1993R2309 — EN — 25.03.1998 — 001.001 — 1
This document is meant purely as a documentation tool and the institutions do not assume any liability for its contents
►B COUNCIL REGULATION (EEC)No 2309/93
of 22 July 1993
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
(OJ L 214, 24.8.1993, p. 1)
Amended by:
Official Journal
No page date
►M1Commission Regulation (EC) No 649/98 of 23 March 1998 L 88 7 24.3.1998
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▼B
COUNCIL REGULATION (EEC)No 2309/93
of 22 July 1993
laying down Community procedures for the authorization and
supervision of medicinal products for human and veterinary useand establishing a European Agency for the Evaluation of Medi-
cinal Products
THE COUNCIL OF THE EUROPEAN COMMUNITIES,
Havingreg ard to the Treaty establishingthe European EconomicCommunity, and in particular Article 235 thereof,
Havingreg ard to the proposal from the Commission(
1),
Havingreg ard to the opinion of the European Parliament(2),
Havingreg ard to the opinion of the Economic and Social Committee(3),
Whereas Council Directive 87/22/EEC of 22 December 1986 on the
approximation of national measures relatingto the placingon themarket of high-technology medicinal products particularly those derivedfrom biotechnology (
4) has established a Community mechanism for
concertation, prior to any national decision relating to a high-technologymedicinal product, with a view to arrivingat uniform decisionsthroughout the Community; whereas this route should be followed,particularly in order to ensure the smooth functioningof the internalmarket in the pharmaceutical sector;
Whereas the experience acquired as a result of Directive 87/22/EEC has
shown that it is necessary to establish a centralized Community authori-zation procedure for technologically advanced medicinal products, inparticular those derived from biotechnology; whereas this procedureshould also be available to persons responsible for placingon themarket medicinal products containingnew active substances which areintended for use in human beings or in food-producing animals;
Whereas in the interest of public health it is necessary that decisions on
the authorization of such medicinal products should be based on theobjective scientific criteria of the quality, the safety and the efficacy ofthe medicinal product concerned to the exclusion of economic or otherconsiderations; whereas, however, Member States should exceptionallybe able to prohibit the use on their territory of medicinal products forhuman use which infringe objectively defined concepts of public orderor public morality; whereas, moreover, a veterinary medicinal productmay not be authorized by the Community if its use would contravenethe legal measures laid down by the Community within the frameworkof the common agricultural policy;
Whereas, in the case of medicinal products for human use, the criteria
of quality, safety and efficacy have been extensively harmonized byCouncil Directive 65/65/EEC of 26 January 1965 on the approximationof provisions laid down by law, regulation or administrative actionrelatingto medicinal products(
5), and the Second Council Directive
75/319/EEC of 20 May 1975 on the approximation of provisions laiddown by law, regulation and administrative action relating to propri-etary medicinal products(
6), and by Council Directive 75/318/EEC of
20 May 1975 on the approximation of the laws of the Member States
(1) OJ No C 330, 31. 12. 1990, p. 1, and
OJ No C 310, 30. 11. 1991, p. 7.
(2) OJ No C 183, 15. 7. 1991, p. 145.
(3) OJ No C 269, 14. 10. 1991, p. 84.
(4) OJ No L 15, 17. 1. 1987, p. 38.
(5) OJ No 22, 9. 2. 1965, p. 369/65. Directive last amended by Directive
92/27/EEC (OJ No L 113, 30. 4. 1992, p. 8).
(6) OJ No L 147, 9. 6. 1976, p. 13. Directive last amended by Directive 92/
27/EEC (OJ No L 113, 30. 4. 1992, p. 8).
1993R2309 — EN — 25.03.1998 — 001.001 — 3
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relatingto analytical pharmaco-toxicolog ical and clinical standards and
protocols in respect of the testingof medicinal products(1);
Whereas in the case of veterinary medicinal products, the same results
have been achieved by Council Directive 81/851/EEC of 28 September1981 on the approximation of the laws of the Member States relatingtoveterinary medicinal products(
2) and by Council Directive 81/852/EEC
of 28 September 1981 on the approximation of the laws of the MemberStates relatingto analytical, pharmaco-toxicolog ical and clinical stan-dards and protocols in respect of the testingof veterinary medicinalproducts(
3);
Whereas the same criteria must be applied to medicinal products which
are to be authorized by the Community;
Whereas only after a single scientific evaluation of the highest possible
standard of the quality, safety or efficacy of technologically advancedmedicinal products, to be undertaken within the European Agency forthe Evaluation of Medicinal Products, should a marketingauthorizationbe granted by the Community by a rapid procedure ensuring closecooperation between the Commission and Member States.
Whereas Council Directive 93/39/EEC of 14 June 1993 amending
Directive 65/65/EEC, 75/318/EEC and 75/319/EEC in respect of medi-cinal products(
4) has provided that in the event of a disagreement
between Member States about the quality, safety or efficacy of a medi-cinal product which is the subject of the decentralized Communityauthorization procedure, the matter should be resolved by a bindingCommunity decision followinga scientific evaluation of the issuesinvolved within a European medicinal product evaluation agency;whereas similar provisions have been laid down in respect of veterinarymedicinal products by Council Directive 93/40/EEC of 14 June 1993amendingDirectives 81/851/EEC and 81/852/EEC on the approx-imation of the laws of the Member States relatingto veterinary medi-cinal products(
5);
Whereas the Community must be provided with the means to undertake
a scientific evaluation of medicinal products which are presented forauthorization in accordance with the centralized Community proced-ures; whereas, furthermore, in order to achieve the effective harmon-ization of the administrative decisions taken by Member States inrelation to individual medicinal products which are presented forauthorization in accordance with decentralized procedures, it is neces-sary to provide the Community with the means of resolvingdisag ree-ments between Member States about the quality, safety and efficacy ofmedicinal products;
Whereas it is therefore necessary to establish a European Agency for
the Evaluation of Medicinal Products (‘the Agency');
Whereas the primary task of the Agency should be to provide scientific
advice of the highest possible quality to the Community institutions andthe Member States for the exercise of the powers conferred upon themby Community legislation in the field of medicinal products in relationto the authorization and supervision of medicinal products;
Whereas it is necessary to ensure close cooperation between the Agency
and scientists workingwithin the Member States;
Whereas, therefore, the exclusive responsibility for preparingthe opin-
ions of the Agency on all matters relating to medicinal products forhuman use should be entrusted to the Committee for Proprietary Medi-cinal Products created by the Second Council Directive 75/319/CEE;
(1) OJ No L 147, 9. 6. 1975, p. 1. Directive last amended by Commission
Directive 91/507/EEC (OJ No L 270, 26. 9. 1991, p. 32).
