The Medicines (Standard Provisions for Licences and Certificates) Amendment Regulations 1977

Made: 6th April 1977

Laid before Parliament: 21st April 1977

Coming into Operation: 12th May 1977

The Secretaries of State respectively concerned with health in England and in Wales, the Secretary of State concerned with health and with agriculture in Scotland, the Minister of Agriculture, Fisheries and Food, the Department of Health and Social Services for Northern Ireland and the Department of Agriculture for Northern Ireland, acting jointly, in exercise of powers conferred by section 47(1) of the Medicines Act 1968 and now vested in them[^f00001] and of all other powers enabling them in that behalf, after consulting such organisations as appear to them to be representative of interests likely to be substantially affected by the following regulations, hereby make the following regulations:—

Citation, interpretation and commencement

1

These regulations, which may be cited as the Medicines (Standard Provisions for Licences and Certificates) Amendment Regulations 1977, shall be read as one with the Medicines (Standard Provisions for Licences and Certificates) Regulations 1971 as amended[^f00002] (hereinafter referred to as “the principal regulations”) and shall come into operation on 12th May 1977.

Amendment of regulation 2(1) of the principal regulations

2

Regulation 2(1) of the principal regulations (interpretation) shall be amended by adding—

• (a) immediately after the definition of “advertisement” the following definitions:—

• “BCG” means the bacillus of Calmette and Guerin;
• “BCG vaccine” means a vaccine that is a preparation of the bacteria in a living pure culture of a strain of the bacillus of Calmette and Guerin;

• (b) immediately after the definition of “medicinal product” the following definitions:—

• “parenteral administration” means administration by breach of the skin or mucous membrane;
• “serum” means a fluid fraction of coagulated blood;
• “smallpox vaccine” means a vaccine that is a preparation of an infective vaccinia virus;
• “toxins” means substances used in the diagnosis, prevention or treatment of disease consisting wholly or partly of poisonous substances derived from specific micro-organisms, plants or animals;
• “vaccines” means antigenic substances which consist wholly or partly of— any micro-organisms, viruses or other organisms in any state, any toxins of microbial origin which have been detoxified (toxoids), or any extracts or derivatives of any micro-organisms or of any viruses, being substances which, when administered to human beings or animals, are used for the prevention or treatment of specific diseases;

Additional regulations

3

The principal regulations shall be amended by adding after Regulation 3 the following regulations:—

(4) (1) In addition to the standard provisions for manufacturer's licences set out in Schedule 2 to these regulations, the standard provisions for manufacturer's licences, including manufacturer's licences of right, relating to vaccines for human use shall be the following— (a) for all vaccines, including smallpox vaccine and BCG vaccine, those provisions set out in Part I of Schedule 4 to these regulations, (b) for smallpox vaccine, those provisions set out in Part II of Schedule 4 to these regulations, and (c) for BCG vaccine, those provisions set out in Part III of Schedule 4 to these regulations. (2) In addition to the standard provisions for manufacturer's licences set out in Schedule 2 to these regulations, the standard provisions for manufacturer's licences, including manufacturer's licences of right, relating to toxins and sera for human use shall be the following— (a) for toxins, those provisions set out in Part IV of Schedule 4 to these regulations, and (b) for sera, those provisions set out in Part V of Schedule 4 to these regulations. (5) (1) In addition to the standard provisions for product licences set out in Part I of Schedule 1 to these regulations, the standard provisions for product licences, including product licences of right, relating to medicinal products to which this regulation applies shall be those provisions set out in Schedule 5 to these regulations. (2) The standard provisions contained in this regulation shall only apply to medicinal products which include a substance or substances specified in paragraphs 1 to 35 in column 1 of Schedule 1 to the Medicines (Control of Substances for Manufacture) Order 1971[^f00003] in the circumstances set out in column 2 of the said Schedule other than medicinal products as aforesaid manufactured, assembled, sold, supplied, imported or exported for use as veterinary drugs.

Additional schedules

4

After Schedule 3 to the principal regulations, there shall be added as Schedules 4 and 5, the Schedules set out in the Schedule to these regulations.

