CELEX: 51990PC0283(02)
Language: en
Date: 1990-11-14
Title: PROPOSAL FOR A COUNCIL DIRECTIVE AMENDING DIRECTIVES 65/65/EEC, 75/318/EEC AND 75/319/EEC IN RESPECT OF MEDICINAL PRODUCTS

No C 330/18                               Official Journal of the European Communities                                   31. 12. 90
              Proposal for a Council Directive amending Directives 65/65/EEC, 75/318/EEC and 75/319/EEC
                                                  in respect of medicinal products
                                                  COM(90) 283 final — SYN 310
                                      (Submitted by the Commission on 14 November 1990)
                                                           (90/C 330/02)
THE COUNCIL OF THE EUROPEAN COMMUNITIES,                              Whereas, with the exception of those medicinal products
                                                                      which are subject to the centralized Community
 Having regard to the Treaty establishing the European                authorization established by Council Regulation (EEC)
 Economic Community, and in particular Article 100a                   No . . . of . . . laying down Community procedures for the
 thereof,                                                             authorization and supervision of medicinal products for
                                                                      human and veterinary use and establishing a European
Having regard to the proposal from the Commission,                    Agency for the Evaluation of Medicinal Products ( 6 ), an
                                                                      authorization to place a medicinal product on the market in
In cooperation with the European Parliament,                          one Member State ought in principle to be recognized by the
                                                                      competent authorities of the other Member States unless
Having regard to the opinion of the Economic and Social               there are serious grounds for supposing that the
 Committee,                                                           authorization of the medicinal product concerned may
                                                                      present a risk to public health; whereas, in the event of a
Whereas it is important to adopt measures with the aim of             disagreement between Member States about the quality, the
progressively establishing the internal market over a period          safety or the efficacy of a medicinal product, a scientific
expiring on 31 December 1992; whereas the internal market             evaluation of the matter should be undertaken by the
 shall comprise an area without internal frontiers in which the       Committee for Proprietary Medicinal Products attached to
 free movement of goods, persons, services and capital is             the European Agency for the Evaluation of Medicinal
ensured;                                                              Products, leading to a single decision on the area of
                                                                      disagreement, binding on the Member States concerned;
Whereas Article 15 (2) of Second Council Directive                    whereas this Decision should be adopted by a rapid
75/319/EEC of 20 May 1975 on the approximation of                     procedure ensuring close cooperation between the
provisions laid down by law, regulation or administrative             Commission and the Member States, in particular through
action relating to proprietary medicinal products ( 1 ), as last      the Standing Committee on Medicinal Products for Human
amended by Directive 89/381/EEC ( 2 ), provides that the              Use created by Article 2b of Directive 75/318/EEC;
Commission shall submit to the Council a proposal
containing appropriate measures leading towards the
                                                                      Whereas in order better to protect public health and avoid
abolition of any remaining barriers to the free movement of
                                                                      any unnecessary duplication of effort during the examination
proprietary medicinal products;
                                                                      of application for authorization to place medicinal products
                                                                      on the market, Member States should systematically prepare
Whereas in the interests of public health it is necessary that        assessment reports in respect of each medicinal product
decision on the authorization to place medicinal products on          which is authorized by them, and exchange the reports upon
the market be exclusively based on the criteria of quality,           request; whereas, furthermore, a Member State should be
safety and efficacy; whereas these criteria have been                 able to suspend the examination of an application for
extensively harmonized by Directive 65/65/EEC of 26                   authorization to place a medicinal product on the market
January 1965 on the approximation of provisions laid down             which is currently under active consideration in another
by law, regulation or administrative action relating to               Member State with a view to recognizing the Decision
medicinal products ( 3 ), as last amended by Directive                reached by the latter Member State;
89/381/ECC, and by Directive 75/319/EEC, and by
Council Directive 75/318/EEC of 20 May 1975 on the
approximation of the laws of the Member States relating to           Whereas following the establishment of the internal market,
analytical, pharmaco-toxicological and clinical standards             specific controls to guarantee the quality of medicinal
and protocols in respect of the testing of medicinal"                products imported from third countries can only be waived if
products (4), as last amended by Directive 89/341 /EEC (5);           appropriate arrangements have been made by the
whereas, however Member States should exceptionally be                Community to ensure that the necessary controls are carried
able to prohibit the use on their territory of medicinal             out in the exporting country;
products which infringe objectively defined concepts of
public order or public morality;
                                                                     Whereas it is desirable to codify and improve the cooperation
                                                                     and exchange of information between Member States
(»)  OJNoL147, 9. 6. 1975, p. 13.
