The Medicines for Human Use (Clinical Trials) Regulations 2004

PART 1 INTRODUCTORY PROVISIONS

Citation and commencement

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

Interpretation

2.—(1) In these Regulations—

“the Act” means the Medicines Act 1968(1);

“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)

a doctor,

(b)

a dentist,

(c)

a nurse, or

(d)

a pharmacist;

“appropriate committee”, for the purpose of any provision of these Regulations under which a function falls to be performed, means such committee established under section 4 of the Act for purposes which consist of or include any of those specified in section 4(3) of the Act as the authority performing that function considers appropriate in the circumstances;

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

(a)

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

(b)

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—

(a)

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

(b)

in relation to a clinical trial conducted at more than one trial site, the authorised health care 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—

(a)

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

(b)

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

(c)

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” means Commission Directive 2003/94/EC(2) laying down the principles and guidelines of good manufacturing practice for medicinal products for human use and for investigational medicinal products for human use;

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

“conducting a clinical trial” includes—

(a)

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

(b)

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

(c)

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

(d)

carrying out any test or analysis—

(i)

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

(ii)

to identify any adverse reactions to those products, or

(iii)

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;

“dentist” means a person registered in the dentists register under the Dentists Act 1984(3) or entered in the list of visiting EEC practitioners under Schedule 4 to that Act;

“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(4);

“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(5), as amended(6);

“doctor” means a registered medical practitioner(7);

“EEA State” means a State which is a Contracting Party to the EEA Agreement;

“EEA Agreement” means the Agreement on the European Economic Area signed at Oporto on 2nd May 1992(8) as adjusted by the Protocol signed at Brussels on 17th March 1993(9);

“electronic signature” means data in electronic form which are attached to or logically associated with other electronic data and which serve as a method of authentication;

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

“the European Medicines Agency” means the European Agency for the Evaluation of Medicinal Products established by Council Regulation (EEC) No. 2309/93 laying down Community procedures for the authorization and supervision of medicinal products for human and veterinary use and establishing a European Agency for the Evaluation of Medicinal Products(10);

“ethics committee” means—

(a)

a committee established or recognised in accordance with Part 2,

(b)

the Ethics Committee constituted by regulations made by the Scottish Ministers under section 51(6) of the Adults with Incapacity (Scotland) Act 2000(11), or

(c)

the Gene Therapy Advisory Committee;

“export” means export to a third country from an EEA State, whether by land, sea or air;

“the Gene Therapy Advisory Committee” means the Gene Therapy Advisory Committee appointed by the Secretary of State to—

(a)

consider and advise on the acceptability of proposals for gene therapy research on human subjects, on ethical grounds, and

(b)

provide advice on developments in gene therapy research and their implications;

“Health and Social Services Board” means a Health and Social Services Board established under the Health and Personal Social Services (Northern Ireland) Order 1972(12);

“Health Board” means a Health Board established under the National Health Service (Scotland) Act 1978(13);

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

“health care professional” means—

(a)

a doctor,

(b)

a dentist,

(c)

a nurse,

(d)

a pharmacist,

(e)

a person registered in a register of ophthalmic opticians maintained under section 7 of the Opticians Act 1989(14),

(f)

a person registered in a register established and maintained under article 5 of Health Professions Order 2001(15),

(g)

a registered osteopath as defined by section 41 of the Osteopaths Act 1993(16), or

(h)

a registered chiropractor as defined by section 43 of the Chiropractors Act 1994(17);

“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)

a Strategic Health Authority, Health Board or Health and Social Services Board,

(b)

a Special Health Authority, Primary Care Trust or Local Health Board established under the National Health Service Act 1977,

(c)

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

(d)

a special health and social services agency established under the Health and Personal Social Services (Special Agencies) (Northern Ireland) Order 1990(18),

(e)

the Dental Practice Board constituted under section 37(1) of the National Health Service Act 1977,

(f)

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

(g)

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

(h)

a National Health Service trust established under the National Health Service and Community Care Act 1990(19) or the National Health Service (Scotland) Act 1978,

(i)

an NHS foundation trust within the meaning of section 1(1) of the Health and Social Care (Community Health and Standards) Act 2003(20), or

