CELEX: 51990PC0283(01)
Language: en
Date: 1990-11-14
Title: PROPOSAL FOR A COUNCIL REGULATION ( EEC ) LAYING DOWN COMMUNITY PROCEDURES FOR THE AUTHORIZATION AND SUPERVISION OF MEDICINAL PRODUCTS FOR HUMAN AND VETERINARY USE AND ESTABLISHING A EUROPEAN AGENCY FOR THE EVALUATION OF MEDICINAL PRODUCTS

31. 12. 90                              Official Journal of the European Communities                                 No C 330/1
                                                                II
                                                        (Preparatory Acts)
                                                    COMMISSION
              Proposal for a Council Regulation (EEC) laying down Community procedures for the authorization
              and supervision of medicinal products for human and veterinary use and establishing a European
                                        Agency for the Evaluation of Medicinal Products
                                                 COM(90) 283 final — SYN 309
                                     (Submitted by the Commission on 14 November 1990)
                                                          (90/C 330/01)
 THE COUNCIL OF THE EUROPEAN COMMUNITIES,                           Whereas the experience acquired as a result of Directive
                                                                    87/22/EEC has shown that it is necessary to establish a
                                                                    centralized Community authorization procedure for
 Having regard to the Treaty establishing the European              technologically advanced medicinal products, in particular
 Economic Community, and in particular Article 100a                 those derived from biotechnology; whereas this procedure
 thereof,                                                           should also be available to persons responsible for marketing
                                                                    medicinal products containing new active substances which
                                                                    are intended for use in human beings or in food-producing
 Having regard to the proposal from the Commission,                 animals;
 In cooperation with the European Parliament,                       Whereas in the interests of public health it is necessary that
                                                                    decisions on the authorization of such medicinal products
                                                                    should be based on the objective scientific criteria of the
Having regard to the opinion of the Economic and Social             quality, the safety and the efficacy of the medicinal product
 Committee,                                                         concerned to the exclusion of economic or other
                                                                    considerations; whereas, however, Member States should
                                                                    exceptionally be able to prohibit the use on their territory of
Whereas it is important to adopt measures with the aim of
                                                                    medicinal products for human use which infringe objectively
progressively establishing the internal market over a period
                                                                    defined concepts of public order or public morality; whereas
expiring on 31 December 1992; whereas the internal market
                                                                    moreover a veterinary medicinal product may not be
shall comprise an area without internal frontiers in which the
                                                                    authorized by the Community if its use would contravene the
free movement of goods, persons, services and capital is
                                                                    rules and objectives laid down by the Community within the
ensured;
                                                                    framework of the common agricultural policy;
Whereas Council Directive 87/22/EEC of 22 December                  Whereas, in the case of medicinal products for human use,
1986 on the approximation of national measures relating to          the criteria of quality, safety and efficacy have been
the placing on the market of high technology medicinal              extensively harmonized by Council Directive 65/65/EEC of
products particularly those derived from biotechnology ( ! )        26 January 1965 on the approximation of provisions laid
has established a Community mechanism for concertation,             down by law, regulation or administrative action relating to
prior to any national decision relating to a high-technology        medicinal products ( 2 ), as last amended by Directive
medicinal product, with a view to arriving at uniform               . . . / . . ./EEC ( 3 ), and   Second     Council    Directive
decisions throughout the Community;
                                                                    (2) OJ No 22, 9. 2. 1965, p. 369/65.
(») OJ No L 15, 17. 1. 1987, p. 38.                                 H OJ No L . . . . . . .
 ---pagebreak---  No C 330/2                                   Official Journal of the European Communities                                     31. 12. 90
 75/319/EEC of 20 May 1975 on the approximation of                       resolving disagreements between Member States about the
 provisions laid down by law, regulation and administrative               quality, safety and efficacy of medicinal products;
  action relating to proprietary medicinal products ('), as last
 amended by Directive . . . / . . ./EEC ( 2 ), and by Council
                                                                         Whereas it is therefore necessary to establish a European
 Directive 75/318/EEC of 20 May 1975 on the
                                                                         Agency for the Evaluation of Medicinal Products ('the
 approximation of the laws of the Member States relating to
                                                                         Agency');
 analytical, pharmaco-toxicological and clinical standards
 and protocols in respect of the testing of medicinal
 products ( 3 ),         as     last amended       by     Directive      Whereas the primary task of the Agency should be to provide
  . . . / . . ./EEC( 4 );                                                scientific advice of the highest possible quality to the
                                                                         Community Institutions and the Member States for the
                                                                         exercise of the powers conferred upon them by Community
 Whereas in the case of veterinary medicinal products, the               legislation in the field of medicinal products in relation to the
 same results have been achieved by Council Directive                    authorization and supervision of medicinal products;
 81/851/EEC of 28 September 1981 on the approximation
 of the laws of the Member States relating to veterinary
 medicinal products ( 5 ), as last amended by Directive                  Whereas it is desirable to ensure close cooperation between
  . . . / . . ./EEC ( 6 ), and by Council Directive 81/852/EEC           the Agency and scientists working within the Member
 of 28 September 1981 on the approximation of the laws of                States;
 the          Member         States  relating    to      analytical,
 pharmaco-toxicological and clinical standards and protocols             Whereas, therefore, the exclusive responsibility for
 in respect of the testing of veterinary medicinal products (7)          preparing the opinions of the Agency on all matters relating
 as last amended by Directive . . . / . . ./EEC (8);                     to medicinal products for human use should be entrusted to
                                                                         the Committee for Proprietary Medicinal Products created
                                                                         by Second Council Directive 75/319/EEC; whereas, in
 Whereas the same criteria must be applied to medicinal                  respect of veterinary medicinal products this responsibility
 products which are to be authorized by the Community;                   should be entrusted to the Committee for Veterinary
                                                                         Medicinal Products created by Council Directive
 Whereas only after a single scientific evaluation of the highest        81/851/EEC;
 possible quality of all the benefits and risks of technologically
 advanced medicinal products, should a marketing                         Whereas the establishment of the Agency will make it
 authorization be granted by the Community by a rapid                    possible to reinforce the scientific role and independence of
 procedure ensuring close cooperation between the                        these two Committees, in particular through the
 Commission and Member States;                                           establishment of a permanent technical and administrative
                                                                         secretariat;
 Whereas Council Directive . . . / . . ./EEC has provided that
 in the event of a disagreement between Member States about              Whereas each Committee should be able to request the
 the quality, safety or efficacy of a medicinal product which is         opinion of a Scientific Council consisting of scientists of
 the subject of the decentralized Community authorization                internationally recognized standing on difficult questions of
procedure, the matter should be resolved by a binding                    a general scientific or ethical nature relating to the
 Community decision following a scientific evaluation of the             authorization of medicinal products;
 issues involved within a European Medicines Evaluation
 Agency; whereas similar provisions have been laid down in
                                                                         Whereas it is also necessary to make provision for the
respect of veterinary medicinal products by Council Directive
                                                                         supervision of medicinal products which have been
 . . . / . . ./EEC;
                                                                         authorized by the Community, and in particular for the
                                                                         intensive monitoring of adverse reactions to those medicinal
Whereas the Community must be provided with the means to                products through Community pharmacovigilance activities
undertake a scientific evaluation of medicinal products                  in order to ensure the rapid withdrawal from the market of
which are presented for authorization in accordance with the             any medicinal product which presents an unacceptable level
centralized Community procedures; whereas, furthermore,                 of risk under normal conditions of use;
in order to achieve the effective harmonization of the
administrative decisions taken by Member States in relation             Whereas the Agency, working in close cooperation with the
to individual medicinal products which are presented for                Commission, should also be entrusted with the task of
authorization in accordance with decentralized procedures,              coordinating the discharge of the various supervisory
it is necessary to provide the Community with a means of                responsibilities of Member States and in particular
                                                                        monitoring the respect of good manufacturing practices,
(')    OJ No L 147, 9. 6. 1975, p. 13.                                  good laboratory practices and good clinical practices;
(*)    OJ No L . . . . . . .
(3)    OJ No L 147, 9. 6. 1975, p. 13.
