No C 308/16 Official Journal of the European Communities 3. 12. 88 
Amended 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(88) 663 final — SYN 114 
(Submitted by the Commission to the Council pursuant to the third paragraph of Article 149 of the 
Treaty on 11 November 1988) 
(88/C 308/08) 
(') OJ No C 36, 8. 2. 1988, p. 25. 
ORIGINAL PROPOSAL AMENDED PROPOSAL 
Title unchanged 
THE COUNCIL OF THE EUROPEAN COMMUNITIES, THE COUNCIL OF THE EUROPEAN COMMUNITIES, 
Having regard to the Treaty establishing the European Visas unchanged 
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, First five recitals unchanged 
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, 
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, 
O OJ No 22, 9. 2. 1965, p. 369/65. 
(2) OJ No L 15, 17. 1. 1987, p. 36. 
O OJ No L 147, 9. 6. 1975, p. 13. 
(4) OJ No L 332, 28. 11. 1983, p. 1. 
3. 12. 88 Official Journal of the European Communities No C 308/17 
ORIGINAL PROPOSAL 
Whereas in accordance with Article 5 of Directive 
87/22/EEC (') 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 immuno­
logical medicinal products before 22 December 1987; 
Whereas, before an authorization to market an immuno­
logical 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 approxi­
mation 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 1987 (2), to take account of 
the special nature of immunological medicinal products 
in close cooperation with the Committee for the Adap­
tation 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, 
(») OJ No L 15, 17. 1. 1987, p. 38. 
(2) OJ No L 147, 9. 6. 1975, p. 1. 
O OJ No L 15, 17. 1. 1987, p. 31. AMENDED PROPOSAL 
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 approxi­
mation 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 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, thus ensuring greater quality, safety and efficacy. 
HAS ADOPTED THIS DIRECTIVE: 
Article 1 
1. Unchanged 
2. For the purposes of this Directive, the following 
definitions shall apply: 
— first indent deleted 
— second indent unchanged 
— third indent unchanged 
NoC 308/18 Official Journal of the European Communities 3. 12. 88 
ORIGINAL PROPOSAL AMENDED PROPOSAL 
'allergen product' shall mean any product which is 
intended to identify or induce a specific acquired 
alteration in the immunological response to an aller-
gising agent, 
vaccines, toxins and sera shall have the meaning 
assigned to them in the Annex of Directive 
75/319/EEC. 
Article 2 
1. The quantitative particulars of an immunological 
medicinal product shall be expressed by mass or by inter­
national units or by units of biological activity or by 
protein content as appropriate to the product concerned. Article 2 
1. The quantitative particulars of an immunological 
medicinal product shall be expressed by mass or by inter­
national units or by units of biological activity or by 
specific protein content where possible 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 
biological activity or to protein content and 'qualitative 
and quantitative composition' shall include the compo­
sition of the product expressed in terms of biological 
activity or of protein content. 2. In respect of immunological products in Directive 
65/65/EEC and 75/319/EEC, the expressions 'quali­
tative and quantitative particulars of the constituents' 
shall include particulars relating to 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. 3. In any document established for the purpose of this 
Direction in which the name of an immunological 
medicinal product is expressed, the common or scientific 
name of the active constituents shall also be included at 
least once. It may be abbreviated in the remaining 
references. 
Article 3 
In addition to the information referred to in Article 4a of 
Directive 65/65/EEC, the summary of product charac­
teristics 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 3 
Unchanged 
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. Article 4 
1. Member States shall take all appropriate steps to 
ensure that the manufacturing processes used in the 
manufacture of immunological products are properly 
validated and attain batch-to-batch consistency. 
Second sentence deleted 
3. 12. 88 Official Journal of the European Communities No C 308/19 
ORIGINAL PROPOSAL 
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 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. AMENDED PROPOSAL 
2. Unchanged 
3. Where, in the interests of public health, the legis­
lation of a Member State so provides, the competent 
authorities may require persons responsible for 
marketing: 
— live vaccines, 
— immunological medicinal products used in the 
primary immunization of infants or of other age 
groups at risk, 
— immunological medicinal products used in public 
health immunization programmes, 
— during a transitional period to be laid down by the 
marketing authorization, immunological medicinal 
products which are novel or which are manufactured 
using novel or modified techniques or which are novel 
for a particular manufacturer, 
to submit to control by a State laboratory or a laboratory 
approved for that purpose samples from each batch of 
the bulk and/or finished product, before release onto the 
market, unless in the case of a batch manufactured in 
another Member State, the competent authority of a 
Member State has previously examined the batch in 
question and declared it to be in conformity with the 
approved specification. Member States shall ensure that 
any such examination is completed within 60 days of the 
receipt of the samples. 
Last sentence deleted 
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. 
Second sentence deleted 
No C 308/20 Official Journal of the European Communities 3. 12. 88 
ORIGINAL PROPOSAL AMENDED PROPOSAL 
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 the first paragraph 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 6 
1. Save in the case provided for in paragraph 2, 
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. In the event of the amendments to Directive 
75/318/EEC referred to in Article 5 not being adopted 
by the date referred to in paragraph 1, this date shall be 
replaced by the date of adoption. 
3. Requests for marketing authorization for products 
covered by this Directive, lodged after the date of 
implementation comply with the provisions of this 
Directive. 
4. This Directive shall be progressively extended to 
existing immunological medicinal products before 31 
December 1992. 
Article 7 
This Directive is addressed to the Member States. Article 7 
Unchanged 
ANNEX ANNEX 
List of vaccines referred to in Article 4 (3) Deleted 
Vaccines for human use, presented or used for the prophyaxis 
of the following diseases: 
— Cholera 
— Diphteria 
— Hepatitis 
— Influenza 
— Measles 
— Mumps 
— Pertussis 
— Polio 
— Rabies 
— Rubella 
— Tetanus 
— Tuberculosis 
— Typhoid 
— Yellow Fever