(j)

a Health and Social Services trust established under the Health and Personal Social Services (Northern Ireland) Order 1991(21);

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

“import”, other than in regulation 13 and Schedule 3, means import into the United Kingdom from a third country, whether by land, sea or air;

“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—

(a)

under a scheme established under—

(i)

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)(22),

(ii)

section 85B of the National Health Service (Scotland) Act 1978 (schemes for meeting losses and liabilities etc. of certain health service bodies in Scotland)(23), or

(iii)

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)(24), or

(b)

in accordance with guidance issued by—

(i)

the Secretary of State,

(ii)

the Scottish Ministers,

(iii)

the National Assembly for Wales, or

(iv)

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—

(a)

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

(b)

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

(c)

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 section 6 of the Act;

“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;

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

“marketing authorization” means—

(a)

a marketing authorization granted by the licensing authority under the Medicines for Human Use (Marketing Authorisations Etc.) Regulations 1994(25),

(b)

a marketing authorization issued by the competent authority of an EEA State, other than the United Kingdom, in accordance with Directive 2001/83/EC,

(c)

a marketing authorization granted by the European Commission under Council Regulation (EEC) 2309/93(26), or

(d)

a product licence granted by the licensing authority for the purposes of section 7 of the Medicines Act 1968(27);

“medicinal product” means—

(a)

a medicinal product within the meaning given by Article 1 of Directive 2001/83/EC, or

(b)

any product which is not a medicinal product within the meaning given by Article 1 of Directive 2001/83/EC, but which is a medicinal product within the meaning given by section 130 of the Act;

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

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

(a)

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

(b)

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,

(c)

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

(d)

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

(e)

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—

(a)

in relation to Great Britain, a person registered in the register of pharmaceutical chemists established in pursuance of the Pharmacy Act 1952 and maintained in pursuance of the Pharmacy Act 1954, and

(b)

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;

“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)

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

(b)

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

(i)

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,

(ii)

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

(iii)

is—

(aa)

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

(bb)

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—

(a)

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;

(b)

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

(c)

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—

(a)

results in death,

(b)

is life-threatening,

(c)

requires hospitalisation or prolongation of existing hospitalisation,

(d)

results in persistent or significant disability or incapacity, or

(e)

consists of a congenital anomaly or birth defect;

“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(28);

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

(a)

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

(b)

without receiving any treatment or product, as a control;

“third country” means a country or territory outside the European Economic Area;

“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;

“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—

(a)

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

(b)

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.

Sponsor of a clinical trial

3.—(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 European Community, or

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

Responsibility for functions under the Directive

4.—(1) For the purposes of the Directive, the competent authority of the United Kingdom shall be the licensing authority.

(2) Subject to paragraph (3), the licensing authority shall perform, as respects the United Kingdom, the functions of the Member State under the Directive.

(3) Paragraph (2) shall not apply in so far as any functions fall to be performed by the exercise of any powers or duties which are conferred by any provision of these Regulations, or by any provision of the Act as applied by these Regulations, on a person or body other than the licensing authority.

PART 2 ETHICS COMMITTEES

United Kingdom Ethics Committees Authority

5.—(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 Secretary of State for Health;

(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 Secretary of State for Health, 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 Secretary of State for Health, 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 Secretary of State, 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 Secretary of State for Health, 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.

Establishment of ethics committees

6.—(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.

Recognition of ethics committees

7.—(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 (5),

where it considers it necessary or appropriate to do so.

Revocation of recognition

8.  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.

Constitution and operation of ethics committees

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

Other functions of the Authority

10.—(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.

PART 3 AUTHORISATION FOR CLINICAL TRIALS AND ETHICS COMMITTEE OPINION

Interpretation of Part 3

11.  In this Part—

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

(a)

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

(b)

the protocol for that trial, or

(c)

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—

(a)

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

(b)

the scientific value of the trial,

(c)

the conduct or management of the trial, or

(d)

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.

Requirement for authorisation and ethics committee opinion

12.—(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 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.

