CELEX: 51988PC0663
Language: en
Date: 1988-11-10
Title: Amended Proposal for a COUNCIL DIRECTIVE amending Directives 65/65/EEC, 75/318/EEC and 75/319/EEC on the approximation of provisions laid down by law, regulation or administrative action relating to proprietary medicinal products#Amended Proposal for a COUNCIL DIRECTIVE extending the scope of Directives 65/65/EEC and 75/319/EEC on the approximation of provisions laid down by law, regulation or administrative action relating to proprietary medicinal products and laying down additional provisions for immunological medicinal products consisting of vaccines, toxins or serums and allergens#Amended Proposal for a COUNCIL DIRECTIVE extending the scope of Directives 65/65/EEC and 75/319/EEC on the approximation of provisions laid down by law, regulation or administrative action relating to proprietary medicinal products and laying down special provisions for medicinal products derived from human plasma#Amended Proposal for a COUNCIL DIRECTIVE extending the scope of Directives 65/65/EEC and 75/319/EEC on the approximation of provisions laid down by law, regulation or administrative action relating to proprietary medicinal products and laying down additional provisions for radiopharmaceuticals#(Submitted by the Commission pursuant to the third paragraph of Article 149 of the Treaty)

ARCHIVES HISTORIQUES
DE LA COMMISSION
COLLECTION RELIEE DES
DOCUMENTS "COM"
COM (88) 663
Vol. 1988/0221
 ---pagebreak--- Disclaimer
Conformément au règlement (CEE, Euratom) n° 354/83 du Conseil du 1er février 1983 concernant
l'ouverture au public des archives historiques de la Communauté économique européenne et de
la Communauté européenne de l'énergie atomique (JO L 43 du 15.2.1983, p. 1) modifié en dernier
lieu par le règlement (UE) 2015/496 du Conseil du 17 mars 2015 (JO L79 du 25. 3.2015, p. 1), ce
dossier est ouvert au public. Le cas échéant, les documents classifiés présents dans ce dossier
ont été déclassifiés conformément à l'article 5 dudit règlement ou sont considérés déclassifiés
conformément aux articles 26(3) et 59(2) de la décision (UE, Euratom) 2015/444 de la
Commission du 13 mars 2015 concernant les règles de sécurité aux fins de la protection des
informations classifiées de l'Union européenne.
In accordance with Council Regulation (EEC, Euratom) No 354/83 of 1 February 1983 concerning
the opening to the public of the historical archives of the European Economic Community and the
European Atomic Energy Community (OJ L 43, 15.2.1983, p. 1), as last amended by Council
Regulation (EU) 2015/496 of 17 March 2015 (OJ L 79, 27.3.2015, p. 1), this file is open to the
public. Where necessary, classified documents in this file have been declassified in conformity
with Article 5 of the aforementioned regulation or are considered declassified in conformity with
Articles (26.3) and 59(2) of the Commission Decision (EU, Euratom) 2015/444 of 13 March 2015
on the security rules for protecting EU classified information.
In Übereinstimmung mit der Verordnung (EWG, Euratom) Nr. 354/83 des Rates vom 1. Februar
1983 über die Freigabe der historischen Archive der Europäischen Wirtschaftsgemeinschaft und
der Europäischen Atomgemeinschaft (ABI. L 43 vom 15.2.1983, S. 1), zuletzt geändert durch die
Verordnung (EU) Nr. 2015/496 vom 17. März 2015 (ABI. L 79 vom 25.3.2015, S. 1), ist dieser Akt
der Öffentlichkeit zugänglich. Soweit erforderlich, wurden die Verschlusssachen in diesem Akt in
Übereinstimmung mit Artikel 5 der genannten Verordnung freigegeben; beziehungsweise werden
sie auf Grundlage von Artikel 26(3) und 59(2) der Entscheidung der Kommission (EU, Euratom)
2015/444 vom      13.   März 2015     über die   Sicherheitsvorschriften für den Schutz von  EU-
Verschlusssachen als herabgestuft angesehen.
 ---pagebreak--- COMMISSION OF THE EUROPEAN COMMUNITIES
                                                     COM(88 ) 663 final - SYN 114
                                                     Brussels , 10 November 1988
                          Amended Proposai for a
                             COUNCIL DIRECTIVE
    amending Directives 65 / 65 / EEC , 75 / 318 / EEC and 75 / 319 / EEC on the
              approximation of provisions laid down by law ,
             regulation or administrative action relating to
                      proprietary medicinal products
                          Amended Proposai for a
                             COUNCIL DIRECTIVE
 extending the scope of Directives 65 / 65 / EEC and 75 / 319 / EEC on the ap ¬
       proximation of provisions laid down by law , regulation or
    administrative action relating to proprietary medicinal products
 and laying down additional provisions for immunological medicinal prod¬
              ucts consisting of vaccines , toxins or serums
                                and allergens
                          Amended Proposai for a
                             COUNCIL DIRECTIVE
   extending the scope of Directives 65 / 65 / EEC and 75 / 319 / EEC on the
               approximation of provisions laid down by law ,
             regulation or administrative action relating to
   proprietary medicinal products and laying down special provisions
             for medicinal products derived from human plasma
                          Amended Proposai for a
                             COUNCIL DIRECTIVE
 extending the scope of Directives 65 / 65 / EEC and 75 / 319 / EEC on the ap¬
        proximation of provisions laid down by law , regulation or
    administrative action relating to proprietary medicinal products
     and laying down additional provisions for radiopharmaceuticals
 ---pagebreak--- COMMISSION OF THE EUROPEAN COMMUNITIES
                                                     C0MC88 ) 663 final - SYN 114
                                                     Brussels , 10 November 1988
                            Amended Proposai for a
                               COUNCIL DIRECTIVE
    amending Directives 65 / 65 / EEC , 75 / 318 / EEC and 75 / 319 / EEC on the
              approximation of provisions laid down by law ,
             regulation or administrative action relating to
                        proprietary medicinal products
                            Amended Proposai for a
                               COUNCIL DIRECTIVE
 extending the scope of Directives 65 / 65 / EEC and 75 / 319 / EEC on the ap ¬
       proximation of provisions laid down by law , regulation or
    administrative action relating to proprietary medicinal products
 and laying down additional provisions for immunological medicinal prod ¬
              ucts consisting of vaccines , toxins or serums
                                 and allergens
                            Amended Proposai for a
                               COUNCIL DIRECTIVE
   extending the scope of Directives 65 / 65 / EEC and 75 / 319 / EEC on the
               approximation of provisions laid down by law ,
             regulation or administrative action relating to
   proprietary medicinal products and laying down special provisions
             for medicinal products derived from human plasma
                            Amended Proposai for a
                               COUNCIL DIRECTIVE
 extending the scope of Directives 65 / 65 / EEC and 75 / 319 / EEC on the ap ¬
        proximation of provisions laid down by law , regulation or
    administrative action relating to proprietary medicinal products
     and laying down additional provisions for radiopharmaceuticals
                ( Submitted by the Commission pursuant to the
               third paragraph of Article 149 of the Treaty )
 ---pagebreak---             Extension of the Pharmaceutical Directives
               to Medicinal Products not yet covered
Four amended proposals submitted by the Commission to the Council
   pursuant to the third paragraph of Article 149 of the Treaty
 ---pagebreak---                                   EXPLANATORY MEMORANDUM
At its part session , the European Parliament approved , on 13 October 1988 , the
four Commission proposals for the extension of the pharmaceutical directives
to medicinal products not yet covered ^ 1 ).
The Commission has decided , in accordance with Article 149 paragraph 3 of the
EEC Treaty to amend its proposals in order to incorporate into the text
24 amendments .
In addition , following technical discussion in the framework of the Council ,
the Commission has decided to make certain other detailed improvements to the
text ; these improvements do not modify the substance of the initial proposal
and     are    fully   compatible   with   the  opinion    expressed    by    the   European
Par I i ament .
These amendments can be summarised as follows :
A)    PROPOSAL I amending Directives 65 / 65 / EEC , 75 / 318 / EEC and 75 / 319/ EEC
      Amendments n° 1 , 2 , 3 , 4 , 7 , 9 and 11 have been incorporated .
      In order      to  improve available    information on banning ,      withdrawals or
      restrictions affecting certain medicinal products moving in and outside
      the Community , the Commission accepts to amend Article 33 , taking into
      account certain aspects of amendment n° 10 .
( 1 ) COM ( 87 ) 697 of 4.1.1988 and O.J. n° C 36 of 8.2.1988
 ---pagebreak---                                                                                 3.
B) PROPOSAL II concerning Immunological medicinal products
   The 3 amendments from Parliament have been Incorporated .
   As far as the batch testing by official     laboratories  is concerned , the
   definition of objective criteria to be included in Article 4 paragraph 3
   has been preferred to the initial   listing of vaccines in an annex , which
   would be difficult to update In time .
C) PROPOSAL III concerning medicinal products derived from human plasma
   The eleven amendments from Parliament have been incorporated .
D) PROPOSAL IV concerning radiopharmaceutical medicinal products
   The three amendments from Parliament have been incorporated .