(4)    OJ No L . . . . . . .                                            Whereas it is necessary to provide for the orderly
(5)    OJNoL317, 6. 11. 1981, p. 1.                                     introduction of Community procedures for the authorization
(6)    OJ No L . . . . . . .                                            of medicinal products alongside the national procedures of
(7)    OJ No L 317, 6. 11. 1981, p. 16.                                 the Member States which have already been extensively
(8)    OJ No L . . . . . . .                                            harmonized by Directives 65/65/EEC, 75/319/EEC and
 ---pagebreak---  31. 12. 90                                  Official Journal of the European Communities                                No C 330/3
 81 /851 /EEC; whereas it is therefore appropriate in the first                                     TITLE II
 instance to limit the obligation to use the new Community
 procedure to medicinal products which are produced by                  AUTHORIZATION AND SUPERVISION OF MEDICINAL
                                                                                         PRODUCTS FOR HUMAN USE
 means of specified biotechnological processes, and to make
 the procedure available on an optional basis only to
 high-technology medicinal products and to medicinal                                              Chapter 1
 products containing totally new active substances; whereas
 the scope of the Community procedures should be reviewed               Submission and examination of applications                  —
 in the light of experience at the latest six years after the entry                authorizations — renewal of authorization
 into force of this Regulation,
                                                                                                    Article 5
 HAS ADOPTED THIS REGULATION:                                           The Committee for Proprietary Medicinal Products
                                                                        established by Article 8 of Directive 75/319/EEC, in this
                                                                        title referred to as 'the Committee', shall be responsible for
                             TITLE I                                    formulating the opinion of the Agency on any question
                                                                        relating to the grant, amendment, suspension or withdrawal
                   DEFINITIONS AND SCOPE
                                                                        of an authorization to place a medicinal product for human
                                                                        use on the market arising in accordance with the provisions
                                                                        of this Regulation.
                             Article 1
 The objective of this Regulation is to lay down Community
 procedures for the authorization and supervision of                                                Article 6
 medicinal products for human and veterinary use and to
                                                                         1.     An application for authorization for a medicinal
 establish a European Agency for the Evaluation of Medicinal
                                                                        product for human use shall be accompanied by the
 Products.
                                                                        particulars and documents referred to in Articles 4 and 4a
                                                                        of Directive 65/65/EEC and Article 2 of Directive
                                                                        75/319/EEC.
                            Article 2
                                                                        2.      The application shall also be accompanied by the fee
 The definitions laid down in Article 1 of Directive
                                                                        payable to the Agency for the examination of the
 65/65/EEC and the definitions laid down in Article 1 (2) of            application.
 Directive 81/851/EEC shall apply to this Regulation.
                                                                        3.      The Agency shall ensure that the opinion of the
                                                                        Committee is given within 210 days of the receipt of a valid
                            Article 3                                   application.
 1.    No medicinal product which is referred to in Part A of           4.      The Agency shall, in consultation with Member States,
the Annex shall be placed on the market within the                      the Commission and interested parties, draw up detailed
Community unless authorization has been granted by the                  guidance on the form in which applications for authorization
Community in accordance with the provisions of this                     are to be presented.
Regulation.
2.     The person responsible for marketing a medicinal                                             Article 7
product referred to in Part B of the Annex may request that
authorization to place the medicinal product on the market              In order to prepare its opinion, the Committee:
be granted by the Community in accordance with the
                                                                       (a) shall verify that the particulars and documents
provisions of this Regulation.
                                                                              submitted in accordance with Article 6 comply with the
                                                                              requirements of Directives 65/65/EEC, 75/318/EEC
                                                                              and 75/319/EEC, and examine whether the conditions
                            Article 4
                                                                              for issuing an authorization to place the medicinal
1.     In order to obtain the authorization referred to in                    product on the market specified in this Regulation are
Article 3, the person responsible for marketing shall submit                  satisfied;
an application to the European Agency for the Evaluation of            (b) may request a laboratory designated for this purpose to
Medicinal Products, hereinafter referred to as 'the                          test the medicinal product, its starting materials, and if
Agency'.                                                                      need be, its intermediate products or other constituent
                                                                              materials in order to ensure that the control methods
2.     The Community shall issue and supervise                               employed by the manufacturer and described in the
authorizations to place medicinal products for human use on                  application documents are satisfactory;
the market in accordance with Title II.
                                                                       (c) may, where appropriate, request the applicant to
3.     The Community shall issue and supervise                               supplement the particulars accompanying the
authorizations to place veterinary medicinal products on the                 application. Where the Committee avails itself of this
market in accordance with Title HI.                                          option, the time limit laid down in Article 6 shall be
 ---pagebreak--- No C 330/4                                 Official Journal of the European Communities                                     31. 12. 90
     suspended until such time as the supplementary                   3.      In the event of an opinion in favour of granting
     information requested has been provided. Likewise, this          authorization to market the medicinal product concerned,
     time limit shall be suspended for the time allowed to the        the following documents shall be annexed to the opinion:
     applicant to prepare oral or written explanations.
                                                                      (a) a draft summary of the product characteristics, as
                                                                            referred to in Article 4a of Directive 65/65/EEC;
                                                                      (b) details of any conditions or restrictions which should be
                            Article 8                                       imposed on the supply or use of the medicinal product
                                                                            concerned, including the conditions under which the
1.     Upon receipt of a written request from the Committee,                medicinal product may be made available to patients,
a Member State shall forward the information necessary to                   having regard to the criteria laid down in Council
verify that the manufacturer of a medicinal product or the                  Directive . . . / . . ./EEC concerning the legal status for
importer from a third country is able to manufacture the                    the supply of medicinal products for human use;
medicinal product concerned and/or carry out the necessary
control tests in accordance with the particulars and                  (c) the draft text of the labelling and package leaflet
documents supplied in accordance with Article 6.                            proposed by the applicant, presented in accordance with
                                                                            Council Directive . . . / . . ./EEC on the labelling of
                                                                            medicinal products for human use and on package
2.     Where it considers it necessary in order to complete its             leaflets.
examination of an application, the Committee may request
the applicant to submit to an inspection of the manufacturing
site of the medicinal product concerned. The inspection,
which shall be completed within the time limit referred to in
Article 6, shall be undertaken by qualified pharmaceutical                                           Article 10
inspectors from the Member States who may, if appropriate,
be accompanied by an inspector from the Agency.                       1.      Within 30 days of the receipt of the opinion, the
                                                                      Commission shall prepare a draft of the Decision to be taken
                                                                      in respect of the application, taking into account the
                                                                      objectives of Community policies and considering all the
                                                                      relevant information. In the event of a draft Decision which
                            Article 9                                 envisages the granting of a marketing authorization, the
                                                                      documents referred to in points (a), (b) and (c) of Article 9 (3)
1.     Where the opinion of the Committee is that:                    shall be annexed. The Commission shall transmit the draft
                                                                      Decision to the Member States and to the applicant.
— the application does not satisfy the criteria              for
    authorization set out in this Regulation, or                      The Commission shall explain in detail the reasons for any
                                                                      differences between the draft Decision and the opinion of the
— the summary of product characteristics proposed by the              Committee.
    applicant in accordance with Article 6 should be
    amended, or
                                                                      2.      The Commission shall adopt the Decision to be taken
— the labelling or package insert of the product is not in            in respect of the application unless, within 30 days, it has
    compliance with Directive . . . / . . ./EEC, or                   received a reasoned request from a Member State to
                                                                      reconsider the matter. The Member State concerned shall
— the authorization should be granted subject to the                  also transmit a copy of its request to the other Member States
    conditions provided for in Article 13 (2),                        and the applicant within the same time limit.
the Agency shall forthwith inform the applicant.                      3.      Within the time limit referred to in paragraph 2, the
                                                                      applicant may submit written observations on the draft
Within 15 days of the receipt of the opinion, the applicant           Decision for consideration by the Commission.
may provide written notice to the Agency that he wishes to
appeal. Within 60 days of the receipt of the grounds for              4.      The Commission        shall examine any reasoned request
appeal, the Committee shall consider whether its opinion              received in accordance         with paragraph 2, in consultation
should be revised, and the reasons for the conclusions                with the Agency, and          after consideration of any further
reached on the appeal shall be annexed to the assessment              observations submitted        by the applicant.
report referred to in paragraph 2.
