment subject to conditions,

the sponsor may, within 28 days, or such extended period as the licensing authority may in any particular case allow, of the notice being given, give notice in writing to the licensing authority of his wish to make written or oral representations to the appropriate committee ....

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

Section 27 Conclusion of clinical trial

(1) Subject to paragraph (2), within 90 days of the conclusion of a clinical trial the sponsor shall notify the licensing authority and the relevant ethics committee in writing that the trial has ended.

(2) If a trial is terminated—

(a) before the date for the conclusion of the trial specified in the protocol for that trial, or

(b) before the event specified in the protocol as the event which indicates the end of the trial has occurred,

the sponsor shall notify the licensing authority and the relevant ethics committee in writing of the termination of the trial within 15 days of the date of termination.

(3) A notification made in accordance with paragraphs (1) or (2) shall contain the particulars specified in Part 4 of Schedule 3.

Section 27A Information sharing

The licensing authority and an ethics committee may disclose to each other any information acquired in carrying out their respective functions under these Regulations where disclosing such information may assist the other body in carrying out its functions under these Regulations.

Section 27B Publication of information

(1) Subject to paragraph (3), the licensing 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 authorisation made under regulation 17;

(b) any amended request for authorisation made under regulation 18, 19 or 20;

(c) any amendment to the protocol made under regulation 23, 24 or 25;

(d) the favourable opinion of the ethics committee given in accordance with regulation 15 or the favourable opinion given by an appeal panel in accordance with paragraph 4 of Schedule 4;

(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 licensing authority must, after consulting such persons as the licensing authority considers appropriate, publish a list of the information which may be made accessible to the public under paragraph (1).

Section 28 Good clinical practice and protection of clinical trial subjects

(1) No person shall—

(a) conduct a clinical trial; or

(b) perform the functions of the sponsor of a clinical trial (whether that person is the sponsor or is acting under arrangements made with that sponsor),

otherwise than in accordance with the conditions and principles of good clinical practice.

(2) Subject to paragraph (5), the sponsor of a clinical trial shall put and keep in place arrangements for the purpose of ensuring that with regard to that trial the conditions and principles of good clinical practice are satisfied or adhered to.

(3) Subject to paragraphs (4) and (5), the sponsor of a clinical trial shall ensure that—

(a) the investigational medicinal products used in the trial, and

(b) any devices used for the administration of such products,

are made available to the subjects of the trial free of charge.

(4) The restriction in paragraph (3) shall not apply in relation to any charge payable by a subject under regulations made under—

(a) the National Health Service Act 1977 ;

(b) the National Health Service (Scotland) Act 1978 ; or

(c) the Health and Personal Social Services (Northern Ireland) Order 1972 ,

in respect of any medicinal products or devices provided in pursuance of those Acts or that Order.

(5) If—

(a) a clinical trial is conducted at more than one trial site; and

(b) the request for authorisation to conduct that trial specifies that in relation to one or more trial sites the duties of the sponsor under paragraphs (2) and (3) are to be performed by a person other than the sponsor,

those duties shall, in relation to that site or those sites, be performed by the person so specified.

Section 29 Conduct of trial in accordance with clinical trial authorisation etc.

Subject to regulation 30, no person shall conduct a clinical trial otherwise than in accordance with—

(a) the protocol relating to that trial, as may be amended from time to time in accordance with regulations 22 to 25;

(b) the terms of—

(i) the request for authorisation to conduct that trial,

(ii) the application for an ethics committee opinion in relation to that trial, and

(iii) any particulars or documents, other than the protocol, accompanying that request or that application,

as may be amended from time to time in accordance with regulations 22 to 25; and

(c) any conditions imposed by the licensing authority under regulation 18(2) or (6), 19(8), 20(5), 24(5) or Schedule 5.

