CELEX: 51993PC0220(01)
Language: en
Date: 1992-06-01
Title: Re-examined proposal for a COUNCIL DIRECTIVE modifying Directives 65/65/EEC, 75/318/EEC and 75/319/EEC relating to medicinal products

COMMISSION OF THE EUROPEAN COMMUNITIES
                                            C0MC93) 220 final - SYN 310,311
                                              Brussels, 1   June 1993
JEW
                          Re-examined proposal for a             SYN 310
                               COUNCIL DIRECTIVE
         modifying Directives 65/65/EEC, 75/318/EEC and 75/319/EEC
                        relating to medicinal products
                          Re-examined proposal for a             SYN 311
                               COUNCIL DIRECTIVE
               modifying Directives 81/851/EEC and 81/852/EEC
           on the approximation of the laws of the Member States
                  relating to veterinary medicinal products
        (presented by the Commission pursuant to Article 149(2)(d)
                              of the EEC Treaty)
 ---pagebreak---                                            - 2
On 21 April 1993 the European Parliament examined three Common Positions
reached by the Council on 17 December 1992 relating to the following proposals of
the Commission:
     proposal for a Council Directive modifying Directives 65/65/EEC, 75/318/EEC
     and 75/319/EEC relating to medicinal products (SYN 310);
     proposal for a Council Directive modifying Directives 81/851/EEC and
      81/852/EEC on the approximation of laws of the Member States relating to
     veterinary medicinal products (SYN 311);
     proposal for a Council Directive repealing Directive 87/22/EEC on the
     approximation of national measures relating to the placing on the market of high
     technology medicinal products, particularly those derived from biotechnology
      (SYN 312).
The parliament has, during the second reading of the co-operation procedure, adopted
13 amendments to the first proposal, 4 amendments to the second proposal and no
amendments to the third proposal.
In accordance with Article 149(2)(d) of the Treaty, the Commission has re-examined
the first two proposals, having it in mind to take up some of the amendments of the
parliament, as described hereafter.
The Commission wishes, meanwhile, to remind the Parliament and the Council that
the decentralised procedure for the authorisation of medicinal products for human and
veterinary use instituted by these Directives will not be able to function in the absence
of the European Medicines Evaluation Agency.
Consequently, the Commission hopes that the Parliament will be prepared rapidly to
give its opinion on the change envisaged by the Council in the legal base of the
proposal for a Regulation laying down Community procedures for the authorisation
and the supervision of medicines for human and veterinary use, and establishing an
European Agency for the evaluation of medicinal products (SYN 309). As far as this
is concerned, the Commission recalls it preference for article 100A as the legal base
for the Regulation.
 ---pagebreak---                                                - 3 -
REVISED PROPOSAL FOR A COUNCIL DIRECTIVE (SYN 310)
MODIFYING DIRECTIVES 65/65/EEC,                          75/318/EEC AND 75/319/EEC
RELATING TO MEDICINAL PRODUCTS
In accordance with Article 149(2)(d) of the Treaty, the Commission has re-examined
the above proposal, having it in mind to take up 5 of the 13 amendments of the
Parliament, as detailed in annex 1. The amendments rejected by the Commission can
be found in annex 2.
i    Amendments accepted by the Commission
     The CoML^esio:- if. i\.ady to accept the amendments whi.h • ! tr-d already
     '-;c?"tfd \\i the I:-" "-.di^g, but which the Council has ;•'•_ ». .i"ed h: ils
     C?.'•• >m:r- r '^i*;"»n
                1         -'  i •      . - . . , . ' ' •
                             ia»ion oi
     Two amendments relating to pharmacovigi!anc\." (Direcih:.. fô/65/FEC
     artiele 10 (Î) and 75/319/EEC article 29g) have the merit ;.-i introducing a
     greater coherence with the corresponding text of articles 46 and 47 of the
     Regulation.
