CELEX: 51988PC0663(02)
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 ADDITIONAL PROVISIONS FOR IMMUNOLOGICAL MEDICINAL PRODUCTS CONSISTING OF VACCINES, TOXINS OR SERUMS AND ALLERGENS

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.
 ---pagebreak---  3. 12. 88                            Official Journal of the European Communities                            No C 308/17
                     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 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             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 ('), as last amended by Directive             medicinal products, as last amended by Directive
87/19/EEC of 22 December 1987 (2), to take account of            87/19/EEC to take account of the special nature of
the special nature of immunological medicinal products           immunological medicinal products in close cooperation
in close cooperation with the Committee for the Adap-           with the Committee for the Adaptation to Technical
tation to Technical Progress of the Directives on the           Progress of the Directives on the Removal of Technical
Removal of Technical Barriers to Trade in the                    Barriers to Trade in the Proprietary Medicinal Products
Proprietary Medicinal Products Sector,                           Sector, thus ensuring greater quality, safety and efficacy.
HAS ADOPTED THIS DIRECTIVE:                                     HAS ADOPTED THIS DIRECTIVE:
                          Article 1                                                       Article 1
1.     In derogation from Article 34 of Directive                1.    Unchanged
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         2.    For the purposes of this Directive, the following
definitions shall apply:                                         definitions shall apply:
— 'immunological medicinal product' shall mean a                — first indent deleted
     product of biological origin which is intended to
     effect the immune system and which is used in the          — second indent unchanged
     diagnosis, prevention or treatment of disease.
     Included are vaccines, toxins and serums and               — third indent unchanged
     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.
 ---pagebreak--- N o C 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                                                        Article 2
1.     The quantitative particulars of an immunological            1.   The quantitative particulars of an immunological
medicinal product shall be expressed by mass or by inter-          medicinal product shall be expressed by mass or by inter-
national units or by units of biological activity or by            national units or by units of biological activity or by
protein content as appropriate to the product concerned.          specific protein content where possible as appropriate to
                                                                  the product concerned.
2.     In Directives 65/65/EEC and 75/319/EEC the                  2.   In respect of immunological products in Directive
expressions 'qualitative and quantitative particulars of the      65/65/EEC and 75/319/EEC, the expressions 'quali-
constituents' shall also include particulars relating to          tative and quantitative particulars of the constituents'
biological activity or to protein content and 'qualitative        shall include particulars relating to biological activity or
and quantitative composition' shall include the compo-            to protein content and 'qualitative and quantitative
sition of the product expressed in terms of biological            composition' shall include the composition of the
activity or of protein content.                                   product expressed in terms of biological activity or of
                                                                  protein content.
3.     Whenever the name of an immunological medicinal             3.   In any document established for the purpose of this
product is expressed, the common or scientific name of             Direction in which the name of an immunological
the active constituents shall also be included.                   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                                                        Article 3
In addition to the information referred to in Article 4a of       Unchanged
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 4                                                        Article 4
 1.    Member States shall ensure that the manufacturing           1.   Member States shall take all appropriate steps to
processes used in the manufacture of immunological                 ensure that the manufacturing processes used in the
products are properly validated and attain batch-to-batch          manufacture of immunological products are properly
consistency. To this end the competent authority may              validated and attain batch-to-batch consistency.
submit samples from up to five in total of the bulk
and/or finished product batches for testing by a state             Second sentence deleted
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.
 ---pagebreak--- 3. 12. 88                             Official Journal of the European Communities                           No C 308/19
                    ORIGINAL PROPOSAL                                                 AMENDED PROPOSAL
2.    For the purpose of implementing Article 8 of               2.    Unchanged
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        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 competent
responsible for marketing the live vaccines, vaccines used       authorities may require persons responsible            for
in the primary immunization of infants, or vaccines used         marketing:
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          — live vaccines,
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             — immunological medicinal products used in the
authority of another Member State has previously                     primary immunization of infants or of other age
examined the batch in question and declared it to be in              groups at risk,
conformity with the approved specification. Member
States shall ensure that any such examination is
                                                                — immunological medicinal products used in public
completed within 60 days of the receipt of the samples.
                                                                     health immunization programmes,
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                 — during a transitional period to be laid down by the
procedure laid down in Article 2c of Directive                       marketing authorization, immunological medicinal
75/318/EEC.                                                          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                                                        Article 5
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 immunological medicinal products             75/319/EEC to cover immunological medicinal products
shall be adopted in accordance with the procedure laid           shall be adopted in accordance with the procedure laid
down in Article 2c of Directive 75/318/EEC. Any such             down in Article 2c of Directive 75/318/EEC.
amendments shall come into effect on the same date as
this Directive.
                                                                 Second sentence deleted
 ---pagebreak--- No C 308/20                                Official Journal of the European Communities                                3. 12. 88
                       ORIGINAL PROPOSAL                                                  AMENDED PROPOSAL
                            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 immunological medicinal products before 31               covered by this Directive, lodged after the date of
December 1992.                                                        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                                                          Article 7
This Directive is addressed to the Member States.                     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