Section 29A Notification of serious breaches

(1) The sponsor of a clinical trial shall notify the licensing authority in writing of any serious breach of—

(a) the conditions and principles of good clinical practice in connection with that trial; or

(b) the protocol relating to that trial, as amended from time to time in accordance with regulations 22 to 25,

within 7 days of becoming aware of that breach.

(2) For the purposes of this regulation, a “serious breach” is a breach which is likely to effect to a significant degree—

(a) the safety or physical or mental integrity of the subjects of the trial; or

(b) the scientific value of the trial.

Section 30 Urgent safety measures

(1) The sponsor and investigator may take appropriate urgent safety measures in order to protect the subjects of a clinical trial against any immediate hazard to their health or safety.

(2) If measures are taken pursuant to paragraph (1), the sponsor shall—

(a) where paragraph (3) applies, as soon as possible; and

(b) in any other case, immediately, and in any event no later than 3 days from the date the measures are taken,

give written notice to the licensing authority and the relevant ethics committee of the measures taken and the circumstances giving rise to those measures.

(3) This paragraph applies for any period during which a disease—

(a) is pandemic; and

(b) is a serious risk to human health or potentially a serious risk to human health.

Section 31 Suspension or termination of clinical trial

(1) If, in relation to a clinical trial—

(a) the licensing authority have objective grounds for considering that—

(i) any condition, restriction or limitation which applies to the conduct of the trial and is set out in the request for authorisation or the particulars or documents accompanying that request, or

(ii) any condition imposed by the licensing authority under regulation 18(2) or (6), 19(8), 20(5), 24(5) or Schedule 5,

is no longer satisfied (either generally or at a particular trial site); or

(b) the licensing authority have information raising doubts about the safety or scientific validity of the trial, or the conduct of the trial at a particular trial site,

the licensing authority may, by a notice served in accordance with paragraph (2), require that the trial, or the conduct of the trial at a particular trial site, be suspended or terminated.

(2) A notice in accordance with paragraph (1) shall be served—

(a) in a case where the suspension or termination applies to the trial generally, on—

(i) the sponsor, or

(ii) the investigator at each trial site;

(b) in a case where the suspension or termination applies to the conduct of a trial at a particular trial site, on—

(i) the sponsor, or

(ii) the investigator at that trial site.

(3) The notice shall specify—

(a) whether the notice applies to the trial generally or to one or more of the trial sites;

(b) whether the notice requires suspension or termination of the trial;

(c) if the notice requires suspension of the trial—

(i) whether the suspension applies until further notice from the licensing authority or for such period as may be specified in the notice, and

(ii) any conditions which are to be satisfied before the trial or, as the case may be, the conduct of the trial at a particular site, may be recommenced; and

(d) whether suspension or termination is to take effect immediately on receipt of the notice or on such date as may be specified in the notice.

(4) If the licensing authority issues a notice under paragraph (1), they shall forthwith inform—

(a) where the notice has not been served on the sponsor, the sponsor;

(b) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

(c) the relevant ethics committee;

(d) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

(e) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

(5) Subject to paragraph (6), at least one week before issuing a notice under paragraph (1) the licensing authority shall, by a notice in writing to the sponsor or the investigator—

(a) inform him that the authority is minded to issue a notice suspending or terminating the trial, or the conduct of a trial at a particular site, and of the reasons why they are so minded; and

(b) advise him that they may, within one week of the date of the notice, furnish the authority with written representations as to whether the trial, or the conduct of the trial at a particular site, should be so suspended or terminated.

(6) Paragraph (5) shall not apply where it appears to the licensing authority that there is an imminent risk to the health or safety of any of the subjects of the clinical trial.

(7) A person on whom a notice has been served in accordance with paragraphs (1) and (2) may, within 28 days, or such extended period as the licensing authority may in any particular case allow, of the notice being given, give notice of his wish to make written or oral representations to the appropriate committee ....

(8) Schedule 5 shall have effect to regulate the procedure for reference to the appropriate committee ... following receipt of a notice in accordance with paragraph (7).

