8. 2. 88 Official Journal of the European Communities No C 36/25 
3. Member States shall ensure that appropriate 
information about actions taken pursuant to 
paragraphs 1 and 2 which may effect the protection of 
public health in third countries is forthwith brought to 
the attention of the World Health Organization with a 
copy to the Committee.' 
10. The first paragraph of Article 34 is hereby amended as 
follows: 
'This Directive shall apply to medicinal products for 
human use in the form of proprietary medicinal 
products or ready-made medicinal products to the 
exclusion of medicinal products which are prepared 
extemporaneously in an individual pharmacy for 
individual patients.' 
11. With the exception of the first paragraph of Article 34, 
all references to 'proprietary medicinal product' or to 
'proprietary product' are replaced by 'medicinal 
product'. 
THE COUNCIL OF THE EUROPEAN COMMUNITIES, 
Having regard to the Treaty establishing the European 
Economic Community, and in particular Article 100A 
thereof, 
Having regard to the proposal from the Commission, 
In cooperation with the European Parliament, 
Having regard to the opinion of the Economic and Social 
Committee, 
Whereas disparities in the provisions laid down by law, 
regulation or administrative action by Member States may 
hinder trade in immunological products within the 
Community; 
Whereas the essential aim of any rules governing the 
production, distribution or use of medicinal products must 
be to ensure a high level of protection of public health; Article 4 
1. Member States shall take the measures necessary to 
comply with this Directive not later than 1 January 1991. 
They shall forthwith inform the Commission thereof. 
2. Requests for marketing authorization lodged after the 
time limit referred to in paragraph 1 must comply with the 
provisions of this Directive. 
3. Articles 1, 2 and 3 of this Directive, where relevant, 
shall be progressively extended to existing medicinal 
products before 31 December 1992. 
Article 5 
This Directive is addressed to the Member States. 
Whereas the provisions laid down by Directive 
65/65/EEC (*), as last amended by Directive 
87/21/EEC (2), and Second Directive 75/319/EEC (3), as 
last amended by Directive 83/570/EEC (4) on the 
approximation of provisions laid down by law, regulation or 
administrative action relating to proprietary medicinal 
products, although appropriate, are inadequate for 
immunological medicinal products consisting of vaccines, 
toxins or serums and allergens; 
Whereas, in accordance with Article 5 of Directive 
87/22/EEC (5) on the approximation of national provisions 
relating to the placing on the market of high technology 
medicinal products, particularly those derived from 
biotechnology, the Commission is required to submit 
proposals to harmonize, along the lines of Directive 
75/319/EEC, the conditions for authorizing the 
manufacture and placing on the market of immunological 
medicinal products before 22 December 1987; 
(M OJ No 22, 9. 2. 1965, p. 369/65. 
(2) OJ No L 15, 17. 1. 1987, p. 36. 
(3) OJ No L 147, 9. 6. 1975, p. 13. 
(4) OJ No L 332, 28. 11. 1983, p. 1. 
(5) OJ No L 15, 17. 1. 1987, p. 38. Proposal for a Council Directive extending the scope of Directives 65/65/EEC and 75/319/EEC on 
the approximation of provisions laid down by law, regulation or administrative action relating to 
proprietary medicinal products and laying down additional provisions for immunological medicinal 
products consisting of vaccines, toxins or serums and allergens 
COM(87) 697 final 
(Submitted by the Commission to the Council on 12 January 1988) 
(88/C 36/03) 
No C 36/26 Official Journal of the European Communities 8. 2. 88 
Whereas, before an authorization to market an 
immunological product can be granted, the manufacturer 
must demonstrate his ability to attain batch-to-batch 
consistency; 
Whereas the Commission should be empowered to adopt any 
necessary changes in the requirements for the testing of 
proprietary medicinal products set out in the Annex to 
Directive 75/318/EEC of 20 May 1975 on. the 
approximation of the laws of the Member States relating to 
analytical, pharmaco-toxicological and clinical standards 
and protocols in respect of the testing of proprietary 
medicinal products (*), as last amended by Directive 
87/ 19/EEC of 22 December 1986 (2), to take account of the 
special nature of immunological medicinal products in close 
cooperation with the Committee for the Adaptation to 
Technical Progress of the Directives on the Removal of 
Technical Barriers to Trade in the Proprietary Medicinal 
Products Sector, 
HAS ADOPTED THIS DIRECTIVE: 
Article 1 
1. In derogation from Article 34 of Directive 
75/319/EEC, and subject to the provisions of this Directive, 
Directives 65/65/EEC and 75/319/EEC shall apply to 
immunological medicinal products consisting of vaccines, 
toxins and serums and allergen products for human use. 
