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S.I. No. 190/2004 - European Communities (Clinical Trials on Medicinal Products For Human Use) Regulations, 2004

Type Statutory Instrument

Publication 2004-04-29

Last updated 2022-08-23

State Repealed superseded text

Text As published

Source Irish Statute Book

articles 52

This is the act as published. Later amendments are not folded into the text below: each one is a separate act in this repository and an entry in this law's history.

10 amending acts · 2022-08-23, S.I. No. 417/2022 - European Communities (Clinical Trials on Medicinal Products for Human…

Reform history JSON API

(ii) responsible for quality control of the investigational medicinal products being manufactured labelled or packaged including the person named as the qualified person for the purposes of Regulation 40 and paragraph 20, or

(iii) in charge of the animals from which are derived any substances used in the production of the investigational medicinal products being manufactured, labelled or packaged, or

(iv) responsible for the culture of any living tissues used in the manufacture of the investigational medicinal products being manufactured, labelled or packaged.

10. (1) The authorisation holder shall -

(a) keep readily available for inspection by a person authorised by the Board durable records of -

(i) the details of manufacture, labelling and packaging of each batch of every investigational medicinal product being manufactured, labelled or packaged under his or her authorisation, and

(ii) the tests carried out thereon including any register or other document referred to in paragraph 3 of Part 2 of Schedule 6,

in such a form that the records will be easily identifiable from the number of the batch as shown on each container in which the investigational medicinal product is sold, supplied or exported; and

(b) permit the person authorised to take copies or make extracts from such records.

(2) Such records shall not be destroyed within the relevant period without the consent of the Board.

11. The authorisation holder shall keep readily available for examination by a person authorised by the Board samples of -

(a) each batch of finished investigational medicinal product manufactured, labelled or packaged under his or her authorisation for at least one year from their expiry date;

(b) each batch of bulk formulated products and of the key packaging components used for each finished product for at least a period of two years from the date on which the clinical trial, for which the relevant batch was manufactured, labelled or packaged, was completed, terminated or discontinued; and

(c) starting materials, other than solvents, gases or water, used in the manufacturing process of each finished product for at least two years after the release of the product. This period may be shortened, with the approval of the Board, if the period of stability of the material, as indicated in the relevant specification, is shorter.

12. The authorisation holder shall make suitable arrangements to ensure that any record or sample referred to in paragraph 10 or 11 is retained for the periods specified in those paragraphs.

13. (1) The authorisation holder shall, in cooperation with the sponsor, implement a system for recording and reviewing complaints in relation to investigational medicinal products manufactured labelled or packaged under his or her authorisation, together with an effective system for recalling promptly and at any time any such investigational medicinal product that have been distributed for use in clinical trials.

(2) The authorisation holder shall -

(a) record and investigate all complaints described in subparagraph (1) of this paragraph; and

(b) immediately inform the Board of any defect which could result in a recall of any such investigational medicinal product distributed for use in clinical trials.

14. Where the authorisation holder has been informed by the Board that any batch of any investigational medicinal product to which his or her authorisation relates has been found not to conform as regards strength, quality or purity with -

(a) the specification of the relevant product; or

(b) the provisions of these Regulations,

he or she shall, if so directed by the Board, withhold such batch from distribution for use in clinical trials, so far as may be reasonably practicable, for such a period not exceeding six weeks as may be specified by the Board.

15. The authorisation holder shall ensure that any tests for determining conformity with the standards and specifications applying to any particular product used in the manufacture shall, except so far as the conditions of the product specification for that product otherwise provide, be applied to samples taken from the investigational medicinal product after all manufacturing processes have been completed, or at such earlier stage in the manufacture as may be approved by the Board.

16. (1) The authorisation holder shall comply with the provisions of the product specification that relate to the supply of that investigational medicinal product for the purposes of the trial.