(9) Where the notice of suspension or termination is referred to an appropriate committee ...it shall remain in force unless revoked in accordance with Schedule 5.

Section 31A Trial master file and archiving

(1) The sponsor shall keep a trial master file for a clinical trial.

(2) The sponsor shall ensure that the trial master file is readily available at all reasonable times for inspection by the licensing authority or any person appointed by the sponsor to audit the arrangements for the trial.

(3) The master file shall at all times contain the essential documents relating to that clinical trial.

(4) The essential documents relating to a clinical trial are those which—

(a) enable both the conduct of the clinical trial and the quality of the data produced to be evaluated; and

(b) show whether the trial is, or has been, conducted in accordance with the relevant requirements of these Regulations .

(5) The essential documents shall contain information specific to each phase of the trial.

(6) The sponsor shall ensure that any alteration to a document contained, or which has been contained, in the trial master file shall be traceable.

(7) The sponsor and the chief investigator shall ensure that the documents contained, or which have been contained, in the trial master file are retained for at least 5 years after the conclusion of the trial and that during that period are—

(a) readily available to the licensing authority on request; and

(b) complete and legible.

(8) The sponsor and chief investigator shall ensure that the medical files of trial subjects are retained for at least 5 years after the conclusion of the trial.

(9) The sponsor shall appoint named individuals within his organisation to be responsible for archiving the documents which are, or have been, contained in the trial master file and, subject to paragraph (2), access to those documents shall be restricted to those appointed individuals.

(10) If there is transfer of ownership of data or documents connected with the clinical trial—

(a) the sponsor shall record the transfer; and

(b) the new owner shall be responsible for data retention and archiving in accordance with paragraphs (2), (7) and (8).

(11) For the purposes of this regulation, an individual is an individual within the sponsor’s organisation where—

(a) he is employed or engaged by the sponsor;

(b) he is acting under arrangements made with the sponsor for the purposes of managing or conducting the clinical trial;

(c) where the sponsor is an individual, he is the sponsor; or

(d) where the sponsor is a body of persons, he is—

(i) a member of the body, or

(ii) employed or engaged by such a member.

Section 32 Notification of adverse events

(1) An investigator shall report any serious adverse event which occurs in a subject at a trial site at which he is responsible for the conduct of a clinical trial immediately to the sponsor.

(2) An immediate report under paragraph (1) may be made orally or in writing.

(3) Following the immediate report of a serious adverse event, the investigator shall make a detailed written report on the event.

(4) Paragraphs (1) to (3) do not apply to serious adverse events specified in the protocol or the investigator’s brochure as not requiring immediate reporting.

(5) Adverse events, other than those to which paragraphs (1) to (3) apply, that are identified in the protocol as critical to evaluations of the safety of the trial shall be reported to the sponsor in accordance with the reporting requirements, including the time periods for such reporting, specified in that protocol.

(6) The reports made under paragraphs (1), (3) and (5) shall identify each subject referred to in the report by a number assigned to that subject in accordance with the protocol for the trial.

(7) The number assigned to a subject in accordance with the protocol must be different from the number of any other subject in that trial, including any subject at a trial site outside the United Kingdom.

(8) Where the event reported under paragraph (1) or (5) consists of, or results in, the death of a subject, the investigator shall supply—

(a) the sponsor; and

(b) in any case where the death has been reported to the relevant ethics committee, that committee,

with any additional information requested by the sponsor or, as the case may be, the committee.

(9) The sponsor shall keep detailed records of all adverse events relating to a clinical trial which are reported to him by the investigators for that trial.

(10) The licensing authority may, by sending a notice in writing to the sponsor, require him to send the records referred to in paragraph (9), or copies of such records, to the authority.

Section 33 Notification of suspected unexpected serious adverse reactions

(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—

(a) recorded; and

(b) reported as soon as possible to—

(i) the licensing authority,

(ii) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

(iii) the relevant ethics committee,

and in any event not later that 7 days after the sponsor was first aware of the reaction.