SCHEDULE 4

PART I — Standard provisions for manufacturer's licences and manufacturer's licences of right relating to vaccines

1

The licence holder shall ensure that the premises on which vaccines are produced and tested shall be under the complete direction and control of a suitably qualified person approved by the licensing authority for the purpose.

2

The licence holder shall provide separate premises or separate parts of premises for the activities specified in the following sub-paragraphs, namely—

• (a) the production and the testing involved in the production of cell cultures for use in the production of vaccine,

• (b) the production and the testing involved in the production of vaccine prepared from viruses, and

• (c) the production and the testing involved in the productions of vaccine prepared from micro-organisms or detoxified microbial toxins,

3

The licences holder shall ensure that any procedure which, in the course of any of the activities specified in the preceding paragraph, involves or might involve—

• (a) the presence of transmissible agents, or

• (b) the use of cell cultures, animal tissues or micro-organisms, other than those from which the vaccine is produced, shall not be carried out in the separate premises or separate parts of premises as aforesaid.

4

The licence holder shall ensure that no person who has been in contact with transmissible agents or experimental animals other than those connected with the vaccine being produced in the separate premises or separate parts of premises as aforesaid shall enter those premises or separate parts of premises on the same day that the contact as aforesaid has been made.

5

Before an animal is used in the production of vaccine the licence holder shall take all reasonable steps to ensure that it is free from disease and to this end shall keep the animal in quarantine and under observation for such period as the licensing authority may direct.

6

• (1) The licence holder shall ensure that animals used in the production of vaccine are isolated and shall provide separate premises (not being the premises or parts of premises referred to in paragraph 2 above) for this purpose.

• (2) The licence holder shall ensure that only persons engaged in the production and testing of vaccine or in the maintenance of animals or premises shall have access to the separate premises in which the animals are isolated.

7

The licence holder shall provide a special room capable of being washed and disinfected in the separate premises referred to in paragraph 6 above for the purpose of—

• (a) the inoculation of animals, and

• (b) the collection of material to be used in the preparation of vaccine.

8

Without prejudice to any other requirements to keep records, where vaccines contain or might contain micro-organisms or microbial toxins the licence holder shall keep a durable record, a readily available for inspection by a person authorised by the licensing authority, of the origin, properties and characteristics of the cell cultures used in the production of those vaccines and shall ensure that the said record is not destroyed for a period of five years from the date when the relevant production occurred.

PART II — Standard provisions for manufacturer's licences and manufacturer's licences of right relating to smallpox vaccine

PART III — Standard provisions for manufacturer's licences and manufacturer's licences of right relating to BCG vaccine

PART IV — Standard provisions for manufacturer's licences and manufacturer's licences of right relating to toxins

PART V — Standard provisions for manufacturer's licences and manufacturer's licences of right relating to sera

9

Without prejudice to any other requirements to keep records, the licence holder shall keep the following durable records relating to the production of sera readily available for inspection by a person authorised by the licensing authority and shall ensure that the said record is not destroyed for a period of five years from the date when the relevant production occurred:—

• (a) as to the cultures used—

• (i) the source from which the culture was obtained,

• (ii) the nature of the material from which the culture was isolated,

• (iii) the date of the isolation, and

• (iv) evidence of the identity and specificity of the culture;

• (b) as to the procedure used in the immunizing of animals—

• (i) the method of preparing the culture or antigen used for immunizations,

• (ii) the dosage and methods employed in administering the culture or antigen, and

• (iii) the time in the course of immunizations at which blood is withdrawn for preparation of the serum;

• (c) the results of any tests which may have been applied to the serum to determine its content of specific antibodies or its specific therapeutic potency.

SCHEDULE 5

PART I — Standard provisions for product licences including product licences of right relating to medicinal products to which regulation 5 of these regulations applies

1

In this Part of this Schedule “expiry date” means the date after which, or the month and year after the end of which, the medicinal product should not be used, or the date before which, or the month and year before the beginning of which, the medicinal product should be used.

2

The licence holder shall, within 28 days of any request made by the licensing authority, supply to the licensing authority a sample of the standard preparation with which each batch of the medicinal product to which the licence relates is or is to be compared, being a sample of such amount as the licensing authority may reasonably require for any examination to be made.

