S.I. No. 374 of 2006

European Communities (Clinical Trials on Medicinal Products for Human Use) (Amendment No. 2) Regulations 2006

I, Mary Harney, Minister for Health and Children, in exercise of the powers conferred on me by section 3 of the European Communities Act 1972 (No. 27 of 1972), for the purpose of giving further effect to Directive 2001/20/EC of 4 April 2001 and for giving effect to Directive 2005/28/EC¹ of 8 April 2005, hereby make the following regulations:-

Citation

1.         These Regulations may be cited as the European Communities (Clinical Trials on Medicinal Products for Human Use) (Amendment No. 2) Regulations 2006.

2.         These Regulations shall be construed as one with the European Communities (Clinical Trials on Medicinal Products for Human Use) Regulations 2004 (S.I. No. 190 of 2004 ) and the European Communities (Clinical Trials on Medicinal Products for Human Use) (Amendment) Regulations 2004 (S.I. No 878 of 2004 ) and may be cited together with those Regulations as the European Communities (Clinical Trials on Medicinal Products for Human Use) Regulations 2004 to 2006.

Interpretation

3.         In these Regulations-

-�the Principal Regulations-� means the European Communities (Clinical Trials on Medicinal Products for Human Use) Regulations 2004 (S.I. No. 190 of 2004 ).

Amendments to the 2004 Regulations

4.         Regulation 4(1) of the Principal Regulations is hereby amended by:

(a)  the substitution of the following for the definition of -�Directive 2001/83/EC-�-

-� -�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 use² as amended by -

(a)  Directive 2002/98/EC of the European Parliament and of the Council setting standards of quality and safety for the collection, testing, processing, storage and distribution of human blood and blood components³ ,

(b)  Commission Directive 2003/63/EC amending Directive 2001/83/EC on the Community code relating to medicinal products for human use⁴ ,

(c)  Directive 2004/24/EC of the European Parliament and of the Council amending, as regards traditional herbal medicinal products, Directive 2001/83/EC on the Community code relating to medicinal products for human use⁵ , and

(d)  Directive 2004/27/EC of the European Parliament and of the Council amending Directive 2001/83/EC on the Community code relating to medicinal products for human use⁶ ;-�;

(b)  the insertion of the following after the definition of -�Commission Directive 2003/94/EC-�-

-� -�Commission Directive 2005/28/EC-� means Commission Directive 2005/28/EC of 8 April 2005 laying down principles and detailed guidelines for good clinical practice as regards investigational medicinal products for human use, as well as the requirements for authorisation of the manufacturing or importation of such products;-�.

5.         The Principal Regulations are hereby amended by the insertion of the following after Regulation 4:

-�The sponsor

4A   (1) A sponsor may delegate any or all of his or her trial-related functions to an individual, a company, an institution or an organisation. However, in all such cases, the sponsor shall remain responsible for ensuring that the conduct of the trials and the final data generated by those trials comply with the Directive, Directive 2005/28/EC and these regulations.

(2)  The investigator and the sponsor may be the same person.-�

6.         Regulation 5 of the Principal Regulations shall be substituted by the following:

-�5.   (1) The Board shall be the competent authority for the purposes of the Directive, Commission Directive 2003/94/EC and Commission Directive 2005/28/EC.

(2)  Subject to paragraph (3), the functions of a Member State and of the competent authority of a Member State, under any of the provisions of the Directive, and of Commission Directives 2004/94/EC and 2005/28/EC, shall be performed by the Board.

(3)  Paragraph (2) shall not apply to those functions of a Member State referred to in -

(a)  Articles 3, 6, 7, 8, 19, 21 and 22 of the Directive;

(b)  Article 17 of Commission Directive 2004/94/EC; and

(c)  Articles 1.3, 24, 29.1, 30.1 and 31 of Commission Directive 2005/28/EC.-�.

7.         Regulation 52(3) of the Principal Regulations shall be hereby amended by the substitution for the words -�referred to in Regulation 24(4)-� by the words -�that is a non-commercial trial conducted by an investigator-sponsor, without the participation of the pharmaceutical industry, in circumstances where the investigator-sponsor has no commercial or financial interest in the outcome of the trial.-�.