 ---pagebreak--- Amended Proposal for a Council Directive amending Directives 65 / 65 / EEC ,
      75 / 318 / EEC and 75 / 319 / EEC on the approximation of provisions
            laid down by law , regulation or administrative action
                    relating to proprietary medicinal products
                   ( Submitted by the Commission to the Council
     pursuant to the third paragraph of Article 149 of the Treaty )
 ---pagebreak---          ORIGINAL PROPOSAL                                      AMENDED PROPOSAL
Council Directive                                   T i t le unchanged .
amending Directives 65 / 65 / EEC , 75 / 318 / EEC
and 75 / 319 / EEC on the approximation of
provisions laid down by law , regulation
or administrative action relating to
proprietary medicinal products
THE COUNCIL OF THE EUROPEAN COMMUNITIES ,
Having regard to the Treaty establishing           Visas unchanged .
the European Economic Community ,         and in
particular Article 100 A thereof ,
Having regard to the proposal from the
Commission ,
In    cooperation      with     the     European
Parliament ^,
Having   regard    to   the   opinion    of   the
Economic and Social Committee^,
Whereas the essential aim of any rules             First recital unchanged .
governing the production , distribution or
use  of    medicinal   products    must   be    to
ensure   a   high   level   of  protection of
public health ,
   1
   2
   3
 ---pagebreak---           ORIGINAL PROPOSAL                                AMENDED PROPOSAL          6-
Whereas     the     Directives      on    the  Whereas       the   directives   on   the
approximation of the laws relating to          approximation of the laws relating to
proprietary medicinal products must be         proprietary medicinal      products must
adapted to scientific progress and take        be adapted to scientific progress and
account of the experience obtained since        take    account    of   the   experience
their adoption ;                               obtained since their      adoption so as
                                                to ensure greater quality , safety and
                                               ef f icacy ;
 Whereas in its conclusions of 15 May 1987     3rd to 6th recitals unchanged
 on improvement in the use of proprietary
 medicinal products by the consumer        the
 Council considered that the system for
 leaflets      accompanying       proprietary
 medicinal      products ,      for     human
 consumption ,    on the market in the
 Community should be improved ;
 Whereas the guarantees of the quality of
 medicinal   products   manufactured   within
 the Community should be maintained by
 requiring compliance with the principles
of good manufacturing practice for
medicinal products irrespective of the
 final destination of the products ;
   4 OJ N° C 178, 7.7.1987, p. 2
 ---pagebreak---   I
                   ORIGINAL PROPOSAL                                       AMENDED PROPOSAL
        Whereas       the     Commission      should       be
        empowered       to   define     in   detail       the
    i
i       principles of good manufacturing practice
        for      medicinal       products      in      close
        cooperation with          the     Committee       for
        Adaptation to Technical Progress of the
        Directives on the Removal of              Technical
        Barriers in the          Proprietary      Medicinal
        Products Sector ;
       Whereas having regard to the Resolution
       of      the       European       Parliament        of
       13 June 1986         on      the     export        of
       pharmaceutical products to the Third
       World ,      measures should be taken to
       improve the provision of information for
       third countries about the conditions of
      use of medicinal           products    within      the
      Member States ;
      Whereas the scope of Directive 65 / 65 / EEC5           Whereas       the     scope       of    Directive
      as last amended by Directive 87/ 21 / EEC^              65 / 65 / EEC    as       last      amended       by
      and Second Directive 75 / 319/ EEC 7 as last            Directive        87 / 21 / EEC      and    Second
                                                O
      amended by Directive 83 / 570 / EEC           on the    Directive 75 / 319 / EEC as          last amended
      approximation of provisions laid down by                by     Directive        83 / 570 / EEC   on     the
      law ,   regulation or administrative action             approximation of provisions laid down
      relating        to     proprietary       medicinal      by law , regu I at ion or administrative
      products      should    be   extended    to     cover   action        relating        to      proprietary
      other ready-made medicinal products which               medicinal products should be extended
      do not comply with the definition of                    to        cover       other          industr ia I ly
      proprietary medicinal products .                        manufactured           medicinal_products
                                                              hitherto excluded :
        5 OJ  No   22 , 9.2.1965 , p. 369 / 65
        6 OJ   No  L 15 , 17.1.1987 , p. 36
        7 OJ   No  L 147 , 9.6.1975 , p. 13
        8 OJ   No  L 332 , 28.11.1983 , p. 1
 ---pagebreak---             ORIGINAL PROPOSAL                                    AMENDED PROPOSAL          8.
Whereas in the Community directives                8th récital deleted
relating to medicinal products the word
" therapeutic "   should   be   understood   as
covering all the medicinal purposes for
which a medicinal product may be
administered to human beings or animals ,
which may be to prevent or treat disease ,
to make a medical diagnosis or to
restore , correct or modify physiological
functions ,
  HAS ADOPTED THIS DIRECTIVE :
   Article 1                                        Article 1
   Council Directive 65 / 65 / EEC of 26 January   Unchanged
   1965 on * the approximation of provisions
   laid down by         law ,     regulation or
   administrative      action      relating     to
   proprietary medicinal products is hereby
   amended as follows :
   1.  In Article 1 ,    the following points 4    1.   In   Article    1,   the   following
       and 5 are inserted :                             points 4 and 5 are inserted :
       "4   Ready-made medicinal product           '4 . Magistral formula :
        Any medicinal product prepared in               any medicinal product prepared in
        advance which does not comply with              a pharmacy    In accordance with a
        the     definition      of    proprietary       prescription    for  an   Individual
        medicinal products and which is                 pat lent .
        marketed in a pharmaceutical form
        which may be used without further
        industrial processing .
 ---pagebreak---            ORIGINAL PROPOSAL                                AMENDED PROPOSAL                9.
   5  Therapeutic                                 5 . Officinal formula :
   The medicinal purpose for which a                   any medicinal product prepared In
   medicinal product is administered to                a pharmacy in accordance with the
   human beings or animals ,               as          prescriptions of a pharmacopoeia
   specified in point 2 ."                             and    which     is    intended    to   be
                                                       suppl led direct I y to the pat ients
                                                       served      by     the     pharmacy      in
                                                       quest ion . '
  2.  Article 2 is amended as follows :           2.    Article 2 is amended as follows :
      " The provisions of Chapters II to V        '1 . The provisions of Chapters II to
        shall apply to medicinal products               V   shall     apply     to    propr letary
        for human use intended to be placed             medicinal     products for human use
        on the   market  in   Member States    in       intended     to    be   placed    on   the
        the form of proprietary medicinal               market   in Member States .
        products or ready-made medicinal
        products    to    the     exclusion    of
        medicinal     products      which     are
        prepared    extemporaneously      in   an
        individual pharmacy      for individual
        patients ."
                                                     2 . Where    a Member      State   authorizes
                                                          the   olaclnq     on    the   market     of
                                                          industrially      produced     medicinal
                                                          Droducts which do not comply with
1                                                         the  definition of        a  proprietary
                                                          medicinal    product ,    it shall   also
                                                          apply       the       provisions        of
                                                          Chapters I I to V to them .
 ---pagebreak---           ORIGINAL PROPOSAL                          AMENDED PROPOSAL             10 .
                                            3 . The provisions of Chapters II       to
                                                V shal I not apply to :
                                                -  medicinal products prepared on
                                                   the   basis  of   a  magistral  or
                                                   officinal formula ;
                                                -  medicinal     products    Intended
                                                   for   research   and   development
                                                   trials ;
                                                -   Intermediate products Intended
                                                   for   further   processing by    an
                                                   authorized manufacturer .
                                           4 . A Member State may . In accordance
                                                with   legislation   In force and to
                                                satisfy    special   needs ,  exclude
                                                from   the provisions of     Chapters
                                                II    to   V   medicinal     products
                                                supplied In response to a genuine
                                                unsolicited order ,    formulated   in
                                                accordance_with_the
                                                specifications    of   an  authorised
                                                health care professional      for use
                                                by his Individual patients on his
                                                direct personal responsibility^*
3. In the title ,   preamble and Chapters  Unchanged
   II     to   V    all    references   to
   " proprietary medicinal product " or to
   "proprietary     product "   shall   be
   replaced by "medicinal product ".
 ---pagebreak---          ORIGINAL PROPOSAL                                AMENDED PROPOSAL               11 '
   In Article 4a ,     the following point   4.    In    Article    4a ,     the   following
   6.6 . is inserted :                             point 6.6 . is inserted :
   ”6.6 . special       precautions     for        '6.6 . special       precautions        for
          disposal of unused product or                    disposal of unused products
          waste        materials ,        if               or  waste materials       derived
          appropriate ".                                   from    the       products ,       if
                                                           appropr i ate . '
>.  In Article 13 ,   the following point 9     5.    In   Article     13 ,    the   following
    is inserted :                                     point 9 is inserted :
    "9 .   special      precautions      for          '9 . special       precautions           for
           disposal of unused product or                   disposal    of    unused   products
                                                           or   waste    materials      derived
           waste materials , if any".
                                                           from the products ,      if any.'
6.   In Article 14 ,    the following fifth   Unchanged
     indent is added :
     " - manufacturer's batch number ".
 ---pagebreak---           ORIGINAL PROPOSAL                                 AMENDED PROPOSAL 12‘
Article 2                                         Article 2
                                                I
In Council Directive 75 / 318 / EEC of 20 May I   Unchanged
1975 on the approximation of the laws of
Member States relating to analytical ,
pharmaco-toxicological      and      clinical
standards and protocols in respect of the
testing     of    proprietary       medicinal
products , all references to " proprietary
medicinal product " or to " proprietary
product" shall be replaced by " medicinal
product ".
Article 3                                         Article 3
Council Directive 75 / 319 / EEC of 20 May        Unchanged
1975 on the approximation of provisions
laid down by law ,          regulation or
administrative     action     relating     to
proprietary medicinal products is hereby
amended as follows :
 ---pagebreak---                                                             AMENDED PROPOSAL                     13 .
         ORIGINAL PROPOSAL
                                                   1.  In    Article        4,     the      text      of
1 . In Article 4, the text of paragraph b
    is amended as follows :                           paragraph         (b)     is      amended       as
                                                      fol lows :
    "(b)    may submit the medicinal
          product , its active principles             '(b ) may      submit      the      medicinal
          or other constituent materials                     product ,         i ts_start ing
          for        testing     by     a    State          materials        and     if   necessary
          laboratory or by a laboratory                      intermediate          products ,        or
          designated for that purpose in                    other      constituent        materials
          order to ensure that the control                   for     testing        by     a     State
          methods         employed       by    the            laboratory          or         by        a
          manufacturer       and    described   in            laboratory       designated          for
          the particulars accompanying the                   that     purpose        in   order       to
          application in accordance with                     ensure       that       the      control
          point 7 of Article 4, second                       methods        employed         by    the
          paragraph ,          of        Directive           manufacturer         and     described
          65 / 65 / EEC are satisfactory ".                   in         the            particulars
                                                             accompanying the application
                                                              in accordance with point 7
                                                             of       Article          4      ( second
                                                             paragraph )         of       Directive
                                                             65 / 65 / EEC are satisfactory.'
 ---pagebreak---           ORIGINAL PROPOSAL                               AMENDED PROPOSAL                14 .