3

Until the expiry date and for six months thereafter the licence holder shall on request supply to the licensing authority in respect of any batch of the medicinal product to which that request applies a sample from the said batch of such amount as the licensing authority may reasonably require for any examination and, if so requested, detailed protocols of the tests which have been applied to the said batch.

4

Where the licence holder has supplied the licensing authority with a sample or protocols or both a sample and protocols in accordance with the preceding paragraph, if the licensing authority so direct, the licence holder shall not sell, supply or export any batch or any part of any batch referred to in the preceding paragraph until he has obtained the consent of the licensing authority in writing to such sale, supply or exportation.

5

Where the licence holder has been informed by the licensing authority that any batch as aforesaid has been found not to conform as regards strength, quality or purity to the specification of that product or with the provisions of the Act or of any regulations made under the Act that are applicable to the medicinal product, he shall, if so directed and so far as may be reasonably practicable, recall all medicinal products already sold or supplied from that batch.

6

Unless and to the extent that the licensing authority otherwise direct in writing, the licence holder shall ensure that a medicinal product to which the licences relates complies with any requirements applicable to it specified in the Compendium of Licensing Requirements for the Manufacture of Biological Medicinal Products prepared and published under section 99 of the Act[^f00004].

7

• (1) Unless the licensing authority otherwise direct in writing, the licence holder shall ensure that any medicinal product which is for parenteral administration satisfies the following tests—

• (a) sterility,

• (b) abnormal toxicity, and

• (c) pyrogens (except in the case of vaccines and preparations of insulin).

• (2) Where the licensing authority has directed that the provisions of the preceding sub-paragraph need not apply, the licence holder shall either—

• (a) ensure that the medicinal product as aforesaid has satisfied the said tests, or

• (b) satisfy himself, taking into consideration—

• (i) the in-process controls carried out during the manufacture of the medicinal product as aforesaid, and

• (ii) the results obtained from testing in accordance with sub-paragraph (1) above other batches of medicinal products of the same description,

that if tested in accordance with sub-paragraph (1) above, the medicinal product as aforesaid would satisfy the said tests.

• (3) The tests referred to in sub-paragraph (1)(a), (b) and (c) above shall be—

• (a) the tests set out in Parts II, III and IV respectively of this Schedule, or

• (b) where the medicinal product as aforesaid is one in respect of which there is a monograph in the European Pharmacopoeia, the tests specified in the European Pharmacopoeia, or

• (c) such other tests as the licensing authority may in any particular case approve.

• (4) The said tests shall be made after every manufacturing process has been completed unless the licence holder has obtained the consent of the licensing authority in writing to testing at an earlier stage in the manufacture.

• (5) The licence holder shall keep readily available for inspection by a person authorised by the licensing authority durable records of all the relevant details of the said tests including records of the examination of each tube, vessel or animal as the case may be and shall ensure that the said records are not destroyed for a period ending six months after the expiry date has passed.

8

The licence holder shall not sell, supply, import or export any medicinal product for parenteral administration unless it has been sealed in a previously sterilised container of a material inert towards that product in such a manner as will preclude the access of micro-organisms.

9

The provisions of this Schedule shall not have effect until 1st September 1977 in relation to a product licence being a licence of right where, immediately before the first appointed day[^f00005] the manufacturer or importation of substances or articles to which the licence relates was authorised by a licence issued under Part I of the Therapeutic Substances Act 1956 or under Part II of the Diseases of Animals Act 1950, or of the Diseases of Animals Act (Northern Ireland) 1958.

PART II — Tests for sterility

10

• (1) If at the examination at the end of the incubation period referred to in the preceding paragraph no growth of micro-organisms is found in the media to which the sample has been applied, the medicinal product shall be regarded as having satisfied the test.

• (2) If at any examination a growth of micro-organisms is found in the media to which the sample has been applied, a further sample may be taken from the batch and tested in accordance with the foregoing provisions of this Part of this Schedule.

• (3) If on examination during or after the incubation of the further sample no growth of micro-organisms is found, the medicinal product shall be regarded as having satisfied the test, but if growth of the same organism is found as was found in the first sample tested, the medicinal product shall be regarded as having failed to satisfy the test.

• (4) If on any examination of the further sample a micro-organism is found, but the same micro-organism as was found in the sample first tested is not found, a third sample may be taken from the batch and tested in accordance with the foregoing provisions of this Part of this Schedule.