8.         The Principal Regulations are hereby amended by the insertion of the following Part after Part 7:

-�Part 7A

INVESTIGATOR-�S BROCHURE, THE TRIAL MASTER FILE AND ARCHIVING

Investigator's brochure

43A.  (1)  The investigator's brochure and any update of the said brochure shall be presented in a concise, simple, objective, balanced and non-promotional form that enables a clinician or potential investigator to understand it and make an unbiased risk-benefit assessment of the appropriateness of the clinical trial to which it relates.

(2)  Where the investigational medicinal product is the subject of a marketing authorisation, the summary of product characteristics may be used instead of the investigator's brochure.

(3)  The sponsor shall validate and update the investigator's brochure at least once a year.

Trial master file

43B.  (1)  The trial master file referred to in Article 15.5 of the Directive shall consist of essential documents which enable both the conduct of a clinical trial and the quality of the data produced to be evaluated. Those documents shall show whether the investigator and the sponsor have complied with the principles and guidelines of good clinical practice and with the applicable requirements and, in particular, with Annex I to Directive 2001/83/EC.

(2)  The content of the essential documents referred to in paragraph (1) shall be in accordance with the specificities of each phase of the clinical trial.

(3)  The trial master file shall provide the basis for the audit by the sponsor's independent auditor and for inspection by the Board.

Archiving

43C.  (1)  The sponsor and the investigator shall retain the essential documents relating to a clinical trial for at least five years after its completion and shall retain those documents for a longer period where so required by other applicable requirements or by an agreement between the sponsor and the investigator.

(2)  In all cases the essential documents shall be archived in a way that ensures that they are readily available, upon request, to the Board.

(3)  The medical files of trial subjects shall be retained for the maximum period of time permitted or required by the hospital, institution or private practice concerned.

(4)  Any transfer of ownership of the data or of documents relating to a clinical trial shall be documented and the new owner shall assume responsibility for data retention and archiving in accordance with this Regulation.

(5)  The sponsor shall appoint individuals within its organisation who are responsible for archives and shall ensure that access to such archives is restricted to the named individuals responsible for the archives.

(6)  The media used to store essential documents shall be such that those documents remain complete and legible throughout the required period of retention and can be made available to the Board upon request.

(7)  Any alteration to records shall be traceable.-�.

9.         Regulation 48 of the Principal Regulations is hereby amended by -

(a)  the substitution of the following for paragraphs (1) and (2):

-�(1)  The Board may appoint such and so many officers as it thinks fit to be authorised officers for the purposes of the enforcement of these Regulations.

(2)  (a) An authorised officer shall be furnished with a warrant of his or her appointment and when exercising a power conferred on him or her under this Regulation, he or she shall, if required by a person thereby affected, produce the warrant to that person for inspection.

(b)  An authorised officer shall carry out such inspections as are necessary to enforce these Regulations and the Directive.

(c)  Without prejudice to subparagraph (b), good clinical practice inspections may be carried out on any of the following occasions:

(i)  before, during or after the conduct of clinical trials;

(ii)  as part of the verification of applications for a marketing authorisation;

(iii)  as a follow-up to the granting of authorisation.-�.

(b)  the insertion of the following after paragraph (4):

-�(4A) An authorised officer shall conduct his or her inspections in accordance with the inspection procedures set out in Chapter 6 of Directive 2005/28/EC including in accordance with the inspection guidance documents developed to support the mutual recognition of inspection findings within the Community.

(4B) When exercising a power under this Regulation, an authorised officer may, subject to any warrant under paragraph (7), be accompanied by such number of-

(a)  other authorised officers,

(b)  inspectors from the competent authority of another Member State, or

(c)  persons with expertise relevant to the matters being examined,

as he or she considers appropriate in the circumstances of the case.

(4C) The Board shall ensure that confidentiality is respected by inspectors and other experts engaged in good clinical practice inspections and, with regard to personal data, that the requirements of the Data Protection Acts 1988 and 2003 are respected.-�.

10.       Part 1 of Schedule 1 to the Principal Regulations is hereby amended by the insertion of the following definition in paragraph (2):

-�-�Declaration of Helsinki-� means the Declaration of Helsinki adopted by the General Assembly of World Medical Association in June 1964, as amended by the General Assembly of the Association in October 1975, October 1983, September 1989 and October 1996;-�.