Supply of investigational medicinal products for the purpose of clinical trials

13.—(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 an investigational medicinal product manufactured or assembled in an EEA State, other than in accordance with the terms of a marketing authorization relating to that product, or imported into an EEA State—

(i) the product has been manufactured, assembled or imported in accordance with the terms of—

(aa) a manufacturing authorisation, or

(bb) an authorisation referred to in Article 13 of the Directive granted by a competent authority of an EEA State other than the United Kingdom, and

(ii) 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.

(3) If an investigational medicinal product has been manufactured or imported prior to 1st May 2004—

(a) the condition specified in paragraph (2)(b)(i) shall apply only in relation to any assembly of that product which takes place on or after that date; and

(b) the conditions specified in paragraph (2)(b)(ii) shall not apply.

(4) The restriction in paragraph (1) shall not apply to the sale or supply of a medicinal product in accordance with the terms of a marketing authorisation relating to that product, other than a marketing authorisation issued by the competent authority of an EEA State other than the United Kingdom.

Application for ethics committee opinion

14.—(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(29).

(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.

Ethics committee opinion

15.—(1) Subject to paragraphs (3) and (4), an ethics committee shall within the specified period following receipt of a valid application, give an opinion in relation to the clinical trial to which the application relates.

(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.

(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.

(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 2 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;

(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 persons incapable of giving informed consent, whether the research is justified having regard to the conditions and principles specified in Part 5 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 pyschosocial 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—

(a)

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—

(i)

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

(ii)

where there is no such consultation, 90 days; or

(b)

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—

(a)

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

(b)

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

Review and appeal relating to ethics committee opinion

16.—(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 13 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).

Request for authorisation to conduct a clinical trial

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

(2) 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 1995(30).

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

Authorisation procedure for clinical trials involving general medicinal products

18.—(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.

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

19.—(1) This regulation applies to clinical trials involving—

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

(b) medicinal products containing genetically modified organisms.

(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 Committee on Safety of Medicines(31); or

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

Authorisation procedure for clinical trials involving medicinal products with special characteristics

20.—(1) This regulation applies to clinical trials—

(a) involving medicinal products—

(i) which do not have a marketing authorization and are referred to in Part A of the Annex to Regulation (EEC) No. 2309/93(32), 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.

Clinical trials conducted in third countries

21.—(1) If the licensing authority receives a valid request for authorisation relating to a clinical trial which is or is to be conducted in a third 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.

Amendments to clinical trial authorisation

22.  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.

Amendments by the licensing authority

23.—(1) Subject to paragraphs (1) and (2), 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.

Amendments by the sponsor

24.—(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—

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

(a)

in writing; and

(b)

accompanied by—

(i)

the particulars specified in Part 3 of Schedule 3, and

(ii)

any fee which may be payable in connection with that notice under the Medicines (Products for Human Use—Fees) Regulations 1995(33).

Modifying or adapting rejected proposals for amendment

25.—(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.

Reference to the appropriate committee or the Medicines Commission

26.—(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 who has been notified by the licensing authority in accordance with regulation 24(4) 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 or, if for the time being there is no such committee, the Medicines Commission(34).

(2) Schedule 5 shall have effect to regulate the procedure for reference to the appropriate committee, or as the case may be, the Medicines Commission following receipt of a notice in accordance with paragraph (1).

Conclusion of clinical trial

27.—(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.

PART 4 GOOD CLINICAL PRACTICE AND THE CONDUCT OF CLINICAL TRIALS

Good clinical practice and protection of clinical trial subjects

28.—(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(35);

(b) the National Health Service (Scotland) Act 1978(36); or

(c) the Health and Personal Social Services (Northern Ireland) Order 1972(37),

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.

Conduct of trial in accordance with clinical trial authorisation etc.

29.  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(4) or Schedule 5.

Urgent safety measures

30.—(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 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.

Suspension or termination of clinical trial

31.—(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(4) 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) competent authorities of each EEA State, other than the United Kingdom;

(c) the relevant ethics committee;

(d) the European Medicines Agency; and

(e) the European Commission.

(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 or, if for the time being there is no such committee, the Medicines Commission.

(8) Schedule 5 shall have effect to regulate the procedure for reference to the appropriate committee or, as the case may be, the Medicines Commission(38) following receipt of a notice in accordance with paragraph (7).