2 . In Article 6,      the last paragraph is j  2.  In Article 6 ,
    replaced by the following :
                                                   the       last paragraph Is amended as
    " The inclusion of a package leaflet            f o I I ows :
      in the packaging of 'over the
      counter medicinal products' shall be          'The        inclusion    of    a     package
      obligatory       unless      all     the      leaflet        in   the     packaging       of
      information required by this Article         medicinal          products      sha I I     be
      can be conveyed on the packaging             obi igatory          unless      al I       the
      itself .                                      informât ion        requ i red   by     this
                                                   Article        can  be  conveyed on         the
      For the purposes of this Article ,           container          and      the    externa I
      'over      the     counter     medicinal     packaging . *
      products'      are    those    medicinal
      products which are placed on the
      market with a view to their direct
      sale to the public , without the need
      for a medical prescription , for use
      in the relief of minor illnesses not
      requiring a medical diagnosis .
      In   the    case   of  other   medicinal
      products .    Member States may require
      that a leaflet be included with the
      packaging .
      Within two years of the date of the
      adoption of this Directive ,         the
      Commission shall present to the
      Council a report on the possibility
       of making more systematic the use ,
       and more legible and intelligible
       the content , of package leaflets ,
       accompanied      if   appropriate     by
       suitable proposals ."
 ---pagebreak---                                                                                                      15 .
                ORIGINAL PROPOSAL                                    AMENDED PROPOSAL
      3.  Article 16(1 ) is amended as follows :          Unchanged
         " 1 . Member    States      shall    take    all
               appropriate     measures     to    ensure
               that the manufacture of medicinal
               products is subject              to the
               holding of         an authorization .
               This manufacturing authorization
               shall be required notwithstanding
               that      the     medicinal     products
               manufactured       are    intended     for
               export ."
    4.   The      following         Article 16a        is   4.  The    following       Article     16a     is
         inserted :
                                                                 inserted :
         " Article 16a
                                                                'Article 16a
           1 . At     the      request       of      the        At      the       request       of       the
               manufacturer     or    the  authorities
                                                                manufacturer , the exporter or the
               of a recipient        country ,    Member        authorities of an importing third
               States    shall      certify    that     a       country ,     Member      States     shall
               manufacturer          of      medicinal
                                                                certify     that    a   manufacturer      of
               products is in possession of the                medicinal          products       is       in
               authorization       referred      to    in
                                                                possession     of     the  authorization
               paragraph 1 of Article 16 .          When        referred     to     in   Article    16(1 ).
               issuing such certificates . Member              When    issuing      such   certificates ,
               States shall have regard to the                  they     shall      comply     with     the
               prevailing               administrative          following conditions :
               arrangements of the World Health
               Organi zation .                                  1 . Member      States       shall     have
                                                                    regard       to     the    prevailing
                                                                    administrative arrangements of
                                                                    the World Health Organization .
(2)
 ---pagebreak---            ORIGINAL PROPOSAL                                   AMENDED PROPOSAL               16 .
   2 . The summary of the product                       2 . For_med i c i na I_products
        characteristics approved by the                      intended for export which are
        Member State      in accordance    with              already   authorized        on   their
        Article 4b of Directive 65 / 65 / EEC                territory ,   they    shall     supply
        shall     be     annexed      to    the              the   summary     of    the    product
        certificate .                                        characteristics as approved in
                                                             accordance with Article 4b of
                                                             Directive 65 / 65 / EEC .
   3 . When the manufacturer        is not   in          3 . When   the manufacturer         is  not
        possession     of      a     marketing i              in possession of a marketing
        authorisation in the country of                      authorization ,          he       shall
        origin ,    he must provide the                      provide        the        authorities
        authorities        responsible      for              responsible      for    establishing
                                                             the certificate referred to in
        establishing       the     certificate
        referred to in paragraph 1 with a                    paragraph 1 with a declaration
        declaration explaining why no                        explaining     why    no     marketing
                                                             authorization      is available.'
        marketing authorisation has been
        obtained ."
5.   In      Article 17 ,       the     following 5.   In     Article    19 ,    the     following
     paragraph d is inserted :                         paragraph ( f ) is inserted :
     "(d )   demonstrate that he complies            ■ f ) to comply with the principles
            with the principles of Good                     and   the   guidelines        of   good
            Manufacturing       Practices     for           manufacturing        practice       for
                                                            medicinal    products       laid   down
            medicinal products laid down by
            Community law ."                                by Community law.'
 ---pagebreak---           ORIGINAL PROPOSAL                              AMENDED PROPOSAL
6.  The     following     Article 17a       is 6. The    following       Article      19a    is
    inserted :                                    inserted :
                                                  'Article 19a
   " Article 17a
                                                      The principles and gu i de I I nes
     The principles of good manufacturing
                                                      of good manufacturing practice
     practices   for   medicinal   products
                                                      for         medicinal          products
     referred     to     in     Article 17,
                                                      referred       to   in   Art icle     19 ,
    paragraph d shall be adopted , in the
                                                      paragraph         (f)      shall       be
     form  of  a  directive   addressed    to
                                                      adopted ,      in   the   form    of    a
    Member States ,    in accordance with
                                                      directive      addressed     to Member
    the     procedure    laid    down      in
                                                      States , in accordance with the
    Article 2c of Directive 75 / 318 / EEC ."
                                                      procedure         laid      down       in
                                                      Article 2c          of       Directive
                                                      75 / 318 / EEC ;              detal led
                                                      guidelines sha I I be pub I I shed
                                                      by   the Commission and         revised
                                                      as    appropriate      to   take    I nto
                                                      consideration        scientific       and
                                                      technical progress.'
 ---pagebreak---          ORIGINAL PROPOSAL                            AMENDED PROPOSAL                18 .
7. In    the     second     paragraph     of 7.  In Article 26 :
   Article 26,          the        following
   subparagraph d is inserted :                 -    the first paragraph Is amended
                                                     as fol lows :
   "(d)   report    periodically    to   the
        competent authorities on whether           'The competent authority of the
        the manufacturer complies with              Member    State     concerned     shall
        the      principles      of     good        ensure    by    means   of   repeated
        manufacturing      practices     for         inspections      that    the     legal
        medicinal products laid down by             requirements          relating         to
        Community law ".                            proprietary medicinal products
                                                    are complied with.'
                                                -   the following third paragraph
                                                     is inserted :
                                                   'The off ic ia Is representing the
                                                    competent        author i ty     sha 1 1
                                                    report     after     each    of     the
                                                    inspect ions     mentioned     in   the
                                                    first paragraph on whether the
                                                    manufacturer compì les with the
                                                    pr inciples     and   guidel ines     of
                                                    good    manufacturing        practice
                                                    laid   down    by   Community      law .
                                                    The   manufacturer         shall      be
                                                    informed    of     the   content      of
                                                    such reports and sha 1 1 be able
                                                    to_demand_a_second
                                                    inspect ion . *
 ---pagebreak---           ORIGINAL PROPOSAL                           AMENDED PROPOSAL                 19 .
8. In Article 30 , the following second       8.  In  Article       30 ,    the   following
   paragraph is inserted :                       second paragraph is Inserted :
   " Upon request , Member States shall           'Upon   reasoned       request ,    Member
                                                 States           shall           forthwith
     forthwith communicate the reports
     referred to in subparagraph d of the        communffcate the reports referred
     second paragraph of Article 26 to           to   in   the     third     paragraph      of
     the competent authorities of another        Article      26     to    the    competent
                                                 authorities       of     another     Member
     Member State . If , after considering
     the reports ,       the Member State        State .    If , after considering the
     receiving the reports considers that        reports ,       the       Member      State
     it cannot accept the conclusions            receiving      the    reports    considers
                                                 that     it     cannot        accept     the
     reached by the competent authority
                                                 conclusions         reached       by     the
     of  the  Member    State   in which  the
                                                 competent authority of the Member
     report  was    established ,   it  shall
                                                 State    in   which     the    report    was
     inform    the     competent    authority
                                                 established ,      it shall     inform the
     concerned of its reasons and may
                                                 competent authority concerned of
     request that a further inspection of
                                                 its    reasons       and     may    request
     the manufacturing establishment be
                                                 further   information .        In the case
     carried out .     If the Member States
                                                 of prolonged disagreement between
     concerned     are    unable   to   reach
                                                 Member       States ,        the     Member
     agreement ,     they   shall   forthwith
                                                 State(s )       shall        inform      the
     inform the Commission ."
                                                 Commission . '
 ---pagebreak---                                                               AMENDED PROPOSAL                 20 .
         ORIGINAL PROPOSAL
9. The following paragraphs 2 and 3 are             9.   The following pragraphs 2 , 3
   added to Article 33 :                                 and 4 are added to Article 33 :
   "2.  The person responsible for the                  '2 . The person responsible for the
        marketing of a medicinal product                     marketing       of      a    medicinal
        shall be obliged to notify the                       product     shall    be obliged        to
        Member States forthwith of any                       notify     the    concerned      Member
        action taken by him to suspend                       States forthwith of any action
        the marketing of a product or to                     taken   by    him   to suspend       the
        withdraw a product from the                          marketing       of     a     medicinal
        market ,     together      with    the               product or to withdraw It from
        reasons for such action .       Member               the market      together with the
        States   shall    ensure   that   this               reasons      for      such      action .
        information is brought         to the                Member     States      shall     ensure
        attention     of     the    Committee                that     this      information         is
        forthwith .                                          brought     to   the    attention of
                                                             the committee forthwith .
     3.  Member States shall ensure that           Unchanged
         appropriate      information     about
         actions      taken      pursuant    to
         paragraphs 1 and 2 which may
         effect the protection of public
         health    in   third    countries    is
         forthwith       brought      to    the
         attention of      the   World   Health
         Organization with a copy to the
         Committee.”
                                                 4 . The    Commission      shall     publish
                                                      an   annual    list    of   medicinal
                                                      products     prohibí ted       ín    the
                                                     Commun I ty      or     subject        to
                                                      special    restrictions       in   more
                                                      than three Member States;'
 ---pagebreak---                                                                                           21 .
            ORIGINAL PROPOSAL                                  AMENDED PROPOSAL
10 . The first paragraph of Article 34 is         10 . The first paragraph of Article 34
     hereby amended as follows :                         is hereby amended as follows.-
     " This    directive     shall    apply    to        'This  Directive   shall     apply    to
       medicinal products for human use in              medicinal   products for human use
       the form of      proprietary medicinal           within   the   limits  mentioned       in
       products    or ready-made medicinal              Article 2 of Directive 65 / 65 / EEC
       products     to    the    exclusion of           as amended . '
       medicinal      products      which     are
       prepared extemporaneously          in an
       individual pharmacy for individual
       patients ."