(2)  OJ No L 181, 28. 6. 1989, p. 44.                                relating to the supervision of medicinal products and in
(3)  OJ No 22, 9. 2. 1965, p. 369/65.                                particular the monitoring of adverse reactions under
(4)  OJ No L 147, 9. 6. 1975, p. 1.
(5)  OJ No L 142, 25. 5. 1989, p. 11.                                (*) See page 1 of this Official Journal.
 ---pagebreak--- 31. 12. 90                                   Official Journal of the European Communities                               No C 330/19
practical conditions of use             through     the   national         Furthermore, the competent authorities shall draw up an
pharmacovigilance centres,                                                 assessment report and comments on the dossier as
                                                                           regards       the     results     of     the     analytical,
                                                                           pharmaco-toxicological tests and the clinical trials of the
                                                                           medicinal product concerned. The assessment report
HAS ADOPTED THIS DIRECTIVE:                                                shall be updated whenever new information becomes
                                                                           available which is of importance for the evaluation of the
                                                                           quality, safety or efficacy of the medicinal product
                                                                           concerned.
                             Article 1
                                                                           (*) O J N o L . . . '
Directive 65/65/EEC is hereby amended as follows:
                                                                        4. Article 6 is replaced by the following:
1. Article 3 is replaced by the following:
                                                                            'Article 6
     'Article 3
                                                                           This Directive shall not affect the application of national
    No medicinal product may be placed on the market of a
                                                                           legislation prohibiting or restricting the use of medicinal
    Member State unless an authorization has been issued by
                                                                           products as contraceptives or abortifacients. The
    the competent authority of that Member State or by the
                                                                           Member States shall communicate the national
    Community.'
                                                                           legislation concerned to the Commission.'
2. Article 4 (2), points 6 and 11 are replaced by the
    following:                                                          5. Article 7 is replaced by the following:
    '6.     Posology, pharmaceutical form, method and                       'Article 7
    route of administration and expected shelf life.                        1.     Member States shall take all appropriate measures
    If applicable, reasons for any precautionary and safety                to ensure that the procedure for granting an
    measures to be taken for the storage of the product, its               authorization to place a medicinal product on the market
    administration to patients and for the disposal of waste               is completed within 210 days of the date of submitting
    products, together with an indication of any potential                 the application.
    risks presented by the product for the environment.'
                                                                           2.      Where a Member State notes that an application
    '11.      Copy of any authorization obtained in another                for authorization submitted after 1 January 1993 is
    Member State or in a third country to place the relevant               already under active examination in another Member
    medicinal product on the market, together with a list of               State, the former Member State may decide to suspend
    those Member States in which an application for                        the detailed examination of the application in order to
    authorization submitted in accordance with this                        await the assessment report prepared by the first
    Directive is under examination and copies of the                       Member State in accordance with Article 4b.
    summary of product characteristics proposed by the
    applicant in accordance with Article 4a or approved by                 The Member State concerned shall inform the first
    the competent authorities in accordance with Article 4b,               Member State and the applicant of its Decision to
    as appropriate, in respect of each Member State                        suspend detailed examination of the application in
    concerned. Details of any Decision to refuse                           question. As soon as it has completed the examination of
    authorization, whether in the Community or a third                     the application and reached a Decision, the first Member
    country and the reasons for that Decision.                             State shall forward a copy of its assessment report to the
                                                                           Member State concerned.