(2) Where the authorisation relates to the labelling or packaging of an investigational medicinal product, and the authorisation holder supplies that investigational medicinal product at such a stage that it does not fully comply with the provisions of the product specification that relate to labelling, that authorisation holder shall communicate the particulars of those provisions to the person to whom that investigational medicinal product has been so supplied.

17. Where in his or her application for a manufacturing authorisation the authorisation holder -

(a) had specified a general classification of investigational medicinal products in respect of which that authorisation was required; or

(b) had given particulars of manufacturing operations and of substances or articles in accordance with paragraph 4 of Schedule 4,

and there has been, or it is proposed that there shall be, a change in such general classification or such particulars, the authorisation holder shall forthwith notify the Board in writing of such change or proposed change.

18. Where -

(a) the manufacturing authorisation relates to the labelling and packaging of an investigational medicinal product;

(b) that investigational medicinal product is not manufactured by the authorisation holder; and

(c) particulars as to the name and address of the manufacturer of, or of the person who imports, that investigational medicinal product had been given by the authorisation holder to the Board,

the authorisation holder shall forthwith notify the Board in writing of any changes in such particulars.

19. The authorisation holder, for the purpose of enabling the Board to ascertain whether there are any grounds -

(a) for suspending, revoking or varying any authorisation granted under these Regulations;

(b) amending the clinical trial authorisation in accordance with Regulation 20 or 21

shall permit, and provide all necessary facilities to enable, any person duly authorised in writing by the Board, on production if required of his or her credentials, to carry out such inspection or to take such samples or copies for the purpose of verifying any statement contained in an application for an authorisation.

20. (1) Subject to Regulation 40, the authorisation holder shall at all times, and in accordance with that Regulation, have a qualified person to carry out the duties referred to in Regulation 40(2).

(2) The authorisation holder shall at all times provide and maintain such staff, premises, equipment and facilities as will enable the qualified person who is at his or her disposal to carry out the said duties.

PART 3 PROVISIONS WHICH MAY BE INCORPORATED IN AN AUTHORISATION RELATING TO THE IMPORTATION OF INVESTIGATIONAL MEDICINAL PRODUCTS

1. The authorisation holder shall -

(a) provide and maintain such staff, premises, equipment and facilities for the handling, storage and distribution of the investigational medicinal products which he or she handles, stores or distributes under his or her authorisation as are necessary to avoid deterioration of the investigational medicinal products;

(b) not use for such purposes premises other than those specified in the authorisation or which may be approved from time to time by the Board; and

(c) ensure that any arrangements he or she makes with a person for the storage and distribution of the investigational medicinal products are adequate to maintain the quality of those products.

2. The authorisation holder shall ensure that -

(a) all manufacture, labelling and packaging operations have been carried out by a duly authorised manufacturer; and

(b) the investigational medicinal products have been manufactured, labeled and packaged, and are imported, in accordance with the principles and guidelines of good manufacturing practice.

3. The authorisation holder shall use, establish and implement an effective quality assurance system involving the active participation of the management and personnel of the different services involved.

4. The authorisation holder shall provide such information as may be requested by the Board concerning the type and quantity of any investigational medicinal products which he or she imports.

5. The authorisation holder shall -

(a) inform the Board before making any structural alterations to, or discontinuance of the use of, premises to which his or her authorisation relates; and

(b) inform the Board of any change that he or she proposes to make in any personnel named in his or her authorisation as responsible for quality control of the investigational medicinal products being imported including the person

named as the qualified person for the purposes of Regulation 40 and paragraph 14.

6. (1) The authorisation holder shall -

(a) keep readily available for inspection by a person authorised by the Board durable records of -

(i) the details of importation of each batch of every investigational medicinal product being imported under his or her authorisation, and

(ii) the tests carried out thereon including any register or other document referred to in paragraph 3 of Part 2 of Schedule 6,

in such a form that the records will be easily identifiable from the number of the batch as shown on each container in which the investigational medicinal product is or is to be sold, supplied or exported; and

(b) permit the person authorised to take copies or make extracts from such records.