11 . With    the   exception    of    the   first  De I eted
     paragraph       of    Article 34 ,       all
     references to " proprietary medicinal
     product " or to " proprietary product "
     shall     be    replaced    by    medicinal
     product .
 ---pagebreak---                                                                              22
         ORIGINAL PROPOSAL                                  AMENDED PROPOSAL
Article 4                                     !  Article 4
                                             l
                                           !
1.  Member States shall take the measures         Unchanged
    necessary to      comply   with   this
    directive not later than 1 January
    1991 .   They shall forthwith inform
    the Commission thereof .
2.  Requests for marketing authorization
    lodged after the time-limit referred
    to in the first paragraph must comply
    with the provisions of this Direc¬
    tive .
3.  Articles 1 ,   2 and 3 of this
    Directive , where relevant , shall be
    progressively extended to existing
    medicinal        products       before
    31 December 1992 ..
Article 5
                                                 Article 5
This Directive is addressed to the Member
                                                Unchanged
States .
 ---pagebreak---   Amended Proposal for a Council Directive extending the scope of
      Directives 65 / 65 / EEC and 75 / 319 / EEC on the approximation
of provisions laid down by law , regulation or administrative action
     relating to proprietary medicinal products and laying down
     additional provisions for immunological medicinal products
       consisting of vaccines , toxins or serums and allergens
             ( Submitted by the Commission to the Council
   pursuant to the third paragraph of Article 149 of the Treaty )
 ---pagebreak---              ORIGINAL PROPOSAL                                  AMENDED PROPOSAL
Council Directive
                                                        Title unchanged
extending        the     scope       of   Directives
65 / 65 / EEC     and     75 / 319 / EEC    on    the
approximation of provisions laid down by
law , regulation or administrative action
relating         to     proprietary        medicinal
products and laying down additional
provisions for immunological medicinal
products consisting of vaccines , toxins
or serums and allergens
THE COUNCIL OF THE EUROPEAN COMMUNITIES ,
Having regard to the Treaty establishing               Visas unchanged
the European Economic Community , and in
particular Article 100 A thereof .
Having regard to the proposal from the
Commission^,
In       coopération       with       the    European
_    . .      .2
Parliament ,
Having      regard    to   the    opinion     of  the
Economic and Social Committee'3,
Whereas disparities in the provisions                 First five recitals unchanged
laid down by law , regulation or adminis¬
trative action by Member States may
hinder trade in immunological products
within the Community ,
 ---pagebreak---              ORIGINAL PROPOSAL                       AMENDED PROPOSAL
Whereas the essential aim of any rules
governing the production , distribution or
use of      medicinal      products     must  be  to
ensure a high         level of       protection of
public health .
Whereas the provisions laid down by
                           4
Directive 65 / 65 / EEC as last amended by
Directive 87/ 21 / EEC ^ and Second Directive
75 /319/ EEC^1 as last amended by Directive
83/ 570/ EEC^ on the approximation of
provisions laid down by law , regulation
or administrative action relating to
proprietary medicinal products , although
appropriate ,         are        inadequate      for
immunological            medicinal          products
consisting of vaccines , toxins or serums
and allergens ,
Whereas     in accordance with Article 5 of
                          8
Directive 87 / 22 / EEC      on the approximation
of national provisions relating to the
placing on the market of high technology
medicinal products , particularly those
derived        from       biotechnology ,        the
Commission       is      required       to    submit
proposals to harmonise , along the lines
of    Directive    75 / 319 / EEC   the   conditions
for     authorizing       the     manufacture    and
placing on the market of immunological
medicinal products before 22 December
1987 ;
4  OJ  No  22 , 9.2.1965 , p. 369 / 65
5  OJ  No  L 15 , 17.1.1987 , p. 36
6  OJ  No  L 147 , 9.6.1975 , p. 13
7  OJ  No  L 332 , 28.11.1983 , p. 1
8 OJ No L 15^17.1.1987 , p. 38
 ---pagebreak---             ORIGINAL PROPOSAL                                  AMENDED PROPOSAL               26 .
  Whereas ,    before an authorization to
 market an immunological product can be
 granted ,        the      manufacturer    must
 demonstrate his ability             to  attain
 batch -to-batch consistency ;
 Whereas      the     Commission    should   be
                                                  Whereas      the    Commission       should   be
 empowered to adopt any necessary changes         empowered       to    adopt    any    necessary
 in the requirements for the testing of           changes     in the requirements for the
 proprietary medicinal products set out in
                                                  testing      of     proprietary       medicinal
 the Annex to Directive 75 /318/ EEC9 of 20       products      set   out    in   the   Annex   to
 May 1975 on the approximation of the laws
                                                  Directive 75 / 318/ EEC of          20 May 1975
of the Member States relating to                  on the approximation of the             laws of
analytical , pharmaco-toxicological and           the     Member       States      relating     to
clinical      standards     and  protocols   in
                                                  analytical ,         pharmaco-toxicological j
respect of the testing of proprietary j
medicinal products , as last amended by I
                                                  and clinical standards and protocols j
                        10   _                  !  in   respect       of    the      testing of j
Directive 87/ 19/ EEC of 22 December 1986 :       proprietary        medicinal      products ^ \
to take account of the special nature of          as     last      amended       by     Directive
immunological medicinal products in close         87/ 19/ EEC of 22 December 1988 < > to
cooperation with the Committee for the            take account of the special nature of
Adaptation to Technical Progress of the           immunological       medicinal      products   in
Directives on the Removal of Technical            close cooperation with the Committee )
Barriers to Trade in the Proprietary              for    the     Adaptation       to    Technical '
Medicinal Products Sector ;                       Progress     of    the   Directives     on  the
                                                  Removal     of     Technical      Barriers   to
                                                  Trade    in    the   Proprietary      Medicinal
                                                  Products        Sector ,      thus     ensuring
                                                  greater quality , safety and efficacy .
HAS ADOPTED THIS DIRECTIVE :
 9 JO No L 147, 9.6.1975 , p. 1
 10 0J No L 15, 17.1.1987, p. 31
 ---pagebreak---          ORIGINAL PROPOSAL                                           AMENDED PROPOSAL           27 .
Article 1                                               Article 1
1.  In derogation from Article 34 of                     1.  Unchanged
    Directive 75 / 319 / EEC , and subject to
    the provisions of this Directive ,
    Directives    65 / 65 / EEC   and    75 / 319 / EEC
    shall      apply        to      immunoLogical
    medicinal     products        consisting         of
    vaccines ,     toxins       and    serums       and
    allergen products for human use .
2.  For the purposes of this Directive ,                2.  For    the   purposes    of    this
    the     following       definitions         shall       Directive ,     the       following
    apply :                                                 definitions shall apply ;
    - " immunological       medicinal       product "       - first indent deleted
      shall mean a product of biological                    - 2nd indent unchanged
      origin which is intended to effect                    - 3rd indent unchanged
      the immune system and which is used
      in the diagnosis ,           prevention or
      treatment of disease .          Included are
      vaccines ,     toxins      and    serums and
      allergens ,
    - " allergen product " shall mean any
      product     which       is     intended        to
      identify     or      induce     a     specific
      acquired       alteration           in        the
      immunological          response        to      an
      allergising agent ,
    - vaccins , toxins and sera shall have
      the meaning assigned to them in the
      Annex of Directive 75 / 319 / EEC .
 ---pagebreak---             ORIGINAL PROPOSAL                                     AMENDED PROPOSAL                 28 .
Article 2
                                                 Article 2
1 . The quantitative particulars of an
                                                 1.  The    quantitative         particulars of
      immunological medicinal product shall
                                                     an        i mmuno I og i ca I      medie inai
     be    expressed    by    mass      or    by     product       shall      be   expressed    by
     international units or by units of              mass or by international units or
     biological activity or by protein
                                                     by units of biological              activity
     content as appropriate to the product
                                                     or    by    spec i f i c   protein   content
     concerned .
                                                     where possible as appropriate to
                                                     the product concerned .
     In     Directives     65 /65 / EEC      and  2.   In     respect         of     immunological
    75 /319/ EEC       the        expressions         products       in     Directive    65/65 / EEC
      qualitative      and      quantitative          and 75/ 319/ EEC ,         the expressions
    particulars of the constituents"                   " qualitative          and     quantitative
    shall also include particulars                    particulars of the constituents "
    relating to biological activity or to             shall           include          particulars
    protein content and "qualitative and              relating       to biological        activity
    quantitative     composition"         shall       or      to     protein        content     and
    include the composition of the                    “ qualitative           and     quantitative
   product expressed in terms of                      composition "          shall    Include   the
   biological activity or of protein                  composition            of     the    product
   content .
                                                      expressed In terms of biological
                                                      activity or of protein content .
 ---pagebreak---              ORIGINAL PROPOSAL                               AMENDED PROPOSAL                   29 .
 3.    Whenever the name of an immunological     3.   In any document          established       for
       medicinal product is expressed ,     the      the purpose of this Directive                 in
        common   or  scientific   name  of  the      which           the     name         of      an
        active   constituents   shall  also  be      immuno log i ca 1     medicinal       product
        included .                                   is     expressed ,       the     common      or
                                                     sc i ent i f i c   name    of   the     active
                                                     const i tuents         sha 1 1    also       be
                                                     included        at  least    once .     It may
                                                     be    abbreviated       in   the    remaining
                                                     references .
                                                Article 3
Artide 3
In addition to the        information referred  Unchanged
to in Article 4a of Directive 65 / 65 / EEC ,
the summary of product characteristics
referred to in point 9 of the second
paragraph of Article 4 of Directive
65 / 65 / EEC shall contain the following
information in respect of immunological
products :
- under point 5.4 ,      information about any
   special precautions to be taken by
   persons handling the immunological
   medicinal product and persons adminis ¬
   tering it to patients , together with
   any precautions to be taken by the
   patient .
 ---pagebreak---            ORIGINAL PROPOSAL
                                                              AMENDED PROPOSAL           30 .
Article 4                                        Art icle 4
1.  Member States shall ensure that the           1.   Member   States   shall   take  aI I
    manufacturing processes used in the                appropriate steps to ensure that
    manufacture of immunological products              the manufacturing processes used
    are properly validated and attain                  in     the      manufacture      of
    batch-to-batch consistency .        To this        immunological      products     are
    end the competent authority may                    properly   validated    and  attain
    submit samples from up to five in                 batch- to-batch consistency .
    total  of   the bulk     and / or  finished
    product batches for testing by a
    state laboratory or a laboratory                  Second sentence deleted
    designated for that purpose , either
    during    the   examination        of   the
    application pursuant to Article 4 of
    Directive 75 / 319 / EEC ,    or after a
    marketing authorisation has been i
    granted .