                                                                      If the Commission considers that the request raises questions
2.     Within 30 days of its adoption, the Agency shall               of a scientific or technical nature requiring further
forward the final opinion of the Committee to the                     examination, it may remit the matter to the Agency. In this
Commission, the Member States and the applicant together              case the Committee shall give a second opinion within a time
with a report describing the assessment of the medicinal              limit of 60 days. Within 30 days of the receipt of the opinion,
product by the Committee and stating the reasons for its              the Commission shall adopt the Decision to be taken in
conclusions.                                                          respect of the application.
 ---pagebreak--- 31. 12. 90                                Official Journal of the European Communities                                 No C 330/5
Otherwise the Decision shall be taken in accordance with the         Regulation shall benefit from the 10-year period of
 procedure laid down in Article 2 b and 2 c of Directive             protection referred to in point 8 of Article 4 (2) of Directive
 75/318/EEC.                                                         65/65/EEC.
                           Article 11                                                           Article 14
 Without prejudice to other provisions of Community law,             The granting of authorization shall not diminish the general
the authorization provided for in Article 3 ahall be refused if,     civil and criminal liability in the Member States of the
 after verification of the information and particulars               manufacturer and, where applicable, of the person
 submitted in accordance with Article 6, it appears that the         responsible for placing the medicinal product on the
 quality, the safety or the efficacy of the medicinal product        market.
have not been adequately demonstrated by the applicant.
Authorization shall likewise be refused if the particulars and
documents provided by the applicant in accordance with
Article 6 of this Regulation are incorrect or if the labelling                                 Chapter 2
and package leaflets proposed by the applicant are not in
accordance with Directive . . . / . . ./EEC.                                           Supervision and sanctions
                           Article 12                                                           Article 15
 1.    Without prejudice to Article 6 of Directive                   1.     After an authorization has been issued, the person
65/65/EEC, a marketing authorization which has been                  responsible for placing the medicinal product on the market
granted in accordance with the procedure laid down in this           must, in respect of the methods of production and control
Regulation shall apply throughout the Community. It shall            provided for in points 4 and 7 of Article 4 (2) of Directive
confer the same rights and obligations in each of the Member         65/65/EEC, take account of technical and scientific
States as a marketing authorization granted by that Member           progress and introduce any changes that may be required to
State in accordance with Article 3 of Directive                      enable the medicinal product to be manufactured and
65/65/EEC.                                                           checked by means of generally accepted scientific methods.
                                                                     These changes must be approved in accordance with this
2.     The refusal of a Community marketing authorization            Regulation.
shall constitute a prohibition on the marketing of the
medicinal product concerned throughout the Community.                2.     The person responsible for marketing shall forthwith
                                                                     inform the Agency of any new information which might
3.     An announcement that authorization has been granted           entail the amendment of the particulars and documents
shall be published for information purposes in the Official          referred to in Article 6 or in the approved summary of the
Journal of the European Communities.                                 product characteristics. In particular the person responsible
                                                                     for marketing shall forthwith inform the Agency of any
4.     Upon request from any interested person, the Agency           prohibition or restriction imposed by the competent
shall make available a detailed summary of the evaluation of         authorities of any country in which the medicinal product is
the medicinal product by the Committee and the reasons for           marketed and of any other new information which might
its opinion in favour of granting authorization after deletion       influence the evaluation of the benefits and risks of the
of any information of a commercially confidential nature.            medicinal product concerned.
                                                                     3.     If the person responsible for marketing proposes to
                          Article 13                                 make any alteration to the information and particulars
                                                                     referred to in Article 6, he shall submit an application to the
                                                                     Agency.
1.     Authorization shall be valid for five years and shall be
renewable for five year periods, on application by the holder
at least three months before the expiry date.                        4.     The Agency shall, in consultation with the
                                                                     Commission, adopt appropriate arrangements for the
2.     In exceptional circumstances and              following       examination of amendments and variations to the terms of a
consultation with the applicant, an authorization may be             marketing authorization.
granted subject to such conditions as appear necessary to
ensure the protection of public health, including specific
obligations to conduct further studies following the granting                                   Article 16
of authorization and specific obligations in respect of the
reporting of adverse reactions to the medicinal product.            When a marketing authorization is granted in accordance
                                                                     with this Regulation, one or more of the Member States shall
3.     Medicinal products which have been authorized by the         act as the competent supervisory authorities to exercise the
Community in accordance with the provisions of this                 responsibilities referred to in Article 17.
 ---pagebreak--- No C 330/6                                  Official Journal of the European Communities                                    31. 12. 90
In the case of medicinal products manufactured within the              2.     The Commission shall in consultation with the Agency
Community, the supervisory authorities shall normally be               forthwith examine the reasons advanced by the Member
the competent authorities of the Member State or Member                State concerned. It may request the opinion of the Committee
States which have granted the manufacturing authorization              within a time limit to be determined by the Commission
provided for in Article 16 of Directive 75/319/EEC in                  having regard to the urgency of the matter. Whenever
respect of the manufacture of the medicinal product                    practicable, the person responsible for marketing shall be
concerned.                                                             invited to provide oral or written explanations.
                                                                       3.     The Commission shall prepare a draft of the Decision
In the case of medicinal products imported from third
                                                                       to be taken which shall be adopted in accordance with the
countries, the supervisory authorities shall be the competent
                                                                       procedure laid down in Article 10.
authorities of the Member States in which the controls
referred to in Article 22 (1) (b) of Directive 75 / 319 / EEC are
                                                                       However, where a Member State has invoked the provisions
carried out unless appropriate arrangements have been made
                                                                       of paragraph 4, the time limit provided for in Article 2 c (3)
between the Community and the exporting country to ensure
                                                                       of Directive 75/318/EEC shall be reduced to 15 calendar
that those controls are carried out in the exporting country
                                                                       days.
and that the manufacturer applies standards of good
manufacturing practice at least equivalent to those laid down
by the Community.                                                      4.     In exceptional cases, where action is urgently necessary
                                                                       to protect public health, a Member State may suspend the use
                                                                       on its territory of a medicinal product which has been
                                                                       authorized in accordance with this Regulation. It shall
                                                                       inform the Commission no later than the following working
                           Article 17                                  day of the reasons for its action. The Commission shall
                                                                       immediately consider the reasons given by the Member State
                                                                       in accordance with paragraph 2 and shall initiate the
1.     The supervisory authorities shall have responsibility
                                                                       procedure provided for in paragraph 3.
for verifying on behalf of the Community that the
manufacturer or the importer from third countries satisfies
                                                                       5.     A Member State which has adopted the suspensive
the requirements laid down in Chapter IV of Directive
                                                                       measures referred to in paragraph 4 may maintain them in
75/319/EEC, and for exercising supervision over persons
                                                                       force until such time as a definitive Decision has been reached
responsible for marketing medicinal products in accordance
                                                                       in accordance with the procedure laid down in
with Chapter V of Directive 75/319/EEC.
                                                                       paragraph 3.
2.     Upon receipt of a reasoned request by any Member
State, or on its own initiative, the Commission may request
the manufacturer or importer to submit to an inspection of
the manufacturing site of the medicinal product concerned,                                       Chapter 3
giving its reasons. The inspection shall be undertaken by
qualified pharmaceutical inspectors from the Member States                                   Pharmacovigilance
who may, if appropriate, be accompanied by an inspector
from the Agency. The report of the inspectors shall be made
available to the Commission, the Committee and the
applicant. In the case of an inspection conducted within the                                      Article 19
Community, the host Member State shall provide all the
practical support necessary to enable the inspectors to                For the purpose of this Chapter, the definitions given in
discharge their responsibilities.                                      Article 29 b of Directive 75/319/EEC shall apply.
                                                                                                  Article 20
                           Article 18
                                                                       The Agency, acting in close cooperation with the national
                                                                       pharmacovigilance centres established in accordance with
1.     Where the supervisory authorities or the competent
                                                                       Article 29 a of Directive 75/319/EEC, shall be responsible
authorities of any other Member State are of the opinion that
                                                                       for the collection and evaluation of information about
the manufacturer or importer from third countries is no
                                                                       adverse reactions to medicinal products which have been
longer fulfilling the obligations laid down in Chapter IV of
                                                                       authorized by the Community in accordance with this
Directive 75/319/EEC, they shall forthwith inform the
                                                                       Regulation.