(2) Such records shall not be destroyed within the relevant period without the consent of the Board.

7. The authorisation holder shall keep readily available for examination by a person authorised by the Board samples of -

(a) each batch of finished investigational medicinal products imported under his or her authorisation for at least a period of one year from their expiry date; and

(b) each batch of bulk formulated products and of the packaging components used for each finished product for at least a period of two years from the date on which the clinical trial, for which the relevant batch was manufactured labelled or packaged, was completed, terminated or discontinued.

8. The authorisation holder shall make suitable arrangements to ensure that any record or sample referred to in paragraph 6 or 7 is retained for the periods specified in those paragraphs.

9. (1) The authorisation holder shall, in cooperation with the sponsor, implement a system for recording and reviewing complaints in relation to investigational medicinal products imported under his or her authorisation, together with an effective system for recalling promptly and at any time any such investigational medicinal product that have been distributed for use in clinical trials.

(2) The authorisation holder shall -

(a) record and investigate all complaints described in subparagraph (1) of this paragraph; and

(b) shall immediately inform the Board of any defect which could result in a recall from distribution for use in clinical trials.

10. Where the authorisation holder has been informed by the Board that any batch of any investigational medicinal product to which his or her authorisation relates has been found not to conform as regards strength, quality or purity with -

(a) the specification of the relevant product; or

(b) the provisions of these Regulations,

11. If the authorisation holder is not the sponsor of the clinical trial for which the investigational medicinal product is manufactured, labelled or packaged, he or she shall comply with the provisions of the product specification that relates to the supply of that investigational medicinal product for use in the trial.

12. Where -

(a) in his or her application for a manufacturing authorisation the authorisation holder had given particulars of manufacturing operations and of substances or articles in accordance with paragraph 4 of Schedule 4; and

(b) there has been, or it is proposed that there shall be, a change in such particulars,

the authorisation holder shall forthwith notify the Board in writing of such change or proposed change.

13. The authorisation holder shall, for the purpose of enabling the Board to ascertain whether there are any grounds -

(a) for suspending, revoking or varying any authorisation;

(b) amending the conduct of a clinical trial in accordance with Regulation 20 or 21

permit, and provide all necessary facilities to enable, any person duly authorised in writing by the Board, on production if required of his or her credentials, to carry out such inspection or to take such samples or copies, in relation to things belonging to, or any business carried on by, the authorisation holder for the purpose of verifying any statement contained in an application for an authorisation.

14. (1) Subject to Regulation 40, the authorisation holder shall at all times, and in accordance with that Regulation, have a qualified person to carry out duties referred to in Regulation 40(2).

(2) The authorisation holder shall at all times provide and maintain such staff, premises, equipment and facilities as will enable the qualified person who is at his or her disposal to carry out the said functions.

SCHEDULE 6

PART 1 MINIMUM QUALIFICATIONS FOR QUALIFIED PERSON

The following are the minimum conditions of qualification for a qualified person:

(a) possession of a diploma, certificate or other evidence of formal qualifications awarded on completion of a university course of study, or a course recognised as equivalent by the Board, extending over a period of at least 4 years of theoretical and practical study in one of the following scientific disciplines: pharmacy, medicine, veterinary medicine, chemistry, pharmaceutical chemistry and technology, and biology.

However:

(i) the minimum duration of the university course may be 3 and a half years where the course is followed by a period of theoretical and practical training of a minimum duration of one year and including a training period of at least 6 months in a pharmacy open to the public, corroborated by an examination at university level;

(ii) where 2 university courses, or 2 courses recognised by the State in question as equivalent co-exist in an EEA State and where one of these extends over 4 years and the other over 3 years, the three-year course leading to a diploma, certificate or other evidence of formal qualifications awarded on completion of a university course or its recognised equivalent shall be considered to fulfil the condition of duration referred to in subparagraph (a) in so far as the diplomas, certificates or other evidence of formal qualifications awarded on completion of both courses are recognised as equivalent by the State in question.