    This information         shall   be    updated     at  regular
    intervals.'                                                            Within 90 days of the receipt of the assessment report,
                                                                           the Member State concerned shall recognize the Decision
3. Article 4b is replaced by the following:                                of the first Member State. However, if the Member State
                                                                           concerned considers that there are serious grounds for
    'Article 4b                                                            supposing that the authorization of the medicinal
                                                                           product may present a risk to public health, it shall
    When the marketing authorization referred to in
                                                                           inform the first Member State, the Committee for
    Article 3 is issued, the person responsible for placing that
                                                                           Proprietary Medicinal Products and the applicant within
    product on the market shall be informed, by the
                                                                           the time limit referred to above, stating its reason in
    competent authorities of the Member State concerned, of
                                                                           detail, and apply the procedures laid down in Chapter III
    the summary of the product characteristics as approved
                                                                           of Directive 7 5 / 3 1 9 / E E C
    by them. The competent authorities shall take all
    necessary measures to ensure that the information given
    in the summary is in conformity with that accepted when             6. The following Article 7a is inserted:
    the marketing authorization is issued or subsequently.                 'Article 7a
    The competent authorities shall forthwith forward a
    copy of the summary to the European Agency for the                     1.     With effect from 1 January 1996, where a Member
    Evaluation of Medicinal Products established by Council                State is informed in accordance with point 11 of Article 4
    Regulation (EEC) No . . . / . . (*)                                    (2) that another Member State has authorized a
 ---pagebreak---  No C 330/20                               Official Journal of the European Communities                                      31. 12. 90
     medicinal product which is the subject of an application         1. Chapter III is replaced by the following:
     for authorization in the Member State concerned, that
     Member State shall forthwith request the authorities of
     the Member State which has granted the authorization of              'CHAPTER III
     the Member State which has granted the authorization to
     forward to it the assessment report referred to in                   Committee for Proprietary Medicinal Products
     Article 4b (2). Within 90 days of the receipt of the
     assessment report, the competent authorities of the
                                                                          Article 8
     Member State concerned shall recognize the
     authorization granted by the other Member State.
                                                                           1.    In order to facilitate the adoption of common
     2.     Notwithstanding paragraph 1, if the Member                    Decisions by Member States on the authorization of
     State concerned considers that there are serious grounds             medicinal products for human use on the basis of the
     for supposing that the authorization of the medicinal                scientific criteria of quality, safety and efficacy, and to
     product may present a risk to public health, it shall                achieve thereby the free movement of medicinal
     inform the Member State which granted the initial                    products, within the Community, a Committee for
     authorization, any other Member States concerned by                  Proprietary Medicinal Products, hereinafter referred to
     the application, and the Committee for Proprietary                   as 'the Committee', is hereby set up. The Committee shall
     Medicinal Products and the applicant within the time                 be attached to the European Agency for the Evaluation
     limit referred to in paragraph 1, stating its reasons in             of Medicinal Products established by Council Regulation
     detail, and apply the procedures laid down in Chapter III            (EEC) No . . . / . . . ( * ) , hereinafter referred to as the
     of Directive 7 5 / 3 1 9 / E E C                                     Agency.
 7. Article 9a is replaced by the following:                              2.     In addition to the other responsibilities conferred
                                                                          upon it by Community law, the Committee shall
     'Article 9a
                                                                          examine any question relating to the grant, amendment,
    After an authorization has been issued, the person                    suspension or withdrawal of authorization for a
    responsible for placing the product on the market must,               medicinal product which is submitted to it in accordance
    in respect of the methods of production and control                   with the provisions of this Directive.
    provided for in points 4 and 7 of Article 4 (2), take
     account of technical and scientific progress and                     3.     The Committee shall adopt its own rules of
    introduce any changes that may be required to enable the             procedure.
    medicinal product to be manufactured and checked by
    means of generally accepted scientific methods. These
    changes must be accepted by the competent authorities of             Article 9
    the Member State concerned.'
                                                                          1.     In order to obtain the recognition in one or more of
8. Article 10 is replaced by the following:                              the Member States of an authorization issued by a
                                                                         Member State in accordance with Article 3 of Directive
     'Article 10                                                          65/65/EEC, the holder of the authorization shall
                                                                         submit an application to the competent authorities of the
     1.     Authorization shall be valid for five years and shall        Member State or Member States concerned, together
    be renewable for five-year periods, on application by the            with the information and particulars referred to in
    holder at least three months before the expiry date.                 Articles 4 , 4 a and 4b of Directive 65/65/EEC. He shall
    2.      In exceptional circumstances, and following                  testify to the identity of the dossier with that accepted by
    consultation with the applicant, an authorization may be             the first Member State, or shall identify any additions or
    granted subject to such conditions as appear necessary to            modifications it may contain. In the latter case, he shall
    ensure the protection of public health, including specific           certify that the summary of product characteristics
    obligations to conduct further studies following the                 proposed by him in accordance with Article 4a of
    granting of authorization and specific obligations in                Directive 65/65/EEC is identical to that accepted by the
    respect of the reporting of adverse reactions to the                 first Member State in accordance with Article 4b of
    medicinal product.'                                                  Directive 65 / 65 /EEC. Moreover, he shall certify that all
                                                                         the dossiers filed as part of this procedure are
                                                                         identical.