2.  For   the   purpose     of     implementing Unchanged
    Article 8 of Directive 65 / 65 / EEC and
    Article 27 of Directive 75 / 319 / EEC ,
    Member States may require persons
    responsible          for          marketing
    immunological products to submit to a
    competent authority copies of all the
    control reports signed by the
    qualified person in accordance with j
    Article 22 of Directive 75 /319/ EEC . j
 ---pagebreak---             ORIGINAL PROPOSAL                                                                     31 .
                                                               AMENDED PROPOSAL
3.  Where it considers it necessary in           3. Where , in the interests of public
    the interests of public health , a              health ,       the    legislation         of    a
    Member    State   may     require    persons    Member       State    so    provides ,        the
    responsible for marketing the           live    competent authorities may require
    vaccines ,     vaccines     used    in   the    persons             responsible              for
    primary immunization of infants , or            market ing :
    vaccines used in public health
                                                         I i ve vacc i nés ,
    immunization programmes , which are
                                                         immuno loq i ca I_med i c i na I
    listed in the Annex to this Directive
                                                         products used          in    the primary
    to submit to a competent authority                   immunization of           infants or of
    samples from each batch of the bulk
                                                         other age groups at risk ,
   and / or     finished       product       for
                                                     -   i mmuno log i ca I_med i c i na I
   examination by a state laboratory or
                                                         products used in public health
   a laboratory designated for that
                                                         immunization programmes ,
   purpose     before     release    onto    the
                                                     -   during      a   transitional        period
   market ,       unless      the     competent          to      be     laid     down      by     the
   authority of another Member State has
                                                         market i no             author i sat ion ,
   previously examined the batch in
                                                         immuno log i ca I               medicinal
   question and declared it to be in
                                                         products       wh i ch   are    novel     or
   conformity       with » the         approved          which      are   manufactured         using
   specification .       Member States shall
                                                         novel      or   modified       technigues
   ensure that any such examination is
                                                         or     which     are      novel     for     a
   completed     within    60 days      of   the         particular manufacturer .
   receipt of the samples .       The Annex to
   this Directive containing the list of             to submit to control by a State
   vaccines which may be submitted for
                                                      laboratory         or      a      laboratory
   examination prior to release may be               approved for that purpose samples
   amended in accordance with the
                                                     from      each     batch      of    the     bulk
   procedure laid down in Article 2c of
                                                     and /or     finished product ,          before
   Directive 75 / 318 / EEC .
                                                     release onto         the market ,       unless
                                                      in      the      case      of      a     batch
                                                     manufactured         in    another      Member
                                                     State ,      the    competent       authority
 ---pagebreak---               ORIGINAL PROPOSAL                                  AMENDED PROPOSAL                  32 .
                                                         of a Member State has previously
                                                         examined       the    batch     in    question
                                                         and      declared        it     to     be      in
                                                         conformity         with      the      approved
                                                         specification .         Member          States
                                                         shall       ensure       that      any      such
                                                         examination        is   completed       within
                                                         60 days      of    the    receipt      of    the
                                                         samples .
                                                          Last sentence deleted
Article 5                                          Article 5
Any amendments which are necessary in the           Any amendments which are necessary in
testing        requirements       for medicinal     the        testing          requirements            for
products       set   out     in   the   Annex   to  medicinal        products      set    out     in    the
Directive 75 / 318 / EEC to take account of         Annex to Directive 75 / 318 / EEC to take
the extension of the scope of Directives            account of the extension of the scope
65 / 65 / EEC and 75 / 319 / EEC to cover immuno¬   of        Directives           65 / 65 / EEC       and
logical medicinal products shall be                 75 / 319 / EEC     to    cover       immunological
adopted in accordance with the procedure            medicinal        products shall         be adopted
laid      down   in  Article 2c      of  Directive  in accordance with the procedure laid
75 / 318 / EEC .    Any such amendments shall       down      in   Article       2c     of    Directive
come into effect on the same date as this           75 / 318 / EEC .
Di rective .
                                                    Second sentence deleted
 ---pagebreak---            ORIGINAL PROPOSAL                                 AMENDED PROPOSAL              33 .
                                                  Art icle 6
Article 6
1.   Member    States     shall   take   the       1 . Save   in the case provided for        in
     necessary   measures    to comply  with           paragraph 2 , Member States shall
     this    Directive    not   later   than           take   the   necessary    measures    to
     1 January 1991 .   They shall forthwith           comply    with   this   Directive    not
     inform the Commission thereof .                   later than 1     January 1991 .    They
                                                       shall      forthwith      inform     the
2.   Requests for marketing authorization              Commission thereof .
     for products covered by this Direc ¬
     tive lodged after the time-limit             2.    In the event of the amendments to
     referred to in the first paragraph                Directive 75 / 318 / EEC   referred   to
     must comply with the provisions of                 in Article 5 not being adopted by
     this Directive .                                  the     date      referred      to     in
                                                       paragraph 1 , this date shall be
3.   This Directive shall be progressively             replaced by the date of adoption .
     extended      to       the     existing
     immunological     medicinal    products
     before 31 December 1992 .                    3.   Requests          for         marketing
                                                       authorization         for      products
                                                       covered by this Directive , lodged j
                                                       after    the   date   of implementati on
                                                                          comply    with    the
                                                       provisions of this Directive .
                                                    4.   This      Directive       shall        be
                                                         progressively        extended          to
                                                         existing    immunological    medicinal
                                                         products before 31 December 1992 .
 Article 7                                     Article 7
  This Directive is addressed to the Member !  Unchanged
  States .                                   i
 ---pagebreak---                  ORIGINAL PROPOSAL                                     34
                                                      AMENDED PROPOSAL
                   ANNEX
                                                         Annex
  LIST OF VACCINES REFERRED TO IN ARTICLE     Deleted
  4(3 )
  Vaccines for human use , presented or used
  for     the   prophyaxis  of  the following
  diseases :
        Choiera
        Diphtheria
        Hepatitis
        Inf luenza
        Measles
        Mumps
        Pertussis
        Polio
        Rabies
        Rubella
        Tetanus
       Tuberculosis
       Typhoid
       Yellow Fever
I
 ---pagebreak---                                                                                  35 .
Amended proposal for a Council Directive extending the scope of Directives
65 / 65 / EEC and 75 / 319 / EEC on the approximation of provisions laid down by
law , regulation or administrative action relating to proprietary medicinal
products and laying down special provisions for medicinal products derived
                                    from human plasma
        ( Submitted by the Commission to the Council pursuant to the third
                        paragraph of Article 149 of the Treaty )
 ---pagebreak---                                                                                                  36 .
              ORIGINAL PROPOSAL                                       AMENDED PROPOSAL
Council Directive                                        Council      Directive   extending   the
extending         the   scope       of    Directives     scope of Directives 65 / 65 / EEC and
65 / 65 / EEC      and   75 / 319 / EEC     on     the   75 / 319 / EEC on the approximation of
approximation of provisions laid down by                 provisions laid down by law , regu-
law , regulation or administrative action                 lation     or   administrative   action
relating          to   proprietary         medicinal     relating to proprietary medicinal
products and laying down additional                      products      and  laying  down  special
provisions for medicinal products derived                provisions      for medicinal   products
from human blood                                         derived from human plasma
 THE COUNCIL OF THE EUROPEAN COMMUNITIES ,
 Having regard to the Treaty establishing                Visas unchanged .
 the European Economic Community ,               and in
 particular Article 100 A thereof .
  Having regard to the proposal from the
  Commission^,
           /
  In       cooperation      with       the     European
  Pari iament^.
  Having       regard  to    the     opinion    of   the
  Economic and Social Committee^,
  Whereas disparities in the provisions                  First to 5th recitals unchanged
  laid down by law , regulation or adminis¬
  trative action by Member States may
  hinder        trade   in     medicinal       products
  derived        from  human     blood     within    the
  Community ;
 ---pagebreak---              ORIGINAL PROPOSAL                           AMENDED PROPOSAL 37
Whereas the essential aim of any                  rules
governing the production , distribution or
use    of    medicinal       products     must   be   to
ensure a high           level of       protection of
public health ;
Whereas       the    provisions        laid   down    by
                             A
Directive 65 / 65 / EEC         as last amended by
Directive 87 / 21 / EEC^ and Second Directive
75 / 319/ EEC^ as last amended by Directive
83 / 570 / EEC     on      the     approximation      of
provisions laid down by law , regulation
or administrative action relating to
proprietary medicinal products , although
appropriate , are inadequate for medicinal
products derived from human blood ;
Whereas      in   accordance with        Article 5 of
                            8
Directive 87 / 22 / EEC on the approximation
of national provisions relating to the
placing on the market of high technology
medicinal products , particularly those
derived          from        biotechnology ,         the
 Commission         is      required       to    submit
 proposals to harmonise ,             along the lines
 of    Directive      75 / 319 / EEC   the  conditions
 for     authorizing         the     manufacture     and
 placing       on    the     market     of    medicinal
 products derived from human blood before
 22 December 1987 ;
  A  OJ   No  22 , 9.2.1965 , p. 369 / 65
  5  OJ   No  L 15 , 17.1.1987 , p. 36
  6   OJ  No  L 1A7 , 9.6.1975 , p. 13
  7   OJ  No  L 332, 28.11.1983 , p. 1
   8  OJ  No  L 15 , 17.1.1987 , p. 38
 ---pagebreak---            ORIGINAL PROPOSAL                             AMENDED PROPOSAL          38 .
