CELEX: 51988PC0663(03)
Language: en
Date: 1988-11-10
Title: 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 PLASMA

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               Council Directive extending the scope of Directives
65/65/EEC and 75/319/EEC on the approximation of                  65/65/EEC and 75/319/EEC on the approximation of
provisions laid down by law, regulation or administrative         provisions laid down by law, regulation or administrative
action relating to proprietary medicinal products and             action relating to proprietary medicinal products and
laying down additional provisions for medicinal products          laying down special provisions for medicinal products
                 derived from human blood                                         derived from human plasma
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 to fifth recitals unchanged
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;
(») 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.
 ---pagebreak---  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,             Whereas the rules designed to guarantee the quality,
safety and efficacy of medicinal products derived from           safety and efficacy of medicinal products derived from
human blood must be applied in the same manner to                human plasma must be applied in the same manner to
both public and private establishments;                          both public and private establishments, and to blood
                                                                 imported from countries outside the EEC;
Whereas, before an authorization to market a medicinal           Seventh recital unchanged
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;
Whereas the Commission should be empowered to adopt              Whereas the Commission should be empowered to adopt
any necessary changes in the requirements for the testing        any necessary changes in the requirements for the testing
of proprietary medicinal products set out in the Annex to        of proprietary medicinal products set out in the Annex to
Directive 75/318/EEC of 20 May 1975 on the approxi-              Directive 75/318/EEC of 20 May 1975 on the approxi-
mation of the laws of the Member States relating to              mation of the laws of the Member States relating to
analytical, pharmaco-toxicological and clinical standards        analytical, pharmaco-toxicological and clinical standards
and protocols in respect of the testing of proprietary           and protocols in respect of the testing of proprietary
medicinal products (2), as last amended by Directive             medicinal products, as last amended by Directive
87/19/EEC of 22 December 1987 (}), to take account of            87/19/EEC to take account of the special nature of
the special nature of medicinal products derived from            medicinal products derived from human plasma in close
human blood in close cooperation with the Committee              cooperation with the Committee for the Adaptation to
for the Adaptation to Technical Progress of the                  Technical Progress of the Directives on the Removal of
Directives on the Removal of Technical Barriers to               Technical Barriers to Trade in Medicinal Products, so as
Trade in the Proprietary Medicinal Products Sector,              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.
 ---pagebreak---  3. 12. 88                             Official Journal of the European Communities                            No C 308/23
                      ORIGINAL PROPOSAL                                               AMENDED PROPOSAL
 HAS ADOPTED THIS DIRECTIVE:                                      HAS ADOPTED THIS DIRECTIVE:
                           Article 1                                                      Article 1
 1.    In derogation from Article 34 of Directive                 1.    In derogation from Article 34 of Directive
 75/319/EEC, and subject to the provisions of this                75/319/EEC, and subject to the provisions of this
 Directive, Directives 65/65/EEC and 75/319/EEC shall             Directive, Directives 65/65/EEC and 75/319/EEC shall
 apply to medicinal products based on blood constituents          apply to medicinal products based on blood constituents
which are prepared industrially by public or private             which are prepared industrially by public or private
 establishments, hereinafter referred to as 'medicinal           establishments, hereinafter referred to as 'medicinal
products derived from human blood'; these medicinal              products derived from human plasma'; these medicinal
products include, in particular, albumin, coagulating            products include, in particular albumin, coagulating
factors and immunoglobulins of human origin.                     factors and immunoglobulins of human origin.
2.    This Directive shall not apply to whole blood, to          2.     Unchanged
plasma or to blood cells of human origin.
3.     Nothing in the present Directive shall in any way         3.     Unchanged
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                                                       Article 2
 1.   The quantitative particulars of a medicinal product         1.   The quantitative particulars of a medicinal product
derived from human blood shall be expressed by mass or           derived from human plasma shall be expressed by mass
by international units or by units of biological activity as     or by international units or by units of biological activity
appropriate to the product concerned.                            as appropriate to the product concerned.
2.    In Directives 65/65/EEC and 75/319/EEC the                 2.    Unchanged
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           3.    In any document, established for the purpose of this
from human blood is expressed, the common or the                 Directive, where the name of a medicinal product
scientific name of the active constituents shall also be         derived from human plasma is expressed, the common or
included.                                                        scientific name of the active constituents shall also be
                                                                 included at least once. It may be abbreviated in the
                                                                 remaining references.
                          Article 3                                                       Article 3
In order to prevent the transmission of infectious               1.    The Member States shall take the necessary
diseases, the Member States shall take into consideration        measures to prevent the transmission of infectious
the measures recommended within the framework of the             diseases. These measures shall at least comprise those
Council of Europe and the World Health Organization              recommended by the Council of Europe and the World
in particular for the selection and testing of blood             Health Organization, particularly with reference to the
donors.                                                          selection and testing of blood donors.