                             Article 2
                                                                         2.      The holder of the marketing authorization shall
                                                                         notify the Committee of this application, inform it of the
In Directive 75/318/EEC, the Committee referred to in
                                                                         Member States concerned and of the dates of submission
Article 2b is hereby renamed 'the Standing Committee on
                                                                         of the application and send it a copy of the authorization
Medicinal Products for Human Use'.
                                                                         granted by the first Member State. He shall also send the
                                                                         Committee copies of any marketing authorization which
                                                                         may have been granted by the other Member States in
                             Article 3                                   respect of the product concerned, and shall indicate
                                                                         whether any application for authorization is currently
Directive 75/319/EEC is hereby amended as follows:                       under consideration in any Member States.
 ---pagebreak--- 31. 12. 90                                 Official Journal of the European Communities                                No C 330/21
    3.     The holder of the authorization shall also inform             made for marketing authorization for a particular
    the Member State which granted the initial authorization             medicinal product, and Member States have adopted
    that an application is being made in accordance with this            divergent Decisions concerning the authorization of the
    Directive and shall notify it of any additions to the                medicinal product, or its suspension or withdrawal from
    original dossier; that Member State may require the                  the market, any Member State, or the Commission, or
    applicant to provide it with all the particulars and                 the person responsible for marketing may refer the
    documents necessary to enable it to check the identify of            matter to the Committee for application of the procedure
    the dossiers filed with the dossiers on which it took its            laid down in Article 13.
    Decision. In addition that Member State shall forward to
    the Member State or Member States concerned by the                   The Member State concerned, the person responsible for
    application a copy of the assessment report established in           marketing or the Commission shall clearly identify the
    accordance with the second paragraph of Article 4b of                question which is referred to the Committee for
    Directive 65/65/EEC.                                                 consideration and, if necessary, shall inform the person
                                                                         responsible for marketing.
    4.     Each Member State concerned shall recognize the
    marketing authorization granted by the first Member                  The Member States and the person responsible for
    State within 90 days of receipt of the application. It shall         marketing shall forward to the Committee all available
    inform the Member State which granted the initial                    information relating to the matter in question.
    authorization, the other Member States concerned by the
    application, the Committee, and the person responsible
    for marketing thereof.                                               Article 12
                                                                         The Member States or the Commission may, in specific
    Article 10                                                           cases where the interests of the Community are involved,
                                                                         refer the matter to the Committee for the application of
    1.     Notwithstanding Article 9 (4), where a Member                 the procedure laid down in Article 13 before reaching a
    State considers that there are serious grounds for                   decision on a request for a marketing authorization or on
    supposing that the authorization of the medicinal                    the suspension or revocation of an authorization, or on
    product concerned may present a risk to public health, it            any other amendment to the terms of a marketing
    shall forthwith inform the applicant, the Member State               authorization which appears necessary, in particular to
    which granted the initial authorization, any other                   take account of the information collected in accordance
    Member States concerned by the application and the                   with Chapter Va of this Directive.
    Committee. The Member State shall state its reasons in
    detail and shall indicate what action may be necessary to            The Member State concerned or the Commission shall
    correct any defect in the application.                               clearly identify the questions which is referred to the
                                                                         Committee for consideration and shall inform the person
    2.     All the Member States concerned shall use their               responsible for marketing.
    best endeavours to reach agreement on the action to be
    taken in respect of the application. They shall provide the          The Member States and the person responsible for
    applicant with the possibility to make his point of view             marketing shall forward to the Committee all available
    known orally or in writing. However, if within 60 days               information relating to the matter in question.
    of the expiry of the time limit referred to in Article 9(4),
    the Member States have not been able to reach agreement
    they shall forthwith refer the matter to the Committee for           Article 13
    the application of the procedure laid down in
    Article 13.                                                           1.    When reference is made to the procedure described
                                                                         in this Article, the Committee shall consider the matter
    3.     Within the time limit referred to in paragraph 2,             concerned and issue a reasoned opinion within 90 days of
    the Member States concerned shall provide the                        the date on which the matter was referred to it.