2. For the purposes of this Directive, the following 
definitions shall apply: 
— 'immunological medicinal product' shall mean a product 
of biological origin which is intended to effect the 
immune system and which is used in the diagnosis, 
prevention or treatment of disease. Included are vaccines, 
toxins and serums and allergens, 
— 'allergen product' shall mean any product which is 
intended to identify or induce a specific acquired 
alteration in the immunological response to an allergising 
agent, 
— vaccins, toxins and sera shall have the meaning assigned 
to them in the Annex to Directive 75/319/EEC. 
Article 2 
1. The quantitative particulars of an immunological 
medicinal product shall be expressed by mass or by 
international units or by units of biological activity or by 
protein content as appropriate to the product concerned. 
2. In Directives 65/65/EEC and 75/319/EEC, the 
expressions 'qualitative and quantitative particulars of the 
constituents' shall also include particulars relating to 
(») OJ No L 147, 9. 6. 1975, p. 1. 
(2) OJNoL 15, 17. 1. 1987, p. 31. biological activity or to protein content and 'qualitative and 
quantitative composition' shall include the composition of 
the product expressed in terms of biological activity.or of 
protein content. 
3. Whenever the name of an immunological medicinal 
product is expressed, the common or scientific name of the 
active constituents shall also be included. 
Article 3 
In addition to the information referred to in Article 4a of 
Directive 65/65/EEC, the summary of product 
characteristics referred to in point 9 of the second paragraph 
of Article 4 of Directive 65/65/EEC shall contain the 
following information in respect of immunological 
products: 
'— under point 5.4, information about any special 
precautions to be taken by persons handling the 
immunological medicinal product and persons 
administering it to patients, together with any 
precautions to be taken by the patient.' 
Article 4 
1. Member States shall ensure that the manufacturing 
processes used in the manufacture of immunological 
products are properly validated and attain batch-to-batch 
consistency. To this end the competent authority may submit 
samples from up to five in total of the bulk and /or finished 
product batches for testing by a State laboratory or a 
laboratory designated for that purpose, either during the 
examination of the application pursuant to Article 4 of 
Directive 75/319/EEC, or after a marketing authorization 
has been granted. 
2. For the purpose of implementing Article 8 of Directive 
65/65/EEC and Article 27 of Directive 75/319/EEC, 
Member States may require persons responsible for 
marketing immunological products to submit to a competent 
authority copies of all the control reports signed by the 
qualified person in accordance with Article 22 of Directive 
75/319/EEC. 
3. Where it considers it necessary in the interests of public 
health, a Member State may require persons responsible for 
marketing the live vaccines, vaccines used in the primary 
immunization of infants, or vaccines used in public health 
immunization programmes, which are listed in the Annex to 
this Directive, to submit to a competent authority samples 
from each batch of the bulk and/or finished product for 
examination by a State laboratory or a laboratory designated 
for that purpose before release onto the market, unless the 
competent authority of another Member State has previously 
examined the batch in question and declared it to be in 
conformity with the approved specification. Member States 
8. 2. 88 Official Journal of the European Communities No C 36/27 
shall ensure that any such examination is completed within 
60 days of the receipt of the samples. The Annex to this 
Directive containing the list of vaccines which may be 
submitted for examination prior to release may be amended 
in accordance with the procedure laid down in Article 2c of 
Directive 75/318/EEC. 
Article 5 
Any amendments which are necessary in the testing 
requirements for medicinal products set out in the Annex to 
Directive 75/318/EEC, to take account of the extension of 
the scope of Directives 65/65/EEC and 75/319/EEC to 
cover immunological medicinal products, shall be adopted in 
accordance with the procedure laid down in Article 2c of 
Directive 75/318/EEC. Any such amendments shall come 
into effect on the same date as this Directive. Article 6 
1. Member States shall take the necessary measures to 
comply with this Directive not later than 1 January 1991. 
They shall forthwith inform the Commission thereof. 
2. Requests for marketing authorization for products 
covered by this Directive lodged after the time limit referred 
to in paragraph 1 must comply with the provisions of this 
Directive. 
3. This Directive shall be progressively extended to 
the existing immunological medicinal products before 
31 December 1992. 
Article 7 
This Directive is addressed to the Member States. 
ANNEX 
LIST OF VACCINES REFERRED TO IN ARTICLE 4 (3) 
Vaccines for human use, presented or used for the prophylaxis of the following diseases: 
Cholera 
Diphtheria 
Hepatitis 
Influenza 
Measles 
Mumps 
Pertussis 
Polio 
Rabies 
Rubella 
Tetanus 
Tuberculosis 
Typhoid 
Yellow Fever