O OJ No L 207, 30. 7. 1986, p. 1.
 ---pagebreak--- 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                                                        Article 4
1.    Member States shall ensure that the manufacturing          1.    Member States shall ensure that the manufacturing
processes used in the manufacture of medicinal products         processes used in the preparation of medicinal products
derived from human blood are properly validated, attain         derived from human plasma are properly validated, attain
batch-to-batch consistency and guarantee the absence of         batch-to-batch consistency and guarantee, in so far as
viral contaminants. To this end the competent authority          the state of technology permits, the absence of viral
may submit samples from up to five in total of the bulk          contaminants. To this end the manufacturer shall notify
and/or finished product batches for testing by a state           the authorities of the proposed method for reducing or
laboratory or a laboratory designated for that purpose,         eliminating the pathogenic viruses which may be trans-
either during the examination of the application pursuant        mitted by medicinal products derived from human
to Article 4 of Directive 75/319/EEC, or after a                plasma. For this purpose the competent authority may
marketing authorization has been granted.                        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               2.    For the purpose of implementing Article 8 of
Directive 65/65/EEC and Article 27 of Directive                  Directive 65/65/EEC and Article 27 of Directive
75/319/EEC, Member States may require persons                    75/319/EEC, Member States may require persons
responsible for marketing medicinal products derived             responsible for marketing medicinal products derived
from human blood to submit to a competent authority              from human plasma to submit to a competent authority
copies of all the control reports signed by the qualified        copies of all the control reports signed by the qualified
person in accordance with Article 22 of Directive                person in accordance with Article 22 of Directive
75/319/EEC.                                                      75/319/EEC.
3.    Where it considers it necessary in the interests of        3.    Where, in the interests of public health, the legis-
public health, a Member State may require persons               lation of a Member State so provides, the appropriate
responsible for marketing medicinal products derived             authorities may require persons responsible for marketing
from human blood to submit to a competent authority              medicinal products derived from human plasma to submit
samples from each batch of the bulk and/or finished              to a competent authority samples from each batch of the
product for examination by a state laboratory or a               bulk and/or finished product for examination by a State
laboratory designated for that purpose before release            laboratory or a laboratory designated for that purpose
onto the market, unless the competent authority of               before release onto the market, unless the competent
another Member State has previously examined the batch           authority of another Member State has previously
in question and declared it to be in conformity with the         examined the batch in question and declared it to be in
approved specifications. Member States shall ensure that         conformity with the approved specifications. Member
any such examination is completed within 30 days of the          States shall ensure that any such examination is
receipt of the samples.                                          completed within 60 days of the receipt of the samples.
 ---pagebreak--- 3. 12. 88                             Official Journal of the European Communities                            No C 308/25
                    ORIGINAL PROPOSAL                                                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 5                                                        Article                        ">
Any amendments which are necessary in the testing                Any amendments which are necessary in the testing
requirements for medicinal products set out in the Annex         requirements for medicinal products set out in the Annex
to Directive 75/318/EEC to take account of the                   to Directive 75/318/EEC to take account of the
extension of the scope of Directives 65/65/EEC and               extension of the scope of Directives 65/65/EEC and
75/319/EEC to cover medicinal products derived from              75/319/EEC to cover medicinal products derived from
human blood shall be adopted in accordance with the              human plasma shall be adopted in accordance with the
procedure laid down in Article 2 (c) of Directive                procedure laid down in Article 2c of Directive
75/318/EEC. Any such amendments shall come into                  75/318/EEC.
effect on the same date as this Directive.
                                                                 Second sentence deleted
                         Article 6                                                        Article 6
1.    Member States shall take the necessary measures to         1.    Save in the case provided for in paragraph 2,
comply with this Directive not later than 1 January 1991.        Member States shall take the necessary measures, to
They shall forthwith inform the Commission thereof.              comply with this Directive not later than 1 January 1991.
                                                                They shall forthwith inform the Commission thereof.
2.    Requests for marketing authorization for products          2.    In the event of the amendments to Directive
covered by this Directive lodged after the time limit            75/318/EEC referred to in Article 5 not being adopted
referred to in the first paragraph must comply with the          by the date referred to in paragraph 1, this date shall be
provisions of this Directive.                                    replaced by the date of adoption.
3.    This Directive shall be progressively extended to          3.    Requests for marketing authorization for products
the existing medicinal products derived from human               covered by this Directive lodged after the date of
blood referred to in Article 1 (1) before 31 December            implementation shall comply with the provisions of this
1992.                                                            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                                                       Article 7
This Directive is addressed to the Member States.                Unchanged