CELEX: 51991PC0382(02)
Language: en
Date: 1991-10-31
Title: Amendment to the proposal for a COUNCIL DIRECTIVE amending Directives 65/65/EEC, 75/318/EEC and 75/319/EEC in respect of medicinal products

COMMISSION OF THE EUROPEAN COMMUNITIES
                                  C0M(91) 382 final - SYN 309-310-311
                                  Brussels, 31 October 1991
  Future system for the free movement of medicinal products
                    in the European Community
               Amendment to the proposal for a                        SYN 309
                   COUNCIL REGULATION (EEC)
  laying down Community provisions for the authorization and
supervision of medicinal products for human and veterinary use
   and establishing a European Agency for the Evaluation of
                       Nedicinal Products
               Amendment to the proposal for a                        SYN 310
                       COUNCIL DIRECTIVE
   amending Directives 65/65/EEC, 75/318/EEC and 75/319/EEC
               in respect of medicinal products
               Amendment to the proposal for a                        SYN 311
                       COUNCIL DIRECTIVE
          amending Directives 81/851/EEC and 81/852/EEC
           in respect of veterinary medicinal products
           (presented by the Commission pursuant to
              Article 149 (3) of the EEC Treaty)
 ---pagebreak---                                 - 1-
                     EXPLANATORY MEMORANDUM
Following the first readings by the Eurpoean Parliament during
its part session of June 1991, the Commission has decided in
accordance with Article 149, paragraph 3 of the EEC Treaty to
amend the following proposals: (1)
1. Proposal for a Council Regulation (EEC) laying down
    Community provisions for the authorization and supervision
    of medicinal products for human and veterinary use and
    establishing a European Agency for the Evaluation of
    Medicinal Products (SYN 309);
2. Proposal for a Council Directive amending Directives
    65/65/EEC, 75/318/EEC and 75/319/EEC in respect of
    medicinal products (SYN 310);
3. Proposal for a Council Directive amending Directives
    81/851/EEC and 81/852/EEC in respect of veterinary
    medicinal products (SYN 311);
 1. O.J. N° C 330, 31.12.1990; COM (90) 283 final
 ---pagebreak---                                - 2-
The Commission has decided to accept:
- a series of amendments which would appear to improve the
  operation or the transparency of the centralized and
  decentralized Community authorization procedures or improve
  the safeguards for industry contained in those procedures;
- amendments which encourage greater cooperation between the
  Community and the World Health Organisation in relation to
  pharmacovigilance ;
- three amendments which provide that medicinal products
  consisting of genetically modified organisms may only be
  authorized for use in the Community if they satisfy the
  substantive requirements of Council Directive 90/220/EEC of
  23 April 1991 on the deliberate release into the environment
  of genetically modified organisms (2)
- that part of amendment 168 which allows the European
  Parliament to nominate two representatives to the Management
  Board of the Agency.
2. O.J. N° L 117, 8.5.1990. p 15
 ---pagebreak---                               - 3-
However, the Commission has decided not to accept;
- those amendments which would substantially change the
  balance between the centralized and decentralized
  procedures, or which would attribute major additional tasks
  to the Agency in the early years of its operation;
- those amendments which seek to amend the substantive rules
  for the authorization of medicinal products as they have
  developed since 1965;
- those amendments which would lay down unduly strict rules of
  a procedural nature which are not found in the legislation of
  any Member State;
- the other amendments of an institutional nature which would
  reduce the rights of Member States, or of the Commission.
In summary therefore, the Commission has accepted, in whole or
in part, 67 of the 155 amendments voted by Parliament.
 ---pagebreak---  ---pagebreak---                                          -4 -
                     Amendment to the proposal for a                                 SYN 309
                           COUNCIL REGULATION (EEC)
    laying down Community provisions for the authorization and
 supervision of medicinal products for human and veterinary use
     and establishing a European Agency for the Evaluation of
                                Medicinal Products
          Original Text
                                                   Amendment to the proposal
                    Visas and recitals 1 - 3          unchanged
      Fourth recital                         Fourth recital
Whereas in the interests of public           Whereas in the interests of public
health     it   is   necessary      that     health    and    the    consumers      of
decisions on the authorization of            medicinal products it is necessary
such medicinal products should be            that decisions on the authorization
based on the objective scientific            of such medicinal products should be
criteria of the quality, the safety          based on the objective scientific
and the efficacy of the medicinal            criteria of the quality, the safety
product concerned to the exclusion           and the efficacy of the medicinal
of economic or other considerations;         product concerned to the exclusion
whereas,    however,    Member    States     of economic or other considerations;
should exceptionally be able to              whereas,    however,    Member     States
prohibit the use on their territory          should exceptionally be able to
of medicinal products for human use          prohibit the use on their territory
which infringe objectively defined           of medicinal products for human use
concepts of oublie order or public          which infringe objectively defined
morality;     whereas     moreover     a    concepts of public order or public
veterinary medicinal product may            morality;      whereas      moreover     a
not be authorized by the Community          veterinary medicinal product may
if its use would contravene the             not be authorized by the Community
ruloB and objectives laid down by            if its use would contravene the
tho Community within the framework          ruios end objectives laid down by
of the common agricultural policy?          tho Community within the framework
                                            of the common agricultural policy*
                             Recitals 5 - 1 1     unchanged
     Twelfth recital                         Twelfth recital
 Whereas the primary task of the              Whereas the primary task of the
 Agency    should    be    to    provide      Agency    should    be     to    provide
 scientific advice of the highest             scientific advice of the highest
 possible quality to the Community            possible quality to the Community
 institutions and the Member States           institutions and the Member States
 for the exercise of the powers               for the exercise of the powers
 conferred upon them by Community            conferred    on them      by Community
 legislation     in   the     field   of      legislation     in   the      field   of
medicinal products in relation to            medicinal products in relation to
 the authorization and supervision of        the authorization and supervision of
medicinal products;                          medicinal products for the purposes
                                              of                           protecting
                                              consumers' interests and ensuring
                                              maximum transparency of procedures;
 ---pagebreak---                                                             - 5 -
                                                                   Amendment to the proposal
                 Original Text
                                        Recitals 13 - 17 unchanged
   Eighteenth r e c i t a l                                    Eighteenth r e c i t a l
  Whereas the Agency, working in c l o s e                     Whereas the Agency, working in close
  cooperation                 with the     Commission,         cooperation   with the Commission,
  should a l s o be entrusted with the                         should also be entrusted with the
  task of coordinating the discharge of                      ** task of coordinating the discharge
  the          various                supervisory              of    the   various      supervisory
  r e s p o n s i b i l i t i e s of Member S t a t e s and    responsibilities of Member States
  in particular monitoring the respect                         and in particular the provision of
  of good manufacturing p r a c t i c e s , good               information    concerning   medicinal
  laboratory                  practices     and        good    products and monitoring the respect
  clinical practices;                                          of good manufacturing practices,
                                                               good laboratory practices and good
                                                               clinical practices;
                                       Nineteenth recital unchanged
                                                                Twentienth recital (new)
                                                                Whereas risks to the
                                                                environment may be associated
                                                                with medicinal products
                                                                containing or consisting of
                                                                genetically modified
                                                                organisms: whereas therefore
                                                                it is necessary to provide for
                                                                an environmental risk
                                                                assessment of such products,
                                                                similar to that provided for
                                                                by Directive 90/220/EEC on the
                                                                deliberate release into the
                                                                environment of genetically
                                                                modified organisms (9).
                                                                together with the assessment
                                                                of the quality, safety and
                                                                efficacy of the product
                                                                concerned within a single
                                                                Community procedure;
n     0. J . N° L 117. 8.5.1990. p. 15
 ---pagebreak---                                                                   - 6-
                        Original Text                                    Amendment to the proposal
                                               Articles 1 - 5 unchanged
              Article 6                                         Article 6
                                         Article 6, paragraph 1, unchanged
              Article 6 (2)                                     Article 6 (2)
                                                                2. In the case of a medicinal
   2.    The application shall also be accompanied by the fee   product containing or consisting
   payable to the Agency for the examination of the
   application.