2.   Amendments rejected by the Commission
     The Commission is not prepared to accept the other eight amendments for the
     following reasons:
     Concerning the amendment of article 7 (2) of Directive 65/65/EEC, the text of
     the common position is preferable because it defines in a more detailed manner
     the mechanism of co-ordination between the Member States when they receive
     simultaneously the same file, and moreover clarifies which documents should be
     exchanged, and what should be the time limits.
 ---pagebreak---                                        - 4
Four amendments introduce concepts and terminology into the field of
pharmacovigilance incompatible with those practised by the Community and
recommended by the World Health Organisation. The amendments concerned
are those to article 10(2) of Directive 65/65/EEC, as well as those to articles 29a,
29b and 29d of Directive 75/319/EEC.
The amendment of article 13(1) third sub-paragraph (a) new of Directive
75/319/EEC aims to establish a right to indemnity when national authorities
initiate hastily the supplementary period of 90 days which is allowed for in order
to examine conflicts in decisions between Member States. The Commission
considers that it falls to the national courts to sanction possible abuses in line
with national law, without having to create a new right of damages under
Community law.
The amendment of article 14 (4) of directive 75/319/EEC calls into doubt again
the unity of the market and of the Community examination criteria, since it
permits a medicinal product, considered through a Community arbitration
procedure not to be efficacious, to remain authorised in the country of origin. It
should be remembered that a traditional medicinal product, of which the efficacy
recognised only by a single Member State, is not affected by the Community
arbitration procedure, unless the firm which markets it itself decides to have it
recognised by other countries, thus taking the risk of seeing it rejected.
The amendment to article 29f first paragraph (a) new of Directive 75/319/EEC
risks creating a system of press censorship. The Commission does not think it
appropriate that national or community authorities should institute a system of
prior authorisation for any information, which concerns medicinal products, even
if it is alarmist.
 ---pagebreak---                                         - 5
          ANNEX 1 AMENDMENTS ACCEPTED BY THE COMMISSION
       Common position of the Council               Amendments
                                   Third recital
Whereas in the interests of public          Whereas in the interests of public
health it is necessary that decisions       health and consumers of medicinal
on the authorization         to place       products   it is necessary        that
medicinal products on the market be         decisions on the authorization to
exclusively based on the criteria of        place medicinal products on the
quality, safety and efficacy; whereas       market be exclusively based on the
these criteria have been extensively        criteria of quality, safety and
harmonized by Council Directive             efficacy; whereas these criteria have
65/65/EEC of 26 January 1965 on the         been   extensively     harmonized   by
approximation of provisions laid down       Directive 65/65/EEC of 26 January
by law, regulation or administrative        1965   on    the    approximation   of
action    relating    to      medicinal     provisions    laid    down   by   law,
products,   by    Council     Directive     regulation or administrative action
75/319/EEC, and by Council Directive        relating to medicinal products, by
75/318/EEC of 20 May 1975 on the            Directive 75/319/EEC, and by Council
approximation of the laws of the            Directive 75/318/EEC of 20 May 1975
Member States relating to analytical,       on the approximation of the laws of
pharmacotoxicological and clinical          the Member      States   relating to
standards and protocols in respect of       analytical,    pharmaco-toxicological
the testing of medicinal products;          and clinical standards and protocols
whereas, however, Member States             in respect of the testing of
should exceptionally be able to             medicinal products; whereas, however,
prohibit the use on their territory         Member States should exceptionally be
of medicinal products which infringe        able to prohibit the use on their
objectively defined      concepts of        territory of medicinal products which
public order or public morality;            infringe objectively defined concepts
                                            of public order or public morality;
 ---pagebreak---                                             - 6 -
           Common position of the Council                 Amendments
                                    ARTICLE 1(4)
           Article 4b, second paragraph a (new) (Directive 65/65/EEC)
                                             Before a medicinal product is placed
                                             on    the    market     the   competent
                                             authorities shall forward to the
                                             European Aaencv for the Evaluation of
                                             Medicinal Products a copy of the
                                             decision together with the summary of
                                             the product characteristics referred
                                             Ço in this Article. The Aaencv shall
                                             give the authorized medicinal product
                                             a European Register number which
                                             shall be marked on the packaging; the
                                             register number shall be preceded bv
                                             the initials of the Member States in
                                             which     the    product    has    been
                                             authorized.
