S.I. No. 40/1993:

MEDICAL PREPARATIONS (LICENSING OF MANUFACTURE) REGULATIONS, 1993.

MEDICAL PREPARATIONS (LICENSING OF MANUFACTURE) REGULATIONS, 1993.

The Minister for Health, in exercise of the powers conferred on him by section 5 of the Health Act, 1947 (No. 28 of 1947) and section 65 of that Act as amended by section 39 of the Health Act, 1953 (No. 26 of 1953) and section 36 of the Misuse of Drugs Act, 1977 (No. 12 of 1977), hereby makes the following regulations:--

1. These Regulations may be cited as the Medical Preparations (Licensing of Manufacture) Regulations, 1993.

2. The Medical Preparations (Licensing of Manufacture) Regulations, 1974 ( S.I. No. 225 of 1974 ) and the Medical Preparations (Licensing of Manufacture) (Amendment) Regulations, 1975 ( S.I. No. 302 of 1975 ) are hereby revoked.

3. In these Regulations--

"the Minister" means the Minister for Health;

"batch" means a quantity which is homogeneous in character and quality produced during a given cycle of manufacture;

"manufacture" includes:

--total and partial manufacture,

--the various processes of dividing up, packaging or presentation,

--formulation, processing, compounding or filling, and

--the importation of a medical preparation from a country other than a Member State of the European communities;

"pharmacist" means a registered pharmaceutical chemist or a registered dispensing chemist and druggist;

"product authorisation" means a product authorisation granted under the Medical Preparations (Licensing, Advertisement and Sale) Regulations, 1984 ( S.I. No. 210 of 1984 ) as amended by the Medical Preparations (Licensing, Advertisement and Sale) (Amendment) Regulations, 1989 ( S.I. No. 347 of 1989 );

"retail sale" means sale to a person buying otherwise than for the purpose of resale;

"qualified person" means a person as defined in Schedule 11 to these Regulations.

4. Subject to the exemptions specified in article 6 of these Regulations, no person shall manufacture for sale any medical preparation except in accordance with a licence granted by the Minister, referred to in these Regulations as a "manufacturer's licence".

5. A manufacturer's licence may relate to medical preparations generally, to medical preparations of a class or description specified in such licence or to one or more medical preparations specified in such licence.

6. Article 4 of these Regulations shall not apply to the manufacture of a medical preparation--

( a ) by or under the supervision of a registered medical practitioner or a registered dentist for one of his patients, or

( b ) by a registered veterinary surgeon for any animal under his care, or

( c ) by or under the supervision of a pharmacist in accordance with a prescription given by a registered medical practitioner, a registered dentist, or registered veterinary surgeon, or

( d ) by or under the supervision of a registered druggist in accordance with a prescription given by a registered veterinary surgeon, or

( e ) on a premises by or under the supervision of a pharmacist or registered druggist for the purpose of retail sales exclusively on those premises otherwise than in accordance with a prescription mentioned in sub-articles (c) and (d) of this article, or

( f ) on premises not exceeding three in number, by or under the supervision of a pharmacist or registered druggist for the purpose of maintaining a stock of a medical preparation for dispensing exclusively on any of these premises as mentioned in sub-articles (c), (d) or (e) of this article, or

( g ) by or under the supervision of a person in charge of a laboratory which is engaged in recognised medical, pharmaceutical, dental or veterinary education, research or analysis and used for such purposes in such a laboratory.

7. (1) The Minister may grant a manufacturer's licence to any person who applies in the form and manner required by the Minister who satisfies the Minister in regard to the medical preparation which he proposes to manufacture, that he has suitable premises, equipment, staff and manufacturing operations and suitable arrangement for quality controls, record-keeping, handling, storage and distribution.

(2) A manufacturer's licence granted under sub-article (1) of this article shall be subject to such conditions as the Minister may specify and may, in particular, include the General Conditions set out in Schedule I.

8. A manufacturer's licence shall remain in force for a period of three years or such shorter period as may be specified in the licence, unless it is sooner revoked by the Minister.

9. There shall be paid ot he Minister an annual fee of £1,250 in respect of each manufacturer's licence.

10. (1) Subject to the provisions of sub-article (4) of this article the Minister shall, within 90 days of the receipt of the application, notify an applicant for a manufacturer's licence of his decision to grant or his proposal to refuse such licence.

(2) If the Minister proposes to refuse a licence, in accordance with sub-article (1) of this article he shall notify the applicant of the reasons for such proposal and invite him to make representations in the matter to him within 30 days of the giving of such notice and the Minister shall consider any such representations.

(3) The Minister shall inform the applicant in writing of his decision regarding such proposed refusal as mentioned in sub-article (2) of this article within 60 days of the notice referred to in that sub-article.

(4) Where the Minister requires further information from the applicant for the purpose of consideration of the application for a manufacturer's licence, the time limit referred to in sub-article (1) of this article shall be suspended until the information required has been supplied.