                                                                of genetically modified organisms
                                                                within the meaning of Article 2
                                                                paragraphs 1 and 2 of Directive
                                                                90/220/EEC on the deliberate
                                                                release into the environment of
                                                                genetically modified organisms,
                                                                the application shall also be
                                                                accompanied by:
                                                                " a copy of the written consent,
                                                                  from the competent authority,
                                                                  to the deliberate release of
                                                                  the genetically modified
                                                                  organisms for research and
                                                                  development purposes provided
                                                                  for in Article 6(4) of
                                                                  Directive 90/220/EEC:
                                                                - the complete technical dossier
                                                                   supplying the information
                                                                  requested in Annexes II and III
                                                                  of Directive 90/220/EEC and the
                                                                  environmental risk assessment
                                                                   resulting from this information
                                                                Articles 11 to 18 of Directive
                                                                90/220/EEC shall not apply to
                                                                medicinal products for human use
                                                                containing or consisting of
                                                                genetically modified organisms.
              Article 6 (3)                                     Article 6(3)
   3.    The Agency shall ensure that the opinion of the        3. The application shall also be
   Committee is given within 210 days of the receipt of a valid accompanied by the fee payable to
   application.                                                 the Agency for the examination of
                                                                the application.
2)
 ---pagebreak---                                                              - 7 -
                      O r i g i n a l Text                            Amendment to the proposa I
           Article       6 (4)                               Article       6 (4)
4. The Agency shall, in consultation with Member States,     4_«_ The Agency s h a l l ensure that
the Commission and interested parties, draw up detailed      the Opinion Of the Committee i s
guidance on the form in which applications for authorization given within 210 day S of the
are to be presented.                                         r e c e i p t of a v a l i d a p p l i c a t i o n .
                                                             In the case of a medicinal
                                                             product containing or consisting
                                                             of genetically modified
                                                             organisms, the opinion of the
                                                             Committee shall take account of
                                                             the environmental safety
                                                             requirements laid down by
                                                             Directive 90/220/EEC.
                                                             Article 6 (5) (new)
                                                             5. The Agency shall, in
                                                             consultation with Member States,
                                                             the Commission and interested
                                                             parties, draw up detailed
                                                             guidance on the form in which
                                                             applications for authorization
                                                             are to be presented.
                                               Articles 7 - 9 unchanged
 ---pagebreak---                                                        -8
                Original Text                                Amendment t o t h e proposal
 Article 10 (1)                                            A r t i c l e 10 ( 1 )
  1. Within 30 days of the receipt of                       1. Within 30 days of the receipt of
  the opinion, the Commission s h a l l                     the opinion, the Commission shall
  prepare a draft of the Decision t o                       prepare a draft of the Decision to
 be        taken          in     respect     of    the      be      taken     in    respect    of the
 a p p l i c a t i o n , taking i n t o account the         application, takina into account the
 o b j e c t i v e s of Community p o l i c i e s and       oblectives of Community policies and
 considering                 all     tho    relevant        considering         all     tho   relevant
 information.                In the event of a              information.         In the event of a
 draft Decision which envisages the                         draft Decision which envisages the
 granting                  of     a     marketing           granting           of     a   marketing
 authorization,                   the     documents         authorization,           the    documents
 referred t o in points ( a ) , (b) and                     referred to in points (a), (b) and
 (c) of A r t i c l e 9(3) s h a l l be annexed.            (c) of Article 9(3) shall be annexed.
The Commission shall transmit the                          The Commission shall transmit the
draft Decision t o the Member States                       draft Decision to the Member States
and to the applicant.                                      and to the applicant.
The Commission                 shall   explain     in     If, exceptionally, the Commission
detail             the      reasons       for     any     Intends to draw up a draft Decision
differences                between      the     draft     which differs from the opinion of
Decision and the opinion of                       the     the Cormrittee, the Commission shall
Committee»                                                explain in detail the reasons for
                                                          any differences.
Article 10 (2)                                            Article 10 (2)
 2. The Commission shall adopt the                         2. The Commission shall adopt the
 Decision to be taken in respect of                        Decision to be taken in respect of
 the application unless, within 30                         the application unless, within 30
 days, it has received a reasoned                          days, it has received a reasoned
 request            from a Member State to                 request       from a Member State to
 reconsider the matter.                   The Member       reconsider the matter.           The Member
 State concerned shall also transmit a                     State concerned shall also transmit a
 copy of itn request to the other                          copy of it n request to the other
 Member           States      and the       applicant      Member       States    and the applicant
 within the same time limit                                within the same time limit.
                                                         The       Member      State     requesting
                                                         reconsideration         shall   provide a
                                                         detailed        justification    baaed on
                                                         scientific evidence or Community
                                                         law.
                         Article 10. paragraphs 3 and 4 unchanged
                                                         Article 10 (5). new
                                                              The Agency shall, upon request,
                                                         inform any interested person of the
                                                         contents of its final opinion.
 ---pagebreak---                                                              -    9
                Original Text                                        Amendment to the proposal
                                             Article 11 unchanged
     Article 12 (1)                                             Article 12 (1)
1.     Without prejudice to Article 6 of Directive
65/65/EEC, a marketing authorization which has been             1.     Without prejudice to Article 6 of Directive
granted in accordance with the procedure laid down in this      65/65/EEC, a marketing authorization which has been
Regulation shall apply throughout the Community. It shall       granted in accordance with the procedure laid down in this
confer the same rights and obligations in each of the Member    Regulation shall apply throughout the Community. It shall
States as a marketing authorization granted by that Member      confer the same rights and obligations in each of the Member
State in accordance with Article 3 of Directive                 States as a marketing authorization granted by that Member
65/65/EEC.                                                      State in accordance with Article 3 of Directive
                                                                65/65/EEC.
                                                                     The       authorized            medicinal
                                                               products shall be entered in the
                                                               Community        Register         of     Medicinal
                                                               Products and they shall be given a
                                                               number which must appear on the
                                                               packaging.
                                         Article 12 (2) unchanged
    Article 12 (3)                                             Article 12 (3)
           An       announcement                   that      3.       Notification            of     marketing
  authorization has been granted shall                       authorization shall be published in
  be      published           for       information          the Official Journal of the European
  purposes in the Official Journal of                        Communities, Quoting the number in
  the European Communities.                                  the Community Register.
                                        Article 12 (4) unchanged
    Article 13 (1)                                             Article 13 (1)
1. Authorization shall be valid for                            1. Authorization shall be valid for
five years and may be renewable for                            five years and may 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.                                       before the expiry date and after
                                                              consideration by the Agency of a
                                                              dossier           containing            up-to-date
                                                              information on pharmacovigilance.
 ---pagebreak---                                                               -10
                                                                      Amendment to the proposa
              Original Text
   Article 13 (2)                                                Article 13 (2)
2.    In exceptional circumstances and following                   2. In exceptional circumstances and
consultation with the applicant, an authorization may be           following        consultation    with the
granted subject to such conditions as appear necessary to
                                                                   applicant.» an authorization may be
ensure the protection of public health, including specific
obligations to conduct further studies following the granting      granted subject/
of authorization and specific obligations in respect of the       to certain specific obligations, to
reporting of adverse reactions to the medicinal product.          be defined and reviewed annually by
                                                                  the Agency, to:
                                                                  - conduct further studies following
                                                                  the granting of authorization;
                                                                  - report adverse reactions          to the
                                                                  medicinal product.
                                                                  Such exceptional decisions may only
                                                                  be    adopted        for objective and
                                                                  verifiable reasons and must be based
                                                                  on one of the causes mentioned in
                                                                  Chapter III of Part III of the
                                                                  Annex to Directive 75/318/EEC.
                                                                       Some products may be authorized
                                                                  only for use in hospitals or for
                                                                  prescription by specialists.
                              Article 13 paragraph 3 unchanged
                                           Article 14 unchanged
                          Article 15 paragraphs 1 - 3                        unchanged
  Article 15 (4)                                                Article 15 (4)
4. The Agency s h a l l , in consultation                      4.      The      Agency       shall,      in
with         the      Commission,               adopt          consultation with the Commission,
appropriate          arrangements           for      the       adopt appropriate arrangements for
examination            of      amendments           and        the examination of amendments and
variations          to      the      terms      of     a       variations       to     the   terms   of   a
marketing authorization.                                       marketing       authorization.         These
                                                               arrangements           shall    include    a
                                                               n o t i f i c a t i o n      system      or
                                                               administrative procedures concerning
                                                               minor changes and define precisely
                                                               the concept of 'a minor change*.