The course shall include theoretical and practical study bearing upon at least the following basic subjects and shall be so balanced as to enable the person concerned to fulfil the obligations specified in Regulation 40(2):

Experimental physics

General and inorganic chemistry

Organic chemistry

Analytical chemistry

Pharmaceutical chemistry, including analysis of medicinal products

General and applied biochemistry (medical)

Physiology

Microbiology

Pharmacology

Pharmaceutical technology

Toxicology

Pharmacognosy (study of the composition and effects of the active principles of natural substances of plant and animal origin).

Insofar as certain diplomas, certificates or other evidence of formal qualifications mentioned in the first paragraph do not fulfil the criteria laid down above, the person concerned shall provide evidence to the Board of adequate knowledge of the subjects involved; and

(b) practical experience for at least 2 years, in one or more undertakings which are authorised to manufacture medicinal products, in the activities of qualitative analysis of medicinal products, of quantitative analysis of active substances and of the testing and checking necessary to ensure the quality of medicinal products provided that the duration of practical experience may be reduced by one year where a university course lasts for at least 5 years and by a year and a half where the course lasts for at least 6 years.

(c) was on or immediately before the coming into force of these Regulations, engaged in, or was entitled to be engaged in, the activities of a qualified person pursuant to the provisions of the Medical Preparations (Licensing of Manufacture) Regulations 1993⁶ , as amended by the Medical Preparations (Licensing of Manufacture) (Amendment) Regulations 1993⁷ , the Medical Preparations (Licensing of Manufacture) (Amendment) Regulations 1996⁸ and the Medicinal Products (Amendment) Regulations 1999⁹ .

PART 2 DUTIES OF QUALIFIED PERSON

1. The qualified person referred to in Regulation 40, is responsible, without prejudice to his or her relationship with the manufacturer or importer, for ensuring:

(a) in the case of investigational medicinal products manufactured in the State, that each batch of medicinal products has been manufactured and checked in compliance with the requirements of Commission Directive 2003/94/EC, the product specification file and the information notified pursuant to Regulation 14;

(b) in the case of investigational medicinal products manufactured in a third country, that each production batch has been manufactured and checked in accordance with standards of good manufacturing practice at least equivalent to those laid down in Commission Directive 2003/94/EC, in accordance with the product specification file, and that each production batch has been checked in accordance with the information notified pursuant to Regulation 14;

(c) in the case of an investigational medicinal product which is a comparator product from a third country, and which is the subject of a marketing authorisation, where the documentation certifying that each production batch has been manufactured in conditions at least equivalent to the standards of good manufacturing practice referred to above cannot be obtained, that each production batch has undergone all relevant analyses, tests or checks necessary to confirm its quality in accordance with the information notified pursuant to Regulation 14.

2. Insofar as the provisions laid down in subparagraphs (a), (b) or (c) of paragraph 1 are complied with, investigational medicinal products shall not have to undergo any further checks if they are imported from another Member State together with batch release certification signed by the qualified person.

3. In all cases, the qualified person shall certify in a register or equivalent document that each production batch satisfies the provisions of this Schedule. The said register or equivalent document shall be kept up-to-date as operations are carried out and shall be retained for not less than 5 years from the date of manufacture or for the period that ends one year after the labelled expiry date of the investigational medicinal product, whichever is the longer period.

SCHEDULE 7

( Regulation 50 )


European Communities (Clinical Trials on Medicinal Products for Human Use) Regulations 2004 (S.I. No. of 2004) CERTIFICATE STATING RESULTS OF TEST, EXAMINATION OR ANALYSIS This Certificate is issued by me, the undersigned, for the purpose of Regulation 50 of the European Communities (Clinical Trials on Medicinal Products for Human Use) Regulations 2004, being^(1)___ ___. I hereby certify that I received, on the __ day of ___ 20 _, from^(2) ___ of ___ a sample of^(3) ___ for test, examination or analysis; which was undamaged, duly sealed and marked^(4) ___. I further certify that the said sample has been tested, examined or analysed by me or under my direction and that the results are as follows:— ^(5) Signature___ Date ___ Address ___ ___ ______ ^(1) Here insert official title of analyst. ^(2) Here insert the name of the sampling officer who submitted the sample for analysis. ^(3) Here insert the name or description of the product. ^(4) Here insert the distinguishing mark on the sample and the date of sampling shown thereon. ^(5) Here insert the relevant results as appropriate.