                                     ARTICLE 1(6)
                        Article 7(1) (Directive 65/65/EEC)
1. Member States shall take all               1. Member States shall take all
appropriate measures to ensure that          appropriate measures to ensure that
the procedure       for granting an          the    procedure    for granting an
authorization to place a medicinal           authorization to place a medicinal
product on the market is completed           product on the market is completed
within 2JL9_ days of the submission of       within V40 days of the date the
a valid application.                         application is submitted.
                                     ARTICLE 1(9)
                       Article 10(1) (Directive 65/65/EEC)
1. Authorization shall be valid for           1. Authorization shall be valid for
five years and shall be renewable for         five years and shall be renewable for
five-year periods, on application by          five-year periods, on application by
the holder at least three months              the holder at least three months
before the expiry date and after              before the expiry date and after the
consideration of a dossier updating           competent authority has considered a
the information previously submitted.         dossier      containing     up-to-date
                                              pharmacovigilance data and the other
                                              information      relevant    to     the
                                              supervision of the medicinal product.
 ---pagebreak---                                          - 7 -
        Common position of the Council               Amendments
                                   ARTICLE 3(3)
                      Article 29g (Directive 75/319/EEC)
In order to facilitate the exchange        In order to facilitate the exchange
of     information             about       of     information            ab ou t
pharmacovigilance      within       the    pharmacovigilance       within     the
Community,    the   Commission,      in    Community,    the    Commission,    in
consultation with the Agency, Member       consultation with the Agency, Member
States and interested parties, shall       States and interested circles, shall
draw up guidance on the collection,        draw up guidance on the collection,
verification and presentation of           verification and presentation of
adverse reaction reports.                  adverse reaction reports.
                                           Such guidance shall take into account
                                           the work carried out bv the WHO on
                                           the harmonization of terminology and
                                           classification in the field of
                                           pharmacovigilance,     It shall also
                                           establish the arrangements for use of
                                            the data-processing network between
                                            the competent authorities in the
                                           event of an alert concerning a
                                           manufacturing    fault    or   serious
                                           undesirable reactions, and other
                                           pharmacovigilance    information    on
                                           medicinal products marketed in the
                                           Community.
 ---pagebreak---                                        - 8 -
        ANNEX 2 AMENDMENTS REJECTED BY THE COMMISSION
     Common position of the Council                Amendments
                                    ARTICLE 1(6)
                       Article 7(2) (Directive 65/65/EEC)
2. Where a Member State notes that an        2. In assessing applications for
application     for      authorization       authorization.      the     competent
submitted after 1 January 1995 is            marketing authorities shall assist
already under active examination in          each Qtfrer anâ ffiây_ entrust one
another Member State in respect of           another with assessments of all or
that medicinal product, the Member           part of the dossier.
State concerned mav decide to suspend
the detailed examination of          the     The competent authorities of the
application in order to await the            Member States shall notify the Agency
assessment report prepared by the            and the other Member States of any
other Member State in accordance with        applications       for     marketing
Article 4b.                                  authorization thev receive.
The" Member State concerned shall            A   Member    State   that    receives
inform the other Member State and the        notification shall. if the same
applicant of its decision to suspend         application for authorization has
derailed - examination        of     the     been submitted in another Member
application in question. As soon as          State, contact the latter with a view
it has completed the examination of          to coordinating their action and
the' application    and     reached    a     issuing    the    assessment    report
decision, the other Member State             jointly.
shall   forward    a copy      of    its
assessment report to the Member State        If the Member States with an interest
concerned.                                   in the application do not reach
                                             agreement, they mav. once all other
Within 90 davs of the receipt of the         possibilities have been exhausted,
assessment report, the Member State          have recourse to the procedure laid
concerned shall either recognize the         down in Chapter III of Directive
decision of the other Member State           75/319/EEC.
and the summary of the product
characteristics as approved bv it.
or. if it considers that there are
grounds for supposing that the
authorization    of   the     medicinal
product concerned mav present a risk
to public health, it shall apply the
procedures set out in Articles 10 to
14 of Directive 75/319/EEC.