• (5) If on any examination during or after the incubation of the third sample no micro-organism is found the medicinal product shall be regarded as having satisfied the test, but if any micro-organism is found the medicinal product shall be regarded as having failed to satisfy the test.

• (6) If the nature of the sample or any other factor makes the result of the test uncertain, then subculture shall be carried out and the subcultures shall be incubated and examined in accordance with the provisions of paragraph 9 above and the provisions of this paragraph.

11

• (1) Notwithstanding the provisions of paragraph 10 above, where the medicinal product is—

• (a) required in an emergency and the licence holder has no filled containers in stock,

• (b) so unstable that the delay occasioned by the completion of the tests for sterility on filled containers would render its sale, supply or exportation in active form impossible, or

• (c) declared by the relevant product licence to be a product to which this paragraph applies,

and, in the case of sub-paragraphs (a) and (b) above, the licensing authority has directed that the provisions of this paragraph shall apply to the medicinal product, the medicinal product may be regarded as having satisfied the tests for sterility if and so long as the conditions specified in the following sub-paragraph are satisfied.

• (2) The conditions referred to in the preceding sub-paragraph are—

• (i) in a case to which sub-paragraph (1)(a) of this paragraph applies, the medicinal product is not sold, supplied or exported unless, before it is filled into containers, the following amounts of the medicinal product are tested for sterility in accordance with the foregoing provisions of this Part of this Schedule—

• (ii) in a case to which sub-paragraphs (1)(b) or (1)(c) of this paragraph applies, the medicinal product is not sold, supplied or exported before a sample is taken and after the sale, supply or exportation the sample is tested in accordance with the foregoing provisions of this Part of this Schedule;

• (iii) if at any examination made during the testing of a sample taken in accordance with the foregoing provisions of this paragraph any growth of micro-organisms is found, the licensing authority and any person to whom the medicinal product was sold, supplied or exported shall be notified forthwith.

PART III — Test for abnormal toxicity

PART IV — Test for pyrogens

Signed

David Ennals — Secretary of State for Social Services — 4th March 1977

John Morris — Secretary of State for Wales — 25th March 1977

Bruce Millan — Secretary of State for Scotland — 31st March 1977

In witness whereof the official seal of the Minister of Agriculture, Fisheries and Food is hereunto affixed on 4th April 1977.

John Silkin — Minister of Agriculture, Fisheries and Food

Sealed with the official seal of the Department of Health and Social Services for Northern Ireland this 5th day of April 1977.

N. Dugdale — Permanent Secretary

Sealed with the official seal of the Department of Agriculture for Northern Ireland this 6th day of April 1977.

J. A. Young — Permanent Secretary

Explanatory note

EXPLANATORY NOTE

These Regulations amend the Medicines (Standard Provisions for Licences and Certificates) Regulations 1971 by adding two new Schedules containing further standard provisions which may be incorporated in licences, namely—

• (a) standard provisions for manufacturer's licences relating to all vaccines, smallpox vaccine, BCG vaccine, toxins and sera, and

• (b) standard provisions for product licences relating to medicinal products which contain the substances listed in paragraphs 1 to 35 of Schedule 1 to the Medicines (Control of Substances for Manufacture) Order 1971, being substances the purity and potency of which cannot be tested by chemical means.

Footnotes

[^f00001]: In the case of the Secretaries of State concerned with health in England and in Wales by virtue of Article 2(2) of, and Schedule 1 to, the Transfer of Functions (Wales) Order 1969 (S.I. 1969/388 (1969 I, p. 1070)), and in the case of the Northern Ireland Departments by virtue of section 40 of, and Schedule 5 to, the Northern Ireland Constitution Act 1973 (c. 36), and paragraph 2(1)(b) of Schedule 1 to the Northern Ireland Act 1974 (c. 28).

[^f00002]: S.I. 1972/1226, 1974/1523 (1972 II, p. 3708; 1974 III, p. 5811).

[^f00003]: S.I. 1971/1200 (1971 II, p. 3506).

[^f00004]: The current edition is Issue I: 1977 taking effect on 1st May 1977.

[^f00005]: 1st September, See S.I. 1971/1153 (1971 II, p. 3393).