Committee and the Commission, stating their reasons in
detail and indicating the course of action proposed.
                                                                       The competent authorities of the Member States and the
                                                                       person responsible for marketing shall ensure that all
The same shall apply where a Member State considers that               relevant information about adverse reactions to medicinal
one of the measures envisaged in Chapter V of Directive                products authorized in accordance with this Regulation are
75/319/EEC should be applied in respect of the medicinal               brought to the attention of the Agency in accordance with the
product concerned.                                                     provisions of this Regulation.
 ---pagebreak--- 31. 12. 90                                 Official Journal of the European Communities                                No C 330/7
                            Article 21                                                           Article 24
                                                                      The Agency shall, in consultation with Member States, the
The person responsible for marketing a medicinal product              Commission and interested parties, draw up detailed
authorized by the Community in accordance with the                    guidance on the collection, verification and presentation of
provisions of this Regulation shall have permanently and              adverse reaction reports.
continuously at his disposal a person responsible for
pharmacovigilance. This person shall be responsible for:
                                                                                                 Article 25
(a) the establishment and maintenance of a system which
      ensures that information about all adverse reactions            1.     The Agency shall publish an annual report on the
      which are reported to the personnel of the company,             operation of the procedures laid down in this Chapter.
      including     its    sales    personnel    and    medical
      representatives, is collected and collated so that it may       2.     Within six years of the entry into force of this
      be accessed at a single point within the Community;             Regulation, the Commission shall publish a detailed review
                                                                      of the operation of the procedures laid down in this Chapter
(b) the preparation and submission of the reports referred to         and shall propose any amendments which may be necessary
      in Article 22 to the competent authorities of the Member        to improve the operation of these procedures.
      States and the Agency in accordance with the
      requirements of this Regulation;                                The Council shall decide on the Commission proposal within
                                                                      one year.
(c) ensuring that any request for the provision of additional
      information necessary for the evaluation of the benefits
      and risks of a medicinal product is answered fully and
      promptly, including the provision of information about                                      TITLE III
      the volume of sales or prescriptions for the medicinal
      product concerned where relevant.                               AUTHORIZATION AND SUPERVISION OF VETERINARY
                                                                                         MEDICINAL PRODUCTS
                                                                                                Chapter 1
                             Article 22
                                                                      Submission and examination of applications                 —
                                                                                authorization — renewal of authorization
1.      The person responsible for marketing shall ensure that
all suspected serious adverse reactions to a medicinal product
authorized in accordance with the provisions of this                                             Article 26
Regulation which are brought to his attention by a qualified
health care professional, whether arising within the                  The Committee for Veterinary Medicinal Products
Community or a third country, are recorded and reported to            established by Article 16 of Directive 81/851/EEC, in this
the Agency within 15 days.                                            title referred to as 'the Committee', shall be responsible for
                                                                      formulating the opinion of the Agency on any question
2.      In addition, the person responsible for marketing shall       relating to the grant, amendment, suspension or withdrawal
be required to maintain detailed records of all other adverse         of an authorization to place a veterinary medicinal product
reactions arising within the Community which are reported             on the market arising in accordance with the provisions of
to him by a qualified health care professional. Unless other          this Regulation.
requirements have been laid down as a condition of the
granting of authorization by the Community, these records
shall be submitted to the Agency immediately upon request                                        Article 27
or at least every six months during the first two years
                                                                      1.      An application for authorization for a veterinary
following authorization and once a year for the following
                                                                      medicinal product shall be accompanied by the particulars
three years. Thereafter, the records shall be submitted at
five-yearly intervals together with the application for renewal       and documents referred to in Articles 5 , 5 a and 7 of
of the authorization, or immediately upon request.                    Directive 81/851/EEC.
                                                                      2.      The application shall also be accompanied by the fee
                                                                      payable to the Agency for the examination of the
                                                                      application.
                             Article 23
                                                                      3.      The Agency shall ensure that the opinion of the
                                                                      Committee is given within 210 days of the receipt of a valid
Each Member State shall report any suspected serious                  application.
adverse reaction arising within its territory to a medicinal
product authorized in accordance with this Regulation to the          4.      The Agency shall, in consultation with Member States,
Agency and the person responsible for marketing within 15             the Commission and interested parties, draw up detailed
days of receipt of a report from a qualified health care              guidance on the form in which applications for authorization
professional.                                                         are to be presented.
 ---pagebreak--- No C 330/8                                  Official Journal of the European Communities                                  31. 12. 90
                            Article 28                                                           Article 30
 In order to prepare its opinion, the Committee:                       1.     Where the opinion of the Committee is that:
 (a) shall verify that the particulars and documents                   — the application does not satisfy the criteria           for
      submitted in accordance with Article 27 comply with                  authorization set out in this Regulation, or
      the requirements of Directives 81/851/EEC and
      81/852/EEC, and examine whether the conditions for               — the summary of product characteristics proposed by the
      issuing an authorization to place the veterinary                     applicant in accordance with Article 27 should be
      medicinal product on the market specified in this                    amended, or
      Regulation are satisfied;
                                                                       — the labelling or package insert of the product is not in
 (b) may request a laboratory designated for this purpose to               compliance with Directive 81/851 /EEC, or
      test the veterinary medicinal product, its starting
      materials, and if need be, its intermediate products or          — the authorization should be granted subject to the
      other constituent materials in order to ensure that the              conditions provided for in Article 34 (2),
      control methods employed by the manufacturer and
      described in the application documents are                       the Agency shall forthwith inform the applicant.
      satisfactory;
 (c) may request a laboratory designated for this purpose to           Within 15 days of the receipt of the opinion, the applicant
      verify, using samples provided by the applicant, that the        may provide written notice to the Agency that he wishes to
      analytical detection method proposed by the applicant            appeal. Within 60 days of the receipt of the grounds for
      in accordance with point 8 of Article 5 (2) of Directive         appeal, the Committee shall consider whether its opinion
      81/851/EEC is suitable for use in routine checks to              should be revised, and the reasons for the conclusions
      reveal the presence of residue levels above the maximum          reached on the appeal shall be annexed to the assessment
      residue level accepted by the Community in accordance            report referred to in paragraph 2.
      with the provisions of Council Regulation (EEC)
      No 2377/90 of 26 June 1990 laying down a                         2.     Within 30 days of its adoption, the Agency shall
      Community procedure for the establishment of                     forward the opinion of the Committee to the Commission,
      maximum residue levels for veterinary medicinal                  the Member States and the applicant together with a report
      products (*);                                                    describing the assessment of the veterinary medicinal product
                                                                       by the Committee and stating the reasons for its
 (d) may, where appropriate, request the applicant to                  conclusions.
      supplement the particulars accompanying the
      application. Where the Committee avails itself of this
      option, the time limit laid down in Article 28 shall be          3.     In the event of an opinion in favour of granting
      suspended until such time as the supplementary                   authorization to market the veterinary medicinal product
      information requested has been provided. Likewise, this          concerned, the following documents shall be annexed to the
      time limit shall be suspended for the time allowed to the        opinion:
      applicant to prepare oral or written explanations.
                                                                       (a) a draft summary of the product characteristics, as
                                                                            referred to in Article 5 a of Directive 81/851/EEC;
                            Article 29                                 (b) in the case of a veterinary medicinal product intended
                                                                            for administration for food-producing animals, a
 1.     Upon receipt of a written request from the Committee,               statement of the maximum residue level which may be
 a Member State shall forward the information necessary to                  accepted by the Community in accordance with
verify that the manufacturer of a veterinary medicinal                      Regulation (EEC) No         /90;
product or the importer from a third country is able to
 manufacture the veterinary medicinal product concerned                (c) details of any conditions or restrictions which should be
and /or carry out the necessary control tests in accordance                 imposed on the supply or use of the veterinary medicinal
with the particulars and documents supplied in accordance                   product concerned, including the conditions under
with Article 27.                                                            which the medicinal product may be made available to
                                                                            users;
2.      Where it considers it necessary in order to complete its
                                                                       (d) the draft text of the labelling and package leaflet,
examination of an application, the Committee may request
                                                                            proposed by the applicant, presented in accordance with
the applicant to submit to an inspection of the manufacturing
                                                                            Chapter VII of Directive 81/851/EEC.
site of the veterinary medicinal product concerned. The
inspection, which shall be completed within the time limit
referred to in Article 27, shall be undertaken by qualified
pharmaceutical inspectors from the Member States, who
may, if appropriate be accompanied by an inspector from the                                      Article 31
Agency.