Whereas the European Community entirely
supports the efforts of         the Council of
Europe      to     promote     voluntary      and
non-remunerated blood donation to attain
self-sufficiency throughout the Community
in the supply "of blood products , and to
ensure the respect of ethical principles
in trade of       therapeutic     substances of
human origin ;
 Whereas the rules designed to guarantee          Whereas    the  rules   designed    to
 the quality ,       safety and efficacy of       guarantee the quality , safety and
medicinal products derived from human             efficacy    of  medicinal   products
blood must be applied in the same manner          derived from human p I asma must be
to      both
        ;
                    public       and      private applied in the same manner to both
establishments ;                                  public and private establishments ,
                                                  and   to blood  Imported  from coun -
                                                   trles outside the EEC :
Whereas ,      before    an   authorization    to 7th Recital unchanged
market a medicinal product derived from
human     blood     can    be    granted,     the
manufacturer must demonstrate his ability ;
 to guarantee batch -to-batch consistency ;
and the absence of viral contamination;
 ---pagebreak---             ORIGINAL PROPOSAL                                         AMENDED PROPOSAL                   39
Whereas      the     Commission        should      be Whereas       the Commission          should be
empowered to adopt any necessary changes              empowered         to adopt      any necessary
in the requirements for the testing of                changes        in   the   requirements          for
proprietary medicinal products set out in              the       testing        of        proprietary
                                                9
the  Annex     to  Directive     75 / 318 / EEC    of medicinal products set out                  In the
20 May 1975 on the approximation of the               Annex     to     Directive      75 / 318 / EEC   of
laws of the Member States relating to                  20 May 1975 on the approximation
analytical ,      pharmaco-toxicological and           of  the     laws of     the Member         States
clinical standards and protocols in                    relating to analytical , pharmaco-
respect of the testing of proprietary                  toxicological         and clinical          stan ¬
medicinal products , as last amended by                dards and protocols in respect of
                        10
Directive 87 / 19 / EEC     of 22 December 1986       the    testing of        proprietary medi ¬
to take account of the special nature of              cinal products ( ), as last amended
medicinal     products     derived     from     human by    Directive         87 / 19 / EEC     of     22
blood    in    close   cooperation       with     the December       1986 ( )    to    take    account
Committee for the Adaptation to Technical             of the special nature of medicinal
Progress of the Directives on the Removal             products derived from human plasma
of  Technical     Barriers    to   Trade     in the   In close cooperation with the Com¬
Proprietary Medicinal Products Sector ,               mittee for the Adaptation to Tech ¬
                                                      nical     Progress of         the    Directives
                                                      on      the      Removal       of     Technical
                                                      Barriers        to   Trade       In   Med I c I na I
                                                      Products ,      so as to ensure greater
                                                      qua I I ty . safety and efficacy ;
     9 JO No L 147 , 9.6.1975 , p. 1
      10 0J No L 15 , 17.1.1987, p. 31
 ---pagebreak---            ORIGINAL PROPOSAL                                     AMENDED PROPOSAL                 A0 -
  HAS ADOPTED THIS DIRECTIVE :
Article 1
                                                                     Article 1
1.   In derogation from            Article 34 of       1.   In derogation from Article 34
     Directive 75 / 319 / EEC ,    and subject to      of    Directive     75 / 319/ EEC ,      and
     the   provisions      of    this   Directive ,    subject to the provisions of this
     Directives    65 / 65 / EEC  and   75 / 319 / EEC Directive ,   Directives       65 / 65 / EEC
     shall    apply   to     medicinal     products    and 75 / 319/ EEC shall apply to
     based on blood constituents which are             medicinal products based on blood
     prepared industrially by public or                constituents which are prepared
     private establishments , hereinafter               industrially by public or private
     referred to as " medicinal products               establishments , hereinafter refer-
     derived from human blood";                these   red   to   as   " medicinal     products
     medicinal      products        include ,       in derived from human plasma ": these
     particular ,       albumin ,      coagulating     medicinal    products      Include ,      In
      factors and immunoglobulins of human             particular albumin ,        coagulating
     origin .                                          factors and immunoglobulins of
                                                       human origin .
2.  This directive shall not apply to                  2.  Unchanged
    whole blood , to plasma or to blood
     cells of human origin .
 ---pagebreak---           ORIGINAL PROPOSAL                                                                 41 .
                                                                 AMENDED PROPOSAL
   Nothing      in    the   present directive      3.     Unchanged
   shall     in    any    way   derogate from
   Counci l         Decision       86/ 346/ EEC1 1
   accept i ng .      in   the   name    of   the
    Community ,      the   European    Agreement
    relating       to     the    exchange      of
    therapeut i c      substances     of    human
    origin .
Article 2                                                             Article 2
1.   The quantitative particulars of a                1 .   The   quantitative    particulars
     medicinal product derived from human             of    a   medicinal   product   derived
       »
     blood shall be expressed by mass or              from human plasma shal I be expres ¬
     by international units or by units of            sed    by  mass  or  by   International
     biological activity as appropriate to            units or      by units of    biological
                                                      activity     as   appropriate   to   the
     the product concerned .
                                                      product concerned .
11 OJ No L 207 , 30.7.1986, p. 1
 ---pagebreak---               ORIGINAL PROPOSAL                                      AMENDED PROPOSAL           42 .
 2.  In       Directives         65 / 65 / EEC     and  2.    Unchanged
     75 / 319 / EEC         the          expressions
     "qualitative            and       quantitative
     particulars of the               constituents"
     shall include particulars relating to
     biological activity and "qualitative
     and quantitative composition" shall
     include        the   composition         of    the
     product        expressed      in       terms    of
     biological activity .
                                                           3.   In  any  document ,   established
3 . Whenever the name of a medicinal |
                                                           for the purpose of this Directive .
    product derived from human blood is !
                                                           where the name of a medicinal pro¬
    expressed ,         the     common       or    the
                                                           duct derived from human plasma        Is
    scientific         name     of     the      active
           »
                                                           expressed ,  the common or      sclent -
    constituents shall also be included .
                                                           fic     name     of      the     active
                                                           constituents      shall      also     be
                                                            Included at  least once .    It may be
                                                           abbreviated     In    the     remaining
                                                           references .
 ---pagebreak---           ORIGINAL PROPOSAL                               AMENDED PROPOSAL                 43 .
Article 3                                                      Article 3
In order to prevent the transmission of     1.     The Member       States shall       take
infectious diseases ,   the Member States   the necessary measures to prevent
shall   take    into   consideration    the the      transmission       of    Infectious
measures recommended within the framework   diseases .       These measures shall at
of the Council of Europe and the World      I east     compr i se   those    recommended
Health Organisation in particular for the   by the Council of Europe and the
selection and testing of blood donors .     World Health Organization , parti ¬
                                            cularly       with     reference      to    the
                                            selection        and    testing    of    blood
                                            donors .
                                             2.     The   Member     States   shall     take
                                              the    necessary     measures    to    ensure
                                              that , where human blood         Is traded .
                                              the   origin     of   the  blood    donation
                                             centre      1s   always    clearly    1 dent 1 -
                                              fled .
                                              3.    Moreover ,     every   guarantee      as
                                              to safety and purity must also be
                                             given as regards          Imports of human
                                              blood     from    countries    outside     the
                                              EEC .
                                              4.    The   Member     States   shall     take
                                              the necessary measures to promote
                                              se 1 f-suf f 1 c lency of    the  iCommun 1 ty
                                              in human blood .        For  this purpose ,
                                              voluntary unpaid donat Ion of blood
                                              shall be encouraged .
 ---pagebreak---            ORIGINAL PROPOSAL                                 AMENDED PROPOSAL                  44 .
Article 4                                                        Article 4
1.  Member States shall ensure that the        1 .   Member      States       shall    ensure
    manufacturing processes used in the        that     the manufacturing processes
    manufacture      of   medicinal   products used    in    the preparation of medi ¬
    derived from human blood are properly      cinal     products derived from human
    validated ,       attain batch-to-batch    p I asma     are    properly        validated ,
    consistency and guarantee the absence      attain batch- to-batch consistency
    of viral contaminants .       To this end  and     guarantee ,       Insofar      as   the
    the competent authority may submit         state of       technology permits ,         the
    samples from up to five in total of        absence of viral contaminants .               To
    the bulk and /or finished product          this    end     the   manufacturer        shall
    batches for testing by a state             notify       the    authorities        of   the
    laboratory or a laboratory designated      proposed       method     for    reducing     or
    for that purpose , either during the        eliminating the pathogenic viruses
    examination       of    the    application  which may be transmitted by medi ¬
    pursuant to Article 4 of Directive          cinal     products derived from human
    75 / 319 / EEC ,  or after a marketing      plasma .      For     this      purpose      the
    authorisation has been granted .            competent        authority        may    submit
                                                 samples from up to five In total
                                                of    the   bulk    and / or   finished    pro ¬
                                                 duct     batches      for    testing     by    a
                                                 State     laboratory or        a   laboratory
                                                 designated         for      that     purpose ,
                                                 either during the examination of
                                                 the      application          pursuant        to
                                                 Article 4 of Directive 75 / 319 / EEC ,
                                                 or after a marketing authorization
                                                 has been granted .
 ---pagebreak---             ORIGINAL PROPOSAL                                 AMENDED PROPOSAL
2. For    the    purpose    of     implementing  2.    For      the    purpose      of     imple ¬
   Article 8 of Directive 65 / 65 / EEC and      menting       Article      8   of    Directive
   Article 27 of      Directive 75 / 319 / EEC , 65 / 65 / EEC and Article 27 of Direc ¬
   Member States may require persons             tive 75 / 319 / EEC , Member States may
   responsible for marketing medicinal           require       persons      responsible       for
   products derived from human blood to          marketing           medicinal         products
   submit      to a    competent authority       derived        from human         plasma      to
   copies     of all   the control reports       submit to a competent authority
   signed by the qualified person in             copies of all the control reports
   accordance       with      Article 22      of signed by the qualified person in
   Directive 75 / 319 / EEC .                    accordance         with     Article     22    of
                                                 D i rect i ve 75 / 319 / EEC .
                                                 3.    Where ,      In    the    Interests     of
3. Where it considers it necessary in
                                                 public health ,         the   legislation of
   the > interests of public health , a
                                                 a    Member      State    so   provides ,    the
   Member State may require persons
   responsible for marketing medicinal           appropr late_author 1 1 les                  may
                                                 require       persons      responsible       for
   products derived from human blood to
   submit to a competent authority               marketing           medicinal         products
                                                 derived         from     human     plasma     to
   samples from each batch of the bulk
                                                 submit       to   a   competent      authority
   and / or      finished       product      for
                                                 samples       from     each    batch    of   the
    examination by a state laboratory or
                                                 bulk     and / or   finished     product     for
    a laboratory designated for that
                                                 examination by a State              laboratory
    purpose before        release onto the
                                                 or     a    laboratory       designated      for
    market ,      unless      the      competent
                                                  that    purpose      before    release onto
    authority of another Member State has
                                                  the    market ,    unless     the   competent
    previously examined the           batch ini
                                                 authority of another Member State
   question and declared it           to be in
                                                 has previously examined the batch
   conformity        with      the      approved  in question and declared It to be
   specifications .       Member States shall
                                                  In   conformity        with    the   approved
   ensure that any such examination is
                                                 specifications .          Member         States
   completed within        60    days    of  the
                                                 shall        ensure       that      any     such
   receipt of the samples .