(2) A sponsor shall ensure that within 8 days of a report in accordance with paragraph (1)(b), any additional relevant information is sent to the persons or bodies listed in that paragraph.

(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—

(a) the licensing authority;

(b) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

(c) the relevant ethics committee,

and in any event not later that 15 days after the sponsor is first aware of the reaction.

(4) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

(5) A sponsor shall ensure that, in relation to each clinical trial in the United Kingdom for which he is the sponsor, the investigators responsible for the conduct of a trial are informed of any suspected unexpected serious adverse reaction which occurs in relation to an investigational medicinal product used in that trial, whether that reaction occurs during the course of that trial or another trial for which the sponsor is responsible.

(6) The licensing authority shall—

(a) keep a record of all suspected unexpected serious adverse reactions relating to an investigational medicinal product which are brought to its attention, whether pursuant to paragraphs (1) or (3) or otherwise; and

(b) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Section 34 Clinical trials conducted in countries other than the United Kingdom

If a clinical trial is being conducted at a trial site in another country in addition to sites in the United Kingdom, the sponsor of that trial shall ensure that all suspected unexpected serious adverse reactions occurring at that site are reported as soon as possible to the licensing authority, and in any event—

(a) in the case of a reaction that is fatal or life-threatening, within 7 days beginning with the day after the sponsor was first aware of the reaction; or

(b) in any other case, within 15 days beginning with the day after the sponsor is first aware of the reaction.

Section 35 Annual list of suspected serious adverse reactions and safety report

(1) As soon as practicable after the end of the reporting year, a sponsor shall, in relation to each investigational medicinal product tested in clinical trials in the United Kingdom for which he is the sponsor furnish the licensing authority and the relevant ethics committees with—

(a) a list of all the suspected serious adverse reactions which have occurred during that year in relation to—

(i) those trials, whether at trial sites in the United Kingdom or elsewhere, or

(ii) any other trials relating to that product which are conducted outside the United Kingdom and for which he is the sponsor,

including those reactions relating to any investigational medicinal product used as a placebo or as a reference in those trials; and

(b) a report on the safety of the subjects of those trials.

(2) In paragraph (1), “ reporting year ”, in relation to an investigational medicinal product, means the year ending on the anniversary of—

(a) in the case of a product which has a marketing authorization, the earliest date on which any such authorization relating to that product was granted or issued; or

(b) in any other case, the earliest date on which any clinical trial—

(i) relating to that product, and

(ii) for which the person responsible for making the report was the sponsor,

was authorised in an any country .

(3) For the purposes of paragraph (2)(b), the date on which a clinical trial was authorised in a country is—

(a) the date on which the trial was authorised by a regulatory body responsible for authorising clinical trials in that country; or

(b) where the clinical trial was conducted in a country without a formal authorisation process, a date designated by the sponsor that is linked to the commencement of the first clinical trial.

Section 36 Requirement for authorisation to manufacture or import investigational medicinal products

(1) Subject to paragraph (2) and regulation 37, no person shall manufacture, assemble or import any investigational medicinal product except in accordance with an authorisation of the appropriate type granted by the licensing authority for the purposes of this regulation (“a manufacturing authorisation”).

(1A) For the purposes of paragraph (1), the appropriate type of authorisation is an authorisation that relates to whichever, or whichever combination, of the following that is appropriate—

(a) manufacture or assembly of investigational medicinal products, except for MM investigational medicinal products and POC investigational medicinal products;

(b) import of investigational medicinal products, except for MM investigational medicinal products and POC investigational medicinal products;

(c) manufacture or assembly of MM investigational medicinal products;

(d) manufacture or assembly of POC investigational medicinal products.

(2) The restriction in paragraph (1) shall not apply to the manufacture or assembly of a medicinal product to the extent that such manufacture or assembly is in accordance with the terms and conditions of a marketing authorization or marketing authorisation issued by the competent authority of an EEA State in accordance with Directive 2001/83/EC relating to that product.