                                  Articles 16 and 17 unchanged
 ---pagebreak---                                                               11 -
                 Original Text                                    Amendment to the proposa I
      Article 18 (1)                                          Article      18 ( 1 )
                                                               1. Where the supervisory authorities
                                                               or the competent authorities of any
                                                               other     Member    State   are of     the
                                                               opinion that the manufacturer or
 1.    Where the supervisory authorities or the competent      importer from third countries       Ls no
authorities of any other Member State are of the opinion that  longer     fulfilling the obligations
the manufacturer or importer from third countries is no        laid down in Chapter IV of Directive
longer fulfilling the obligations laid down in Chapter IV of   7&/319/EEC,      they   ahall   forthwith
Directive 75/319/EEC, they shall forthwith inform the          inform      the    Committee    and    the
Committee and the Commission, stating their reasons in         Commission, stating their reasons in
detail and indicating the course of action proposed.           detail and indicating the course of
                                                               notion proposed.
The same shall apply where a Member State considers that
one of the measures envisaged in Chapter V of Directive       The sane shall apply where a Member
75/319/EEC should be applied in respect of the medicinal      State or the Commission considers
product concerned.
                                                              that one of the measures envisaged
                                                              in Chapter V             or     Chapter Va of
                                                              Direcitve           75/319/EEC         should be
                                                              applied in respect of the medicinal
                                                              product concerned.
                           Article 18 paragraphs 2 and 3 unchanged.
     Article 18 (4)                                           Article 18(4)
    4. In exceptional case*, where action                       4. In exceotional caeee^ where action
     ia urgently necessary to protect                            is urgently necessary to protect
    public health, a Member State may                           public health, a Member State may
    suspend the use on its territory of a                       3ubpend th« use on its territory of a
    nedicinal product which has been                            -edicinal product which has been
    authorized in accordance with this                          authorized in accordance with this
    Regulation.             It shall inform the                 Regu1a t i on, if it finds    the foi lowing:
    Commission            no     later       than     the
    following working day of the reasons
                                                                (1) The severity of the harm that
    for its action. The Commission shall
                                                                    cou Id     be    caused    by    the
    immediately           consider       the     reasons
                                                                    medicinal product cannot await
    given        by     the      Member      State      in
                                                                    the definitive decision of the
    accordance with paragraph 2 and shall
                                                                    Comrcigaion;
    initiate the procedure provided for
    in paragraph 3.                                            (2) There is a likelihood that the
                                                                    medicinal     product will cause
                                                                    t he__ suspected harm during the
                                                                    Commission's deliberations;
                                                               (3) The risk to patients currently
                                                                    taking the medicinal product
                                                                    occasioned by the removal of
                                                                    the product from the market • is
                                                                    out-weighed by the degree of
                                                                    harm posed by the product.
 ---pagebreak---                                                        12 -
         Original Text                                   Amendment to the proposal
                                                      The Member State in Question shall
                                                      inform the Commission no later than
                                                      the following working day of the
                                                      reasons for its action.             It shall
                                                      also Inform the health authorities
                                                      of the other Member States.                 The
                                                      Commission          shall       immediately
                                                      consider the reasons given by the
                                                     Member State in accordance with
                                                     paragraph 2 and shall initiate the
                                                     procedure provided for in paragraph
                                                      3.     In such cases the Member State
                                                      in question shall immediately take
                                                     the necessary measures to inform the
                                                     public.
     Article 18 (5) unchanged
                                                    A r t i c l e 18 ( 6 ) . new
                                                            The Agency s h a l l , upon r e q u e s t ,
                                                     inform any i n t e r e s t e d person of the
                                                     contenta of t h e Committee's opinion
                                                     referred t o in paragraph 2.
                              A r t i c l e s 19 - 21 unchanged
                  A r t i c l e 22 paragraphs 1 and 2 unchanged
                                                   A r t i c l e 22 ( 3 ) . new
                                                    The person responsible for marketing
                                                    shall accompany           the records of
                                                    adverse reactions with an analysis
                                                    of      the      data     regarding      such
                                                    reactions, in order to make them
                                                    easier to understand.
 Article 23                                        Article 23
Each Member State shall report any                 Each Member State shall organize the
suspected serious adverse reaction                 pharmacovlqilance service within its
arising within its territory to a                  territory           according        to    the
medicinal    product      authorized         in    provisions of Article 24. It shall
accordance with this Regulation to                 report        any    suspected
the    Agency     and       the       person       serious adverse reaction arising
responsible for marketing within 15                within its territory to a medicinal
days of receipt of a report from a                 product        authorized       in accordance
qualified health care professional.                with this Regulation to the Agency
                                                   and     the person         responsible     for
                                                   marketing within 15 days of receipt
                                                   of a report from a qualified health
                                                   care professional.
 ---pagebreak---                                           13 -
                                                Amendment to the proposal
         Original    Text
 Article 24                               Article 24
The Agency shall, in consultation         The           C o m m i s s io n      shall,       in
with Member States/ the Commission        consultation with the Agency, Member
and   interested   parties, draw up       States             and      interested     parties,
detailed guidance on the collection,      approve detailed guidance, common to
verification    and presentation of       all the Member States                      on the
adverse reaction reports.                 collection,                  verification       and
                                          presentation of adverse reaction
                                          reports. These reports shall have a
                                          format similar to that used by the
                                          World Health Organization;
                                                                        The    Agency
                                       c o n s u l t a t i o n with t h e Member S t a t e s
                                       and t h e Commission, s h a l l s e t up a
                                       data-processing                  network    for   the
                                       r a p i d t r a n s m i s s i o n of data between
                                       t h e competent Community a u t h o r i t i e s
                                       in t h e event of an a l e r t r e l a t i n g t o
                                       faulty               manufacture,            serious
                                       undesirable               effects        and    other
                                       pharmacovigilance                   data   regarding
                                       medicinal products marketed in the
                                       Community.
                            Article 25  unchanged
                                         A r t i c l e 25a J new
                                          The Agency shall collaborate wich
                                          the World Health Organization on
                                          international pharmocovigilance and
                                          shall take the necessary steps to
                                          submit promptly to the World Health
                                          Organization                   appropriate      and
                                          adequate information regarding the
                                          measures taken in the Community
                                          which may have a bearing on public
                                          health protection in third countries
                                          and shall send a copy thereof to tne
                                          Commission and the Member States.
 ---pagebreak---                                                                    - 14 -
                    original Text                                Amendment to the proposal
                                                Article 26 unchanged
                Article 27                                          Article 27
                                         Article 27, paragraph 1, unchanged
                Article 27 (2)                                      Article 27 (2)
                                                                   2. In the case of a veterinary
   2.    The application shall also be accompanied by the fee      medicinal product containing or
   payable to the Agency for the examination of the
   application.
                                                                   consisting of genetically
                                                                   modified organisms within the
                                                                   meaning of Article 2 paragraphs 1
                                                                   and 2 of Directive 90/220/EEC on
                                                                   the deliberate release into the
                                                                   environment of genetically
                                                                   modified organisms, the
                                                                   application shall also be
                                                                   accompanied by:
                                                                   " a copy of the written consent,
                                                                      from the competent authority,
                                                                      to the deliberate release of
                                                                      the genetically modified
                                                                      organisms for research and
                                                                      development purposes provided
                                                                      for in Article 6(4) of
                                                                      Directive 90/220/EEC:
                                                                   - the complete technical dossier
                                                                      supplying the information
                                                                      requested in Annexes II and III
                                                                      of Directive 90/220/EEC and the
                                                                      environmental risk assessment
                                                                      resulting from this information
                                                                   Articles 11 to 18 of Directive
                                                                   90/220/EEC shall not apply to
                                                                   veterinary medicinal products
                                                                   containing or consisting of
                                                                   genetically modified organisms.