    Committee with a detailed statement of the matters on
    which they have been unable to reach agreement and the               In case of urgency, on a proposal from its chairman, the
    reasons for their disagreement. A copy of this                       Committee may agree to impose a shorter deadline.
    information shall be provided to the applicant.
                                                                         2.     In order to consider the matter, the Committee
    4.     As soon as he is informed that the matter has been            may appoint one of its members to act as rapporteur. The
    referred to the Committee, the applicant shall forthwith             Committee may also appoint individual experts to advise
    forward to the Committee a copy of the information and               it on specific questions. When appointing experts, the
    particular referred to in Article 9 (1).                             Committee shall define their tasks and specify the time
                                                                         limit for the completion of these tasks.
    Article 11                                                           3.     In the cases referred to in Article 10 and 11, before
                                                                         issuing its opinion, the Committee shall provide the
    If several applications submitted in accordance with                 person responsible for marketing with an opportunity to
    Articles 4 and 4a of Directive 65/65/EEC have been                   present written or oral explanations.
 ---pagebreak--- ^oC330B22                                     COfficial journal of the European Communities                                                31.12.^0
   In the case referred to in A r t i c l e d the person                            criteria laid down in Directive . . . g . . B ^ C
   responsiblefor placing t h e m e d i c i n a l p r o d u c t o n t h e           concerning the legal status for the supply of
   market may he asked to explain himself orally or in                              medicinal products for human use^
   writing.
                                                                             ^      the draft te^t of the labelling and package leaflet,
                                                                                    proposed by the applicant presented in accordance
   If it considers it appropriate, the Committee may invite                         with D i r e c t i v e . . . B . , . B L ^ C on the labelling of
   any other person to provide information relating to the                          medicinal products for human use and on package
   matter before itD                                                                leaflets.
   ^beCommitteemaysuspendthetimelimitreferredtoin
   paragraphiinordertoallowthe person responsible for
   marketing to prepare explanations'
                                                                              i.       Within 30 days ofthe receipt of the opinion ofthe
                                                                             Committee,the Commission shall prepareadraft of the
   ^.      Where the opinion of the Committee is that^                       Decision to be taken in respect ofthe application taking
                                                                             into account the objectives of Community policies and
   — the application does not satisfy the criteria for                       considering all relevant information. In the event o f a
        authorisation set out in this Directive, or                          draft Decision which envisages the granting of a
                                                                             marketing authorisation, the documents referred to in
   — the summary of product characteristics proposed by                      points ^ , d ^ a n d ^ o f Article 1 3 ^ s h a l l be annexed.
        the applicant in accordance with Article ^a of                       I^he Commission shall transmitthe draft Decision to the
        Directive 6 ^ B 6 ^ L ^ C should be amended, or                      member states and to the applicant.
   — thelabellingorpackageleafletoftheproductisnotin
                                                                              .The Commission shall explain in detail the reasons for
        compliance with D i r e c t i v e . . g . . ^ ^ C , o r
                                                                             any differences between the draft Decision and the
                                                                             opinion of the Committee.
   — the authorisation           should      granted     subject      to
        conditions, or
                                                                             2.        I^he Commission shall adopt the Decision to be
   — an existing marketing authorisation should be                           takeninrespectoftheapplication unless, within30days,
        suspended amended or withdrawn,                                      ithasreceivedareasonedrequestfroma^iember^tateto
                                                                             reconsider the matter. Lhe member ^tate concerned
   theAgencyshallforthwithinformthepersonresponsible                         s h a l l a l s o t r a n s m i t a c o p y o f its request to the other
   for marketing. Within t o d a y s of the receiptof the                    member states and the applicant within the same time
   opinion, the person responsible for marketing may                         limit.
   provide written notice to the Agency that he wishes to
   appeal.Within 60 days of the receipt ofthe grounds for                    3.        Within the time limit referred to in paragraph 2,
   appeal,theCommitteeshallconsiderwhetheritsopinion                         the applicant may submit written observations on the
   should be revised, and the reasons for the conclusions                    draft Decision for consideration by the commission.
   reached on the appeal shall be annexed to the assessment
   report referred to in p a r a g r a p h s
                                                                             ^.        l^he Commission shall examine any reasoned
                                                                             request received in accordance with paragraph 2, in
   ^       Within 30 days of its adoption, the Agency shall                  consultation with the Agency, and after consideration of
   forward the final opinion of the Committee to the                         any further observations submitted by the applicant.