(2) OJ No L 317, 6. 11. 1981, p. 1. Directive last amended by Directive 93/
40/EEC (OJ No 214, 24. 8. 1993).
(3) OJ No L 317, 6. 11. 1981, p. 16. Directive last amended by Directive
93/40/EEC (OJ No 214, 24. 8. 1993).
(4) See page 22 of this Official Journal.
(5) See page 31 of this Official Journal.
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whereas in respect of veterinary medicinal products this responsibility
should be entrusted to the Committee for Veterinary Medicinal Productscreated by Directive 81/851/EEC;
Whereas the establishment of the Agency will make it possible to
reinforce the scientific role and independence of these two Committees,in particular through the establishment of a permanent technical andadministrative secretariat;
Whereas it is also necessary to make provisions for the supervision of
medicinal products which have been authorized by the Community, andin particular for the intensive monitoringof adverse reactions to thosemedicinal products through Community pharmacovigilance activities inorder to ensure the rapid withdrawal from the market of any medicinalproduct which presents an unacceptable level of risk under normalconditions of use;
Whereas the Commission, workingin close cooperation with the
Agency, and after consultation with Member States, should also beentrusted with the task of coordinatingthe discharg e of the varioussupervisory responsibilities of Member States and in particular theprovisions of information about medicinal products, monitoringtherespect of good manufacturing practices, good laboratory practices andgood clinical practices;
Whereas the Agency should also be responsible for coordinating the
activities of the Member States in the field of the monitoringof adversereactions to medicinal products (pharmacovigilance);
Whereas it is necessary to provide for the orderly introduction of
Community procedures for the authorization of medicinal productsalongside the national procedures of the Member States which havealready been extensively harmonized by Directives 65/65/EEC, 75/319/EEC and 81/851/EEC; whereas it is therefore appropriate in thefirst instance to limit the obligation to use the new Community proce-dure to certain medicinal products; whereas the scope of theCommunity procedures should be reviewed in the light of experience atthe latest six years after the entry into force of this Regulation;
Whereas risks to the environment may be associated with medicinal
products containingor consistingof g enetically modified org anisms;whereas therefore it is necessary to provide for an environmental riskassessment of such products similar to that provided for by CouncilDirective 90/220/EEC of 23 April 1990 on the deliberate release intothe environment of genetically modified organisms(
1), together with
the assessment of the quality, safety and efficacy of the productconcerned within a single Community procedure;
Whereas the Treaty does not provide, for the adoption of a uniform
system at Community level, as provided for by this Regulation, powersother than those of Article 235,
HAS ADOPTED THIS REGULATION:
TITLE 1
DEFINITIONS AND SCOPE
Article 1
The purpose of this Regulation is to lay down Community procedures
for the authorization and supervision of medicinal products for humanand veterinary use and to establish a European Agency for the Evalu-ation of Medicinal Products.
The provisions of this Regulation shall not affect the powers of the
Member States’ authorities as regards the price setting of medicinalproducts or their inclusion in the scope of the national health system of
(1) OJ No L 117, 8. 5. 1990, p. 15.
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the Member States’ authorities or their inclusion in the scope of the
social security schemes on the basis of health, economic and socialconditions. For example, the Member States may choose from themarketingauthorization those therapeutic indications and pack sizeswhich will be covered by their social security organizations.
Article 2
The definitions laid down in Article 1 of Directive 65/65/EEC and those
laid down in Article 1 (2) of Directive 81/851/EEC shall apply for thepurposes of this Regulation.
The person responsible for placingthe medicinal products covered by
this Regulation on the market must be established in the Community.
Article 3
1. No medicinal product referred to in Part A of the Annex may be
placed on the market within the Community unless a marketingauthori-zation has been granted by the Community in accordance with theprovisions of this Regulation.
2. The person responsible for placingon the market a medicinal
product referred to in Part B of the Annex may request that authoriza-tion to place the medicinal product on the market be granted by theCommunity in accordance with the provisions of this Regulation.
3. Before entry into force of this Regulation and after consultation of
the Committee for Proprietary Medicinal Products, Parts A and B of theAnnex as regards medicinal products for human use shall be re-exam-ined in the light of scientific and technical progress with a view tomakingany amendments necessary which will be adopted under theprocedure laid down in Article 72.
4. Before entry into force of this Regulation and after consultation of
the Committee for Veterinary Medicinal Products, Parts A and B of theAnnex as regards veterinary medicinal products shall be re-examined inthe light of scientific and technical progress with a view to making anyamendments necessary which will be adopted under the procedure laiddown in Article 72.
5. The procedures referred to in paragraphs 3 and 4 shall continue to
apply after entry into force of this Regulation.
Article 4
1. In order to obtain the authorization referred to in Article 3, the
person responsible for placinga medicinal product on the market shallsubmit an application to the European Agency for the Evaluation ofMedicinal Products, hereinafter referred to as ‘the Agency',set up underTitle IV.
2. The Community shall issue and supervise marketingauthoriza-
tions for medicinal products for human use in accordance with Title II.
3. The Community shall issue and supervise marketingauthoriza-
tions for veterinary medicinal products in accordance with Title III.
TITLE II
AUTHORIZATION AND SUPERVISION OF MEDICINAL PRODUCTS
FOR HUMAN USE
CHAPTER 1
Submission and examination of applications — authorizations —
renewal of authorization
Article 5
The Committee for Proprietary Medicinal Products established by
Article 8 of Directive 75/319/EEC, in this Title referred to as ‘theCommittee', shall be responsible for formulatingthe opinion of theAgency on any question concerning the admissibility of the files
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submitted in accordance with the centralized procedure, the granting,
variation, suspension or withdrawal of an authorization to place a medi-cinal product for human use on the market arisingin accordance withthe provisions of this Title and pharmacovigilance.
Article 6
1. An application for authorization for a medicinal product for
human use must be accompanied by the particulars and documentsreferred to in Articles 4 and 4a of Directive 65/65/EEC, in the Annex toDirective 75/318/EEC and in Article 2 of Directive 75/319/EEC.
2. In the case of a medicinal product containingor consistingof
genetically modified organisms within the meaning of Article 2 (1) and(2) of Directive 90/220/EEC, the application must also be accompaniedby:
— a copy of any written consent or consents of the competent authori-
ties to the deliberate release into the environment of the geneticallymodified organisms for research and development purposes whereprovided for by Part B of Directive 90/220/EEC,
— the complete technical dossier supplyingthe information requested
in Annexes II and III to Directive 90/220/EEC and the environ-mental risk assessment resultingfrom this information; the results ofany investigations performed for the purposes of research or devel-opment.