(3) Regulation 36A sets out additional requirements in relation to the manufacture and assembly of MM investigational medicinal products.

(4) Regulation 36B sets out additional requirements in relation to the manufacture and assembly of POC investigational medicinal products.

Section 36A Manufacture of MM investigational medicinal products

(1) No person shall manufacture or assemble an MM investigational medicinal product unless—

(a) the activity and product type is specified in a manufacturing authorisation (MM); and

(b) there is an MM (IMP) master file relating to the product and the product is manufactured and assembled in accordance with that master file.

(2) Paragraph (1) does not apply to the manufacture or assembly of an MM investigational medicinal product to the extent that the manufacture or assembly is in accordance with the terms and conditions of a UK marketing authorisation or a marketing authorisation issued by the competent authority of an EEA State in accordance with Directive 2001/83/EC relating to that product.

Section 36B Manufacture of POC investigational medicinal products

(1) No person shall manufacture or assemble a POC investigational medicinal product unless—

(a) the activity and product type is specified in a manufacturing authorisation (POC); and

(b) there is a POC (IMP) master file relating to the product and the product is manufactured and assembled in accordance with that master file.

(2) Paragraph (1) does not apply to the manufacture or assembly of a POC investigational medicinal product to the extent that the manufacture or assembly is in accordance with the terms and conditions of a UK marketing authorisation or a marketing authorisation issued by the competent authority of an EEA State in accordance with Directive 2001/83/EC relating to that product.

Section 37 Exemption for hospitals and health centres

(1) The restriction imposed by regulation 36(1) shall not apply to the assembly of an investigational medicinal product where the conditions specified in paragraph (2) are satisfied.

(2) The conditions referred to in paragraph (1) are that—

(a) the assembly is carried out in—

(i) in a hospital or health centre, and

(ii) by a doctor, a pharmacist or a person acting under the supervision of a pharmacist; and

(b) the investigational medicinal products are assembled exclusively for use in—

(i) that hospital or health centre, or

(ii) any other hospital or health centre which is a trial site for the clinical trial in which the product is to be used.

Section 38 Application for manufacturing authorisation

(1) An application for the grant of a manufacturing authorisation shall be—

(a) made to the licensing authority;

(b) in writing; and

(c) signed by or on behalf of the applicant.

(2) Every application for the grant of a manufacturing authorisation shall specify which, if any, of the standard provisions referred to in regulation 40(4) it is desired shall be excluded or modified in relation to the grant of the authorisation.

(3) Subject to paragraph (3A), every application for the grant of a manufacturing authorisation shall be accompanied by—

(a) the particulars specified in Schedule 6 to these regulations; and

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

(3A) No fee need accompany an application for the grant of a manufacturing authorisation where arrangements have been made with the licensing authority for the payment of the fee referred to in paragraph (3)(b) other than at the time of the application.

(4) The application and any accompanying material shall be supplied to the licensing authority in the English language.

Section 39 Consideration of application for manufacturing authorisation

(1) Subject to paragraph (3) and regulation 40, the licensing authority shall consider a valid application for a manufacturing authorisation and grant, or refuse to grant, an authorisation within a period not exceeding 90 days from the date the application is received.

(2) Following receipt of an application, the licensing authority may give a notice in writing to the applicant requesting him to provide further information relating to—

(a) the particulars referred to in regulation 38(3); or

(b) the qualified person referred to in regulation 43.

(3) Where the licensing authority give a notice pursuant to paragraph (2), the period specified in paragraph (1) shall be suspended from the date the notice is given and shall recommence only on receipt of the information requested.

(4) If the application for a manufacturing authorisation relates (wholly or partially) to the importation of investigational medicinal products, the licensing authority may, if they think fit, require the production by the applicant of an undertaking, given by the manufacturer of any such products, to permit—

(a) the premises where they are or are to be manufactured; and

(b) the operations carried on or to be carried on in the course of manufacturing them,

to be inspected by or on behalf of the licensing authority.