   Commission, the member states and the person
   responsible for marketing together with a report,                         If the Commission considers that the request raises
   describing the assessment of the medicinal product and                    questions of ascientific or technicalnaturerequiring
   the reasons for its conclusions.                                          further examination, it may remit thematter to the
                                                                             Agency.In this case the Committee shall giveasecond
                                                                             opinion withinatime limit of60days.Within30daysof
   In the event of an opinion in favour of grantingor                        the receipt of the opinion, the Commission shall adopt
   maintaining an authorisation to market the medicinal                      the Decision to be taken in respect of the application.
   productconcemed, the followingdocuments shall be
   annexed to the opinions
                                                                             C^therwisetheDecisionshallbetakeninaccordancewith
   ^d adraft summary of the product characteristics,as                       theprocedurelaiddowninArticle2band2cofDirective
         referred to in Article ^a of Directive 6 ^ B 6 ^ ^ C ^              ^^31^E^C
   ^     details of any conditions or restrictions which                     ^.        ADecisionadoptedin accordance with thisArticle
         should be imposed on the supply or use of the                       shall beaddressedtothe^iember^tatesconcemedbythe
         medicinal product concerned, included tbe                           matter and to thepersonresponsibleformarketing.^fbe
         conditions under which the medicinal product may                    ^viember^tates shall either grant orwithdrawmarketing
         be made available to patients, having regard to the                 authorisation,or make any adjustment to the terms ofa
 ---pagebreak--- 31. 12. 90                                Official Journal of the European Communities                               No C 330/23
    marketing authorization which may be necessary to                    made by the Community with the exporting country to
     comply with the Decision within 30 days of its                      ensure that the manufacturer of the medicinal product
     notification. They shall inform the Commission and the              applies standards of good manufacturing practice at least
     Committee thereof.                                                  equivalent to those laid down by the Community and to
                                                                         ensure that the controls referred to under (b) have been
    Article 15                                                           carried out in the exporting country, the qualified person
     Any application by the person responsible for marketing             may be relieved of responsibility for those controls.'
     to amend the terms of a marketing authorization which
     has granted in accordance with the provisions of this
     Chapter shall be submitted to all the Member States
     which have previously authorized the medicinal product          3. The following Chapter Va is inserted after Article 29:
     concerned.
     The Agency shall, in consultation with the Commission,
     adopt appropriate arrangements for the examination by              'CHAPTER Va
    the Committee of amendments or variations to a
    marketing authorization which has been granted in
     accordance with the provisions of this Chapter.                     Pharmacovigilance
    The procedures laid down in Articles 13 and 14 shall
     apply by analogy to variations and amendments of
    marketing authorizations.                                           Article 29a
    Article 15a
     1.    Where a Member State considers that the                      In order to ensure the adoption of appropriate regulatory
    amendment of the terms of a marketing authorization                 decisions concerning the continued authorization of
    which has been granted in accordance with the                       medicinal products within the Community, having
    provisions of this Chapter or its suspension or                     regard to information obtained about adverse reactions
    withdrawal is necessary, the Member State concerned                 to medicinal products under practical conditions of use,
    shall forthwith refer the matter to the Committee for the           the Member States shall establish a pharmacovigilance
    application of the procedures laid down in Articles 13              system for collecting information about adverse
    and 14.                                                             reactions to medicinal products in human beings and for
    2.     In exceptional cases, where action is urgently               the scientific evaluation of such information.
    necessary to protect public health, until a definitive
    decision is adopted, a Member State may suspend the use
    of the medicinal product concerned on its territory. It
    shall inform the Commission no later than the following             Article 29b
    working day of the reasons for its action.
    Article 15b                                                         For the purpose of this Directive, the following
                                                                        definitions shall apply:
    Articles 15 and 15a shall apply by analogy to medicinal
    products authorized by Member States following an
                                                                        — 'adverse reaction' shall mean a reaction which is
    opinion of the Committee given in accordance with
                                                                            noxious and unintended and which occurs at doses
    Article 4 of Directive 87/22/EEC before 1 January
                                                                            normally used in man for the prophylaxis, diagnosis
    1993.