 ---pagebreak---                                        - 9
      Common position of the Council              Amendments
                                   ARTICLE 1(9)
           Article 10(2), first subparagraph (Directive 65/65/EEC)
2. In exceptional circumstances, and       2. In     exceptional     and   duly
following consultation with the            substantiated    circumstances,   and
applicant, an authorization may be         following consultation with the
granted subject to certain specific        applicant, an authorization may be
obligations, including:                    granted subject to certain specific
                                           obligations, defined and reviewed
                                           annually bv the Agency, to:
   the carrying out of further                conduct further studies following
   studies following the granting of          the granting of authorization;
   authorization;
-  the   notification     of    adverse    -  report    side-effects    of   the
   reactions    to    the     medicinal       medicinal product.
   product.
 ---pagebreak---            C o m m o n position of the Council               Amendments
                                          ARTICLE 3 d )
                          Article 13(1), third subparagraph a (new)
                                      (Directive 75/319/EEC)
                                                   Anv delays arising in the marketing
                                                   of a medicinal product because this
                                                   procedure has been initiated hastily
                                                   or with the sole intention of causing
                                                   a delay mav entitle the applicant to
                                                   demand compensation in accordance
                                                   with the legislation applicable in
                                                   the Member State in question.
                                           Article 3(1)
*«V                          Article 14(4) (Directive 75/319/EEC)
    A decision adopted in accordance with          A decision adopted in accordance with
    this Article shall be addressed to              this Article shall be addressed to
    the Member States concerned by the              the Member States concerned by the
    matter and to the person responsible           matter and to the person responsible
    for marketing.        The Member States         for marketing.    The Member States
    shall either grant or withdraw                  shall either grant or withdraw
    marketing authorization, or make any           marketing authorization, or make any
    adjustment to the terms of a                    adjustment to the terms of a
    marketing authorization which may be            marketing authorization which may be
    necessary to comply with the decision          necessary to comply with the decision
    within 30 days of its notification.            within 30 days of its notification.
    They shall inform the Commission and            In adopting its decision, the Member
    the Committee thereof.                          State in which the authorization was
                                                    originally granted shall take into
                                                    account experience with the medicinal
                                                    product in question.     An existing
                                                   national authorization may be upheld,
                                                    even in the event of a prior negative
                                                    Decision in accordance with this
                                                   Article, if the medicinal product is
                                                   harmless and of high gualitv. They
                                                    shall inform the Commission and the
                                                   Committee thereof.
 ---pagebreak---                                          11 -
    Common position of the Council                  Amendments
                                      ARTICLE 3(3)
                         Article 29a (Directive 75/319/EEC)
 In order to ensure the adoption of             In order to ensure the adoption of
 appropriate     regulatory    decisions        appropriate    regulatory    decisions
 concerning the medicinal products              concerning        the     continued
 authorized within the Community,               authorization of medicinal products
 having regard to information obtained          within the Community, having regard
 about adverse reactions to medicinal           to information obtained about the
 products under normal conditions of            side-effects of medicinal products
 use,    the    Member    States    shall       under normal conditions of use,
 establish a pharmacovigilance system.          Member States shall establish a
 This system shall be used to collect           pharmacovigilance       system     for
 information        useful     in      the      collecting information about the
 surveillance of medicinal products,            side-effects of medicinal products in
 with particular reference to adverse           human beings and for the scientific
 reactions in human beings, and to              evaluation of such information, such
 evaluate        such      information          that the information about side-
 scientifically.                                effects is systematically related to
                                                the information on the consumption of
                                                medicinal products.