European Communities (Clinical Trials on Medicinal Products for Human Use) Regulations 2004 (S.I. No. of 2004) CERTIFICATE STATING RESULTS OF TEST, EXAMINATION OR ANALYSIS This Certificate is issued by me, the undersigned, for the purpose of Regulation 50 of the European Communities (Clinical Trials on Medicinal Products for Human Use) Regulations 2004, being^(1)___ ___. I hereby certify that I received, on the __ day of ___ 20 _, from^(2) ___ of ___ a sample of^(3) ___ for test, examination or analysis; which was undamaged, duly sealed and marked^(4) ___. I further certify that the said sample has been tested, examined or analysed by me or under my direction and that the results are as follows:— ^(5) Signature___ Date ___ Address ___ ___ ______ ^(1) Here insert official title of analyst. ^(2) Here insert the name of the sampling officer who submitted the sample for analysis. ^(3) Here insert the name or description of the product. ^(4) Here insert the distinguishing mark on the sample and the date of sampling shown thereon. ^(5) Here insert the relevant results as appropriate.


	GIVEN under my Official Seal this 29th day of April 2004.
	MICHEAL MARTIN ______ Minister for Health and Children

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 2001/20/EC on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use.

The Regulations provide that the Irish Medicines Board will exercise the functions of the competent authority for the purposes of the Directive and for the purposes of supervision and enforcement as required by the Regulations. The Regulations also introduce measures for the establishment and operation of Ethics Committees that are required to give an opinion before a clinical trial may commence. This includes arrangements for obtaining a single ethics committee opinion in the case of multi-centre trials. The matters to be considered by Ethics Committees are set out in Regulation 13 of the Regulations.

The Regulations also provide for an Ethics Committee Supervisory Body, the functions of which for the time being are to be discharged by the Minister. The primary function of this Body is to grant recognition in respect of Ethics Committees that are required to be established for the purposes of the Regulations. The composition of Ethics Committees, including certain procedures in regard to their operation, is set out in Schedule 2. This composition reflects the requirements set out in the Directive.

An Ethics Committee as envisaged by the Directive “is an independent body in a Member State consisting of health care professionals and non-medical members, whose responsibility it is to protect the trials, safety and wellbeing of human subjects involved in a trial and to provide public assurance of that protection, by, among other things, expressing an opinion on the trial protocol, the suitability of the investigators and the adequacy of facilities, and on the methods and documentation to be used to inform trial subjects and obtain their informed consent”. All of these objectives have been provided for in these Regulations.

The conditions and principles for the protection of clinical trials subjects are set out in Schedule 1 and are consistent with the principles contained in the 1996 version of the Helsinki Declaration. The detailed conditions, that are to apply in relation to a subject giving consent, are also set out in that Schedule in relation to subjects who are able to consent, in relation to minors, and in relation to incapacitated adults. Where the conduct of a clinical trial is subject to the provisions of these Regulations, the Control of Clinical Trials Acts 1987 and 1990 will not apply.

Footnotes

OJ L. 121, 01.05.2001, p.34.

OJ L.262, 14.10.2003, p.22.

OJ No. L.311, 28.11.2001, p.67.

OJ No. L1, 03.01.1994, p.572.

OJ No. L214, 24.08.1993, p1.

S.I. No. 40 of 1993

S.I. No. 68 of 1993

S.I. No. 42 of 1996

S.I. No. 188 of 1999

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