3. 12. 88 Official Journal of the European Communities No C 308/21 
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 special provisions for 
medicinal products derived from human (') 
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 308/09) 
(') OJ No C 36, 8. 2. 1988, p. 28. 
ORIGINAL PROPOSAL AMENDED PROPOSAL 
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 medicinal products 
derived from human blood 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 special provisions for medicinal products 
derived from human plasma 
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 medicinal products derived from 
human blood 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 0) as last amended by Directive 
87/21/EECC), 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 
medicinal products derived from human blood; THE COUNCIL OF THE EUROPEAN COMMUNITIES, 
Visas unchanged 
First to fifth recitals unchanged 
(») 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. 
No C 308/22 Official Journal of the European Communities 3. 12. 88 
ORIGINAL PROPOSAL AMENDED 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 manu­
facture and placing on the market of medicinal products 
derived from human blood before 22 December 1987; 
Whereas the European Community entirely supports the 
efforts of the Council of Europe to promote voluntary 
and non-remunerated blood donation to attain self-suffi­
ciency throughout the Community in the supply of blood 
products, and to ensure the respect of ethical principles 
in trade of therapeutic substances of human origin; 
Whereas the rules designed to guarantee the quality, 
safety and efficacy of medicinal products derived from 
human blood must be applied in the same manner to 
both public and private establishments; Whereas the rules designed to guarantee the quality, 
safety and efficacy of medicinal products derived from 
human plasma must be applied in the same manner to 
both public and private establishments, and to blood 
imported from countries outside the EEC; 
Whereas, before an authorization to market a medicinal 
product derived from human blood can be granted, the 
manufacturer must demonstrate his ability to guarantee 
batch-to-batch consistency and the absence of viral 
contamination; Seventh recital unchanged 
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 (2), as last amended by Directive 
87/19/EEC of 22 December 1987 (}), to take account of 
the special nature of medicinal products derived from 
human blood 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, 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 
medicinal products derived from human plasma in close 
cooperation with the Committee for the Adaptation to 
Technical Progress of the Directives on the Removal of 
Technical Barriers to Trade in Medicinal Products, so as 
to ensure greater quality, safety and efficacy; 
(') OJ No L 15, 17. 1. 1987, p. 38. 
(2) OJ No L 147, 9. 6. 1975, p. 1. 
(3) OJ No L 15, 17. 1. 1987, p. 31. 
3. 12. 88 Official Journal of the European Communities No C 308/23 
ORIGINAL PROPOSAL 
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 medicinal products based on blood constituents 
which are prepared industrially by public or private 
establishments, hereinafter referred to as 'medicinal 
products derived from human blood'; these medicinal 
products include, in particular, albumin, coagulating 
factors and immunoglobulins of human origin. 
2. This Directive shall not apply to whole blood, to 
plasma or to blood cells of human origin. 
3. Nothing in the present Directive shall in any way 
derogate from Council Decision 86/346/EEC (') 
accepting, in the name of the Community, the European 
Agreement relating to the exchange of therapeutic 
substances of human origin. 
Article 2 
1. The quantitative particulars of a medicinal product 
derived from human blood shall be expressed by mass or 
by international units or by units of biological activity 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 include particulars relating to bio­
logical activity and 'qualitative and quantitative compo­
sition' shall include the composition of the product 
expressed in terms of biological activity. 
3. Whenever the name of a medicinal product derived 
from human blood is expressed, the common or the 
scientific name of the active constituents shall also be 
included. 
Article 3 
In order to prevent the transmission of infectious 
diseases, the Member States shall take into consideration 
the measures recommended within the framework of the 
Council of Europe and the World Health Organization 
in particular for the selection and testing of blood 
donors. 
O OJ No L 207, 30. 7. 1986, p. 1. AMENDED PROPOSAL 
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 medicinal products based on blood constituents 
which are prepared industrially by public or private 
establishments, hereinafter referred to as 'medicinal 
products derived from human plasma'; these medicinal 
products include, in particular albumin, coagulating 
factors and immunoglobulins of human origin. 
2. Unchanged 
3. Unchanged 
Article 2 
1. The quantitative particulars of a medicinal product 
derived from human plasma shall be expressed by mass 
or by international units or by units of biological activity 
as appropriate to the product concerned. 
2. Unchanged 
3. In any document, established for the purpose of this 
Directive, where the name of a medicinal product 
derived from human plasma 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 
1. The Member States shall take the necessary 
measures to prevent the transmission of infectious 
diseases. These measures shall at least comprise those 
recommended by the Council of Europe and the World 
Health Organization, particularly with reference to the 
selection and testing of blood donors. 
No C 308/24 Official Journal of the European Communities 3. 12. 88 
ORIGINAL PROPOSAL AMENDED PROPOSAL 
2. The Member States shall take the necessary 
measures to ensure that, where human blood is traded, 
the origin of the blood donation centre is always clearly 
identified. 
3. Moreover, every guarantee as to safety and purity 
must also be given as regards imports of human blood 
from countries outside the EEC. 
4. The Member States shall take the necessary 
measures to promote self-sufficiency of the Community in 
human blood. For this purpose, voluntary unpaid 
donation of blood shall be encouraged. 
Article 4 
1. Member States shall ensure that the manufacturing 
processes used in the manufacture of medicinal products 
derived from human blood are properly validated, attain 
batch-to-batch consistency and guarantee the absence of 
viral contaminants. 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 ensure that the manufacturing 
processes used in the preparation of medicinal products 
derived from human plasma are properly validated, attain 
batch-to-batch consistency and guarantee, in so far as 
the state of technology permits, the absence of viral 
contaminants. To this end the manufacturer shall notify 
the authorities of the proposed method for reducing or 
eliminating the pathogenic viruses which may be trans­
mitted by medicinal products derived from human 
plasma. For this purpose 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 medicinal products derived 
from human blood 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. 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 medicinal products derived 
from human plasma 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 medicinal products derived 
from human blood 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 specifications. Member States shall ensure that 
any such examination is completed within 30 days of the 
receipt of the samples. 3. Where, in the interests of public health, the legis­
lation of a Member State so provides, the appropriate 
authorities may require persons responsible for marketing 
medicinal products derived from human plasma 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 specifications. Member 
States shall ensure that any such examination is 
completed within 60 days of the receipt of the samples. 
3. 12. 88 Official Journal of the European Communities No C 308/25 
ORIGINAL PROPOSAL 
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 medicinal products derived from 
human blood shall be adopted in accordance with the 
procedure laid down in Article 2 (c) 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 the first paragraph must comply with the 
provisions of this Directive. 
3. This Directive shall be progressively extended to 
the existing medicinal products derived from human 
blood referred to in Article 1 (1) before 31 December 
1992. 
Article 7 
This Directive is addressed to the Member States. AMENDED PROPOSAL 
Article 4a 
The procedure for marketing authorization for medicinal 
products derived from human plasma shall be that laid 
down in Directive 87/22/EEC. 
Article "> 
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 medicinal products derived from 
human plasma shall be adopted in accordance with the 
procedure laid down in Article 2c of Directive 
75/318/EEC. 
Second sentence deleted 
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 shall comply with the provisions of this 
Directive. 
4. This Directive shall be progressively extended to 
existing medicinal products derived from human plasma, 
referred to in Article 1 (1), before 31 December 1992. 
Article 7 
Unchanged