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

PART 5 PHARMACOVIGILANCE

Notification of adverse events

32.—(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.

Notification of suspected unexpected serious adverse reactions

33.—(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) the competent authorities of any EEA State, other than the United Kingdom, in which the trial is being conducted, and

(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) the competent authorities of any EEA State, other than the United Kingdom, in which the trial is being conducted; and

(c) the relevant ethics committee,

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

(4) For the purposes of paragraphs (1) to (3), the sponsor may fulfil his obligations to report or provide information to the licensing authority and the competent authorities of any EEA State, other than the United Kingdom, by entering the report or information in the European database established in accordance with Article 11 of the Directive.

(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) ensure that the details of those reactions are entered in the European database established in accordance with Article 11 of the Directive, whether by the sponsor or the authority.

Clinical trials conducted in third countries

34.  If a clinical trial is being conducted at a trial site in a third 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 entered into the European database established in accordance with Article 11 of the Directive.

Annual list of suspected serious adverse reactions and safety report

35.—(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 EEA State.

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

(a) in the case of the United Kingdom, the date on which the trial was authorised by the licensing authority in accordance with these Regulations, or

(b) in the case of any other EEA State, the date on which the trial was authorised by the competent authority of that EEA State in accordance with the Directive.

PART 6 MANUFACTURE AND IMPORTATION OF INVESTIGATIONAL MEDICINAL PRODUCTS

Requirement for authorisation to manufacture or import investigational medicinal products

36.—(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 granted by the licensing authority for the purposes of this regulation (“a manufacturing authorisation”).

(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 relating to that product.

Exemption for hospitals and health centres

37.—(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.

Application for manufacturing authorisation

38.—(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) 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 1995(39).

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

Consideration of application for manufacturing authorisation

39.—(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.

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

Grant or refusal of manufacturing authorisation

40.—(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 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.

Application and effect of manufacturing authorisation

41.  A manufacturing authorisation shall apply only in relation to—

(a) the descriptions of investigational medicinal products;

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

(c) the premises,

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

Obligations of manufacturing authorisation holder

42.  The holder of a manufacturing authorisation shall comply with—

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

(b) the provisions referred to in regulation 40(3).

Qualified persons

43.—(1) Subject to paragraphs (4) and (5), the holder of a manufacturing authorisation must have at his disposal the services of at least one qualified person who is responsible for carrying out the duties referred to in paragraph 2.

(2) A qualified person shall be responsible for carrying out the duties specified in Article 13(3) and (4) of the Directive, in accordance with that Article, in respect of the investigational medicinal products manufactured, assembled or imported in accordance with the authorisation in question.

(3) A qualified person shall perform his functions under these Regulations in accordance with the Code of Practice for Qualified Persons in the Pharmaceutical Industry, published jointly by the Institute of Biology, the Royal Pharmaceutical Society of Great Britain and the Royal Society of Chemistry in March 2004(40).

(4) If the holder of the authorisation satisfies the requirements as to qualifications and experience specified in paragraph (a) or (b) of the definition of “qualified person” in regulation 2(1), he may act as the qualified person in accordance with paragraph (2) for the purposes of that authorisation.

(5) For the purposes of this paragraph, but without prejudice to paragraph (6) below, the holder of the authorisation may regard a person as satisfying the provisions of the said Article 49 or 50, as respects formal qualifications if he produces evidence that—

(a) he is a member of—

(i) the Institute of Biology,

(ii) the Pharmaceutical Society,

(iii) the Royal Society of Chemistry, or

(iv) such other body as may appear to the licensing authority to be an appropriate body for the purpose of this paragraph; and

(b) he is regarded by the body of which he is a member as so satisfying those provisions.

(6) Where, after giving the holder of the authorisation and the person acting as a qualified person the opportunity of making representations to them (orally or in writing), the licensing authority are of the opinion that—

(a) the person so acting does not satisfy—

(i) the provisions of the said Articles 49 and 50 of Directive 2001/83/EC as respects qualifications and experience, or

(ii) the requirements as to qualifications and experience specified in paragraph (b) of the definition of “qualified person” in regulation 2(1); or

(b) he is failing to carry out the duties referred to in paragraph (2) adequately or at all,

and have notified the holder of the authorisation accordingly in writing, the holder of the authorisation shall not permit that person to act as a qualified person.