Articles 11 to 18 of Directive 90/220/EEC shall not apply to medicinal
products for human use containingor consistingof g enetically modifiedorganisms.
3. The application must also be accompanied by the fee payable to
the Agency for the examination of the application.
4. The Agency shall ensure that the opinion of the Committee is
given within 210 days of the receipt of a valid application.
In the case of a medicinal product containingor consistingof g eneti-
cally modified organisms, the opinion of the Committee shall respectthe environmental safety requirements laid down by Directive 90/220/EEC to ensure that all appropriate measures are taken to avoidadverse effects on human health and the environment which might arisefrom the deliberate release or placingon the market of g eneticallymodified org anisms. Duringthe process of evaluatingapplications formarketingauthorizations for products containingor consistingof g eneti-cally modified organisms, necessary consultations will be held by therapporteur with the bodies set up the Community or the Member Statesin accordance with Directive 90/220/EEC.
5. The Commission shall, in consultation with the Agency, the
Member States and interested parties, draw up detailed guidance on theform in which applications for authorization are to be presented.
Article 7
In order to prepare its opinion, the Committee:
(a) shall verify that the particulars and documents submitted in accord-
ance with Article 6 comply with the requirements of Directives65/65/EEC, 75/318/EEC and 75/319/EEC, and examine whether theconditions specified in this Regulation for issuing a marketingauthorization for the medicinal product are satisfied;
(b) may ask for a State laboratory or a laboratory designated for this
purpose to test the medicinal product, its startingmaterials and, ifneed be, its intermediate products or other constituent materials inorder to ensure that the control methods employed by the manufac-turer and described in the application documents are satisfactory;
(c) may, where appropriate, request the applicant to supplement the
particulars accompanyingthe application within a specific timelimit. Where the Committee avails itself of this opinion, the timelimit laid down in Article 6 shall be suspended until such time asthe supplementary information requested has been provided. Like-
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wise, this time limit shall be suspended for the time allowed to the
applicant to prepare oral or written explanations.
Article 8
1. Upon receipt of a written request from the Committee, a Member
State shall forward the information establishingthat the manufacturer ofa medicinal product or the importer from a third country is able tomanufacture the medicinal product concerned and/or carry out thenecessary control tests in accordance with the particulars and documentssupplied pursuant to Article 6.
2. Where it considers it necessary in order to complete its exam-
ination of an application, the Committee may require the applicant tosubmit to a specific inspection of the manufacturingsite of the medi-cinal product concerned. The inspection, which shall be completedwithin the time limit referred to in Article 6, shall be undertaken byinspectors from the Member State who possess the appropriate qualifi-cations and who may, if need be, be accompanied by a rapporteur orexpert appointed by the Committee.
Article 9
1. Where the opinion of the Committee is that:
— the application does not satisfy the criteria for authorization set out
in this Regulation, or
— the summary of the product characteristics proposed by the appli-
cant in accordance with Article 6 should be amended, or
— the labellingor packag e leaflet of the product is not in compliance
with Council Directive 92/27/EEC of 31 March 1992 on the label-lingof medicinal products for human use and on packag e leaf-lets(
1), or
— the authorization should be granted subject to the conditions
provided for in Article 13 (2),
the Agency shall forthwith inform the applicant. Within 15 days of
receipt of the opinion, the applicant may provide written notice to theAgency that he wishes to appeal. In that case he shall forward thedetailed grounds for his appeal to the Agency within 60 days of receiptof the opinion. Within 60 days of the receipt of the grounds for appeal,the Committee shall consider whether its opinion should be revised, andthe conclusions reached on the appeal shall be annexed to the assess-ment report referred to in paragraph 2.
2. Within 30 days of its adoption, the Agency shall forward the final
opinion of the Committee to the Commission, the Member States andthe applicant together with a report describing the assessment of themedicinal product by the Committee and statingthe reasons for itsconclusions.
3. In the event of an opinion in favour of granting the relevant
authorization to place the medicinal product concerned on the market,the followingdocuments shall be annexed to the opinion:
(a) a draft summary of the product characteristics, as referred to in
Article 4a of Directive 65/65/EEC;
(b) (b) details of any conditions or restrictions which should be
imposed on the supply or use of the medicinal product concerned,includingthe conditions under which the medicinal product may bemade available to patients, havingreg ard to the criteria laid down inCouncil Directive 92/26/EEC of 31 March 1992 concerningtheclassification for the supply of medicinal products for humanuse (
2), without prejudice to the provisions in Article 3 (4) of that
Directive;
(1) OJ No L 113, 30. 4. 1992, p. 8.
(2) OJ No L 113, 30. 4. 1992, p. 5.
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(c) the draft text of the labellingand packag e leaflet proposed by the
applicant, presented in accordance with Directive 92/27/EEC,without prejudice to the provisions of Article 7 (2) of that Directive;
(d) the assessment report.
Article 10
1. Within 30 days of receipt of the opinion, the Commission shall
prepare a draft of the decision to be taken in respect of the application,takingaccount of Community law.
In the event of a draft decision which envisages the granting of
marketingauthorization, the documents referred to in Article 9 (3) (a),(b) and (c) shall be annexed.
Where, exceptionally, the draft decision is not in accordance with the
opinion of the Agency, the Commission shall also annex a detailedexplanation of the reasons for the differences.
The draft decision shall be forwarded to the Member States and the
applicant.
2. A final decision on the application shall be adopted in accordance
with the procedure laid down in Article 73.
3. The rules of procedure of the Committee referred to in Article 73
shall be adjusted to take account of the tasks incumbent upon it inaccordance with this Regulation.
These adjustments shall involve the following:
— except in cases referred to in the third subparagraph of paragraph 1,
the opinion of the StandingCommittee shall be obtained in writing ,
— each Member State is allowed at least 28 days to forward written
observations on the draft decision to the Commission,
— each Member State is able to require in writingthat the draft
decision be discussed by the StandingCommittee, g ivingits reasonsin detail.
Where, in the opinion of the Commission, the written observations of a
Member State raise important new questions of a scientific or technicalnature which have not been addressed in the opinion of the Agency, theChairman shall suspend the procedure and refer the application back tothe Agency for further consideration.
The provisions necessary for the implementation of this paragraph shall
be adopted by the Commission in accordance with the procedure laiddown in Article 72.
4. The Agency shall, upon request, inform any person concerned of
the final decision.
