CELEX: 51984PC0437(05)
Language: en
Date: 1984-09-25
Title: PROPOSAL FOR A COUNCIL DIRECTIVE AMENDING DIRECTIVE 65/65/EEC ON THE APPROXIMATION OF PROVISIONS LAID DOWN BY LAW, REGULATION OR ADMINISTRATIVE ACTION RELATING TO PROPRIETARY MEDICINAL PRODUCTS

5. 11. 84                             Official Journal of the European Communities                               No C 293/43
                             dose range. However, in most cases it will be necessary to develop suitable cold
                             analytical methods to separate and assay quantitatively the metabolites and/or the
                             parent compound.
                       (d) Interpretation of data
                             The mathematical methods used (graphical representation, computer analysis,
                             pharmacokinetic formulas) should be stated, including the confidence limits.
                       (e) Presentation and evaluation of the results
                             In summarizing data obtained from more than one subject, it is usually preferable
                            to analyze individual data and at a later stage to average the pharmacokinetic con-
                            stants so obtained.
                             Proper statistical analysis of the data obtained should be made and the inter- and
                             intra-individual variations estimated, in at least some of the studies where the num-
                             ber of subjects is large enough.
             Proposal for a Council Directive amending Directive 65/65/EEC on the approximation
             of provisions laid down by law, regulation or administrative action relating to proprietary
                                                       medicinal products
                                                        COM(84)     437final
                            (Submitted by the Commission to the Council on 3 October 1984)
                                                         (84/C 293/05)
THE COUNCIL OF THE EUROPEAN                                          results of pharmacological and toxicological tests or
COMMUNITIES,                                                         clinical trials do not have to be provided with a view
                                                                     to obtaining authorization for a medicinal product
Having regard to the Treaty establishing the Euro-                   which is essentially similar to an authorized prod-
pean Economic Community, and in particular                           uct, while ensuring that innovative firms are not
Article 100 thereof,                                                 placed at a disadvantage;
Having regard to the proposal from the Commis-
sion,                                                                Whereas additional details were provided in respect
                                                                     of the application of the abovementioned provision
Having regard to the opinion of the European Par-                    by Council Directive 75/318/EEC of 20 May 1975
liament,                                                             on the approximation of the laws of the Member
                                                                     States relating to analytical, pharmaco-toxicological
                                                                     and clinical standards and protocols in respect of
Having regard to the opinion of the Economic and
                                                                     the testing of proprietary medicinal products (3), as
Social Committee,                                                    amended by Directive 8 3 / 5 7 0 / E E C ;
Whereas point 8 of the second paragraph of
Article 4 of Council Directive 6 5 / 6 5 / E E C ('), as last
amended by Directive 83/570/EEC (2) provides that                    Whereas, however, considerations of public policy
various types of proof of the safety and efficacy of a               are against the repetition of tests on animals or trials
proprietary medicinal product may be put forward                     in man without pressing reasons;
in an application for marketing authorization
depending upon the objective situation of the medi-
cinal product in question;                                           Whereas it is also advisable to make the packaging
                                                                     of certain medicinal products, particularly sought
Whereas experience has shown that it is advisable to                 after by drug addicts, more commonplace by sup-
                                                                     pressing the obligation to mark the outer packaging
stipulate more precisely the cases in which the
(')  OJ No 22, 9. 2. 1965, p. 369/65.
O    OJ No L 332, 28. 11. 1983, p. 1.                                O    OJ No L 147, 9. 6. 1975, p. 1.
 ---pagebreak--- No C 293/44                          Official Journal of the European Communities                              5. 11.84
and the container of medicines classified as narcot-                               uent or constituents of the proprie-
ics with a special sign,                                                           tary product have a well-established
                                                                                   medicinal use with recognized effi-
                                                                                   cacy and an acceptable level of
                                                                                   safety;
HAS ADOPTED THIS DIRECTIVE:
                                                                             (iii) or that the proprietary product is
                                                                                   essentially similar to a product
                                                                                   which has been authorized for more
                          Article 1
                                                                                   than 10 years in the country con-
                                                                                   cerned by the application;
Directive 65/65/EEC is hereby amended as follows:
                                                                             however, where the proprietary product
1. Point 8 of the second paragraph of Article 4 is                           is intended for a different therapeutic
     hereby replaced by the following text:                                  use from that of the other medicinal
                                                                             products marketed or is to be adminis-
     '8. Results of:                                                         tered by different routes or in different
         — physico-chemical, biological or micro-                            doses, the results of appropriate phar-
              biological tests,                                              macological and toxicological tests
                                                                             and/or of appropriate clinical trials
         — pharmacological and toxicological tests,                          must be provided.
         — clinical trials.                                              (b) in the case of a new proprietary product
         However, and without prejudice to the law                           containing known constituents not hith-
         relating to the protection of industrial and                        erto used in combination for therapeu-
         commercial property:                                                tic purposes, the results of pharmacol-
                                                                             ogical and toxicological tests and of
         (a) the applicant shall not be required to
                                                                             clinical trials relating to that combina-
              provide the results of pharmacological
                                                                             tion must be provided, but it shall not
              and toxicological tests or the results of
                                                                             be necessary to provide references relat-
              clinical trials if he can demonstrate:
                                                                             ing to each individual constituent.'
              (i) either that the proprietary product
                   is essentially similar to a product          2.  Article 16 is repealed.
                   authorized in the country con-
                   cerned by the application and that
                   the person responsible for the mar-                                   Article 2
                   keting of the original proprietary
                   product has consented to the phar-           Member States shall take the measures necessary to
                   macological, toxicological or clini-         comply with this Directive no later than 1 January
                   cal references contained in the file         1986. They shall forthwith inform the Commission
                   on the original proprietary medi-            thereof.
                   cinal product being used for the
                   purpose of examining the applica-
                   tion in question;                                                      Article 3
              (ii) or, by reference to the published
                   scientific literature, that the constit-     This Directive is addressed to the Member States.