Variation of manufacturing authorisation

44.—(1) The licensing authority may vary a manufacturing authorisation, whether on the application of the holder of the authorisation or otherwise.

(2) Subject to the following provisions of this regulation, if the holder of a manufacturing authorisation makes a valid application to vary the manufacturing authorisation the licensing authority shall consider the application and—

(a) in a case where the effect of the variation would be to change the—

(i) the types of investigational medicinal products,

(ii) the manufacturing, assembling or importation operations,

(iii) the premises,

(iv) the technical equipment and control facilities,

in respect of which the authorisation has been granted, may vary or refuse to vary the authorisation within a period not exceeding 30 days from the date the application is received;

(b) in any other case, may vary or refuse to vary the authorisation within such period as the licensing authority consider appropriate.

(3) If the application falls within paragraph (2)(a), but it appears to the licensing authority to be necessary to conduct an inspection of any premises to which the variation relates, the authority may vary or refuse to vary the authorisation within a period not exceeding 90 days from the date the application is received.

(4) Following receipt of a valid application to vary a manufacturing authorisation, the licensing authority may give a notice in writing to the applicant requesting him to provide further information relating to the contents of the application or any particulars relevant to the application.

(5) Where the licensing authority give a notice pursuant to paragraph (4), and a period specified in paragraph (2)(a) or paragraph (3) applies, that period shall be suspended from the date the notice is given and shall recommence only on receipt of the information requested.

(6) The provisions of Schedule 8 shall have effect where the licensing authority propose to vary a manufacturing authorisation otherwise than on the application of the holder of the authorisation.

(7) Where the licensing authority—

(a) vary a manufacturing authorisation, otherwise than in accordance with a valid application by the holder of the authorisation; or

(b) after consideration of such an application, refuse to vary a manufacturing authorisation,

the licensing authority shall notify the holder of that authorisation in writing, stating the reasons for their decision.

(8) In this regulation, “valid application” means an application—

(a) made to the licensing authority;

(b) in writing and signed by or on behalf of the applicant;

(c) specifying the variation requested by the applicant;

(d) accompanied by—

(i) such particulars as are necessary to enable the licensing authority to consider the application, and

(ii) any fee which may be payable in connection with that application under the Medicines (Products for Human Use—Fees) Regulations 1995(41); and

(e) where the application, and any accompanying material, is in the English language.

Suspension and revocation of manufacturing authorisation

45.—(1) The licensing authority may by a notice in writing to the holder of a manufacturing authorisation, forthwith or from a date specified in the notice, suspend the authorisation for such period as the authority may determine, or revoke the authorisation, on one or more of the following grounds—

(a) the holder is not carrying out, or has indicated by a notice in writing that he is no longer to carry out, the manufacturing, assembly or importation operations to which the authorisation relates;

(b) the particulars accompanying the application in accordance with regulation 38(3), were false or incomplete in a material particular;

(c) a material change of circumstances has occurred in relation to any of those matters or particulars;

(d) the holder of the authorisation has failed to any material extent to comply with his obligations under regulation 42 or 43(1);

(e) the holder has manufactured, assembled or, as the case may be, imported investigational medicinal products otherwise than in accordance with the terms of the authorisation;

(f) the holder has manufactured or assembled investigational medicinal products otherwise than in accordance with—

(i) in the case of products manufactured before a request for authorisation to conduct the clinical trial involving those products has been made in accordance with regulation 17 or any equivalent provisions in any EEA State other than the United Kingdom, the specification for the product provided by the person who is to act as the sponsor of the proposed clinical trial,

(ii) in the case of products manufactured for the purpose of export, the specification for the product provided by the person to whose order the products are manufactured, or

(iii) in any other case, the specification for the product contained in the investigational medicinal product dossier for that product;

(g) the qualified person has failed to carry out the duties referred to in regulation 43(2), adequately or at all; and

(h) the holder of the authorisation does not have the staff, premises, equipment or facilities necessary for carrying out properly—

(i) the manufacture or assembly operations to which the authorisation relates, or

(ii) the importation operations to which the authorisation relates,

including any handling, storage or distribution activities relating to those operations.