                                                                       1.    Within 30 days of the receipt of the opinion, the
(>) OJ No L 224, 18. 8. 1990, p. 1.                                    Commission shall prepare a draft of the Decision to be taken
 ---pagebreak---  31. 12. 90                                 Official Journal of the European Communities                                     No C 330/9
 in respect of the application taking into account the                        treated animals do not contain residues which might
 objectives of Community policies and considering all                         constitute a health hazard for the consumer or is
 relevant information. In the event of a draft Decision which                 insufficiently substantiated;
 envisages the granting of a marketing authorization, the
 documents referred to in points (a), (b), and (c) of Article 30       3. the veterinary medicinal product is offered for sale for a
 (3) shall be annexed. The Commission shall transmit the                      use prohibited under other Community provisions.
 draft Decision to the Member States and to the applicant.
                                                                       Authorization shall likewise be refused if the particulars and
                                                                       documents provided by the applicant in accordance with
 The Commission shall explain in detail the reasons for any            Article 27 of this Regulation are incorrect or if the labelling
 differences between the draft Decision and the opinion of the         and package leaflets proposed by the applicant are not in
 Committee.                                                            accordance with Chapter VII of Directive 81/851/EEC.
 2.     The Commission shall adopt the Decision to be taken
 in respect of the application unless, within 30 days, it has                                       Article 33
 received a reasoned request from a Member State to
 reconsider the matter. The Member State concerned shall               1.        Without prejudice to Article 4 of Council Directive
 also transmit a copy of its request to the other Member States        . . . / . . ./EEC extending the scope of Directive
 and the applicant within the same time limit.                         81/851/EEC on the approximation of the laws of the
                                                                       Member States relating to veterinary medicinal products,
                                                                       and laying down additional provisions for immunological
 3.     Within the time limit referred to in paragraph 2, the
                                                                       veterinary medicinal products, a marketing authorization
 applicant may submit written observations on the draft
                                                                       which has been granted in accordance with the procedure
 Decision for consideration by the Commission.
                                                                       laid down in this Regulation shall apply throughout the
                                                                       Community. It shall confer the same rights and obligations in
4.      The Commission     shall examine any reasoned request          each of the Member States as a marketing authorization
received in accordance      with paragraph 2, in consultation          granted by that Member State in accordance with Article 4 of
 with the Agency, and      after consideration of any further          Directive 81/851/EEC.
 observations submitted    by the applicant.
                                                                       2.        The refusal of a Community marketing authorization
                                                                       shall constitute a prohibition on the marketing and
If the Commission considers that the request raises questions          administration to animals of the veterinary medicinal
of a scientific or technical nature requiring further                  product concerned throughout the Community.
examination, it may remit the matter to the Agency. In this
case the Committee shall give a second opinion within a time           3.        An announcement that authorization has been granted
limit of 60 days. Within 30 days of the receipt of the opinion,        shall be published for information purposes in the Official
the Commission shall adopt the Decision to be taken in                Journal of the European Communities.
respect of the application.
                                                                      4.         Upon request from any interested person, the Agency
Otherwise the Decision shall be taken in accordance with the           shall make available a detailed summary of the evaluation of
procedure laid down in Article 2 b and 2 c of Directive               the veterinary medicinal product by the Committee and the
81/852/EEC.                                                           reasons for its opinion in favour of granting authorization,
                                                                      after deletion of any information of a commercially
                                                                      confidential nature.
                            Article 32                                                             Article 34
                                                                       1.        Authorization shall be valid for five years and shall be
Without prejudice to other provisions of Community law,               renewable for five-year periods, on application by the holder
the authorization provided for in Article 3 shall be refused if,      at least three months before the expiry date.
after verification of the information and particulars
submitted in accordance with Article 27, it appears that:             2.        In exceptional circumstances, and              following
                                                                      consultation with the applicant, an authorization may be
1. the veterinary medicinal product is harmful under the              granted subject to such conditions as appear necessary to
     conditions of use stated at the time of the application for      ensure the protection of human or animal health, including
     authorization, is not efficacious or the applicant has not       specific obligations to conduct further studies following the
     provided sufficient proof of efficacy as regards the             granting of authorization and specific obligations in respect
     species of animal which is to be treated, or its qualitative     of the reporting of adverse reactions to the veterinary
     and quantitative composition is not as stated;                   medicinal product.
2. the withdrawal period recommended by the applicant is              3.        Veterinary medicinal products which have been
     not long enough to ensure that foodstuffs obtained from          authorized by the Community in accordance with the
 ---pagebreak--- No C 330/10                               Official Journal of the European Communities                                   31. 12. 90
provisions of this Regulation shall benefit from the 10-year                                    Article 37
period of protection referred to in point 10 of Article 5 (2) of
Directive 81/851 /EEC.                                               When a marketing authorization is granted in accordance
                                                                     with this Regulation, one or more of the Member States shall
                                                                     act as the competent supervisory authorities to exercise the
                                                                     responsibilities referred to in Article 38.
                           Article 35
                                                                     In the case of veterinary medicinal products manufactured
The granting of authorization shall not diminish the general,
                                                                     within the Community, the supervisory authorities shall
civil and criminal liability in the Member States of the
                                                                     normally be the competent authorities of the Member State
manufacturer and, where applicable, of the person
                                                                     or Member States which have granted the manufacturing
responsible for placing the veterinary medicinal product on
                                                                     authorization provided for in Article 24 of Directive
the market.
                                                                     81/851/EECin respect of the manufacture of the veterinary
                                                                     medicinal product concerned.
                                                                     In the case of veterinary medicinal products imported from
                                                                     third countries, the supervisory authorities shall be the
                         Chapter 2                                   competent authorities of the Member States in which the
                                                                     controls referred to in Article 30 (1) (b) of Directive
                  Supervision and sanctions                          81/851/EEC are carried out unless appropriate
                                                                     arrangements have been made between the Community and
                                                                     the exporting country to ensure that those controls are
                                                                     carried out in the exporting country and that the
                           Article 36                                manufacturer applies standards of good manufacturing
                                                                     practice at least equivalent to those laid down by the
1.     After an authorization has been issued, the person            Community.
responsible for placing the veterinary medicinal product on
the market must, in respect of the methods of production and
control provided for in points 4 and 9 of Article 5 (2) of
Directive 81/851/EEC, take account of technical and                                             Article 38
scientific progress and introduce any changes that may be
required to enable the veterinary medicinal product to be            1.     The supervisory authorities shall have responsibility
manufactured and checked by means of generally accepted              for verifying on behalf of the Community that the
scientific methods. These changes must be accepted by the            manufacturer or the importer from third countries satisfies
Community.                                                           the requirements laid down in Chapter V of Directive
                                                                     81/851/EEC, and for exercising supervision over persons
Upon request from the Commission, the person responsible             responsible for marketing medicinal products in accordance
for placing the veterinary medicinal product on the market           with Chapter VI of Directive 81/851/EEC.
shall also review the analytical detection methods provided
for in point 8 of Article 5 (2) of Directive 81/851 /EEC and         2.     Upon receipt of a reasoned request of any Member
propose any changes which may be necessary to take account           State, or on its own initiative, the Commission may request
of technical and scientific progress.                                the manufacturer or importer to submit to an inspection of
                                                                     the manufacturing site of the veterinary medicinal product
2.     The person responsible for marketing shall forthwith          concerned, giving its reasons. The inspection shall be
inform the Agency of any new information which might                 undertaken by qualified pharmaceutical inspectors from the
entail the amendment of the particulars and documents                Member States who may, if appropriate, be accompanied by
referred to in Article 27 or in the approved summary of the          an inspector from the Agency. The report of the inspectors
product characteristics. In particular the person responsible        shall be made available to the Commission, the Committee
for marketing shall forthwith inform the Agency of any               and the applicant. In the case of an inspection conducted
prohibition or restriction imposed by the competent                  within the Community, the host Member State shall provide
authorities of any country in which the veterinary medicinal         all the practical support necessary to enable the inspectors to
product is marketed and of any other new information which           discharge their responsibilities.
might influence the evaluation of the benefits and risks of the
medicinal product concerned.