Article 11
Without prejudice to other provisions of Community law, the authoriza-
tion provided for in Article 3 shall be refused if, after verification of theinformation and particulars submitted in accordance with Article 6, itappears that the quality, the safety or the efficacy of the medicinalproduct have not been adequately or sufficiently demonstrated by theapplicant.
Authorization shall likewise be refused if the particulars and documents
provided by the applicant in accordance with Article 6 are incorrect orif the labellingand packag e leaflets proposed by the applicant are not inaccordance with Directive 92/27/EEC.
Article 12
1. Without prejudice to Article 6 of Directive 65/65/EEC, a
marketingauthorization which has been g ranted in accordance with theprocedure laid down in this Regulation shall be valid throughout theCommunity. It shall confer the same rights and obligations in each of
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the Member States as a marketingauthorization g ranted by that Member
State in accordance with Article 3 of Directive 65/65/EEC.
The authorized medicinal products shall be entered in the Community
RegisterofMedicinalProducts and shall be given a number which must
appear on the packaging.
2. The refusal of a Community marketingauthorization shall consti-
tute a prohibition on the placingon the market of the medicinal productconcerned throughout the Community.
3. Notification of marketingauthorization shall be published in the
OfficialJournaloftheEuropeanCommunities , quotingin particular the
date of authorization and the number in the Community Register.
4. Upon request from any interested person, the Agency shall make
available the assessment report of the medicinal product by theCommittee for Proprietary Medicinal Products and the reasons for itsopinion in favour of granting authorization, after deletion of any infor-mation of a commercially confidential nature.
Article 13
1. Authorization shall be valid for five years and shall be renewable
for five-year-periods, on application by the holder at least three monthsbefore the expiry date and after consideration by the Agency of adossier containingup-to-date information on pharmacovig ilance.
2. In exceptional circumstances and followingconsultation with the
applicant, an authorization may be granted subject to certain specificobligations, to be reviewed annually by the Agency.
Such exceptional decisions may be adopted only for objective and
verifiable reasons and must be based on one of the causes mentioned inPart 4 G of the Annex to Directive 75/318/EEC.
3. Some products may be authorized only for use in hospitals or for
prescription by some specialists.
4. Medicinal products which have been authorized by the
Community in accordance with the provisions of this Regulation shallbenefit from the 10-year period of protection referred to in point 8 ofthe second paragraph of Article 4 of Directive 65/65/EEC.
Article 14
The granting of authorization shall not diminish the general civil and
criminal liability in the Member States of the manufacturer or, whereapplicable, of the person responsible for placingthe medicinal producton the market.
CHAPTER 2
Supervision and sanctions
Article 15
1. After an authorization has been issued in accordance with this
Regulation, the person responsible for placing the medicinal product onthe market shall, in respect of the methods of production and controlprovided for in points 4 and 7 of the second paragraph of Article 4 ofDirective 65/65/EEC, take account of technical and scientific progressand make any amendments that may be required to enable the medicinalproducts to be manufactured and checked by means of generallyaccepted scientific methods. The aforementioned person must apply forapproval for these amendments in accordance with this Regulation.
2. The person responsible for placingthe medicinal product on the
market shall forthwith inform the Agency, the Commission and theMember States of any new information which might entail the amend-ment of the particulars and documents referred to in Articles 6 or 9 or inthe approved summary of the product characteristics. In particular theaforementioned person shall forthwith inform the Agency, the Commis-sion and the Member States of any prohibition or restriction imposed by
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the competent authorities of any country in which the medicinal product
is placed on the market and of any other new infomation which mightinfluence the evaluation of the benefits and risks of the medicinalproduct concerned.
3. If the person responsible for placingthe medicinal product on the
market proposes to make any alteration to the information and particu-lars referred to in Articles 6 and 9, he shall submit an application to theAgency.
4. The Commission shall, in consultation with the Agency, adopt
appropriate arrangements for the examination of variations to the termsof a marketingauthorization.
These arrangements shall include a notification system or administrative
procedures concerningminor variations and define precisely the conceptof ‘a minor variation'.
These arrangements shall be adopted by the Commission in the form of
an implementingReg ulation in accordance with the procedure laiddown in Article 72.
Article 16
In the case of medicinal products manufactured within the Community,
the supervisory authorities shall be the competent authorities of theMember State or Member States which have granted the manufacturingauthorization provided for in Article 16 of Directive 75/319/EEC inrespect of the manufacture of the medicinal product concerned.
In the case of medicinal products imported from third countries, the
supervisory authorities shall be the competent authorities of the MemberStates in which the controls referred to in Article 22 (1) (b) of Directive75/319/EEC are carried out unless appropriate arrangements have beenmade between the Community and the exportingcountry to ensure thatthose controls are carried out in the exportingcountry and that themanufacturer applies standards of good manufacturing practice at leastequivalent to those laid down by the Community.
A Member State may request assistance from another Member State or
the Agency.
Article 17
1. The supervisory authorities shall have responsibility for verifying
on behalf of the Community that the person responsible for placingthemedicinal product on the market or the manufacturer or importer fromthird countries satisfies the requirements laid down in Chapter IV ofDirective 75/319/EEC and for exercisingsupervision over such personsin accordance with Chapter V of Directive 75/319/EEC.
2. Where, in accordance with the second paragraph of Article 30 of
Directive 75/319/EEC, the Commission is informed of serious differ-ences of opinions between Member States as to whether the personresponsible for placingthe medicinal product on the market or a manu-facturer or importer established within the Community is satisfyingtherequirements referred to in paragraph 1, the Commission may, afterconsultation with the Member States concerned, request an inspectorfrom the supervisory authority to undertake a new inspection of theaforementioned person, the manufacturer or the importer; the inspectorin question may be accompanied by an inspector from a Member Statewhich is not party to the dispute and/or by a rapporteur or expertnominated by the Committee.
3. Subject to any arrangements which may have been concluded
between the Community and third countries in accordance with thesecond subparagraph of Article 16, the Commission may, upon receiptof a reasoned request from a Member State, the Committee for Propri-etary Medicinal Products, or on its own initiative, require a manufac-turer established in a third country to submit to an inspection. Theinspection shall be undertaken by appropriately qualified inspectorsfrom the Member States, who may, if appropriate, be accompanied by arapporteur or expert nominated by the Committee. The report of the
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inspectors shall be made available to the Commission, the Member
States and the Committee for Proprietary Medicinal Products.
Article 18
1. Where the supervisory authorities or the competent authorities of
any other Member State are of the opinion that the manufacturer orimporter from third countries is no longer fulfilling the obligations laiddown in Chapter IV of Directive 75/319/EEC, they shall forthwithinform the Committee and the Commission, statingtheir reasons indetail and indicatingthe course of action proposed.