(2) The suspension or revocation of an authorisation under this regulation may be—

(a) total; or

(b) limited to investigational medicinal products—

(i) of one or more descriptions, or

(ii) manufactured, assembled or stored on any particular premises or in a particular part of any premises.

(3) The provisions of Schedule 8 shall have effect where the licensing authority propose to suspend or revoke a manufacturing authorisation in accordance with this regulation.

(4) Where the licensing authority suspend or revoke a manufacturing authorisation in accordance with this regulation, they shall notify the holder of that authorisation in writing, stating the reasons for their decision to suspend or revoke the authorisation.

PART 7 LABELLING OF INVESTIGATIONAL MEDICINAL PRODUCTS

Labelling

46.—(1) An investigational medicinal product shall be labelled in accordance with Article 15 of Commission Directive 2003/94/EC(42).

(2) Paragraph (1) shall not apply where the investigational medicinal product is—

(a) for use in a clinical trial with the characteristics specified in the second paragraph of Article 14 of the Directive;

(b) dispensed to a subject in accordance with a prescription given by an authorised health care professional; and

(c) labelled in accordance with the requirements of Schedule 5 to the Medicines for Human Use (Marketing Authorisations Etc.) Regulations 1994(43) that apply in relation to dispensed relevant medicinal products.

PART 8 ENFORCEMENT AND RELATED PROVISIONS

Application of enforcement provisions of the Act

47.—(1) Sections 107 to 116, 118, 119, 121 to 125, 127, 129, 131 and 132(1) of, and Schedule 3 to, the Act shall apply for the purposes of these Regulations, but with the modifications specified in Schedule 9.

(2) In those provisions as applying by virtue of paragraph (1), a reference to any part of those provisions or a part of any of them is a reference to the provision or part as so applying.

Infringement notices

48.—(1) If an enforcement authority have objective grounds for considering that any person has contravened any provision to which this regulation applies, they may serve upon that person a notice in writing (in these Regulations referred to as an “infringement notice”)—

(a) informing him of the authority’s grounds for considering that the person has contravened one or more of those provisions;

(b) specifying the relevant provision of these Regulations;

(c) specifying the measures which the person must take in order to ensure that the contravention does not continue or, as the case may be, does not recur;

(d) requiring the person to take those measures, within such period as may be specified in the notice;

(e) warning the person that unless the requirements of sub-paragraph (d) are met, further action may be taken in respect of the contravention.

(2) An infringement notice may include directions as to the measures to be taken by the person on whom the notice is served to ensure that the contravention does not continue or, as the case may be, does not recur, including the different ways of securing compliance.

(3) If an enforcement authority serves an infringement notice in accordance with paragraph (1), they shall forthwith inform—

(a) the competent authorities of each EEA State, other than the United Kingdom;

(b) the relevant ethics committee; and

(c) the European Commission.

(4) This regulation applies to regulations 22(b), 27, 28(1) to (3), 29, 30(2) and 32 to 35.

(5) In this regulation, “enforcement authority” means any Minister or body on whom a duty or power to enforce any provisions of these Regulations is imposed or conferred by or under sections 108 to 110 of the Act as applied by regulation 47.

Offences

49.—(1) Any person who contravenes any of the following provisions—

(a) regulation 12(1) and (2);

(b) regulation 13(1);

(c) regulation 27;

(d) regulation 28(1) to (3);

(e) regulation 29;

(f) regulation 30(2);

(g) regulation 32(1), (3), and (5) to (9)

(h) regulation 33(1) to (5)

(i) regulation 34

(j) regulation 35(1);

(k) regulation 36(1);

(l) regulation 42; and

(m) regulation 43(1) and (6),

shall be guilty of an offence.

(2) Any person who has in his possession a medicinal product for the purpose of selling or supplying it in contravention of regulation 13(1) shall be guilty of an offence.

(3) Any person who fails to comply with a notice of suspension or termination served on him under regulation 31, unless that notice has been withdrawn or revoked by the licensing authority, shall be guilty of an offence.