                Article 27 (3)                                      Article 27 (3)
                                                                   3^ The application shall also be
    3.    The Agency shall ensure that the opinion of the          accompanied by the fee payable to
    Committee is given within 210 days of the receipt of a valid   the Agency for the examination of
    application.
                                                                   the application.
3)
 ---pagebreak---                                                              - 15 -
                   Original Text                                    Amendment to the proposal
        Article 27 (4)                                         Article   27  (4)
                                                             4. The Agency shall ensure that
4.    The Agency shall, in consultation with Member States,  the opinion of the Committee is
the Commission and interested parties, draw up detailed      given within 210 days of the
guidance on the form in which applications for authorization receipt of a valid application.
are to be presented.
                                                             In the case of a veterinary
                                                             medicinal product containing or
                                                             consisting of genetically
                                                             modified organisms, the opinion
                                                             of the Committee shall take
                                                             account of the environmental
                                                             safety requirements laid down by
                                                             Directive 90/220/EEC.
                                                             Article 27 (5) (new)
                                                             5_i_ The Agency shall, in
                                                             consultation with Member States,
                                                             the Commission and interested
                                                             parties, draw up detailed
                                                             guidance on the form in which
                                                             applications for authorization
                                                             are to be presented.
                                        Articles 28 - 30 unchanged
 ---pagebreak---                                                                    16-
             Original        Text                                   Amendment to the proposa
 A r t i c l e 31     (1)                                               A r t i c l e 31     (1)
 1.    Within 30 days of the receipt of the opinion, ths               1.     Within 30 days of the receipt of the opinion, the
 Commission shall prepare a draft of the Decision to be taker.         Commission shall prepare a draft of the Decision to be taken
 in respect of the application taking into account the
                                                                         in respect of the application taking into account the
 objectives of Community policies and considering all
                                                                         objectives of Community policies and considering all
 relevant information. In the event of a draft Decision which
                                                                         relevant information. In the event of a draft Decision which
 envisages the granting of a marketing authorization, the
                                                                         envisages the granting of a marketing authorization, the
 documents referred to in points (a), (b), and (c) of Article 30
                                                                        documents referred to in points (a), (b), and (c) of Article 30
 (3) shall be annexed. The Commission shall transmit the
                                                                        (3) shall be annexed. The Commission shall transmit the
 draft Decision to the Member States and to the applicant.
                                                                        draft Decision to the Member States and to the applicant.
      The Commission            shall explain                in       If, exceptionally, the Commission
      detail        the       reasons           for       any         intends to draw up a draft Decision
      differences           between          the       draft         which differs from the opinion of
     Decision and the opinion of the                                 the Camiittee^ the Commission shall
     Committee.                                                      explain in detail the reasons for
                                                                     any differences.
Article 31 (2)                                                   Article 31 (2)
2. The Commission shall adopt the                                2. The Commission shall adopt the
Decision to be taken in respect of                               Decision to be taken in respect of
the application unless, within 30                                the application unless, within 30
days, it has received a reasoned                                 days, it has received a reasoned
request        from a Member               State to              request      from a Member              State to
reconsider the matter.                  The Member               reconsider the matter.                The Member
State concerned shall also transmit a                            State concerned shall also transmit a
copy of it:i request to the other                                copy of it.i request to the other
Member        States     and the           applicant             Member      States      and     the      applicant
within tho same time limit.                                      within the same time limit.
                                                               The     Member          State        requesting
                                                               reconsideration          shall       provide
                                                               detailed       juetification           based
                                                               scientific       evidence        or     Community
                                                               law.
                    Article 31, paragraphs 3 and 4 unchanged
                                                                 Article 31 (5). new
                                                                       The Agency shall, upon request.
                                                                  Inform any Interested person of the
                                                                  contents of its final opinion.
 ---pagebreak---                                                               - 17 ..
                 Original Text                                            Amendment to the proposal
                                             Article 32 unchanged
      Article 33 (1)                                                       Article 33 (1)
 1.       Without prejudice to Article 4 of Council Directive       1.        Without prejudice to Article 4 of Council Directive
. . . / . . ./EEC extending the scope of Directive                  . . . / . . ./EEC extending the scope of Directive
81/851 /EEC on the approximation of the laws of the                81/851 /EEC on the approximation of the laws of the
Member States relating to veterinary medicinal products,           Member States relating to veterinary medicinal products,
and laying down additional provisions for immunological            and laying down additional provisions for immunological
veterinary medicinal products, a marketing authorization           veterinary medicinal products, a marketing authorization
which has been granted in accordance with the procedure            which has been granted in accordance with the procedure
laid down in this Regulation shall apply throughout the            laid down in this Regulation shall apply throughout the
Community. It shall confer the same rights and obligations in      Community. It shall confer the same rights and obligations in
each of the Member States as a marketing authorization             each of the Member States as a marketing authorization
granted by that Member State in accordance with Article 4 of       granted by that Member State in accordance with Article 4 of
Directive 81/851/EEC.                                              Dircctive'81/851/EEC.
                                                                                The     authorized          medicinal
                                                                  products shall be entered in the
                                                                  Community Register of Veterinary
                                                                  Medicinal Products and thev shall be
                                                                  given a number which muet appear on
                                                                  the packaging.
                                        Article 33 (2) unchanged
    Article 33 (3)                                              Article            33   (3)
   3.       Ajn_    a nnouncement                 that          3. Notification                   of      marketing
   authorisation has been granted shall                         authorization shall be published in
   be published for information purposes                        the Official Journal of the European
    in the Official Journal of the                              Communities, quoting the number in
   European Communities.                                        the Community Register of Veterinary
                                                                Medicinal Products.
                                        Article 33 (4) unchanged
   Article 34 (l)                                              Article 34 (1)
 1. Authorisation shall be valid for                           1. Authorization shall be valid for
 five years and may be renewable for                           five years and may be renewable for
 five-year période, on application by                          five-year periods, on application by
 the holder at leaet three months                              the holder at least three months
 before the expiry date.                                       before the expiry date and after
                                                               consideration bv the Aoencv of a
                                                               dossier             containing          up-to-date
                                                               information on pharmacovloilance.
 ---pagebreak---                                                                - 18 -
              Original Text                                      Amendment to the proposa
 A r t i c l e 34 (2)                                                  A r t i c l e 34 (2)
2.     In exceptional circumstances, and following
consultation with the applicant, an authorization may be               2. In exceptional circumstances, and
granted subject to such conditions as appear necessary to              following            consultation    with   the
ensure the protection of human or animal health, including             aDD)leant, an authorization may be
specific obligations to condua further studies following the           granted subject t o /
granting of authorization and specific obligations in respect
                                                                               certain        specific   obligations
of the reporting of adverse reactions to the veterinary
medicinal product.                                                    defined and reviewed annually by the
                                                                      Agency,
                                                                     Z to          conduct       further     studies
                                                                         following             the    granting    of
                                                                         authorization;
                                                                      - to report adverse .reactions to
                                                                         the            veterinary       medicinal
                                                                         products.
                              A r t i c l e 34 paragraph 3 unchanged
                                          A r t i c l e 35 unchanged
                           A r t i c l e 36 paragraphs 1 - 3                    unchanged
 A r t i c l e 36 (4)                                         A r t i c l e 36 (4)
4. The Agency s h a l l , in accordance                       4. The Agency s h a l l , in accordance
with         the       Commission,              adopt         with         the           Commission,     adopt
appropriate           arrangements         for        the     appropriate arrangements for the
examination             of     amendments            and      examination                of   amendments and
variations           to     the terms of                a     variations             to the      terms of     a
marketing authorization.                                      marketing            authorization.         These
                                                              arrangements s h a l l include a system
                                                              of    n o t i f i c a t i o n or administrative
                                                              procedures               to take     account   of
                                                              changes of minor importance.
                                  Articles 37 and 38 unchanged
 ---pagebreak---                                                                   - 19 -
                      Original Text                                         Amendment to the proposal
          A r t i c l e 39 (1)                                       A r t i c l e 39 (1)
1.     Where the supervisory authorities or the competent            1.       Where the supervisory authorities or the competent
authorities of any other Member State are of the opinion that        authorities of any other Member State are of the opinion that
the manufacturer or importer from third countries is no              the manufacturer or importer from third countries is no
longer fulfilling the obligations laid down in Chapter V of          longer fulfilling the obligations laid down in Chapter V of
Directive 81/851/EEC they shall forthwith inform the                 Directive 81/851/EEC they shall forthwith inform the
Committee and the Commission, stating their reasons in               Committee and the Commission, stating their reasons in
detail and indicating the course of action proposed.                 detail and indicating the course of action proposed.