(5) The Minister may revoke a licence already granted under these regulations.

(6) If the Minister proposes to revoke a licence, in accordance with sub-article (5) of this article, he shall notify the holder of the reasons for such proposal and invite him to make representations in the matter to him within 30 days of the giving of such notice and the Minister shall consider any such representations.

(7) The Minister shall inform the licence holder in writing of his decision regarding such proposed revocation as mentioned in sub-article (6) of this article within 60 days of the notice referred to in that sub-article.

11. These Regulations shall be enforced and executed by officers of the Minister and by health boards and their officers.

SCHEDULE I

GENERAL CONDITIONS SUBJECT TO WHICH MANUFACTURER'S LICENCES ARE GRANTED

1. The licence holder shall not, without the prior approval of the Minister, manufacture any medical preparation other than one which has been specified in his application for a licence to the Minister or which has subsequently been notified in writing to the Minister, and which has been specified in the licence either as such or as a class of medical preparation which may be manufactured by him.

2. The licence holder shall provide and maintain such premises, equipment and staff as are necessary for the carrying out, in accordance with his licence and any relevant product authorisation in force, of such stages of the manufacture of the medical preparations as are undertaken by him and he shall not carry out any such manufacture except at the premises specified in the licence or such other premises as may be approved in writing from time to time by the Minister.

3. The licence holder shall provide and maintain such premises, equipment, facilities, and staff for the handling, storage and distribution of the medical preparations which he handles, stores or distributes under his licence as are necessary to avoid deterioration of such products and he shall not use for such purposes premises other than those specified in the licence or such other premises which may be approved in writing from time to time by the Minister.

4. The licence holder shall conduct all manufacturing operations in such a way as to ensure that the medical preparations conform with the standards of strength, quality and purity applicable to them whether under the relevant product authorisations, or under any pharmacopoeial standard or other specification to which they may be manufactured.

5. The licence holder shall either--

( a ) provide and maintain such premises, equipment, facilities and staff as are necessary for carrying out any tests of strength, quality or purity of the medical preparations that he manufacturers as required by the relevant product authorisation and in accordance with the requirements of good manufacturing practice for medicinal products, as may be specified by the Minister, or

( b ) make arrangements with a person approved in writing by the Minister for such tests to be carried out on his behalf by that person.

6. The licence holder shall notify the Minister in writing before making any material alteration in the premises or equipment used under his licence, or in the operations in which they are used and he shall notify the Minister in writing or any change that he proposes to make in any personnel named in his licence as respectively being--

( a ) responsible for the quality control of the medical preparations being manufactured including the person named as the qualified person for the purposes of paragraph 7 of this Part of this Schedule, or

( b ) responsible for supervising the production operations, or

( c ) responsible for biological or microbiological controls used in the manufacture or testing of the medical preparations being manufactured.

7. (1) If the licence holder is not himself a qualified person who as respects qualifications and experience satisfies the provisions of Schedule II of these Regulations to carry out the functions specified in sub-paragraph (3) below, he shall at all times have at his disposal the services of a person (hereinafter referred to as the qualified person).

(2) The licence holder shall at all times provide and maintain such staff, premises and facilities as will enable the qualified person to carry out the said functions.

(3) The functions to be carried out by the qualified person shall be as follows:--

( a ) to ensure that every batch of medical preparation to which the licence relates has been manufactured and checked in compliance with:--

(i) the laws in force in the State in respect of such product,

(ii) the provisions of this manufacturer's licence, and

(iii) the provisions of the product authorisation or other standard which relates to the said product.

( b ) to certify in a register, or other equivalent document appropriate for the purpose, whether each production batch of the medical preparation to which the licence relates satisfies the requirements set out in sub-paragraph (a) above and to ensure that such register or other document is regularly maintained and in particular that the appropriate entries in such register or other document are made as soon as practicable after each such batch has been manufactured.

(4) Where, after giving the licence holder and the person acting as the qualified person the opportunity of making representations to him (either orally or in writing), the Minister is of the opinion that the person so acting is failing to carry out the functions specified in sub-paragraph (3) above and has notified the licence holder accordingly in writing, the licence holder shall not permit that person to continue to act as the qualified person so long as the said notification has not been withdrawn by the Minister.

(5) The Minister may require the licence holder temporarily to suspend the person acting as such qualified person upon the commencement of administrative or disciplinary proceedings against him for failure to fulfil his functions in accordance with sub-paragraph (3) above and the licence holder shall not permit that person to act as the qualified person pending the determination of such proceedings.

8. The licence holder shall keep readily available for inspection by the officer responsible for the enforcement or execution of these regulations durable records of the details of manufacture of each batch of every medical preparation being manufactured under his licence and of the tests carried out thereon, including any register or other document referred to in paragraph 7 (3) (b) above, in such form that the records will be easily identifiable from the number of the batch as shown on each container in which the medical preparation is sold, supplied or exported and he shall permit such officer to take copies or make extracts from such records.

