CELEX: 51984PC0437(02)
Language: en
Date: 1984-09-25
Title: PROPOSAL FOR A COUNCIL DIRECTIVE AMENDING DIRECTIVE 75/318/EEC ON THE APPROXIMATION OF THE LAWS OF MEMBER STATES RELATING TO ANALYTICAL, PHARMACO-TOXICOLOGICAL AND CLINICAL STANDARDS AND PROTOCOLS IN RESPECT OF THE TESTING OF PROPRIETARY MEDICINAL PRODUCTS

No C 293/4                         Official Journal of the European Communities                            5. 11. 84
                                                          ANNEX
                              LIST OF HIGH-TECHNOLOGY' MEDICINAL PRODUCTS
              A. Medicinal products developed by means of new biotechnological processes
                  which make use of genetic recombination, hybridoma technology, aneuploid cell strains and
                  enzyme bioreactors.
                  For example:
                  — new vaccines, particularly synthetic vaccines,
                  — new antibiotics,
                  — interferons,
                  — immunotoxins,
                  — hormones, particularly peptide hormones (human insulin; growth hormone),
                  — monoclonal antibodies and DNA hybridization probes used in vivo,
                  — enzymes such as urokinase,
                  — blood proteins or substitutes thereof: alpha I, antitrypsin, human seralbumin, factor
                      VIII, etc.
              B.  Other high-technology medicinal products
                  — Medicinal products administered by means of new delivery systems which constitute a
                      major innovation: transcutaneous systems, encapsulation in liposomes or polymers,
                      drug targeting systems, etc.
                  — Medicinal products containing a new substance claimed to be of major therapeutic
                      interest.
                  — New medicinal products based on radioisotopes.
                  — Medicinal products the manufacture of which is based upon an advanced technique
                      such as two-dimensional electrophoresis under gravity or microgravity.
             Proposal for a Council Directive amending Directive 75/318/EEC on the approximation
             of the laws of Member States relating to analytical, pharmaco-toxicological and clinical
                 standards and protocols in respect of the testing of proprietary medicinal products
                                                   COM(84)     437final
                          (Submitted by the Commission to the Council on 3 October 1984)
                                                     (84/C 293/02)
THE COUNCIL OF THE EUROPEAN                                     Having regard to the opinion of the Economic and
COMMUNITIES,                                                    Social Committee;
Having regard to the Treaty establishing the Euro-
pean Economic Community, and in particular
Article 100 thereof;
Having regard to the proposal from the Commis-
sion;                                                           Whereas the testing of proprietary medicinal prod-
                                                                ucts must regularly be adapted to scientific and
Having regard to the opinion of the European Par-               technical progress in order to ensure optimum pro-
liament;                                                        tection of public health in the Community;
 ---pagebreak--- 5. 11.84                              Official Journal of the European Communities                         No C 293/5
Whereas, in order to achieve such optimum protec-                    Article 2b
tion of health, the resources allocated to pharma-
ceutical research must not be squandered on obso-                     1. A Committee on the Adaptation to Tech-
lete or repetitive tests resulting from divergences                  nical Progress of the Directives on the Removal
between the Member States in assessing the state of                  of Technical Barriers to Trade in the Proprietary
the art in science and technology;                                    Medicinal Products Sector, hereinafter called
                                                                     "the Committee", is hereby set up; it shall con-
                                                                     sist of representatives of the Member States
                                                                     with a representative of the Commission as
Whereas, for ethical reasons, it is necessary to                      chairman.
replace existing methods as soon as scientific and
technical advances so allow by methods involving                     2. The Committee shall adopt its own rules of
as few laboratory animals as possible;                               procedure.
                                                                     Article 2c
Whereas it is therefore necessary to introduce a
rapid procedure for adapting to technical progress                   1. Where the procedure laid down in this
the requirements regarding the testing of medicinal                  Article is to be followed, matters shall be
products listed in the Annex to Council Directive                    referred to the Committee by the chairman,
75/318/EECC), as amended by Directive 83/570/                        either on his own initiative or at the request of
EEC (2), whilst ensuring close cooperation between                   the representative of a Member State.
the Commission and the Member States within a
'Committee for the Adaptation to Technical pro-                      2. The representative of the Commission shall
gress of the Directives on the Removal of Technical                  submit to the Committee a draft of the measures
Barriers to Trade in the Proprietary Medicinal Prod-                 to be adopted. The Committee shall deliver its
ucts Sector';                                                        opinion on the draft within a time limit set by
                                                                     the chairman, having regard to the urgency of
                                                                     the matter. It shall act by a qualified majority,
                                                                     the votes of the Member States being weighted
Whereas the requirements relating to the testing of                  as provided in Article 148 (2) of the Treaty. The
medicinal products must also be capable of rapid                     chairman shall not vote.
revision by the same procedure, having regard to the
evolution of test methods and of good laboratory                     3. (a) The Commission shall adopt the mea-
practices recognized by the Community or in inter-                             sures envisaged where they are in
national trade in medicinal products,                                          accordance with the opinion of the
                                                                               Committee.