(4A) If the application for a manufacturing authorisation relates (wholly or partially) to an MM investigational medicinal product, the licensing authority shall take into consideration the arrangements for—

(a) supervising and controlling operations at a modular unit specified in the application; and

(b) ensuring that manufacture or assembly is under appropriate control so that the MM investigational medicinal product consistently meets the requirements in the MM (IMP) master file when manufactured at that modular unit.

(4B) If the application for a manufacturing authorisation relates (wholly or partially) to a POC investigational medicinal product, the licensing authority shall take into consideration the arrangements for—

(a) supervising and controlling operations at any POC (IMP) site specified in the application; and

(b) ensuring that manufacture or assembly is under appropriate control so that the POC investigational medicinal product consistently meets the requirements in the POC (IMP) master file when manufactured at that site.

(5) In this regulation, “ valid application ” means an application which complies with the provisions of regulation 38.

Section 40 Grant or refusal of manufacturing authorisation

(1) The licensing authority shall grant a manufacturing authorisation only if—

(a) the applicant—

(i) has complied with the requirements of regulation 38,

(ii) has at his disposal—

(aa) the services of staff, and

(bb) suitable and sufficient premises, technical equipment and control facilities,

complying with the requirements of Commission Directive 2003/94/ EC , as regards the manufacture or import, and control, of the products to which the authorisation relates and the storage of such products,

(iii) has at his disposal the services of at least one qualified person, and

(iv) if a notice has been given under regulation 39(2), has provided the information requested by the licensing authority; and

(b) they have established that the particulars supplied pursuant to regulation 38(3) are accurate.

(2) Subject to paragraph (1), the licensing authority may grant a manufacturing authorisation in respect of any or all of—

(a) the descriptions of investigational medicinal products;

(b) the manufacturing, assembling or importation operations; or

(c) the premises,

specified in the application made pursuant to regulation 38.

(3) The licensing authority may grant a manufacturing authorisation containing—

(a) any provisions to be incorporated in the authorisation in accordance with paragraph (4); or

(b) such other provisions as the licensing authority consider appropriate.

(4) The provisions specified—

(a) in the case of a manufacturing authorisation relating to the manufacture or assembly of investigational medicinal products, in Part 2 of Schedule 7; and

(b) in the case of a manufacturing authorisation relating to the importation of investigational medicinal products, in Part 3 of Schedule 7,

may be incorporated by the licensing authority in any manufacturing authorisation, with or without modifications and either generally or in relation to investigational medicinal products of any particular class.

(5) The provisions of Schedule 8 shall have effect where the licensing authority propose—

(a) to refuse to grant a manufacturing authorisation; or

(b) to grant a manufacturing authorisation otherwise than in accordance with the application.

(6) Where the licensing authority—

(a) refuse to grant a manufacturing authorisation; or

(b) grant a manufacturing authorisation otherwise than in accordance with the application,

and the applicant requests the authority to state their reasons, the licensing authority shall give the applicant a notice in writing stating the reasons for their decision.

Section 41 Application and effect of manufacturing authorisation

A manufacturing authorisation shall apply only in relation to—

(a) the descriptions of investigational medicinal products;

(b) the manufacturing, assembling or importation operations; ...

(bb) in the case of an authorisation relating to the inactivation of viral or non-conventional agents, the manufacturing process; and

(c) except in the case of an MM investigational medicinal product or a POC investigational medicinal product, the premises,

specified in the application made pursuant to regulation 38 and in respect of which the authorisation is granted.

Section 42 Obligations of manufacturing authorisation holder

The holder of a manufacturing authorisation shall—

(a) comply with the principles and guidelines of good manufacturing practice;

(b) comply with the provisions referred to in regulation 40(3);

(c) allow the licensing authority access to his premises at any reasonable time; and

(d) put and keep in place arrangements which enable the qualified person to carry out his duties, including placing at his disposal all the necessary facilities.