CELEX: 51984PC0437(03)
Language: en
Date: 1984-09-25
Title: 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 TEESTING OF VETERINARY MEDICINAL PRODUCTS

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;
 ---pagebreak--- 5. 11.84                             Official Journal of the European Communities                         No C 293/7
Whereas the testing of veterinary medicinal prod-                   progress shall be adopted in accordance with
ucts must regularly be adapted to scientific and                    the procedure laid down in Article 2c below.
technical progress in order to safeguard the health of
consumers of livestock products and to ensure opti-
mum protection of animal health in the Com-                         Article 2b
munity;
                                                                     1. A Committee for the Adaptation to Tech-
                                                                    nical Progress of the Directives on the Removal
Whereas, in order to achieve this optimum protec-                   of Technical Barriers to Trade in the Veterinary
tion of public health, the resources allocated to                   Medicinal Products Sector, hereinafter called
pharmaceutical research must not be squandered on                   "the Committee", is hereby set up; it shall con-
obsolete or repetitive tests resulting from diver-                  sist of representatives of the Member States with
gences between the Member States in assessing the                   a representative of the Commission as chair-
state of the art in science and technology;                         man.
                                                                    2. The Committee shall adopt its own rules of
Whereas, for ethical reasons, it is necessary to                    procedure.
replace the existing methods as soon as scientific
and technical advances so allow by methods involv-
ing as few laboratory animals as possible;                          Article 2c
                                                                    1. Where the procedure laid down in this
Whereas it is therefore necessary to introduce a                    Article is to be followed, matters shall be
rapid procedure for adapting to technical progress                  referred to the Committee by the chairman,
the requirements regarding the testing of the medi-                 either on his own initiative or at the request of
cinal products listed in the Annex to Council Direc-                the representative of a Member State.
tive 81/852/EEC ('), whilst ensuring close coopera-
tion between the Member States and the Commis-                      2. The representative of the Commission shall
sion within a 'Committee for the Adaptation to                      submit to the Committee a draft of the measures
Technical Progress of the Directives on the Removal                 to be adopted. The Committee shall deliver its
of Technical Barriers to Trade in the Veterinary                    opinion on the draft within a time limit set by
Medicinal Products Sector',                                         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
 HAS ADOPTED THIS DIRECTIVE:                                                  Committee, or if no opinion is adopted,
                                                                              the Commission shall without delay
                                                                              propose to the Council the measures to
                         Article 1                                            be adopted. The Council shall act by a
                                                                              qualified majority.
 Directive 81/852/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
  1. The following Articles 2a, 2b and 2c are                                 be adopted by the Commission.'
     inserted:
      'Article 2a                                               2.   Part 2 of the Annex, 'Toxicological and Pharma-
                                                                     cological Tests' is hereby amended as follows:
     Any changes which are necessary in order to
     adapt the Annex to take account of technical                    (a) The following paragraph is inserted after
                                                                          the two introductory paragraphs:
                                                                          'The Member States shall ensure that the
 (') OJ No L 317, 6. 11. 1981, p. 16.                                     laboratory tests are executed in conformity
 ---pagebreak--- No C 293/8                          Official Journal of the European Communities                             5. 11. 84
         with the principles of good laboratory prac-                   obtained from the animals used in the
         tice recognized by Community law in the                        study. The single dose toxicity tests should
         field of tests on dangerous substances or, in                  be conducted in such a way that signs of
         the absence thereof, with those recom-                         acute toxicity are revealed and the mode of
         mended by the Organization for Economic                        death assessed as far as reaspnably possible.
         Cooperation and Development.'                                  In suitable species a quantitative evaluation
     (b) In Chapter I (B) (1) the fourth subparagraph                   of the approximate lethal dose and informa-
         is replaced by the following:                                  tion on the dose-effect relationship should
                                                                        be obtained, but a high level of precision is
         'This study will cover the signs observed,                     not required.'
         including local reactions. The period during
         which the test animals are observed shall be
         fixed by the investigator as being adequate
         to reveal tissue or organ damage or recov-                                     Article 2
         ery, usually for a period of 14 days but not
         less than seven days, but without exposing            Member States shall take the measures necessary to
         the animals to prolonged suffering. Animals           comply with this Directive no later than 1 January
         dying during the observation period should            1986. They shall forthwith inform the Commission
         be subject to autopsy as also should all ani-         thereof.
         mals surviving to the end of the observation
         period.     Histopathological       examination
         should be considered on any organ showing                                      Article 3
         macroscopic changes at autopsy. The maxi-
         mum amount of information should be                   This Directive is addressed to the Member States.
              Proposal for a Council recommendation concerning tests relating to the placing on the
                                       market of proprietary medicinal products
                                                   COM(84)    437final
                           (Submitted by the Commission to the Council on 3 October 1984)
                                                     (84/C 293/04)
THE COUNCIL OF THE EUROPEAN                                     products ('), the Council adopted a first series of
COMMUNITIES,                                                    notes for guidance intended to prevent differences
                                                                of interpretation in the implementation of the stan-
Having regard to the Treaty establishing the Euro-              dards and protocols for the testing of proprietary
pean Economic Community,                                        medicinal products provided for by Council Direc-
                                                                tive 75/318/EEC of 20 May 1975 on the approxima-
Having regard to the proposal from the Commis-                  tion of the laws of the Member States relating to
sion,                                                           analytical, pharmaco-toxicological and clinical stan-
                                                                dards and protocols in respect of the testing of pro-
Having regard to the opinion of the European Par-               prietary medicinal products (2), as amended by
                                                                Directive 83/570/EEC ( 3 );
liament,
Having regard to the opinion of the Economic and
Social Committee,                                               Whereas the adoption of new notes for guidance,
                                                                supplementing those annexed to recommendation
Whereas in Council recommendation 83/571/EEC                    83/571/EEC, will help to promote the free move-
of 26 October 1983 concerning tests relating to the             ment of proprietary medicinal products by facilitat-
placing on the market of proprietary medicinal
                                                                (2)  OJ No L 147, 9. 6. 1975, p. 1.
(')  OJ No L 332, 28. 11. 1983, p. 11.                          (3)  OJNoL332, 28. 11. 1983, p. 1.