                                                 examination Is completed within 60
                                                 days       of     the     receipt      of    the
                                                 samples .
 ---pagebreak---             ORIGINAL PROPOSAL                                  AMENDED PROPOSAL                     46 .
                                                                     Article 4 a
                                                   The       procedure         for       marketing
                                                    author 1 zat Ion      for   med 1 c 1 na 1i   pro-
                                                    ducts     der 1 ved    from   human         plasma
                                                    sha 1 1  be that      laid down       I n D 1 ree-
                                                    t Ive 87 / 22 / EEC .
Article 5                                                             Article 5
Any amendments which are necessary in the          Any amendments which are necessary
testing requirements for medicinal                 in the testing requirements for
products set out in the Annex to                   medicinal products set out In the
Di receive 75 / 318 / EEC to take account of       Annex     to Directive 75 / 318 / EEC            to
the extension of the scope of Directives           take account of           the extension of
65 / 65 / EEC and 75 / 319 / EEC to cover medici ¬ the scope of Directives 65/ 65 / EEC
 nal products derived from human blood             and 75 / 319 / EEC to cover medicinal
 shall be adopted in accordance with the           products derived from human p I asma
 procedure laid down in Artie le 2(c ) of           shall      be    adopted     in    accordance
 Directive 75 / 318 / EEC .       Any such amend¬  with     the    procedure      laid down          In
 ments shall come into effect on the same           Article           2c      of         Directive
 date as this Directive .                           75 / 318 / EEC .
                                                    2nd sentence deleted .
 ---pagebreak---                                                           AMENDED PROPOSAL                   47 .
            ORIGINAL PROPOSAL
Article 6                                                         Article 6
1.   Member    States    shall   take   the   1•     Save In the case provided for
     necessary measures     to comply  with    In    paragraph 2 . Member States
     this    Directive   not   later   than   shall take the necessary measures
     1 January 1991 .  They shall forthwith   to comply with this Directive not
     inform the Commission thereof .          later than 1 January 1991 .                  They
                                              shall      forthwith        inform     the   Com¬
 2.   Requests for marketing authorization   mission thereof .
      for products covered by this Direc¬
      tive lodged after the time-limit       2.     In the event of the amendments
      referred to in the first paragraph     to    Directive        75 / 318 / EEC   referred
                                             to    In Article 5 not           being adopted
      must comply with the provisions of
                                             by    the    date    referred      to   In  para-
      this Directive .
                                             graph       1 ,    this    date shall be
                                             replaced by the date of adoption .
3.   This Directive shall be progressively
     extended tro the existing medicinal
     products derived from human blood       3.     Requests             for        marketing
     referred to in Article 1 , paragraph 1  authorization for products covered
     before 31 December 1992 .               by this Directive lodged after the
                                             date of implementation                      shall
                                              comply with the provisions of this
                                              D I rect 1 ve .
                                              4.    This        Directive          shall     be
                                              progressively extended to existing
                                              medicinal         products       derived     from
                                              human       p I asma .     referred       to   In
                                              Article        1(1 ),   before     31   December
                                               1992 .
  Article 7
                                                          Article 7
  This Directive is addressed to the Member Unchanged
  States .
 ---pagebreak--- Amended proposal for a Council Directive extending the scope of Directives
65 / 65 / EEC and 75 / 319/ EEC on the approximation of provisions laid down by
law , regulation or administrative action relating to proprietary medicinal
products and laying down additional provisions for radiopharmaceuticals
            ( Submitted by the Commission to the Council pursuant to the
                    third paragraph of Article 149 of the Treaty )
 ---pagebreak---               ORIGINAL PROPOSAL                                 AMENDED PROPOSAL
Council Directive
                                                      Title
                                                         /
                                                            unchanged
extending        the     scope       of   Directives   /
65 / 65 / EEC     and     75 / 319 / EEC    on    the
approximation of provisions laid down by
law ,     regulation or administrative action
relating         to    proprietary         medicinal
products and laying down additional
provisions for radiopharmaceuticals
THE COUNCIL OF THE EUROPEAN COMMUNITIES ,             Visas unchanged
Having regard to the Treaty establishing
the European Economic Community , and in
particular Article 100 A thereof .
Having regard to the proposal from the
Commission”* ,
In       cooperation       with       the    European
Parliament ^,
Having       regard   to    the    opinion    of  the
Economic and Social Committee ^,
Whereas       disparities      in    the  provisions
                                                       First to fourth recitals unchanged
currently laid down by law , regulation or
administrative action by Member States
may hinder trade in radiopharmaceuticals
within the Community ;
    1
    2
    3
 ---pagebreak---              ORIGINAL PROPOSAL                    AMENDED PROPOSAL 50 .
Whereas the essential aim of any rules
governing the production , distribution or
use of medicinal products must be to
                ø
ensure a high level of protection of
public health ;
Whereas the provisions laid down by
                          4
Directive 65 / 65 / EEC as last amended by
Directive 87/21 / EEC^ and Second Directive
75/319/EEC^ as last amended by Directive
83/ 570/ EEC^ on the approximation of
provisions laid doun by law ,          régulation
or administrative action relating to
proprietary medicinal products , although
appropriate          are       inadéquate     for
radiopharmaceuticals ;
        »
Whereas    in accordance with Article        5 of
                         B
Directive 87 / 22 / EEC on the approximation
of national provisions relating to the
placing on the market of high technology
medicinal products , particularly those
 derived      from       biotechnology ,      the
 Commission       is     required     to   submit
 proposals to harmonise , along the lines
 of Directive 75 / 319 / EEC ,     the conditions
 for authorizing          the   manufacture   and
 placing        on         the      market     of
 radiopharmaceuticals         before  22 December
 1987 ;
    4  0J No  22 , 9.2.1965 , p. 369 / 65
    5  0J No  L 15 , 17.1.1987 , p. 36
    6  OJ No  L 147 , 9.6.1975 , p. 13
    7  OJ No  L 332 , 28.11.1983, p. 1
    8  OJ No  L 15 , 17.1.1987 , p. 38
 ---pagebreak---             ORIGINAL PROPOSAL                            AMENDED PROPOSAL               51 .
Whereas       in       the       case      of  Whereas    in   the    case   of   radio¬
radiopharmaceuticals authorization should      pharmaceutical s ,    generators ,   kits
be required for industrially prepared          and     precursors        authorization
 radiopharmaceuticals ,    generators ,   kits should    be      required ;     whereas ,
 and     precursor     radiopharmaceuticals ;  however ,  a spec I f I c authorization
 whereas ,      however ,      a      separate should not be required for         rad lo-
 authorization should not be required for      pharmaceut I ca I s  In  their   finished
 radiopharmaceuticals     in  their   finished form which are made up exclusively
 form which are made up exclusively from       from   authorized     kits ,  generators
                                               or  rad lopharmaceut I ca I s  in  health
 authorized kits ,   generators or precursor
 radiopharmaceuticals      in   health    care care establishments ;
 establishments ;
 ---pagebreak---            ORIGINAL PROPOSAL                                  AMENDED PROPOSAL                52 .
Whereas    the     Commission     should    be     Whereas     the   Commission     should   be
empowered to adopt any necessary changes         I empowered to adopt any necessary
in the requirements for the testing of           i changes In the requirements for
proprietary medicinal products set out in        ! the testing of proprietary medl-
the Annex to Directive 75 /318 / EEC^ of 20     J  cinal products set out In the
May 1975 on the approximation of the laws       |  Annex to Directive 75/ 318/ EEC of
of the Member States            relating to    \   20 May 1975 on the approximation
analytical ,    pharmaco-toxicological and     !   of the laws of the Member States
clinical    standards    and   protocols    in     relating to analytical , pharmaco-
respect of the testing of proprietary          i    toxicological      and clinical       stan­
medicinal products , as last amended by            dards and protocols        in respect of
Directive 87/ 19/ EEC^ of 22 December 1986          the      testing      of       proprietary
to take account of the special nature of           medicinal       products (   ).     as  last
radiopharmaceuticals in close coopération           amended by Directive 87 / 19 / EEC of
with the Committee for the Adaptation to            22   December       1986 ( )      to   take
Technical Progress of the Directives on             account    of   the special      nature of
the   Removal   of   Technical   Barriers   to      radiopharmaceuticals            in    close
Trade    in the      Proprietary     Medicinal      cooperation with the Committee for
Products Sector ;                                   the      Adaptation      to       Technical
                                                    Progress of the Directives on the
                                                    Removal    of   Technical    Barriers     to
                                                    Trade In the Proprietary Medicinal
                                                    Products Sector , thus ensuring the
                                                     qreater_quai 1 1 y ,_sa f et y_and
                                                     efficacy     of   the   medicinal      pro-
                                                     ducts ;
   9 0J No L 147 , 9.6.1975 , p. 1
   10 0J No L 15 , 17.1.1987 , p. 31
 ---pagebreak---             ORIGINAL PROPOSAL                                  AMENDED PROPOSAL 53 .
Whereas         any       rules         governing    > Unchanged
radiopharmaceuticals        must     take       into
account the provisions of Directive
84/466/ Euratom^ of 3 September 1984
laying    down     basic   measures      for     the
radiation        protection       of       persons
undergoing       medical     examination , or
treatment ; whereas account should also be
                                         12
taken of Directive 80 / 836 / Euratom         which
amends the Directives laying down the
basic safety standards for the health
protection of the general public and
workers against the dangers of ionizing
radiation     as   last  amended     by    Council
Directive 84/ 467/ Euratom^ of 3 September
1984 ,    the    objective   of    which     is   to
prevent     the    exposure    of    workers      or
patients to excessive or unnecessarily
high levels of ionizing radiation , and in
particular of Article 5c thereof , which -
 requires    prior    authorisation       for    the
 addition    of   radioactive     substances      to
 medicinal    products   as well     as    for   the
 importation of such medicinal products ,
 11 OJ No L 265 , 5.10.1984 , p. 1
 12 OJ No L 246 , 17.9.1980 , p. 1
 13 OJ No L 265 , 5.10.1984 , p. 4
 ---pagebreak---              ORIGINAL PROPOSAL                                    AMENDED PROPOSAL                 54 .