The same shall apply where a Member State or the Commission
considers that one of the measures envisaged in Chapter V or Va ofDirective 75/319/EEC should be applied in respect of the medicinalproduct concerned or where the Committee for Proprietary MedicinalProducts has delivered an opinion to that effect in accordance withArticle 20.
2. The Commission shall in consultation with the Agency forthwith
examine the reasons advanced by the Member State concerned. It shallrequest the opinion of the Committee within a time limit which it shalldetermine having regard to the urgency of the matter. Whenever practic-able, the person responsible for placingthe medicinal product on themarket shall be invited to provide oral or written explanations.
3. The Commission shall prepare a draft of the Decision to be taken
which shall be adopted in accordance with Article 10.
However, where a Member State has invoked the provisions of para-
graph 4, the time limit provided for in Article 73 shall be reduced to 15calendar days.
4. Where urgent action is essential to protect human or animal health
or the environment, a Member State may suspend the use on its territoryof a medicinal product which has been authorized in accordance withthis Regulation. It shall inform the Commission and the other MemberStates no later than the followingworkingday of the reasons for itsaction. The Commission shall immediately consider the reasons givenby the Member State in accordance with paragraph 2 and shall initiatethe procedure provided for in paragraph 3.
5. A Member State which has adopted the suspensive measures
referred to in paragraph 4 may maintain them in force until such time asa definitive decision has been reached in accordance with the procedurelaid down in paragraph 3.
6. The Agency shall, upon request, inform any person concerned of
the final decision.
CHAPTER 3
Pharmacovigilance
Article 19
For the purpose of this Chapter, the definitions given in Article 29b of
Directive 75/319/EEC shall apply.
Article 20
The Agency, acting in close cooperation with the national pharmacovi-
gilance systems established in accordance with Article 29a of Directive75/319/EEC, shall receive all relevant information about suspectedadverse reactions to medicinal products which have been authorized bythe Community in accordance with this Regulation. If necessary theCommittee may, in accordance with Article 5, formulate opinions onthe measures necessary to ensure the safe and effective use of suchmedicinal products. These measures shall be adopted in accordance withthe procedure laid down in Article 18.
The person responsible for placingthe medicinal product on the market
and the competent authorities of the Member States shall ensure that allrelevant information about suspected adverse reactions to medicinal
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products authorized in accordance with this Regulation are brought tothe attention of the Agency in accordance with the provisions of thisRegulation.
Article 21
The person responsible for the placingon the market of a medicinal
product authorized by the Community in accordance with the provisionsof this Regulation shall have permanently and continuously at hisdisposal an appropriately qualified person responsible for pharmacovigi-lance.
That qualified person shall be responsible for the following:
(a) the establishment and maintenance of a system which ensures that
information about all suspected adverse reactions which arereported to the personnel of the company and to medical representa-tives, is collected, evaluated and collated so that it may be accessedat a single point within the Community;
(b) the preparation of the reports referred to in Article 22 for the
competent authorities of the Member States and the Agency inaccordance with the requirements of this Regulation;
(c) ensuringthat any request from the competent authorities for the
provision of additional information necessary for the evaluation ofthe benefits and risks of a medicinal product is answered fully andpromptly, includingthe provision of information about the volumeof sales or prescriptions for the medicinal product concerned.
Article 22
1. The person responsible for placingthe medicinal product on the
market shall ensure that all suspected serious adverse reactions occur-ringwithin the Community to a medicinal product authorized in accord-ance with the provisions of this Regulation which are brought to hisattention by a health care professional, are recorded and reported imme-diately to the Member States in whose territory the incident occurred,and in no case later than 15 days followingthe receipt of the informa-tion.
The person responsible for placingthe medicinal product on the market
shall ensure that all suspected serious unexpected adverse reactionsoccurringin the territory of a third country, are reported immediately toMember States and the Agency and in no case later than 15 daysfollowingthe receipt of the information.
The arrangements for the reporting of suspected unexpected adverse
reactions which are not serious, whether arisingin the Community or ina third country, shall be adopted in accordance with Article 26.
2. In addition, the person responsible for placingthe medicinal
product on the market shall be required to maintain detailed records ofall suspected adverse reactions occurringwithin or outside theCommunity which are reported to him by a health care professional.Unless other requirements have been laid down as a condition of theg rantingof the marketingauthorization by the Community, theserecords shall be submitted to the Agency and Member States imme-diately upon request or at least every six months duringthe first twoyears followingauthorization and once a year for the followingthreeyears. Thereafter, the records shall be submitted at five-yearly intervalstogether with the application of renewal of the authorization, or imme-diately upon request. These records shall be accompanied by a scientificevaluation.
Article 23
Each Member State shall ensure that all suspected serious adverse
reactions occurringwithin their territory to a medicinal product author-ized in accordance with the provisions of this Regulation which arebrought to their attention are recorded and reported immediately to theAgency and the person responsible for placing the medicinal product on
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the market, and in no case later than 15 days followingthe receipt of the
information.
The Agency shall inform the national pharmacovigilance systems.
Article 24
The Commission in consultation with the Agency, Member States, and
interested parties, shall draw up guidance on the collection, verificationand presentation of adverse reaction reports.
The Agency, in consultation with the Member States and the Commis-
sion, shall set up a data-processingnetwork for the rapid transmission ofdata between the competent Community authorities in the event of analert relatingto faulty manufacture, serious adverse reactions and otherpharmacovigilance data regarding medicinal products marketed in theCommunity.
Article 25
The Agency shall collaborate with the World Health Organization on
international pharmacovigilance and shall take the necessary steps tosubmit promptly to the World Health Organization appropriate andadequate information regarding the measures taken in the Communitywhich may have a bearingon public health protection in third countriesand shall send a copy thereof to the Commission and the MemberStates.
Article 26
Any amendment which may be necessary to update the provisions of
this chapter to take account of scientific and technical progress shall beadopted in accordance with the provisions of Article 72.
TITLE III
AUTHORIZATION AND SUPERVISION OF VETERINARY MEDI-
CINAL PRODUCTS
CHAPTER 1
Submission and examination of applications — authorization —
reneval of authorization
Article 27
The Committee for Veterinary Medicinal Products established by
Article 16 of Directive 81/851/EEC, in this Title referred to as ‘theCommittee', shall be responsible for formulatingthe opinion of theAgency on any question concerning the admissibility of the filessubmitted in accordance with the centralized procedure, the granting,variation, suspension or withdrawal of an authorization to place a veter-inary medicinal product on the market arisingin accordance with theprovisions of this Title and pharmacovigilance.