Such records shall be retained for not less than five years from the date of manufacture or for the period which ends one year after the labelled expiry date of the medical preparation whichever is the longer period.

9. The licence holder shall keep such documents as will facilitate the withdrawal or recall from sale, supply or exportation of any mdeical preparation to which the licence relates. Such documents shall be available for inspection by an officer responsible for the enforcement or execution of these regulations.

10. The licence holder shall keep an adequate sample of each batch and of each active constituent used in the manufacture of such medical preparation to which the licence relates for the period which ends one year after the labelled expiry date of the preparation, and shall furnish on request by the Minister a sufficient sample of each such batch for the purpose of any test, examination or analysis which may be required by the Minister.

11. Where the licence holder has been informed by the Minister that any part of a batch of medical preparation to which his licence relates has been found not to conform as regards strength, quality of purity with the specifications of the relevant product he shall, if so directed by the Minister immediately withhold the remainder of that batch from sale, supply or exportation and, insofar as may be practicable, immediately recall all supplies already sold, supplied or exported from that batch.

12. Where the licence holder has been informed by the Minister that a medical preparation to which his licence relates has been found to give rise to unacceptable adverse reactions, he shall, if so directed by the Minister, immediately withhold that preparation from sale supply or exportation and, insofar as may be practicable, immediately recall all supplies of such preparation already sold, supplied or exported.

13. The licence holder shall ensure that any tests for determining conformity with the standards and specifications applying to any medical preparation to which the licence relates, shall, except insofar as the conditions of the relevant product authorisation may otherwise permit or require, be applied to samples taken from the medical preparation after all manufacturing processes have been completed, and/or at such earlier stage(s) in the manufacture as may be required or approved in writing by the Minister.

14. The licence holder, who is not the holder of a product authorisation in rspect of a medical preparation to which the licence relates, shall comply with any provisions of such authorisation which relate to the sale or supply of that medical preparation and shall, by means of a label or otherwise, communicate the particulars of such provisions as they relate to mode of sale or supply or restriction as to sale of supply to any person to whom the licence holder sells or supplies that medical preparation.

15. The licence holder shall not dispose of any medical preparation to which his licence relates except in accordance of the laws of the State.

16. The licence holder shall supply such information as may be requested by the Minister for the purposes of these regulations about the medical preparations currently being manufactured and about the operations being carried out in relation to such manufacture.

17. The licence holder, for the purpose of enabling the Minister to ascertain whether there are any grounds for suspending, revoking or varying any licence or authorisation granted under these regulations or the Medical Preparations (Licensing, Advertisement and Sale) Regulations 1984 and 1989, shall permit and provide all necessary facilities to enable any officer responsible for the enforcement or execution of the said regulations to carry out such inspection, to take such samples or to take copies of any documents in relation to any business carried on by the licence holder, for the purose of verifying any statement contained in an application for a licence or authorisation.

SCHEDULE II

QUALIFIED PERSON

A qualified person is a person who fulfils the following minimum conditions of qualification:

( 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 Minister, extending over a period of at least four years of theoretical practical study in one of the following scientific disciplines: pharmacy, medicine, veterinary medicine, chemistry, pharmaceutical chemistry and technology, biology. However:

--the minimum duration of the university course may be three 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 six months in a pharmacy open to the public, corroborated by an examination at university level;

--where two university courses or two courses recognised by the State in question as equivalent co-exist in a Member State of the European Economic Community and where one of these extends over four years and the other over three 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 this sub-paragraph 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 paragraph 7 (3) of Schedule 1:

Experimental physics

General and inorganic chemistry

Organic chemistry

Analytical chemistry

Pharmaceutical chemistry, including analysis of medical products

General and applied biochemistry (medical)

Physiology

Microbiology

Pharmacology

Pharmaceutical technology

Toxicology

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

In so far as certain diplomas, certificates and 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 Minister of adequate knowledge of the subjects involved;

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

GIVEN under the Official Seal of the Minister for Health, this 11th day of February, 1993.

BRENDAN HOWLIN,

Minister for Health.

The Minister for Finance hereby consents to Article 9 of these regulations.

Dated this 11th day of February, 1993.

BERTIE AHERN,

Minister for Finance.

EXPLANATORY NOTE.

These Regulations consolidate the statutory controls in relation to the manufacture of medical preparations for human use and take into consideration the manufacturing requirements set out in EEC Council Directive 75/319 as amended, including commission Directive 91/356/EEC of 13th June, 1991 (O.J. of the European Communities No. L193 of 17/7/91 pages 30-33). The regulations also provide for an increase in the fee charged for licences granted in respect of the manufacture of medical preparations.