11.       Part 2 of Schedule 1 to the Principal Regulations shall be substituted by the following:

-�PART 2

CONDITIONS AND PRINCIPLES THAT APPLY TO ALL CLINICAL TRIALS

1.  Clinical trials shall be conducted in accordance with the ethical principles set out in the Declaration of Helsinki and the requirements of these Regulations.

2.  Before the trial is initiated, the foreseeable risks and inconveniences shall have been weighed against the anticipated benefit for each trial subject and other present and future patients.

3.  A clinical trial shall only be initiated if an ethics committee and the Board comes to the conclusion that the anticipated therapeutic and public health benefits justify the risks and may be continued only if compliance with this requirement is permanently monitored.

4.  The rights, safety, and well being of the trial subjects shall prevail over interests of science and society.

5.  The available non-clinical and clinical information on an investigational medicinal product shall be adequate to support the proposed clinical trial.

6.  Clinical trials shall be scientifically sound, and guided by ethical principles in all their aspects.

7.  A clinical trial shall be conducted in compliance with the protocol that has a favourable opinion from an ethics committee and it shall not be conducted if the sponsor has been informed by the Board of any grounds for non-acceptance.

8.  The medical care given to, and medical decisions made on behalf of, subjects shall always be the responsibility of an appropriately qualified registered medical practitioner or, when appropriate, of a qualified registered dentist.

9.  Each individual involved in conducting a trial shall be qualified by education, training, and experience to perform his or her respective task(s).

10. Subject to the other provisions of this Schedule relating to consent, freely given, informed consent shall be obtained from every subject prior to clinical trial participation.

11. All clinical trial information shall be recorded, handled, and stored in such a way that it can be accurately reported, interpreted and verified, while the confidentiality of records of the trial subject remains protected.

12. Investigational medicinal products used in the trial shall be -

(a)  manufactured or imported, and handled and stored, in accordance with the principles and guidelines of good manufacturing practice, and

(b)  used in accordance with the approved protocol.

13. The necessary procedures to secure the quality of every aspect of the trial shall be complied with.

14. The rights of each subject to physical and mental integrity, to privacy and to the protection of the data concerning him in accordance with the Data Protection Acts 1988 and 2003 are safeguarded.

15. Provision has been made for insurance or indemnity to cover the liability of the investigator and sponsor, which may arise in relation to the clinical trial.

16. The clinical trial protocol shall provide for the definition of inclusion and exclusion of subjects participating in a clinical trial, monitoring and publication policy.

17. The investigator and sponsor shall consider all relevant guidance with respect to commencing and conducting a clinical trial.-�.

12.       In Parts 4 and 5 of Schedule 1 to the Principal Regulations, paragraphs 18 and 17 respectively are hereby deleted.

13.       In paragraph 4 of Schedule 2 to the Principal Regulations, the following subparagraphs shall be inserted:

-�(5)  The standing orders and standing operating procedures adopted under subparagraph (3) shall include the procedures necessary to implement the requirements set out in these Regulations and in particular the provisions of Regulation 13 and the requirement for a single ethics committee opinion as set out in Article 7 of the Directive.

(6)  An ethics committee shall, in every case, retain the essential documents relating to a clinical trial, as referred to in Article 15.5 of the Directive, for at least three years after completion of the trial. Those documents shall be retained for a longer period, where so required under other applicable requirements.

(7)  An ethics committee shall ensure, through an appropriate and efficient system of communication, an effective exchange of information between the committee and the Board.-�.

Explanatory Note

(This note is not part of the Instrument and does not purport to be a legal interpretation)

The purpose of these Regulations is to implement Directive 2005/28/EC laying down principles and detailed guidelines for good clinical practice as regards investigational medicinal products for human use.

The Regulations lay down the principles of good clinical practice and the detailed guidelines in line with those principles for the design, conduct and reporting of clinical trials on human subjects involving such products.

The Regulations also lay down detailed guidelines on the documentation relating to clinical trials, archiving, qualification of inspectors and inspection procedures.

¹ OJ L. 91, 09.04.2005, p.13.

² OJ No. L. 311, 28.11.2001, p.67.

³ OJ No. L. 33, 08.02.2003, p.30.

⁴ OJ No. L. 159, 27.06.2003, p.46.

⁵ OJ No. L. 136, 30.04.2004, p.85.

⁶ OJ No. L. 136, 30.4.2004, p.34.