  HAS ADOPTED THIS DIRECTIVE :
Article 1                                                               Art lele   1
1.    In  derogation      from  Article      34    of   Unchanged
     Directive 75 / 319/ EEC and subject to
     the provisions of this Directive , the
     provisions     of    Directives    65 / 65 / EEC
     and     75 /319/ EEC    shall     apply       to
     radiopharmaceuticals for human use ,
     excluding radionuclides in the form
     of sealed sources .
2 . For the purposes of this directive,
                                                      2.    For    the    purposes       of     this
     the     following      definitions       shall
     apply :                                          Directive ,    the following definl -
                                                      t Ions sha l I app I y :
     - 'radiopharmaceutical *        shall     mean
                                                      - 'radiopharmaceutical' shall mean
        any medicinal product which ,          when
                                                         any    medicinal      product       which ,
        ready for use , contains one or more
                                                         when ready for use , contains one
        radionuclides               ( radioactive
                                                         or   more    radionuclides        ( radio¬
        isotopes ) included for a medicinal
                                                         active Isotopes )      included for a
        purpose .
                                                         medicinal purpose ,
     - 'generator' shall mean any system
                                                      - 'generator'        shall      mean       any
        incorporating a          fixed parent
                                                         system Incorporating a fixed
        radionuclide from which is produced
                                                         parent    radionuclide      from     which
        a daughter radionuclide which is to
                                                         is produced a daughter              radio¬
        be removed by elution and used in a
                                                         nuclide which       Is to be removed
        radiopharmaceutical .
                                                         by   elution     or    by   any      other
                                                         method    and   used     In   a    radio-
                                                         pharmaceut ica I ,
 ---pagebreak---            ORIGINAL PROPOSAL                                  AMENDED PROPOSAL                55 ■
   - 'kit'   shall    mean   any   industrial    - 'kit'     shall      mean    any  prepara-
      preparation to be reconstituted or           tlon     to    be      reconstituted     or
      combined with    radionuclides in the        combined     with       radionuclides    In
      final radiopharmaceutical ,     usually       the   final       radiopharmaceutical ,
      prior to its administration .                usually prior to Its administra ¬
                                                   tion .
   - 'precursor        radiopharmaceutical'      - 'precursor' shall mean any other
      shall mean any other industrially            radionuclide         produced     for  the
      produced    radionuclide      for    the     rad lo- 1 abe 1 1 i ng      of     another
      radio-labelling        of       another      substance      prior      to   administra-
      substance prior to administration .          tion .
3.  Nothing in this directive shall in             Unchanged
    any way derogate from the Community
     rules for the radiation protection of
    persons undergoing medical examina-
    tion    or    treatment    or    from    the
     Community rules laying down the basic
     safety    standards    for   the    health
     protection of the general public and
     workers    against    the    dangers     of
     ionizing radiation .
 ---pagebreak---             ORIGINAL PROPOSAL                              AMENDED PROPOSAL                  56 .
                  9 •
Article 2                                                        Article 2
The    authorization      referred    to   in  The   authorization       referred       to   In
Article 3 of Directive 65 / 65 / EEC shall be  Article     3   of   Directive     65 / 65 / EEC
required for generators , kits , precursor     shall be required for generators ,
radiopharmaceuticals       and   industrially  kits ,       precursor        radiopharma- ,
prepared radiopharmaceuticals .      However , ceutlcals       and    Industrially        pre¬
authorization shall not be required for a      pared              radiopharmaceuticals .
radiopharmaceutical in its ready for use       However ,     authorization       shall      not
form,     if- the radiopharmaceutical is       be   required       for   a   radiopharma-
prepared by an approved person in an           ceutical      prepared at      the   time     of
approved     health     care    establishment  use     by     a    person     or      by     an
                                               estab 1 1 shment                author 1 zed .
exclusively from authorized generators ,
kits   or   precursor    radiopharmaceuticals  according to national          leglslat Ion ,
in   accordance    with   the  manufacturer 's to use     such medicinal       products       In
instructions .                                 an approved health care establish¬
                                               ment    exclusively      from    authorized
                                               generators ,        kits    or     precursor
                                               radiopharmaceuticals In accordance
                                               with     the   manufacturer 's       instruc -
                                               t ions .
 ---pagebreak---           ORIGINAL PROPOSAL                             AMENDED PROPOSAL 57 .
Article 3                                                  Article 3
In addition to the requirements set out       Unchanged
in Article 4 of Directive 65 / 65 / EEC ,  an
application for authorization to market a
generator    shall   also   contain       the
following information and particulars :
- a general description of the system
  together with a detailed description of
  the components of the syst'em which may
  effect the composition or quality of
  the daughter nucleid preparation .
  qualitative       and        quantitative
                             t
  particulars of the eluate.j
 ---pagebreak---             ORIGINAL PROPOSAL                              AMENDED PROPOSAL 58 .
Article A                                                   Art le le 4
For radiopharmaceuticals ,     in addition to    Unchanged
the information referred to in Article 4a
of Directive 65 / 65 / EEC , the summary of
product characteristics referred to in
point 9 of the second paragraph of
Article 4    of  Directive   65 / 65 / EEC shall
contain the following additional points 7
and 8 :
" 7 . full details of radiation dosimetry ;
  8. Additional detailed instructions for
      preparation, and where appropriate,
      maximum storage time during which any
      intermediate preparation such as an
      eluate or the ready to use
      Pharmaceutical will conform with its
      specifications ."
 ---pagebreak---            ORIGINAL PROPOSAL                                   AMENDED PROPOSAL
Artide 5
                                                                Article 5
The outer carton and the tin of medicinal
               t                                     Unchanged
products containing radionuclides shall
be   labelled     in   accordance    with       the
regulations for the safe transport of
radioactive materials       laid down by the
International      Atomic     Energy     Agency .
Moreover , the labelling shall comply with
the following provisions :
a)  The label on the shielding shall
     include the particulars mentioned in
     Article 13     of  Directive    65 / 65 / EEC .
     In addition , the labelling on the
     shielding shall explain in full the
     codings used on the vial and shall
     indicate ,    where   necessary ,      for    a
     given time and date ,       the amount of
     radioactivity per dose or per vial
     and the number of capsules or , for
     liquids , the number of millilitres in
     the container ;
 b)  The vial    shall   be labelled with the
      following information :
     - the name or code       of  the medicinal
        product     including the name or
        chemical symbol of the radionuclide
      - the batch identification and expiry
        date
      - the     international      symbol        for
        radioactivity
      - the name of the manufacturer
      - the   amount    of    radioactivity       as
        specified under a ) above .
 ---pagebreak---             ORIGINAL PROPOSAL                                  AMENDED PROPOSAL
Artide 6                                                        Article 6
1.  Member    States    shall    ensure     that   a Unchanged
    detai led     instruction        leaflet      is
    enclosed     with     the      packaging of
    radiopharmaceuticals ,            generators ,
    kits               or                precursor
    radiopharmaceuticals .           The text of
    this leaflet shall be established in
    accordance     with     the   provisions      of
    Article 6 of Directive 75 / 319 / EEC and
    shall    contain     all    the    information
    referred to therein .            In addition ,
    the    leaflet       shall      include      any
    precautions to be taken by the user
    and     the      patient        during       the
    preparation and administration of the
         /
    product and special precautions for
    the disposal of the container and its
    unused contents .
2.   Member States shall permit the use of
     user information       leaflets which have
     been established in more than one of
     the   languages       of     the     Community
     provided      that       the      information
     contained      in     all     the     language
     versions of the leaflet is identical .
 ---pagebreak---                ORIGINAL PROPOSAL                                       AMENDED PROPOSAL
Article 7                                                                  Article 7
Any amendments which are necessary in the               Any amendments which are necessary
testing requirements              for     medicinal      In    the    testing    requirements      for
products       set    out    in    the   Annex    to    medicinal       products set out       In the
Directive 75 / 318 / EEC to take account of             Annex      to   Directive 75 / 318 / EEC    to
the extension of the scope of Directives                 take    account     of   the extension of
65 / 65 / EEC and 75 / 319 / EEC to cover radio¬         the scope of Directives 65 / 65 / EEC
                                                         and    75 / 319 / EEC   to   cover    radio¬
pharmaceuticals         shall    be    adopted    in
                                                         pharmaceutical s        shall   be   adopted
 accordance with the procedure laid down
 in Article 2 c of         Directive 75 / 318 / EEC .
                                                         in    accordance with       the    procedure
                                                         laid down       In Article 2c of      Dlrec -
 Any     such   amendments      shall    come   into
                                                         t I ve 75 / 318 / EEC .
 effect      on    the    same    date     as   this
 Directive .
                                                         2nd sentence deleted .
 Article 8                                                                Article 8
 1.    Member      States      shall     take    the  1•      Save In the case provided for
                                                       in paragraph 2 . Member States
       necessary measures to           comply   with
       this     Directive not          later    than  shall take the necessary measures
       1 January 1991 . They shall forthwith          to comply with this Directive not
       inform the Commission thereof .                later than 1 January 1991 .               They
                                                      s ha l I fort hw ith inform the Comm i s –
                                                      s ion thereof .
 ---pagebreak---                                                          AMENDED PROPOSAL               62 .
           ORIGINAL PROPOSAL
2 . Requests for marketing authorization    2.   In the event of the amendments
     for products covered by this Direc¬    to  Directive    75 / 318 / EEC   referred
     tive lodged after the time-limit       to  in Article 7 not being adopted
     referred to in the first paragraph     by the date referred to           In para-
     must comply with the provisions of     graph    1.   this date shall be
     this Directive .                       replaced by the date of adoption .
 3.  This Directive shall be progressively
     extended    to   existing   medicinal  3.   Requests for marketing autho¬
     products covered by this Directive     rization    for  products covered by
     before 31 December 1992 .              this   Directive     lodged     after  the
                                            date   of implementation
                                            comply with the provisions of this
                                            Direct Ive .
                                            4.   This     Directive        shall     be
                                            progressively extended to existing
                                            rad lopharmaceut leal            medicinal
                                            products covered by this Directive
                                            before 31    December   1992 .
Article 9                                                 Article 9
This Directive is addressed to the Member  Unchanged
States .