Article 28
1. An application for authorization for a veterinary medicinal product
must be accompanied by the particulars and documents referred to inArticles 5, 5a and 7 of Directive 81/851/EEC.
2. In the case of a veterinary medicinal product containingor
consisting of genetically modified organisms within the meaning ofArticle 2 (1) and (2) of Directive 90/220/EEC, the application must alsobe accompanied by:
— a copy of any written consent or consents of the competent authori-
ties to the deliberate release into the environment of the geneticallymodified organisms for research and development purposes whereprovided for in Part B of Directive 90/220/EEC,
— the complete technical dossier supplyingthe information requested
in Annexes II and III to Directive 90/220/EEC and the environ-mental risk assessment resultingfrom this information; the results of
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any investigations performed for the purposes of research or devel-
opment.
Articles 11 to 18 of Directive 90/220/EEC shall not apply to veterinary
medicinal products containingor consistingof g enetically modifiedorganisms.
3. The application shall also be accompanied by the fee payable to
the Agency for the examination of the application.
4. The Agency shall ensure that the opinion of the Committee is
given within 210 days of the receipt of a valid application.
In the case of a veterinary medicinal product containingor consistingof
genetically modified organisms, the opinion of the Committee shallrespect the environmental safety requirements laid down by Directive90/220/EEC to ensure that all appropriate measures are taken to avoidadverse effects on human health and the environment which might arisefrom the deliberate release into the environment or placingon themarket of genetically modified organisms. During the process of evalu-atingapplications for marketingauthorizations for veterinary medicinalproducts containingor consistingof g enetically modified org anisms,necessary consultations shall be held by the rapporteur with the bodiesset up by the Community or the Member States in accordance withDirective 90/220/EEC.
5. The Commission shall, in consultation with the Agency, the
Member States and interested parties, draw up detailed guidance on theform in which applications for authorization are to be presented.
Article 29
In order to prepare its opinion, the Committee:
(a) shall verify that the particulars and documents submitted in accord-
ance with Article 28 comply with the requirements of Directives81/851/EEC and 81/852/EEC and examine whether the conditionsspecified in this Reg ulation for issuinga marketingauthorizationare satisfied;
(b) may ask for a State laboratory or a laboratory designated for this
purpose to test the veterinary medicinal product, its startingmate-rials and, if need be, its intermediate products or other constituentmaterials in order to ensure that the control methods employed bythe manufacturer and described in the application documents aresatisfactory;
(c) may request a State laboratory or laboratory designated for this
purpose to verify, usingsamples provided by the applicant, that theanalytical detection method proposed by the applicant in accordancewith point 8 of the second paragraph of Article 5 of Directive81/851/EEC is suitable for use in routine checks to reveal thepresence of residue levels above the maximum residue levelaccepted by the Community in accordance with the provisions ofCouncil Regulation (EEC) No 2377/90 of 26 June 1990 layingdown a Community procedure for the establishment of maximumresidue limits of veterinary medicinal products in foodstuffs ofanimal origin (
1);
(d) may, where appropriate, request the applicant to supplement the
particulars accompanyingthe application within a specific timelimit. Where the Committee avails itself of this option, the timelimit laid down in Article 28 shall be suspended until such time asthe supplementary information requested has been provided. Like-wise, this time limit shall be suspended for the time allowed to theapplicant to prepare oral or written explanations.
(1) OJ No L 224, 18. 8. 1990, p. 1. Regulation last amended by Regulation
No 762/92 (OJ No L 83, 28. 3. 1992, p. 14).
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Article 30
1. Upon receipt of a written request from the Committee, a Member
State shall forward the information establishingthat the manufacturer ofa veterinary medicinal product or the importer from a third country isable to manufacture the veterinary medicinal product concerned and/orcarry out the necessary control tests in accordance with the particularsand documents supplied pursuant to Article 28.
2. Where it considers it necessary in order to complete its examinina-
tion of an application, the Committee may require the applicant tosubmit to a specific inspection of the manufacturingsite of the veter-inary medicinal product concerned. The inspection, which shall becompleted within the time limit referred to in Article 28, shall beundertaken by inspectors from the Member State who possess theappropriate qualifications and who may, if need be, be accompanied bya rapporteur or expert appointed by the Committee.
Article 31
1. Where the opinion of the Committee is that:
— the application does not satisfy the criteria for authorization set out
in this Regulation,
or
— the summary of the product characteristics proposed by the appli-
cant in accordance with Article 28 should be amended,
or
— the labellingor packag e insert of the product is not in compliance
with Directive 81/851/EEC,
or
— the authorization should be granted subject to the conditions
provided for in Article 35 (2),
the Agency shall forthwith inform the applicant. Within 15 days of
receipt of the opinion, the applicant may provide written notice to theAgency that he wishes to appeal. In that case he shall forward thedetailed grounds for his appeal to the Agency within 60 days of receiptof the opinion. Within 60 days of the receipt of the grounds for appeal,the Committee shall consider whether its opinion should be revised, andthe reasons for the conclusion reached on the appeal shall be annexed tothe assessment report referred to in paragraph 2.
2. Within 30 days of its adoption, the Agency shall forward the final
opinion of the Committee to the Commission, the Member States andthe applicant together with a report describing the assessment of theveterinary medicinal product by the Committee and statingthe reasonsfor its conclusions.
3. In the event of an opinion in favour of granting the relevant
authorization to market the veterinary medicinal product, the followingdocuments shall be annexed to the opinion:
(a) the draft summary of the product characteristics, as referred to in
Article 5a of Directive 81/851/EEC; where necessary this willreflect differences in the veterinary conditions pertainingin theMember States;
(b) in the case of a veterinary medicinal product intended for adminis-
tration to food-producinganimals, a statement of the maximumresidue level which may be accepted by the Community in accord-ance with Regulation (EEC) No 2377/90;
(c) details of any conditions or restrictions which should be imposed on
the supply or use of the veterinary medicinal product concerned,includingthe conditions under which the veterinary medicinalproduct may be made available to users, in accordance with thecriteria laid down in Directive 81/851/EEC;
(d) the draft text of the labellingand packag e insert proposed by the
applicant, presented in accordance with Directive 81/851/EEC;
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(e) the assessment report.
Article 32
1. Within 30 days of receipt of the opinion, the Commission shall
prepare a draft of the decision to be taken in respect of the application,takingaccount of Community law.
In the event of a draft decision which envisages the granting of
marketingauthorization, the documents referred to in Article 31 (3) (a),(b), (c) and (d) shall be annexed.