                                 ARTICLE 3(3;
                Article 29b, indents (Directive 75/319/EEC)
"adverse     reaction"     means    a          "side-effects" means a reaction
reaction which is harmful and                 which is harmful and unintended
unintended and which occurs at                and which occurs at doses normally
doses normally used in man for the            used in man for the prophylaxis,
prophylaxis,       diagnosis      or          diagnosis or treatment of disease
treatment of disease or the                   or     the     modification       of
modification     of    physiological          physiological function;
function;
"serious adverse reaction" means              "serious side-effects" means an
an adverse reaction which is                  unfavourable reaction which is
fatal,       1ife-threatening,                fatal,      1ife-threatening,
disabling,     incapacitating,    or          disabling,     incapacitating,    or
which results in or prolongs                  which results in hospitalization
hospitalization;                              or prolonged hospitalization;
"unexpected     adverse    reaction"          "unexpected side-effects" means an
means an adverse reaction which is            unfavourable reaction which is not
not mentioned in the summary of               mentioned    in the summary of
product characteristics;                      product characteristics;
 serious      unexpected     adverse          "serious unexpected side-effects"
reaction"     means    an    adverse          means an unfavourable reaction
reaction which is both serious and            which    is   both    serious    and
unexpected.                                   unexpected.
 ---pagebreak---        Common position of the Council                Amendments
                                    ARTICLE 3(3)
                     Article 29d(1)(Directive 75/319/EEC)
1. The person responsible for placing        1. The    person   responsible    for
the medicinal product on the market          placing the medicinal product on the
shall be required to record and to           market shall be required to record
report all suspected serious adverse         and to report all suspected serious
reactions which are brought to his           unexpected side-effects which are
attention    by    a    health     care      brought to his attention by a
professional    to   the     competent       qualified health care professional to
authorities immediately, and in any          the     competent      authorities
case within 15 days of their receipt         immediately, and in any case within
at the latest-                               15 days of their receipt.
                                   ARTICLE 3(3)
         Article 29f, first paragraph a (new) (Directive 75/319/EEC)
                                            The Member States shall take steps to
                                            ensure that pharmacovigilance data
                                            which is not officially confirmed and
                                            which mav give rise to unnecessary
                                            alarm is not disseminated.        The
                                            dissemination of data which has not
                                            been officially confirmed, if it
                                            proves to be inaccurate, mav be the
                                            subject of compensation in accordance
                                            with the legislation of each Member
 ---pagebreak---                                            - 13 -
REVISED PROPOSAL FOR A COUNCIL DIRECTIVE SYN 311
MODIFYING DIRECTIVES 81/851/EEC AND 81/852/EEC ON THE
APPROXIMATION OF LAWS OF THE MEMBER STATES RELATING TO
VETERINARY MEDICINAL PRODUCTS
In accordance with Article 149(2)(d) of the Treaty, the Commission has re-examined
the above proposal, in order to assimilate three of the four amendments from the
parliament, as detailed in annex 1. The amendment rejected can be found in annex 2.
1.   Amendments accepted by the Commission
     The Commission is prepared to accept the amendments which it had already
     accepted during the first reading, but which the Council did not retain in its
     common position.
     The role given to the European Agency (Directive 81/851/EEC, article 5b, third
     paragraph new) in attributing European number to each medicinal product which
     is authorised in the Community in the future will contribute to a greater
     transparency of the market. The present wording of this amendment envisages
     that the countries which have authorised the medicine should be mentioned,
     which will avoid any risk of confusion with the numbers attributed to community
     authorisations.
     The reduction of the duration of the national examination procedure from 210
     days to 140 (Directive X1/85 l/EEC, article 8( I )) takes account of the fact that, as
     a general rule, the national procedure concerns conventional medicines, and not
     high-technology medicines dealt with under the centralised procedure, the
     examination of which requires a longer time-limit, of the order of 210 days.
     The amendment relating to pharmacovigilance (Directive 81/851/EEC article
     42g) has the merit of introducing a greater coherence with the corresponding text
     of articles 46 and 47 of the Regulation.