  The same shall apply where a Member State considers that           The sane shall                       apply         where a
  one of the measures envisaged in Chapter VI of Directive          Member State or                         the Commission
  81/851/EEC should be applied in respect of the veterinary          considers that one of the measures
  medicinal product concerned.                                       envisaged in Chapter VI or Chapter
                                                                     Via of Directive 81/851/EEC should
                                                                    be applied in                       respect           of the
                                                                    veterinary                      medicinal             product
                                                                     concerned.
                                   Article 39 paragraphs 2 - 5                       unchanged
                                                                    Article 39 (6). new
                                                                      A. The Agency shall, upon request,
                                                                     Inform any interested person of the
                                                                     contents of the Committee's opinion
                                                                     referred to in paragraph 2.
                                             A r t i c l e s 40 - 42 unchanged
                                 A r t i c l e 43 paragraphs 1 and 2 unchanged
                                                                    A r t i c l e 43 ( 3 ) . new
                                                                    The person r e s p o n s i b l e for marketing
                                                                    shall        accompany t h e records of
                                                                    adverse r e a c t i o n s with an a n a l y s i s
                                                                    of        the      data       regarding          such
                                                                    reactions, in o r d e r t o make them
                                                                    e a s i e r t o understand.
 ---pagebreak---                                                               -21} -
              Original Text                                  Amendment to the proposal
  Article 44                                                    Article 44
   Each Member State shall report any                               Each Member State shall organize the
   suspected serious adverse reaction                               pharmacovigilance service within its
   arising within its territory to a                                territory             according        to    the
   veterinary              medicinal             product            provisions of A r t i c l e 45. I t shall
   authorized in accordance with this                               report        any      suspected
   Regulation to the Agency and the                                 serious adverse reaction                 arising
   person        responsible           for     marketing            within           its      territory       to    a
   within       15 days of receipt of a                             veterinary             medicinal        product
   report from a qualified health care                              authorized in accordance with t h i s
   professional .                                                   Regulation to the Agency and the
                                                                    person responsible for marketing
                                                                    within 15 days of r e c e i p t of a
                                                                    report from a qualified health care
                                                                    professional.
  A r t i c l e 45                                              A r t i c l e 45
                                                                  The        C o m m i s s i on     shal 1       in
The Agency shall, in consultation with Member States, the
                                                                  consultation with the Agency• Member
Commission and interested parties, draw up detailed
guidance on the collection, verification and presentation of
                                                                  States and the interested parties,
adverse reaction reports to veterinary medicinal products.        approve detailed guidance, common to
                                                                  the Member States /
                                                                                         on     the   collection,
                                                                  verification           and    presentation     of
                                                                  adverse reaction reports.                   These
                                                                  reports shall have a format similar
                                                                  to that used by the World Heal th
                                                                  Organ 1zat i on
                                                                 The Agency, in consultation with the
                                                                Member States and the Commission,
                                                                 shall       set      up    a    data-processing
                                                                 network for the rapid transmission
                                                                 of      data      between       the   competent
                                                                Community authorities in the event
                                                                of an alert              relating     to faulty
                                                                manufacture,             serious     undesirable
                                                                effects and other pharmacovigi!ance
                                                                data regarding medicinal                products
                                                                marketed in the Community.
                                         Article        46    unchanged
 ---pagebreak---                                               -21 -
          Original Text                         Amendment to the proposa
                             A r t i c l e 47 unchanged
                                                     A r t i c l e 47a (new)
                                                                  The Agency shall collaborate
                                                      with the World Health Organization
                                                      on International pharmocovigilance
                                                      and shall take the necessary steps
                                                      to submit promptly to the World
                                                      Health Organization appropriate and
                                                      adequate Information regarding the
                                                      measures taken 1n the Community
                                                      which may have a bearing on public
                                                      health protection in third countries
                                                      and shall send a copy thereof to the
                                                      Commission and the Member States.
  Article 48                                    Article 48
In order to promote the protection               In order to promote the protection
of public health throughout the                  of public health and con s umcrs "o f
Community     and   the   adoption of            medicinal products throughout the
uniform regulatory decisions based               Community v and the adoption           of
on scientific criteria concerning                uniform regulatory decisions based
the marketing and use of medicinal               on scientific criteria concerning
products, the objective of the                   the marketing and rational use of
Agency shall be to provide the                   medicinal products, the objective Y>f
Member States and the Institutions               the Agency shall be to provide the
of the Community with the best                   Member States and the Institutions
possible scientific advice on any                of the Community with the best
question relating to the evaluation              possible scientific advice on any
of the quality, the safety or the                question relating to the evaluation
efficacy of medicinal products for               of the quality, the safety or the
human or veterinary use which 1s                 efficacy of medicinal products for
referred to 1t 1n accordance with                human or veterinary use which 1s
the    provisions      of    Community           referred to 1t in accordance with
legislation relating to medicinal                the    provisions          of   Community
products.                                        legislation relating to medicinal
                                                 products.
   In particular the Agency           shall      In particular the Agency shall
   undertake the following taskst                undertake the following tasks:
 ---pagebreak---                                            -22 -
            Original Text                  Amendment to the proposal
                      Article 48, points (a) and (b) unchanged
  Point (c)                                 Point (c)
    the       continuing      supervision,          the continuing      supervision,
   under practical conditions of                    under practical conditions of
   use, of medicinal products which                 use, of medicinal produces
   have been authorized within the                  which have been authorized
   Community and the provision of                   within the Community and the
    advice on the measures necessary                provision of advice on the
   to ensure the safe and effective                 measures necessary to ensure
    use      of      these   products, In           the safe and effective use of
    p a r t i c u l a r . following    the          these products, in particular
   evaluation of reports of adverse                 by collecting, evaluating and
    reactions (pharmacovigi! ance);                 making available through the a
                                                    database the information on
                                                    adverse    reactions     to thé
                                                    medicinal products in question
                                                    (pharmacovigi!ance);
            Article 48, points (d), (e), (f) and (g) unchanged
  Point (h)                                  Point (h)
where necessary, to advise and to             to advise andT at the' request of the
allow for direct dialogue between             applicant, to allow for direct
the applicant and the Agency on the           dialogue between the applicant and
conduct of the various tests and              the Agency on the conduct of the
trials necessary to demonstrate the           various tests and trials necessary
quality, safety and efficacy of               to demonstrate the quality, safety
medicinal products.                           and efficacy of medicinal products.
                           Article 48, point (i) unchanged
                                             Point ( j ) . new
                                              regi stering         al 1    the
                                              authorizations for medicinal
                                              products     granted    in    the
                                              European Community;
                                             Point (k). new
                                             the    provision    to    health
                                             professionals of scientific
                                             information on the medicinal
                                             products authorized by this
                                             Regulation.
 ---pagebreak---                                                                -23   -
                 Original Text                                  Amendment to the proposal
                                              A r t i c l e 49 unchanged
                               A r t i c l e 50 paragraphs 1 - 3               unchanged
                                                                       A r t i c l e 50 (4) (new)
                                                                       The opinions adopted by
                                                                       the Committees shall be
                                                                       made available to anyone
                                                                       requesting them.
                                       Articles 51 and 52 unchanged
                             Article 53 paragraphs 1 and 2 unchanged
              Article 53 paragraph 3, first four indents unchanged
                                                                Fifth indent (new)
                                                                       a list of medicinal products
                                                                       which        have   been   granted
                                                                       authorization, those for which
                                                                       authorization has been refused
                                                                       or withdrawn and those whose
                                                                       information         records   have
                                                                       undergone significant changes.
                                   Article 53 paragraph 4 unchanged
                                                                Article 53 (5). new
                                                                  The executive director may not have
                                                                  any direct or indirect interests in
                                                                  the pharmaceutical Industry which
                                                                  would affect his impartiality.