3.     If the person responsible for marketing proposes to                                      Article 39
make any alteration to the information and particulars
referred to in Article 27, he shall submit an application to the      1.    Where the supervisory authorities or the competent
Agency.                                                              authorities of any other Member State are of the opinion that
                                                                     the manufacturer or importer from third countries is no
4.     The Agency shall, in accordance with the Commission,          longer fulfilling the obligations laid down in Chapter V of
adopt appropriate arrangements for the examination of                Directive 81/851 /EEC they shall forthwith inform the
amendments and variations to the terms of a marketing                Committee and the Commission, stating their reasons in
authorization.                                                       detail and indicating the course of action proposed.
 ---pagebreak--- 31. 12. 90                                 Official Journal of the European Communities                                 No C 330/11
The same shall apply where a Member State considers that              relevant information about adverse reactions to veterinary
one of the measures envisaged in Chapter VI of Directive              medicinal products authorized in accordance with this
 81/851 /EEC should be applied in respect of the veterinary           Regulation are brought to the attention of the Agency in
 medicinal product concerned.                                         accordance with the provisions of this Regulation.
 2.     The Commission shall in consultation with the Agency
 forthwith examine the reasons advanced by the Member
 State concerned. It may request the opinion of the Committee                                    Article 42
 within a time limit to be determined by the Commission
having regard to the urgency of the matter. Whenever                  The person responsible for marketing a veterinary medicinal
practicable, the person responsible for marketing shall be            product authorized by the Community in accordance with
 invited to provide oral or written explanations.                     the provisions of this Regulation shall have permanently and
                                                                      continuously at his disposal a person responsible for
 3.     The Commission shall prepare a draft of the Decision          pharmacovigilance. This person shall be responsible for:
to be taken which shall be adopted in accordance with the
                                                                      (a) the establishment and maintenance of a system which
procedure laid down in Article 31.
                                                                           ensures that information about all adverse reactions
                                                                           which are reported to the personnel of the company,
However, where a Member State has invoked the provisions
                                                                           including its sales personnel, is collected and collated so
of paragraph 4, the time limit provided for in Article 2 c (3)
                                                                           that it may be accessed at a single point within the
 of Directive 81/852/EEC shall be reduced to 15 calendar
                                                                           Community;
days.
                                                                      (b) the preparation and submission of the reports referred to
4.      In exceptional cases, where action is urgently necessary           in Article 44 to the competent authorities of the Member
to protect human or animal health, a Member State may                      States and the Agency in accordance with the
suspend the use on its territory of a veterinary medicinal                 requirements of this Regulation;
product which has been authorized in accordance with this
Regulation. It shall inform the Commission no later than the          (c) ensuring that any request for the provision of additional
following working day of the reasons for its action. The                   information necessary for the evaluation of the benefits
Commission shall immediately consider the reasons given by                 and risks,of a veterinary medicinal product is answered
the Member State in accordance with paragraph 2 and shall                  fully and promptly, including the provision of
initiate the procedure provided for in paragraph 3.                        information about the volume of sales or prescriptions
                                                                           for the veterinary medicinal product concerned, where
5.     A Member State which has adopted the suspensive                     relevant.
measures referred to in paragraph 4 may maintain them in
force until such time as a definitive Decision has been reached
in accordance with the procedure laid down in
paragraph 3.                                                                                     Article 43
                                                                      1.    The person responsible for marketing shall ensure that
                                                                      all suspected serious adverse reactions to a veterinary
                                                                      medicinal product authorized in accordance with the
                          Chapter 3                                   provisions of this Regulation which are brought to his
                                                                      attention by a veterinarian, whether arising within the
                       Pharmacovigilance                              Community or a third country, are recorded and reported to
                                                                      the Agency within 15 days.
                                                                      2.    In addition, the person responsible for marketing shall
                           Article 40
                                                                      be required to maintain detailed records of all other adverse
                                                                      reactions arising within the Community which are reported
For the purpose of this Chapter, the definitions given in
                                                                      to him by a veterinarian. Unless other requirements have
Article 42 b of Directive 81/851/EEC shall apply.
                                                                      been laid down as a condition of the granting of
                                                                      authorization by the Community, these records shall be
                                                                      submitted to the Agency immediately upon request or at least
                           Article 41                                 every six months during the first two years following
                                                                      authorization and once a year for the following three years.
The Agency, acting in close cooperation with the national             Thereafter, the records shall be submitted at five-yearly
pharmacovigilance centres established in accordance with              intervals together with the application for renewal of the
Article 42 a of Directive 81/851/EEC, shall be responsible            authorization, or immediately upon request.
for the collection and evaluation of information about
adverse reactions to veterinary medicinal products which
have been authorized by the Community in accordance with
this Regulation.                                                                                 Article 44
The competent authorities of the Member States and the                Each Member State shall report any suspected serious
person responsible for marketing shall ensure that all                adverse reaction arising within its territory to a veterinary
 ---pagebreak--- No C 330/12                               Official Journal of the European Communities                                   31. 12. 90
medicinal product authorized in accordance with this                 In particular, the Agency shall undertake the following
Regulation to the Agency and the person responsible for              tasks:
marketing within 15 days of receipt of a report from a
qualified health care professional.                                  (a) the coordination of the scientific evaluation of the
                                                                          quality, safety and efficacy of medicinal products which
                                                                          are subject to Community marketing authorization
                                                                          procedures;
                          Article 45
                                                                     (b) the presentation of assessment reports, summaries of
The Agency shall, in consultation with Member States, the                 product characteristics, labels and package inserts for
Commission and interested parties, draw up detailed                       these medicinal products;
guidance on the collection, verification and presentation of
adverse reaction reports to veterinary medicinal products.           (c) the continuing supervision, under practical conditions
                                                                          of use, of medicinal products which have been
                                                                          authorized within the Community and the provision of
                                                                          advice on the measures necessary to ensure the safe and
                          Article 46                                      effective use of these products, in particular following
                                                                          the evaluation of reports of adverse reactions
1.     The Agency shall publish an annual report on the                   (pharmacovigilance);
operation of the procedures laid down in this Chapter.
                                                                     (d) coordinating the discharge of the various supervisory
2.     Within six years of the entry into force of this                   responsibilities which have been conferred on the
Regulation, the Commission shall publish a detailed review                Community and the Member States in particular in
of the operation of the procedures laid down in this Chapter              respect of the verification of compliance with the
and shall propose any amendments which may be necessary                   principles of good manufacturing practice, good
to improve the operation of these procedures.                             laboratory practice and good clinical practice;
                                                                     (e) to provide technical assistance for the maintenance of a
The Council shall decide on the Commission proposal no
                                                                          data base on medicinal products which is available for
later than one year after its submission.
                                                                          public use;
                                                                     (f)  to promote technical cooperation between the
                                                                          Community, its Member States, international
                                                                          organizations and third countries on scientific and
                           TITLE IV                                       technical issues relating to the evaluation of medicinal
                                                                          products;
THE EUROPEAN AGENCY FOR THE EVALUATION OF
                   MEDICINAL PRODUCTS                                (g) to assist the Community and the Member States in the
                                                                          provision of information about medicinal products to
                                                                          the public;
                         Chapter 1                                   (h) where necessary, to advise and to allow for direct
                                                                          dialogue between the applicant and the Agency on the
                     Tasks of the Agency                                  conduct of the various tests and trials necessary to
                                                                          demonstrate the quality, safety and efficacy of medicinal
                                                                          products.
                          Article 47
                                                                     (i)  advising on the maximum levels for residues of
                                                                          veterinary medicinal products which may be accepted in
A European Agency for the Evaluation of Medicinal                         foodstuffs of animal origin in accordance with
Products, hereinafter referred to as 'the Agency', is hereby              Regulation (EEC) No 2377/90.
established.