Where, exceptionally, the draft decision is not in accordance with the
opinion of the Agency, the Commission shall also annex a detailedexplanation of the reasons for the differences.
The draft decision shall be forwarded to the Member States and the
applicant.
2. A final decision on the application shall be adopted in accordance
with the procedure laid down in Article 73.
3. The rules of procedure of the Committee referred to in Article 73
shall be adjusted to take account of the tasks incumbent upon it inaccordance with this Regulation.
These adjustments shall involve the following:
— except in the cases referred to in the third subparagraph of para-
graph 1, the opinion of the Standing Committee shall be obtained inwriting,
— each Member State is allowed at least 28 days to forward written
observations on the draft decision to the Commission,
— each Member State is able to require in writingthat the draft
decision be discussed by the StandingCommittee g ivingits reasonsin detail.
Where, in the opinion of the Commission, the written observations of a
Member State raise important new questions of a scientific or technicalnature which have not been addressed in the opinion of the Agency, theChairman shall suspend the procedure and refer the application back tothe Agency for further consideration.
The provisions necessary for the implementation of this paragraph shall
be adopted by the Commission in accordance with the procedure laiddown in Article 72.
4. The Agency shall, upon request, inform any person concerned of
the final decision.
Article 33
Without prejudice to other provisions of Community law, the authoriza-
tion provided for in Article 3 shall be refused if, after verification of theinformation and particulars submitted in accordance with Article 28, itappears that:
1. the veterinary medicinal product is harmful under the conditions of
use stated at the time of the application for authorization, has notherapeutic effect or the applicant has not provided sufficient proofof such effect as regards the species of animal which is to be treated,or its qualitative and quantitative composition is not as stated;
2. the withdrawal period recommended by the applicant is not long
enough to ensure that foodstuffs obtained from treated animals donot contain residues which might constitute a health hazard for theconsumer or is insufficiently substantiated;
3. the veterinary medicinal product is offered for sale for a use prohib-
ited under other Community provisions.
Authorization shall likewise be refused if the particulars and documents
provided by the applicant in accordance with Article 28 are incorrect orif the labellingand packag e inserts proposed by the applicant are not inaccordance with Chapter VII of Directive 81/851/EEC.
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Article 34
1. Without prejudice to Article 4 of Council Directive 90/677/EEC of
13 December 1990 extendingthe scope of Directive 81/851/EEC on theapproximation of the laws of the Member States relatingto veterinarymedicinal products (
1), and layingdown additional provisions for
immunological veterinary medicinal products, a marketing authorizationwhich has been granted in accordance with the procedure laid down inthis Regulation shall apply throughout the Community. It shall conferthe same rights and obligations in each of the Member States as amarketingauthorization g ranted by that Member State in accordancewith Article 4 of Directive 81/851/EEC.
The authorized veterinary medicinal products shall be entered in the
Community Register of Medicinal Products and shall be given a numberwhich must appear on the packaging.
2. The refusal of a Community marketingauthorization shall consti-
tute a prohibition on the placingon the market of the veterinary medi-cinal product concerned throughout the Community.
3. Notification of marketingauthorization shall be published in the
OfficialJournaloftheEuropeanCommunities , quotingin particular the
date of authorization and the number in the Community Register.
4. Upon request from any interested person, the Agency shall make
available the assessment report of the veterinary medicinal product bythe Committee for Veterinary Medicinal Products and the reasons for itsopinion in favour of granting authorization, after deletion of any infor-mation of a commercially confidential nature.
Article 35
1. Authorization shall be valid for five years and shall be renewable
for five-year periods, on application by the holder at least three monthsbefore the expiry date and after consideration by the Agency of adossier containingup-to-date information on pharmacovig ilance.
2. In exceptional circumstances and followingconsultations with the
applicant, authorization may be granted subject to certain specific obli-gations, to be reviewed annually by the Agency.
Such exceptional decisions may be adopted for objective and verifiable
reasons.
3. Veterinary medicinal products which have been authorized by the
Community in accordance with the provisions of this Regulation shallbenefit from the 10-year period of protection referred to in point 10 ofthe second paragraph of Article 5 of Directive 81/851/EEC.
Article 36
The granting of authorization shall not diminish the general civil and
criminal liability in the Member States of the manufacturer or, whereapplicable, of the person responsible for placingthe veterinary medi-cinal product on the market.
CHAPTER 2
Supervision and sanctions
Article 37
1. After an authorization has been issued in accordance with this
Regulation, the person responsible for placing the veterinary medicinalproduct on the market shall, in respect of the methods of production andcontrol provided for in points 4 and 9 of the second paragraph of Article5 of Directive 81/851/EEC, take account of technical and scientificprogress and make changes that may be required to enable the veter-
(1) OJ No L 373, 31. 12. 1990, p. 26.
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inary medicinal product to be manufactured and checked by means of
generally accepted scientific methods. The aforementioned person mustapply for approval for these changes in accordance with this Regulation.
Upon a request from the Commission, the person responsible for
placingthe veterinary medicinal product on the market shall also reviewthe analytical detection methods provided for in point 8 of the secondparagraph of Article 5 of Directive 81/851/EEC and propose anychanges which may be necessary to take account of technical andscientific progress.
2. The person responsible for placingthe veterinary medicinal
product on the market shall forthwith inform the Agency, the Commis-sion and the Member States of any new information which might entailthe amendment of the particulars and documents referred to in Articles28 and 31 or in the approved summary of the product characteristics. Inparticular the aforementioned person shall forthwith inform the Agency,the Commission and the Member States of any prohibition or restrictionimposed by the competent authorities of any country in which theveterinary medicinal product is marketed and of any other new informa-tion which might influence the evaluation of the benefits and risks ofthe veterinary medicinal product concerned.
3. If the person responsible for placingthe veterinary medicinal
product on the market proposes to make any alteration to the informa-tion and particulars referred to in Articles 28 and 31, he shall submit anapplication to the Agency.
4. The Commission shall, in consultation with the Agency, adopt
appropriate arrangements for the examination of variations to the termsof a marketingauthorization.
These arrangements shall include a notification system or administrative
procedures concerningminor variations and define precisely the conceptof ‘a minor variation'.
These arrangements shall be adopted by the Commission in the form of
an implementingReg ulation in accordance with the procedure laiddown in Article 72.
Article 38
In the case of veterinary medicinal products manufactured within the
Community, the supervisory authorities shall be the competent authori-ties of the Member State or Member States which have granted themanufacturingauthorization provided for in Article 24 of Directive85/851/EEC in respect of the manufacture of the veterinary medicinalproduct concerned.