     Article 54 (1)                                             Article 54 (1)
                                                                 1. The            Manag ement    Board shall
1.    The management board shall consist of two
representatives from each Member State and two
                                                                consist            of    two   représenta t ives
representatives of the Commission. One representative shall     from          each       Membe r   State, two
have specific responsibilities relating to medicinal products   represen tatives of the Commi ssion
for human use and one relating to veterinary medicinal          and two repres entat ives appo inted
products.                                                       by the European Parliament. One
                                                                represen tative shal 1 have spe<icif ic
                                                                responsi bilitie s               relating     to
                                                                medicina 1 products for human use
                                                                and one relat ing               to veter inary
                                                                medicina 1 products.
 ---pagebreak---                                                                -24 -
                Original Text                                   Amendment to the proposal
                              Article 54 paragraphs 2 - 5                        unchanged
                                         Articles 55 -64 unchanged
                              Article 65 paragraphs 1 - 4 unchanged
                                                                         Article 65 (5). (new)
                                                                         Article 52 (2) shall apply
                                                                         similarly to members of
                                                                         the Scientific Council.
                                             Article 66 unchanged
    Article 67                                                   Article 67
     All decisions              to grant,          refuse,        All decisions to grant, refuse,
     amend, suspend, withdraw or revoke a                         amend, suspend, withdraw or revoke a
     marketing        authorization which are                     marketing authorization which are
     taken       in      accordance          with      this       taken        in     accordance           with     this
     regulation shall state in detail the                         regulation shall state in detail the
     reasons on which they are based.                             reasons on which they are based.
     Such decisions shall be notified to                          Such decisions shall be notified to
     the party concerned, who shall be                            the party concerned, who shall be
     able       to     exercise          the      remedies        able       to      exercise         the     remedies
     conferred upon him under the EEC                             conferred upon him under the EEC
     Treaty.                                                      Treaty, in particular pursuant to
                                                                  its Article 173.
                                      Articles 68 and 69 unchanged
    Article 70                                                   Article 70
Without prejudice to Article 68, and without prejudice to the      Without prejudice to Article 68, and without prejudice to the
Protocol on the Privileges and Immunities of the European          Protocol on the Privileges and Immunities of the European
Communities, each Member State shall determine the                 Communities, each Member State shall determine the
penalties to be applied for the infringement of the provisions      penalties to be applied for the infringement of the provisions
of this Regulation. The penalties shall be sufficient to            of this Regulation. The penalties shall be sufficient to
promote compliance with those measures.                             promote compliance with those measures.
Member States shall forthwith inform the Commission of the          The      Member         States         shall      also
institution of any infringement proceedings.                        determine           penalties           to     ensure
                                                                    compliance with professional secrecy
                                                                    on the part of the members of the
                                                                    Agency         In     accordance         with      the
                                                                    provisions of Article 62.
                                                                   Member States shall forthwith inform the Commission of the
                                                                   institution of any infringement proceedings.
                                        Articles 71 - 73 unchanged
                                                   Annex unchanged
 ---pagebreak---                                                        -25 -
                                Amendment to the proposal for a                                    SYN 310
  2.                                       COUNCIL DIRECTIVE
         amending Directives 65/65/EEC, 75/318/EEC and 75/319/EEC
                                 in respect of medicinal products
           O r i g i n a l Text                          Amendment to the proposal
                         V i s a s and r e c i t a l s 1 and 2 unchanged
  Third recital                                         Third recital
 Whereas in the interests of public                     Whereas in the interests of public
 health     it       is     necessary        that       health and consumers of medicinal
 decisions on the authorization to                      products        it    is   necessary     that
 place medicinal products on the                        decisions on the authorization to
 market be exclusively based on the                     place medicinal products on the
 criteria of quality, safety and                        market be exclusively based on the
 efficacy; whereas these criteria                       criteria of quality, safety and
 have been extensively harmonized by                    efficacy; whereas these criteria
 Directive 65/65/EEC. of 26 January                     have been extensively harmonized by
 1965    on     the       approximation        of       Directive 65/65/EEC of 26 January
 provisions        laid       down     by    law,       1965      on     the    approximation      of
 regulation or administrative action                    provisions         laid    down     by law,
 relating to medicinal products, as                     regulation or administrative action
 last     amended            by      Directive          relating to medicinal products, as
89/381/EEC,           and      by     Directive         last       amended        by     Directive
 75/319/EEC,           and       by     Council         89/381/EEC,          and    by     Directive
Directive 75/318/EEC of 20 May 1975                     75/319/EEC,           and     by     Council
on the approximation of the laws of                    Directive 75/318/EEC of 20 May 1975
the    Member        States       relating     to      on the approximation of the laws of
analytical,        pharmaco-toxicological              tho      Member      States     relating to
and clinical standards and protocols                   analytical,         pharmaco-toxicological
in    respect      of      the     testing     of      and clinical standards and protocols
medicinal products, as last amended                    in     respect      of    the    testing of
by Directive 89/341/EEC; whereas,                      medicinal products, as last amended
however,      Member          States      should       by Directive 89/341/EEC; whereas,
exceptionally be able to prohibit                      however,        Member      States     should
the use on their territory of                          exceptionally be able to prohibit
medicinal products which infringe                      the use on their territory of
objectively       defined         concepts of          medicinal products which infringe
public order or public morality;                       objectively        defined     concepts of
                                                       public order or public morality;
                                                        New recital inserted after
                                                        third recital
                                                          Whereat; _ there       already     exist    in
                                                          Commuait y. law adequate rules for the
                                                          evaluation          and    monitoring      of
                                                          nr.edi çijna 1    products      laying   down
                                                         maximum levels of guality, safety
                                                          and efficacy and allowing the mutual
                                                          recognition of measures taken by the
                                                          authorities       in the Member States
                                                         with regard to medicinal products;
                                 Remaining recitals unchanged
 ---pagebreak---                                                     -26 -
       Original Text                                  Amendment to the proposa I
          A r t i c l e 1 ( 1 ) , ( D i r e c t i v e 65/65/EEC, A r t i c l e 3)
    No medicinal product may be placed                      No medicinal product may be placed
    on the market of a Member State                         on the market of a Member S t a t e
    unless an authorization has been                        unless an a u t h o r i z a t i o n has been
    Issued bv the competent authority of                    obtained      in       accordance        with
    that   Member         Sfrgf    or.—fey—fcfee.           Community r u l e s .
    CommunItVt
                              A r t i c l e 1(2) unchanged
          A r t i c l e 1 (3) ( D i r e c t i v e 65/65/EEC, A r t i c l e 4b)
                                                     Third paragraph, new
                                                      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
                                                      medicinal      product        a       European
                                                      Register    number      which       shall be
                                                      marked on the packaging.
                              Article 1 (4) unchanged
         Article 1 (5) ( Directive 65/65/EEC Article 7(1))
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 210 days of the date of                          within 140 days of the date of
submitting the application.                             submitting tho application.
                                paragraph 2 unchanged
                         Article 1 (6) and (7) unchanged
 ---pagebreak---                                         -27 -
          Original Text                    Amendment to the proposal
           Article 1 (8), (Directive 65/65/EEC, Article 10)
  1. Authorization shall be valid for        1. Authorization shall be valid for
  five years and may be renewable for        five years and may 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.                   before the expiry date and after
                                            consideration                        of a
                                            dossier       containing      up-to-date
                                             information on pharmacovigilance.
                                             2. In exceptional circumstances,, and
 2. In exceptional circumstances, and        following     consultation, with      the
 following    consultation, with    the      applicant, an authorization may be
 applicant, an authorization may be         granted subject
 granted subject to such conditions          to certain      specific    obligations,
 as appear necessary to ensure the
 protection     of    public    health,      including:
 including specific obligations to                the carrying      out of further
conduct further studies following                 studies following the granting
 the granting of authorization and                of authorization;
 specific obligations in respect of
the reporting of adverse reactions                the    notification     of   adverse
to the medicinal product.                         reactions     to    the    medicinal
                                                  product.
                                             These decisions shall be taken in
                                             accordance with the provisions of
                                             Chapter III, Part III of the Annex
                                             to Directive 75/318/EEC.