                          Article 48
                                                                                              Chapter 2
In order to promote the protection of public health
throughout the Community and the adoption of uniform                                    Structure of the Agency
regulatory decisions based on scientific criteria concerning
the marketing and use of medicinal products, the objective of
the Agency shall be to provide the Member States and the
Institutions of the Community with the best possible                                           Article 49
scientific advice on any question relating to the evaluation of
the quality, the safety or the efficacy of medicinal products        1.     The opinion of the Agency on any question relating to
for human or veterinary use which is referred to it in               the quality, safety or efficacy of medicinal products for
accordance with the provisions of Community legislation              human use shall be given by the Committee for Proprietary
relating to medicinal products.                                      Medicinal Products.
 ---pagebreak--- 31. 12. 90                                Official Journal of the European Communities                                 No C 330/13
2.     The opinion of the Agency on any question relating to         efficacy of medicinal products, together with an indication of
the quality, safety or efficacy of veterinary medicinal              their qualifications and specific areas of expertise.
products shall be given by the Committee for Veterinary
Medicinal Products.                                                  This list shall be updated as necessary.
3.     In addition to a permanent technical and                      2.     On a proposal from the Committee for Proprietary
administrative secretariat, each Committee may arrange to            Medicinal Products or the Committee for Veterinary
be assisted by working parties and expert groups.                    Medicinal Products, the executive director may entrust
                                                                     specific tasks to rapporteurs or experts. The provision of
                                                                     services by rapporteurs or experts shall be governed by a
The secretariat shall ensure appropriate coordination                written contract between the Agency and the person
between the work of the two Committees.                              concerned, or where appropriate between the Agency and.his
                                                                     employer. The person concerned, or his employer, shall be
4.     The Committee for Proprietary Medicinal Products              remunerated in accordance with a fixed scale of fees to be
and the Committee for Veterinary Medicinal Products may,             established by the financial regulation adopted by the
if they consider it appropriate, seek guidance from the              management board.
Scientific Council referred to in Article 65 on important
questions of a general scientific or ethical nature.                 3.     The executive director may also have recourse to the
                                                                     services of experts for the discharge of other specific
                                                                     responsibilities of the Agency, in particular the inspections
                                                                     referred to in Articles 8, 17, 29 and 38.
                           Article 50
1.     The Committee for Proprietary Medicinal Products                                         Article 52
and the Committee for Veterinary Medicinal Products shall
each consist of scientific advisors nominated by Member              1.     The Membership of the Committee for Proprietary
States for a term of three years which shall be renewable.           Medicinal Products and the Committee for Veterinary
They shall be chosen by reason of their scientific expertise         Medicinal Products shall be made public. When each
and their role and experience in the evaluation of medicinal         appointment is published, the professional qualifications of
products for human and veterinary use as appropriate.                each member shall be specified.
Before nominating members to the Committee, the Member
States shall consult to ensure that the composition of each
                                                                     2.     Committee members, rapporteurs or experts may not
Committee reflects the various scientific disciplines necessary
                                                                     hold financial or other interests in the pharmaceutical
for the evaluation of medicinal products.                            industry which could affect their impartiality. All indirect
                                                                     interests which could relate to this industry shall be entered in
The executive director or his representative and                     a register held by the executive director which the public may
representatives of the Commission shall be entitled to attend        consult.
all meetings of the Committees, their working parties and
expert groups.
                                                                                                Article 53
Members of each Committee may arrange to be accompanied
by experts.
                                                                     1.     The executive director shall be appointed by the
                                                                     management board, on a proposal from the Commission, for
2.     In addition to their task of providing an objective           a period of five years, which shall be renewable.
scientific advice to the Community and Member States on the
questions which are referred to them, the members of each            2.     The executive director shall be the legal representative
Committee shall ensure that there is appropriate                     of the Agency. He shall be responsible:
coordination between the work of the Agency and the work
of scientific advisory bodies established in Member States.          — for the day to day administration of the Agency,
                                                                     — for the provision of appropriate scientific and technical
3.     The Member States shall refrain from giving any                   support for the Committee for Proprietary Medicinal
instruction to Members of the Committees which is                        Products and the Committee for Veterinary Medicinal
incompatible with the tasks referred to in paragraph 2.                  Products, and their working parties and expert
                                                                         groups,
                                                                     — for ensuring that the time limits laid down in Community
                           Article 51                                    legislation for the adoption of opinions by the Agency are
                                                                         respected,
1.     The Member States shall transmit to the executive             — for ensuring appropriate coordination between the
director a list of rapporteurs and experts with proven                   Committee for Proprietary Medicinal Products and the
experience in the evaluation of the quality, safety and                  Committee for Veterinary Medicinal Products,
 ---pagebreak--- No C 330/14                               Official Journal of the European Communities                                   31. 12. 90
— for the preparation of the statement of revenue and                undertakings for obtaining a Community marketing
    expenditure and the execution of the budget of the                authorization and for other services provided by the
    Agency,                                                          Agency.
— for all staff matters.                                              2.     The expenditure of the Agency shall include the staff,
                                                                      administrative, infrastructure and operational expenses and
3.     Each year, the executive director shall submit to the         expenses resulting from contracts entered into with third
management board for approval:                                       parties.
— a draft report covering the activities of the Agency in the
    previous year, including information about the number             3.     Before 31 January each year the management board
    of applications evaluated within the Agency, and the time         shall draw up an estimate of revenue and expenditure which
    taken for the completion of the evaluation,                       shall be in balance for each financial year which shall be the
                                                                      same as a calendar year. This estimate shall be forwarded to
— a draft programme of work for the coming year,                     the Commission and the Member States.
— the draft annual accounts for the previous year,
                                                                     4.      The Commission shall include an appropriate
— the draft budget for the coming year.                              contribution to the Agency in the preliminary draft budget of
                                                                     the European Communities. The budget of the European
4.     The executive director shall approve all financial            Communities shall each year under a specific heading in the
expenditure of the Agency.                                           operational part include a contribution to the Agency.
                                                                      5.     The management board, after obtaining the opinion of
                          Article 54                                 the Commission, shall adopt the statement of revenue and
                                                                     expenditure at the beginning of the financial year adjusting it
1.     The management board shall consist of two                     to the contribution granted to the Agency and to its other
representatives from each Member State and two                       resources.
representatives of the Commission. One representative shall
have specific responsibilities relating to medicinal products        6.      The management board shall adopt the financial
for human use and one relating to veterinary medicinal               regulations of the Agency, in agreement with the
products.                                                            Commission.
2.     The term of office of the representatives shall be three      7.      Before 31 March each year, the management board
years. It shall be renewable.                                        shall transmit to the Commission and to the Court of
                                                                     Auditors the accounts for all revenues and expenditure by the
3.     The management board shall elect its chairman for a           Agency during the preceding year. The Court of Auditors
term of three years and shall adopt its rules of procedure.          shall examine the accounts in accordance with the provisions
                                                                     of Article 206 a of the EEC Treaty.
Decisions of the management board shall be adopted by a
two-thirds majority.                                                 8.      Before 31 October each year, the Commission shall
                                                                     submit the accounts and the report of the Court of Auditors
4.     The executive director shall provide the secretariat of       to the Council together with its own observations. The
the management board and shall be entitled to attend the             management board shall be discharged in respect of the
meetings of the board unless it decides otherwise. In this case,     implementation of the budget in accordance with the
a representative of the Commission shall prepare the record          procedure laid down in Article 206 b of the EEC Treaty.
of the meeting.
5.     Before 31 January each year, the management board                                        Article 56
shall adopt the general report on the activities of the Agency
for the previous year and its programme of work for the              The fees referred to in Article 55 (1) shall be established by
coming year and forward them to the Member States, the               the Council on a proposal from the Commission, following
Commission, the Council, the European Parliament and the             consultation of organizations representing the interests of the
Scientific Council.                                                  pharmaceutical industry at the Community level.
                         Chapter 3                                                             Chapter 4
                     Financial provisions                                       General provisions governing the Agency
                          Article 55                                                            Article 57
1.    The revenues of the Agency shall consist of a                  The Agency shall have legal personality. In all Member States
contribution from the Community, and the fees paid by                it shall benefit from the widest powers granted by law to legal
 ---pagebreak--- 31. 12. 90                                 Official Journal of the European Communities                                No C 330/15
persons. In particular it may acquire and dispose of real             3.     The management board, in agreement with the
property and chattels and institute legal proceedings.                Commission, shall adopt the necessary implementing
                                                                      provisions.