 2.  Amendments rejected by the Commission
     The Commission is not prepared to accept the amendment of article 15(1) of
     Directive 81/851/EEC, because it introduces into the five yearly re-examination
     of the authorization of a veterinary medicinal product concepts which are not
     clear and which appear to move away from the customary criteria of
     authorization (quality, security and efficacy).
 ---pagebreak---                                        - 14 -
         AjsiNRy t AMENDMENTS ACCEEEEDBYJTHE_COMMISSION
     Common position of the Council                   Amendments
                                     ARTICLE 1(5)
                          Article 5b, third paragraph (new)
                                (Directive 81/851/EEC)
                                               Before a medicinal product is placed
                                               on     the     market    the     competent
                                               authorities shall forward to the
                                                European Agency for the Evaluation of
                                               Medicinal Products a copy of the
                                               decision together with the summary of
                                                the product characteristics referred
                                                to in this Article. The Agency shall
                                                give    the     authorized    veterinary
                                                medicinal product a European Register
                                                number which shall be marked on the
                                                packaging; the registration number
                                                shall be preceded by the initials of
                                                the Member       State in which the
                                                product's use has been authorized.
                                    ARTICLE 1(6)
                                    Article 8(1)
                               (Directive 81/851/EEC)
  1. Member States shall take all             1. Member States shall take all
 appropriate measures to ensure that          appropriate measures to ensure that
 the   procedure    for   granting    an      the    procedure     for   granting     an
 authorization to place a veterinary          authorization to place a medicinal
 medicinal product on the market is           product on the market is completed
 completed within 210 days of the             within 140 days of the date the
 submission of a valid application.           application is submitted.
                                  ARTICLE 1(12)
                                   Article 42g
                             (Directive 81/851/EEC)
In order to facilitate the exchange         In order to facilitate the exchange
of     information             about       of        information              about
pharmacovigilance       within     the     pharmacovigilance           within      the
Community,    the    Commission,    in     Community,        the    Commission,     in
consultation with the Agency, Member        consultation with the Agency, Member
States and interested parties, shall        States and interested circles, shall
draw up guidance on the collection,        draw up detailed guidance on the
verification and presentation of            collection,         verification       and
adverse reaction reports.                   presentation      of adverse reaction
                                            reports.      Such guidance shall take
                                            into account the work carried out bv
                                            the WHO on the harmonization of
                                            terminology and classification in the
                                            field of pharmacovigilance, where
                                            this can be used in connection with
                                            veterinary medicinal products. The
                                            guidance shall also establish the
                                            arrangements for the use of the
                                            information       network    among     the
                                            competent„au_thori tips in the__event_pf
                                            JLQ-JLU\lJL^QI?gf-LU3Jnq a nianuf acturinq
                                            fault or serious adverse reactions,
                                            as well as other pharmacovigilance
                                            information on veterinary medicinal
                                            products marketed in the Community.
 ---pagebreak---                                       - 15 -
        ANNfiX 2 AMENDMENTS REJECT*vn KV Jim           COMMISSION
    Common position of the Council                 Amendments
                                   ARTICLE 1(9)
                                 Article 15(1)
                             (Directive 81/851/EEC)
1. Authorization shall be valid for        1. Authorization shall be valid for
five years and shall be renewable for      five years and shall be renewable for
five-year periods, on application by       five-year periods, on application by
the holder at least three months           the holder at least three months
before the expiry date and after           before the expiry date and after the
consideration of a dossier updating        competent body has considered a
the information previously submitted.      dossier      containing     _ updated
                                           pharmacovigilance data and the other
                                           information    relevant      to    the
                                           monitoring of the product.
                                            When delivering its ' opinion the
                                            responsible body shall take account
                                            off any new information available on
                                            side-effects    of. ,. ^ 3   medicinal
                                            product, its efficacy and its olacs
                                            in its therapeutic class.
 ---pagebreak---  ---pagebreak---                                             M
                                                                     ISSN 0254-1475
                                                              COM(93) 220 final
                                                      DOCUMENTS
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                                 Catalogue number : CB-CO-93-247-EN-C
                                                             ISBN 92-77-55872-.'
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