                             Article 2 unchanged
           Article 3 (1) (Directive 75/319/EEC, Chapter III)
                    Articles 8 - 1 1 , proposal unchanged
                         Article 12, first paragraph
The Member States or the Commission        The Member States, the Commission or
may, in specific cases where the           the    applicant     himself    may,    in
interests    of   the   Community   are    specific cases where the interests
involved, refer the matter to the          of   the    Community    are    involved,
Committee for the application of the       refer the matter to the Committee
procedure laid down in Article 13          for     the    application       of    the
before reaching a decision on a            procedure laid down in Article 13
request        for    a    marketing       before reaching a decision on a
authorization or on the suspension         request         for    a     marketing
or revocation of an authorization,         authorization or on the suspension
or on any other amendment to the           or revocation of an authorization,
terms of a marketing authorization         or on any other amendment to the
which     appears     necessary,     1n    terms of a marketing authorization
particular to take account of the          which     appears      necessary,       in
information collected in accordance        particular to take account of the
with Chapter Va of this Directive.         Information collected in accordance
                                           with Chapter Va of this Directive.
 ---pagebreak---                                          "28 -
        Original Text                      Amendment to the proposal
               Article 12 paragraphs 2 and 3 unchanged
                            Article 13 unchanged
                  Article 14 paragraphs 1 - 5               unchanged
                        Article 14 paragraph 6, new
                                               6 . The          procedure   pursuant    to
                                              A r t i c l e s 8 t o 14 shall not apply in
                                              the           instances      covered      by
                                              Article 9(21 of Directive . . . on
                                              homeopathic           medicinal    products
                                              (COM(90) 0072 final - SYN 251i.
                            Article 15 unchanged
                                  Article 15a
 1. Where a Member State considers           1. Where a Member State considers
 that the amendment of the terms of a        that the amendment of the terms of a
 marketing authorization which has           marketing authorization which has
 been granted in accordance with the         been granted in accordance with the
 provisions of this chapter or its           provisions of this chapter or its
 suspension      or    withdrawal     is     suspension             or    withdrawal      is
 necessary,      the    Member    State      necessary,             the    Member    State
 concerned shall forthwith refer the         concerned shall forthwith refer the
 matter to the Committee for the            matter to the Committee for the
 application of the procedures laid          application of the procedures laid
 down in Articles 13 and 14.                down in Articles 13 and 14.
                                             2. In           exceptional     cases_   where
2. In   excentional      cases,   where      action           is urgently necessary to
action   is urgently necessary to            protect           public   health,   until    a
protect   public    health,   until   a     definitive decision is adopted, a
definitive decision is adopted, a           Member State may suspend the use of
Member State may suspend the use of         the medicinal product concerned oh
the medicinal product concerned on           its territory jf it finds the foil
its territory.     It shall inform the
Commission    no     later   than   the
following working day of the reasons
for its actions.                              (1)        The severity of the harm that
                                              could be caused by the medicinal
                                              product cannot await the definitive
                                             decision of the Commission;
                                              (2) There is a likelihood that the
                                             medicinal product will cause the
                                             suspected               harm    during     the
                                             Commissions deliberations;
 ---pagebreak---                                                       -29
            Original Text                                Amendment to the proposal
                                                                (3) The r i s k to p a t i e n t s currently
                                                               taking          the     medicinal      product
                                                               occasioned by the removal of the
                                                               product from the market i s out-
                                                               weighed by the degree of harm caused
                                                               by the product i t s e l f .
                                                               The Member S t a t e concerned shall
                                                               inform the Commission no l a t e r than
                                                               the following working day of the
                                                               reasons for i t s a c t i o n s .
                                    A r t i c l e 15b unchanged
                                  A r t i c l e 15c paragraph 1
1. The Agency shall                publish an                1. The Agency s h a l l          publish a
annual report on the operation of                           biennial report on the operation of
the procedures l a i d down in t h i s                      the procedures l a i d down in t h i s
Chapter.                                                    Chapter and s h a l l forward i t for
                                                             Information            to   the      European
                                                            Parliament and the Council.
                           Article 15c paragraph 2 unchanged
                                 Article 3 (2) unchanged
                   Article 3 (3) (Directive 75/319/EEC Article 29a)
   In order t o ensure the adoption of                     In order to ensure the adoption of
   appropriate           regulatory        decisions       appropriate            regulatory     decisions
   concerning               the      continued             concerning                the     continued
   authorization of medicinal products                     authorization of medicinal products
   within the Community, having regard                     within the Community, having regard
   to        information       obtained          about     to       information        obtained      about
   adverse           reactions    to      medicinal        adverse           reactions    to     medicinal
   products under practical conditions                     products under p r a c t i c a l conditions
   of       use,       Member     States         shall     of       use,       Member    States      shall
   e s t a b l i s h a pharmacovigilance system            e s t a b l i s h a pharmacovigilance system
   for        collecting     information         about     for c o l l e c t i n g information about
   adverse           reactions    to      medicinal        adverse           reactions    to     medicinal
   products in human beings and for the                    products in human beings and for the
   scientific           evaluation        of      such     scientific           evaluation       of   such
   information.                                            information,              such    that      the
                                                           information about adverse reactions
                                                           i s systematically related to the
                                                           information on the consumption of
                                                           medicinal products.
 ---pagebreak---                                                                    - 30 -
                    Original Text                                   Amendment to the proposal
                                                Article 29b unchanged
                                Article 29c points (a) and (b) unchanged
                                                  Article 29c point c
(c)       ensuring that any request from                               (c) ensuring that any request from
          the competent authority for the                                     the competent authority for the
         provision                   of     additional                        provision                    of     additional
          information necessary for the                                       information necessary for the
         evaluation of the benefits and                                       evaluation of the benefits and
         risks of a medicinal product 1s                                      risks of a medicinal product 1s
         answered fully and promptly,                                         answered             fully       and    promptly,
         including               the     provision          of                Including                the      provision         of
         information about the volume of                                      Information about the volume of
         sales or prescriptions for the                                       sales or prescriptions for the
         medicinal              product       concerned,                     medicinal product concerned.
         where relevant.
                                  Articles 29d, 29e and 29f unchanged
                                                            Article 29g
       In o r d e r t o f a c i l i t a t e t h e exchange               In order t o f a c i l i t a t e t h e exchange
       of             i n f o r m a t i o n              about           of            i n f o r m a t i o n                about
       pharmacovigilance                      within           the       pharmacovigilance                       within          the
       Community,              the     Agency     shall,        in       Community, t h e Commission s h a l l , in
       c o n s u l t a t i o n w i t h Member S t a t e s , t h e        c o n s u l t a t i o n w i t h t h e Agency and t h e
       Commission                and      the     interested             i n t e r e s t e d p a r t i e s , draw up d e t a i l e d
      p a r t i e s , draw up d e t a i l e d guidance                   guidance                on       the     collection,
      on t h e c o l l e c t i o n , v e r i f i c a t i o n and         verification               and p r e s e n t a t i o n   of
      presentation                of     adverse        reaction         adverse            reaction         reports.           Such
      reports.                                                           guidance s h a l l t a k e i n t o account t h e
                                                                         format used by t h e World Health
                                                                         Organization.
                                                           Article      29h
Where a s a r e s u l t o f t h e e v a l u a t i o n               Where as a result of the evaluation
of       adverse              reaction      reports,         a      of adverse                 reaction        reports, a
Member S t a t e i s c o n s i d e r i n g amending                 Member State is considering amending
the          terms             of      a     marketing              the        terms             of        a    marketing
a u t h o r i z a t i o n o r i t s s u s p e n s i o n or          authorization or its suspension or
withdrawal,                  it     shall      forthwith            withdrawal,                 it     shall      forthwith
inform t h e Agency.                                                inform the Agency and the holder of
                                                                    the marketing authorization.
  In case of urgency, the Member State concerned may                  In case of urgency, the Member State concerned may
  suspend the marketing of a medicinal product, provided              suspend the marketing of a medicinal product, provided
  the Agency is informed at the latest on the following               the Agency is informed at the latest on the following
  working day.'                                                       working day.'