                             Article 58
                                                                                                  Article 62
1.     The contractual liability of the Agency shall be
                                                                      Members of the management board, the executive director,
governed by the law applicable to the contract in question.
                                                                      the staff of the Agency, the members of Committees attached
The Court of Justice of the European Communities shall
                                                                      to the Agency and their working parties, experts and any
have jurisdiction to give judgment pursuant to any
                                                                      other persons participating in the work of the Agency,
arbitration clause contained in a contract concluded by the
                                                                      including observers, shall be obliged, even after their duties
Agency.                                                               have ceased, not to disclose information of the kind covered
                                                                      by the obligation of professional secrecy.
2.     In the case of non-contractual liability, the Agency
shall, in accordance with the general principles common to
the laws of the Member States, make good any damage
caused by itself or by its servants in the performance of their                                   Article 63
duties.
                                                                      The management board may, in agreement with the
                                                                      Commission, invite representatives of international
The Court of Justice shall have jurisdiction in any dispute
                                                                      organizations with interest in the scientific and technical
relating to compensation for such damages.
                                                                      evaluation of medicinal products such as:
3.     The personal liability of its servants towards the             — the European Pharmacopoeia,
Agency shall be governed by the relevant conditions applying
to the staff of the Agency.                                           — the European Free Trade Association,
                                                                      — the Nordic Council on Medicines,
                                                                      — the World Health Organization,
                             Article 59
                                                                      to participate as observers in the work of the Agency.
Member States, members of the management board and
third parties directly involved may refer to the Commission
any act of the Agency, whether express or implied, for the                                        Article 64
Commission to examine the legality of that Act.
                                                                      The management board shall, in agreement with the
Referral to the Commission shall be made within 15 days of            Commission, develop appropriate contacts between the
the day on which the party concerned first became aware of            Agency and the representatives of the industry, consumers
the act in question.                                                  and patients and the professions.
The Commission shall take a decision within one month. If
no decision has been taken within this period, the case shall                                     Article 65
be deemed to have been dismissed.
                                                                      1.     A Scientific Council shall be established and attached
                                                                      to the Agency.
                             Article 60                               2.     The Scientific Council shall consist of not less than five
                                                                      and not more than nine persons of outstanding and
The Protocol on the Privileges and immunities of the                  internationally recognized ability with particular knowledge
European Communities shall apply to the Agency.                       of scientific and ethical issues relating to medicinal products
                                                                      for human or veterinary use.
                                                                      3.     The members of the Scientific Council shall be
                             Article 61
                                                                      nominated by the Council on a proposal from the
                                                                      Commission for a term of four years. Their appointments
1.     Apart from officials and other staff seconded by an            shall be renewable.
institution of the European Communities, the Agency shall
have its own personnel to whom will be applied a special              4.     The Scientific Council shall advise for the Committee
regime, to be decided by a Council Regulation, adopted by a           for Proprietary Medicinal Products or the Committee for
qualified majority on a proposal from the Commission.                 Veterinary Medicinal Products on any question which is
                                                                      submitted to it in accordance with Article 49. In addition, the
2.     In respect of its personnel, the Agency shall exercise the     Scientific Council shall be able to comment on the annual
powers which have been devolved to the Authority invested             report on the operation of the Agency prepared in accordance
with the power of nomination.                                         with Article 55.
 ---pagebreak--- No C 330/16                             Official Journal of the European Communities                                   31. 12. 90
                          Article 66                               penalties to be applied for the infringement of the provisions
                                                                   of this Regulation. The penalties shall be sufficient to
The Agency shall take up its responsibilities on 1 January         promote compliance with those measures.
1993.
                                                                   Member States shall forthwith inform the Commission of the
                                                                   institution of any infringement proceedings.
                           TITLE V                                                            Article 71
             GENERAL AND FINAL PROVISIONS                          Within three years of the entry into force of this Regulation
                                                                   the Commission shall produce a report on whether the level
                                                                   of harmonization achieved by the present Regulation and by
                                                                   Council Directive 90/167/EEC of 26 March 1990 laying
                          Article 67
                                                                   down the conditions governing the preparation, placing on
                                                                   the market and use of medicated feedingstuffs (*) is
Al Decisions to grant, refuse, amend, suspend, withdraw or
                                                                   equivalent to that provided for in Council Directive
revoke a marketing authorization which are taken in
                                                                   70/524/EEC of 23 November 1970 concerning additives in
accordance with this Regulation shall state in detail the
                                                                   animal feedingstuffs ( 2 ), accompanied if necessary by the
reasons on which they are based. Such Decisions shall be
                                                                   proposals to modify the status of the coccidiostats and other
notified to the party concerned, who shall be able to exercise
                                                                   medicinal substances covered by that Directive.
the remedies conferred upon him under the EEC Treaty.
                                                                   The Council shall decide on the Commission proposals no
                                                                   later than one year after their submission.
                          Article 68
1.     An authorization to market a medicinal product                                         Article 72
coming within the scope of this Regulation shall not be
refused, amended, suspended, withdrawn or revoked except           Within six years of the entry into force of this Regulation, the
on the grounds set out in this Regulation.                         Commission shall publish a general report on the experience
                                                                   acquired as a result of the operation of the procedures laid
2.     An authorization to market a medicinal product              down in this Regulation, in Chapter HI of Directive
coming within the scope of this Regulation shall not be            75/319/EEC and in Chapter IV of Directive 81/851/EEC
granted, refused, amended, suspended, withdrawn or                 together with any appropriate proposals for amendments, to
revoked except in accordance with the procedures set out in        Article 3 and the Annex in order to extend the scope of the
this Regulation.                                                   procedures laid down in this Regulation to other categories
                                                                   of medicinal products, on an obligatory or a voluntary
                                                                   basis.
                          Article 69
                                                                   The Council shall decide on the Commission proposals no
In respect of medicinal products coming within the scope of        later than one year after their submission.
this Regulation, and in order to exercise the responsibilities
imposed upon them by this Regulation, the competent
authorities of the Community shall be able to exercise all the                                Article 73
powers conferred on the competent authorities of the
Member States by Directives 65/65/EEC,         75/319/EEC,         This Regulation shall enter into force on the third day
and81/851/EEC.                                                     following its publication in the Official Journal of the
                                                                   European Communities.
                          Article 70                               Titles I, II, III and V shall apply from 1 January 1993.
Without prejudice to Article 68, and without prejudice to the
Protocol on the Privileges and Immunities of the European          This Regulation shall be binding in its entirety and directly
Communities, each Member State shall determine the                 applicable in all Member States.
                                                                   0) OJ No L 92, 7. 4. 1990, p. 42.
                                                                   (*) OJ No L 270, 14. 12. 1970, p. 1.
 ---pagebreak--- 31. 12. 90                                 Official Journal of the European Communities                                     No C 330/17
                                                                  ANNEX
                                                                  PART A
           Medicinal products developed by means of one of the following biotechnological processes:
           — recombinant DNA technology,
           — controlled expression of genes coding for biologically active proteins in prokaryotes and eukaryotes including
               transformed mammalian cells,
           — hybridoma and monoclonal antibody methods.
           Veterinary medicinal products, including those not derived from biotechnology, intended primarily for use as
           performance enhancers in order to promote the growth of treated animals or to increase yields from treated
           animals.
                                                                  PARTB
           Medicinal products developed by other biotechnological processes, which, in the opinion of the Agency, constitute
           a significant innovation.
           Medicinal products administered by means of new delivery systems which, in the opinion of the Agency, constitute
           a significant innovation.
           Medicinal products presented for an entirely new indication which, in the opinion of the Agency, is of significant
           therapeutic interest.
           Medicinal products based on radio-isotopes which, in the opinion of the Agency, are of significant therapeutic
           interest.
           New medicinal products derived from human blood or human plasma.
           Medicinal products the manufacture of which employs processes which, in the opinion of the Agency, demonstrate
           a significant technical advance such as two-dimensional electrophoresis under micro-gravity.
           Medicinal products intended for administration to human beings containing a new active substance which, on the
           date of entry into force of this regulation, was not authorized by any Member State for use in a medicinal product
           intended for use in human beings.
           Veterinary medicinal products intended for use in food-producing animals containing a new active substance
           which, on the date of entry into force of this Regulation, was not authorized by any Member State for use in
           food-producing animals.