                                                                            or therapy of disease or for the modification of
    Article 15c                                                             physiological function,
    1.     The Agency shall publish an annual report on the
    operation of the procedures laid down in this                       — 'serious adverse reaction' shall mean an adverse
    Chapter.                                                                reaction which is fatal, life-threatening, disabling,
                                                                            incapacitating, or which results in hospizalization or
    2.     Within six years of the date referred to in the first            prolonged hospitalization.
    subparagraph of Article 4 ( 1 ) , the Commission shall
    publish a detailed review of the operation of the
    procedures laid down in this chapter and shall propose
    any amendments which may be necessary to improve the                Article 29c
    operation of these procedures.
    The Council shall decide on the Commission proposal
                                                                        The person responsible for marketing shall have
    within one year of its submission.
                                                                        permanently and continuously at his disposal a person
    (*) O J N o L . . . '                                               responsible for pharmacovigilance. This person shall be
                                                                        responsible for:
2. The third subparagraph of Article 22 (1) is replaced by
   the following:
                                                                        (a) the establishment and maintenance of a system
   'In the case of medicinal products imported from a third                  which ensures that information about all adverse
   country, where appropriate arrangements have been                         reactions which are reported to the personnel of the
 ---pagebreak--- No C 330/24                              Official Journal of the European Communities                                     31. 12. 90
        company, including its sales personnel and                      Article 29f
        medicinal representatives, is collected and collated
        at a single point;                                              The Member States shall ensure that, report of serious
                                                                        adverse reactions are brought to the attention of the
   (b) the preparation and submission to the competent                  Agency and the person responsible for marketing within
        authorities of the reports referred to in Article 29d,          15 days of their receipt.
        in such form as may be laid down by those
        authorities;                                                    Article 29g
   (c) ensuring that any request from the competent                     In order to facilitate the exchange of information about
        authority for the provision of additional                       pharmacovigilance within the Community, the Agency
        information necessary for the evaluation of the                 shall, in consultation with Member States, the
        benefits and risks of a medicinal product is                    Commission and interested parties, draw up detailed
        answered fully and promptly, including the                      guidance on the collection, verification and presentation
        provision of information about the volume of sales              of adverse reaction reports.
        or prescriptions for the medicinal product
        concerned, where relevant.
                                                                        Article 29b
   Article 29d                                                          Where as a result of the evaluation of adverse reaction
                                                                        reports, a Member State is considering amending the
   1.     The person responsible for marketing shall be                 terms of a marketing authorization or its suspensions or
   required to record and to report all suspected serious               withdrawal, it shall forthwith inform the Agency.
   adverse reactions which are brought to his attention by a
   qualified health care professional to the competent                  In case of urgency, the Member State concerned may
   authorities within 15 days of their receipt.                         suspend the marketing of a medicinal product, provided
                                                                        the Agency is informed at the latest on the following
                                                                        working day.'
   2.     In addition, the person responsible for marketing
   shall be required to maintain detailed records of all other
   adverse reactions which are reported to him by a
   qualified health care professional. Unless other
   requirements have been laid down as a condition of the                                       Article 4
   granting of authorization, these records shall be
   submitted to the competent authorities immediately               Member States shall take all appropriate measures to comply
   upon request or at least every six month during the first        with the provisions of this Directive, with the exception of
   two years following authorization, and once a year for           Article 1 (6), before 1 January 1993. They shall forthwith
   the following three years. Thereafter, the records shall be      inform the Commission thereof.
   submitted at five yearly intervals together with the
   application for renewal of the authorization, or
                                                                    Member States shall take all appropriate measures to comply
   immediately upon request.
                                                                    with Article 1 (6) of this Directive before 1 January 1996.
                                                                    They shall forthwith inform the Commission thereof.
   Article 29e
                                                                    When Member States adopt these provisions, these shall
   The Member States shall take all appropriate measures            contain a reference to this Directive or shall be accompanied
   to encourage doctors and other health care professionals         by such reference at the time of their official publication. The
   to report adverse reactions to the competent                     procedure for such reference shall be adopted by Member
   authority.                                                       States.
   The Member States may impose specific requirements on
   medical practitioners, in particular in respect of the
   reporting of serious or unexpected adverse reactions, or                                     Article 5
   where such reporting is a condition of the marketing
   authorization.                                                   This Directive is addressed to the Member States.