                                           Articles 4 and 5 unchanged
 ---pagebreak---                                                      - 31 "
                             Amendment to the proposal for a
 3.                                   COUNCIL DIRECTIVE                                        SYN 311
                      anending Directives 81/851/EEC and 81/852/EEC
                        in respect of veterinary medicinal products
             Original Text                            Amendment to the proposal
                               Visas and r e c i t a l s unchanged
                                        A r t i c l e 1 (1)
     ( D i r e c t i v e 81/851/EEC, A r t i c l e 4 ( 1 ) , f i r s t        sub-paragraph)
No veterinary medicinal product may                      No veterinary medicinal product may
be placed on the market of a Member                     be placed on the market of a Member
S t a t e u n l e s s an authorization has              State unless an authorization has
been        issued        by   the   competent          been obtained in accordance with
authority of that Member State or by                    Community r u l e s .
the Community.
                           Articles    1 (2) and 1 (3) unchanged
                Article 1 (4) Directive 81/851/EEC, Article 5b
                                                       Third paragraph, new
                                                        Before    a veterinary         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.
                                        Article 1(5)
             (Directive 81/851/EEC Article 8, first paragraph)
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 210 days of the date of                          within 140 days of the date of
submitting the application.                             submitting the application.
                                   paragraph 2 unchanged
                          Articles    1 (6) and 1 (7) unchanged
 ---pagebreak---                                                                  -32  -
                                                                   Amendment to the proposal
              Original Text
                                                  A r t i c l e 1 (8)
                  ( D i r e c t i v e 81/851/EEC A r t i c l e 15 paragraph 1 )
 1. A u t h o r i z a t i o n s h a l l be v a l i d f o r             1. A u t h o r i z a t i o n s h a l l be v a l i d for
 f i v e years and may be renewable f o r                              f i v e y e a r s and may be renewable for
 f i v e - y e a r p e r i o d s , on a p p l i c a t i o n by         f i v e - y e a r p e r i o d s , on a p p l i c a t i o n by
 the holder a t l e a s t t h r e e months                             the holder a t l e a s t three months
 before t h e e x p i r y d a t e .                                    before t h e e x p i r y date and a f t e r
                                                                       consideration                                           of a
                                                                       dossier            containing              up-to-date
                                                                       information on pharmacovigilance.
                                           paragraph 2 unchanged
                  Article 1 (9) (Directive 81/851/EEC Chapter IV)
                              Articles          16 - 19 proposal unchanged
                                      Article 20 first paragraph
  The Member States or the Commission                                The Member States, the Commission or
  may, in specific cases where the                                   the        applicant           himself     may, in
  Interests            of the Community are                          specific cases where the interests
  involved, refer the matter to the                                  of the Community                     are involved,
  Committee for the application of the                               refer the matter to the Comité for
  procedure laid down in Article 21                                  the application of the procedure
  before reaching a decision on a                                    laid down in Article 21 before
  regueat                for         a      marketing                reaching a decision on a request for
  authorization or on the suspension                                 a marketing authorization or on the
  or revocation of an authorization,                                 suspension          or revocation of an
  or on any other amendment to the                                   authorization,              or on any other
  terms of a marketing authorization                                 amendment           to the terms                 of a
  which           appears           necessary,              in       marketing             authorization               which
  particular to take account of the                                  appears necessary, in particular to
  information collected in accordance                                take account of the information
 with Chapter Via of this Directive.                                 collected            in accordance                  with
                                                                     Chapter Via of this Directive.
                         A r t i c l e 20 paragraphs 2 and 3 unchanged
                                     A r t i c l e 21 - 23b unchanged
                                                     A r t i c l e 23c
1. The Agency                   shall     publish          an           1. The Agency                   shall   publish a
annual report on the operation of                                      biennial report on the operation of
the procedures laid down in t h i s                                    the procedures l a i d down in t h i s
Chapter.                                                               Chapter and s h a l l forward i t for
                                                                        information                to      the      European
                                                                       Parliament and the Council.
                                        paragraph 2 unchanged
                                     Article 1 (10) unchanged
 ---pagebreak---                                                                   - 33 -
                   Original Text                                     Amendment to the proposal
                                                     A r t i c l e 1 (11)
                                  ( D i r e c t i v e 81/851/EEC Chapter Via)
                                                        A r t i c l e 42a
 In order to ensure the adoption of appropriate \                         In order to ensure the adoption of appropriate
 regulatory Decisions concerning the continued                            regulatory Decisions concerning the continued
 authorization of veterinary medicinal products within                    authorization of veterinary medicinal products within
 the Community, having regard to information obtained
                                                                         the Community, having regard to information obtained
 about adverse reactions to veterinary medicinal
                                                                         about adverse reactions to veterinary medicinal
 products under practical conditions of use, the Member
                                                                         products under practical conditions of use, the Member
 States shall establish a pharmacovigilance system for
                                                                         States shall establish a pharmacovigilance system for
 collecting information about adverse reactions to
                                                                         collecting information about adverse reactions to
 veterinary medicinal products and for the scientific
 evaluation of such information.                                         veterinary medicinal products and for the scientific
                                                                         evaluation of such information s u c h         that      the
                                                                                    Information about a d v e r s e r e a c t i o n s
                                                                                    i s systematically related t o the
                                                                                   information on t h e consumption of
                                                                                   medicinal products.
                                             Article 42b unchanged
                            Article 42c points (a) and (b) unchanged
                                               Article 42cpoint (c)
(c) ensuring that any request from the competent                       (c) ensuring that any request from the competent
      authority for the provision of additional                              authority for the provision of additional
      information necessary for the evaluation of the                        information necessary for the evaluation of the
      benefits andrisksof a veterinary medicinal product                     benefits and risks of a veterinary medicinal product
     is answered fully and promptly, including the                           is answered fully and prompdy, including the
     provision of information about the volume of sales                      provision of information about the volume of sales
     for the veterinary medicinal product concerned,                         for the veterinary medicinal product concerned.
     wfrere relevant.
                                Articles 42d, 42e, and 42f unchanged
                                                       Article 42g
   In order t o f a c i l i t a t e the exchange                     In order t o f a c i l i t a t e the exchange
  of            i n f o r m a t i o n               about            of            i n f o r m a t i o n            about
  pharmacovigilance                      within         the          pharmacovigilance                      within         the
  Community,              the    Agency       shall,       in        Community, the Commission s h a l l , in
  c o n s u l t a t i o n with Member S t a t e s , the              c o n s u l t a t i o n with the Agency and the
  Commission                and     the       Interested             i n t e r e s t e d p a r t i e s , draw up d e t a i l e d
  p a r t i e s , draw up d e t a i l e d guidance                   guidance               on       the     collection,
  on the c o l l e c t i o n , v e r i f i c a t i o n and           verification              and presentation              of
  presentation               of    adverse         reaction          adverse reaction                    reports.       Such
  reports.                                                           guidance s h a l l take into account the
                                                                     format used by the World Health
                                                                     Organization.
 ---pagebreak---                                                             - 34 -
           Original Text                                         Amendment to the proposa
                                                A r t i c l e 42h
Where as a r e s u l t of the evaluation                      Where as a result of the evaluation
of     adverse       reaction        reports,        a        of adverse          reaction        reports, a
Member State i s considering amending                         Member State is considering amending
the       terms        of     a       marketing               the       terms        of      a     marketing
authorization or i t s suspension or                          authorization or its suspension or
withdrawal,          it     shall        forthwith            withdrawal,          it shall           forthwith
inform the Agency.                                            inform the Agency and the holder of
                                                              the marketing authorization.
 In case of urgency, the Member State concerned may             In case of urgency, the Member State concerned may
 suspend the marketing of a medicinal product, provided         suspend the marketing of a medicinal product, provided
 the Agency is informed at the latest on the following          the Agency is informed at the latest on the following
 working day.'                                                  working day.*
                                  Articles 2 - 4               unchanged
 ---pagebreak---  ---pagebreak---  ---pagebreak---                                   - 3s-
                                                                     ISSN 0254-1475
                                                              COM(91) 382 final
                                                      DOCUMENTS
EN                                                                              03
                                 Catalogue number : CB-CO-91-407-EN-C
                                                             ISBN 92-77-75861-9
Office for Official Publications of the European Communities
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