                                                                          (b) Where the measures envisaged are not
                                                                               in accordance with the opinion of the
                                                                               Committee, or if no opinion is adopted,
 HAS ADOPTED THIS DIRECTIVE:                                                   the Commission shall without delay
                                                                               propose to the Council the measures to
                                                                               be adopted. The Council shall act by a
                         Article 1                                             qualified majority.
 Directive 75/318/EEC is hereby amended as fol-                           (c) If, within three months of the proposal
 lows:                                                                         being submitted to it, the Council has
                                                                               not acted, the proposed measures shall
                                                                               be adopted by the Commission.'
 1. The following Articles 2a, 2b and 2c are
     inserted:
                                                                  2.  Part 2 of the Annex, 'Toxicological and Pharma-
                                                                      cological Tests' is hereby amended as follows:
      'Article 2a
                                                                      (a) The following paragraph is inserted after
     Any changes which are necessary in order to                           the introductory paragraph:
     adapt the Annex to take account of technical
     progress shall be adopted in accordance with                          'The Member States shall ensure that the
     the procedure laid down in Article 2c.                                safety tests are executed in conformity with
                                                                           the principles of good laboratory practice
                                                                           recognized by Community law in the field
 (') OJ No L 147, 9. 6. 1975, p. 1.                                        of tests on dangerous substances, or in the
 Q   OJ No L 332, 28. 11. 1983, p. 1.                                      absence thereof, with those recommended
 ---pagebreak--- No C 293/6                        Official Journal of the European Communities                               5. 11.84
        by the Organization for Economic Coopera-                       macroscopic changes at autopsy. The maxi-
        tion and Development.'                                          mum amount of information should be
                                                                        obtained from the animals used in the
    (b) In Chapter I (B) 'Toxicity', the text of para-
                                                                        study. The single dose toxicity tests should
        graph 1 is replaced by the following:
                                                                        be conducted in such a way that signs of
        ' 1. Single dose toxicity                                       acute toxicity are revealed and the mode of
        An acute test infers a qualitative and quan-                    death assessed as far as reasonably possible.
        titative study of the toxic reactions which                     In suitable species a quantitative evaluation
        may result from a single administration of                      of the approximate lethal dose and informa-
        the active substance or substances con-                         tion on the dose-effect relationship should
        tained in the proprietary medicinal product,                    be obtained, but a high level of precision is
                                                                        not required.
        in the proportions and physico-chemical
        state in which they are present in the actual                   These studies may give some indication of
        product.                                                        the likely effects of acute overdosage in
        The acute toxicity test must be carried out                     man and may be useful for the design of
        on two or more mammalian species of                             toxicity studies requiring repeated dosing
        known strain unless a single species can be                     on the relevant animal species.
        justified. At least two different routes of                     In the case of active substances in combina-
        administration shall normally be used, one                      tion, the study must be carried out in such a
        being identical with or similar to that pro-                    way as to check whether or not there is en-
        posed for use in human beings and the                           hancement of toxicity or if novel toxic
        other ensuring systemic absorption of the                       effects occur.'
        substance.
        This study will cover the signs observed,
        including local reactions. The period during                                    Article 2
        which the test animals are observed shall be
         fixed by the investigator as being adequate           Member States shall take the measures necessary in
        to reveal tissue or organ damage or recov-             order to comply with this Directive no later than
         ery, usually for a period of 14 days but not          1 January 1986. They shall forthwith inform the
         less than seven days, but without exposing            Commission thereof.
         the animals to prolonged suffering. Animals
         dying during the observation period should
         be subject to autopsy as also should all ani-
         mals surviving to the end of the observation                                   Article 3
         period.     Histopathological     examination
         should be considered on any organ showing             This Directive is addressed to the Member States.
              Proposal for a Council Directive amending Directive 81/852/EEC 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 veterinary medicinal products
                                                  COM(84) 437final
                           (Submitted by the Commission to the Council on 3 October 1984)
                                                    (84/C 293/03)
THE COUNCIL OF THE EUROPEAN                                     Having regard to the proposal from the Commis-
COMMUNITIES,                                                    sion;
                                                                Having regard to the opinion of the European Par-
                                                                liament;
Having regard to the Treaty establishing the Euro-
pean Economic Community, and in particular                      Having regard to the opinion of the Economic and
Article 100 thereof;                                            Social Committee;