(4) Where an investigational medicinal product is manufactured, assembled or imported in contravention of regulation 36(1), any person who sells or supplies the product for the purposes of a clinical trial knowing or having reasonable cause to suspect that it was so manufactured, assembled or imported shall be guilty of offence.

(5) Where an investigational medicinal product is imported in contravention of regulation 36(1), any person who, otherwise than for the purpose of performing or exercising a duty or power imposed or conferred by or under these Regulations, the Act or any other enactment, is in possession of the product knowing or having reasonable cause to suspect that it was so imported shall be guilty of offence.

(6) Any sponsor who sells or supplies, or procures the sale or supply, of an investigational medicinal product—

(a) to a subject for the purposes of a clinical trial; or

(b) to a person for the purpose of administering the product to such a subject,

the labelling of which does not comply with regulation 46, shall be guilty of an offence.

(7) Any person who sells or supplies an investigational medicinal product—

(a) to a subject for the purposes of a clinical trial; or

(b) to a person for the purpose of administering the product to such a subject,

the labelling of which does not comply with regulation 46, knowing, or having reasonable cause to believe, that the labelling does not so comply, shall be guilty of an offence.

False or misleading information

50.—(1) Any person who in the course of—

(a) making an application for an ethics committee opinion;

(b) making a request for authorisation to conduct a clinical trial; or

(c) making an application for the grant or variation of a manufacturing authorisation,

provides to the licensing authority or an ethics committee any relevant information which is false or misleading in a material particular shall be guilty of an offence.

(2) Any person who—

(a) is conducting a clinical trial authorised in accordance with these Regulations;

(b) is a sponsor of such a clinical trial;

(c) while acting under arrangements made with a sponsor of such a clinical trial, performs the functions of that sponsor; or

(d) holds a manufacturing authorisation,

and who, for the purposes of these Regulations, provides to the licensing authority or an ethics committee any relevant information which is false or misleading in a material particular shall be guilty of an offence.

(3) Any person who, for the purpose of being engaged as a qualified person in accordance with regulation 43, provides to the licensing authority or to the holder of a manufacturing authorisation any information which is false or misleading in a material particular shall be guilty of an offence.

(4) In this regulation, “relevant information” means any information which is relevant to an evaluation of—

(a) the safety, quality or efficacy of an investigational medicinal product;

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

(c) whether, with regard to a clinical trial, the conditions and principles of good clinical practice are being satisfied or adhered to.

Defence of due diligence

51.—(1) A person does not commit an offence under these Regulations if he took all reasonable precautions and exercised all due diligence to avoid the commission of that offence.

(2) Where evidence is adduced which is sufficient to raise an issue with respect to that defence, the court or jury shall assume that the defence is satisfied unless the prosecution proves beyond reasonable doubt that it is not.

Penalties

52.  A person guilty of an offence under these Regulations shall be liable—

(a) on summary conviction to a fine not exceeding the statutory maximum or to imprisonment for a term not exceeding three months or to both;

(b) on conviction on indictment to a fine or to imprisonment for a term not exceeding two years or to both.

PART 9 MISCELLANEOUS PROVISIONS

Construction of references to specified publications

53.—(1) Where any authorisation granted under these Regulations refers to a specified publication, but not to any particular edition of that publication, then, for the purpose of determining whether anything done, at a time when the authorisation is in force, is done in accordance with the authorisation, the reference shall, unless the authorisation otherwise expressly provides, be construed as a reference to the current edition of that publication as in force at that time.

(2) In this regulation any reference to the current edition of a specified publication as in force at a particular time is a reference to the edition of that publication in force, under whatever title, at that time together with any amendments, additions and deletions made to it up to that time.

(3) In this regulation, “specified publication” has the meaning given by section 103(1) of the Act(44).

Consequential and other amendments to enactments

54.  The provisions of the enactments specified in Schedule 10 are amended as there specified.

Revocations

55.  The enactments specified in column (1) of Schedule 11 are revoked to the extent specified in column (3) of that Schedule.

Transitional provisions

56.  The transitional provisions set out in Schedule 12 shall have effect.

Signed by authority of the Secretary of State for Health

Warner

Parliamentary Under Secretary of State,

Department of Health

31st March 2004