In the case of veterinary medicinal products imported from third coun-
tries, the supervisory authorities shall be the competent authorities ofthe Member States in which the controls referred to in Article 30 (1) (b)of Directive 81/851/EEC are carried out unless appropriate arrange-ments have been made between the Community and the exportingcountry to ensure that those controls are carried out in the exportingcountry and that the manufacturer applies standards of good manufac-turingpractice at least equivalent to those laid down by the Community.
A Member State may request assistance from another Member State or
the Agency.
Article 39
1. The supervisory authorities shall have responsibility for verifying
on behalf of the Community that the person responsible for placingtheveterinary medicinal product on the market, or manufacturer or importerfrom third countries satisfies the requirements laid down in Chapter Vof Directive 81/851/EEC and for exercisingsupervision over suchpersons in accordance with Chapter VI of Directive 81/851/EEC.
2. Where, in accordance with the second paragraph of Article 39 of
Directive 81/851/EEC, the Commission is informed of serious differ-ences of opinion between Member States as to whether the personresponsible for placingthe veterinary medicinal product on the market
1993R2309 — EN — 25.03.1998 — 001.001 — 19
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or a manufacturer or importer established within the Community issatisfyingthe requirements referred to in parag raph 1, the Commissionmay, after consultation with the Member States concerned, request aninspector from the supervisory authority to undertake a new inspectionof the aforementioned person, the manufacturer or the importer; theinspector in question may be accompanied by an inspector from aMember State which is not party to the dispute and/or by a rapporteuror expert nominated by the Committee.
3. Subject to any arrangements which may have been concluded
between the Community and third countries in accordance with thesecond paragraph of Article 38, the Commission may, upon receipt of areasoned request from a Member State, the Committee for VeterinaryMedicinal Products, or on its own initiative, require a manufacturerestablished in a third country to submit to an inspection. The inspectionshall be undertaken by appropriately qualified inspectors from theMember States, who may, if appropriate, be accompanied by a rappor-teur or expert nominated by the Committee. The report of the inspectorsshall be made available to the Commission, the Member States and theCommittee for Veterinary Medicinal Products.
Article 40
1. Where the supervisory authorities or the competent authorities of
any other Member State are of the opinion that the manufacturer orimporter from third countries is no longer fulfilling the obligations laiddown in Chapter V of Directive 81/851/EEC, they shall forthwithinform the Committee and the Commission, statingtheir reasons indetail and indicatingthe course of action proposed.
The same shall apply where a Member State or the Commission
considers that one of the measures envisaged in Chapter VI of Directive81/851/EEC should be applied in respect of the veterinary medicinalproduct concerned or where the Committee for Veterinary MedicinalProducts has delivered an opinion to that effect in accordance withArticle 42.
2. The Commission shall in consultation with the Agency forthwith
examine the reasons advanced by the Member State concerned. It shallrequest the opinion of the Committee within a time limit to be deter-mined by the Commission having regard to the urgency of the matter.Whenever practicable, the person responsible for placingthe veterinarymedicinal product on the market shall be invited to provide oral orwritten explanations.
3. The Commission shall prepare a draft of the Decision to be taken
which shall be adopted in accordance with the procedure laid down inArticle 32.
However, where a Member State has invoked the provisions of para-
graph 4, the time limit provided for in Article 73 shall be reduced to 15calendar days.
4. Where urgent action is essential to protect human or animal health
or the environment, a Member State may suspend the use on its territoryof a veterinary medicinal product which has been authorized in accord-ance with this Regulation. It shall inform the Commission and the otherMember States no later than the followingworkingday of the reasonsfor its action. The Commission shall immediately consider the reasonsgiven by the Member State in accordance with paragraph 2 and shallinitiate the procedure provided for in paragraph 3.
5. A Member State which has adopted the suspensive measures
referred to in paragraph 4 may maintain them in force until such time asa definitive decision has been reached in accordance with the procedurelaid down in paragraph 3.
6. The Agency shall, upon request, inform any person concerned of
the final decision.
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CHAPTER 3
Pharmacovigilance
Article 41
For the purpose of this Chapter, the definitions given in Article 42 of
Directive 81/851/EEC shall apply.
Article 42
The Agency, acting in close cooperation with the national pharmacovi-
gilance systems established in accordance with Article 42a of Directive81/851/EEC, shall receive all relevant information about suspectedadverse reactions to veterinary medicinal products which have beenauthorized by the Community in accordance with this Regulation. Ifnecessary the Committee may, in accordance with Article 27, formulateopinions on the measures necessary to ensure the safe and effective useof such veterinary medicinal products. These measures shall be adoptedin accordance with the procedure laid down in Article 40.
The person responsible for placingthe veterinary medicinal product on
the market and the competent authorities of the Member States shallensure that all relevant information about suspected adverse reactions toveterinary medicinal products authorized in accordance with this Regu-lation are brought to the attention of the Agency in accordance with theprovisions of this Regulation.
Article 43
The person responsible for the placingon the market of a veterinary
medicinal product authorized by the Community in accordance with theprovisions of this Regulation shall have permanently and continuouslyat his disposal an appropriately qualified person responsible for pharma-covigilance.
That qualified person shall be responsible for the following:
(a) the establishment and maintenance of a system which ensures that
information about all suspected adverse reactions which arereported to the personnel of the company and to its representativesis collected, evaluated and collated so that it may be accessed at asingle point within the Community;
(b) the preparation of the reports referred to in Article 44 for the
competent authorities of the Member States and the Agency inaccordance with the requirements of this Regulation;
(c) ensuringthat any request from the competent authorities for the
provision of additional information necessary for the evaluation ofthe benefits and risks of a veterinary medicinal product is answeredfully and promptly, includingthe provision of information about thevolume of sales or prescriptions for the veterinary medicinalproduct concerned.
Article 44
1. The person responsible for placinga veterinary medicinal product
on the market shall ensure that all suspected serious adverse reactionsoccurringwithin the Community to a veterinary medicinal productauthorized in accordance with the provisions of this Regulation whichare brought to his attention are recorded and reported immediately tothe Member States in whose territory the incident occurred, and in nocase later than 15 days followingthe receipt of the information.
The aforementioned person shall ensure that all suspected serious unex-
pected adverse reactions occurringin the territory of a third country, arereported immediately to the Member States and the Agency and in nocase later than 15 days followingthe receipt of the information.
The arrangements for the reporting of suspected unexpected adverse
reactions which are not serious, whether arisingin the Community or ina third country, shall be adopted in accordance with Article 48.
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2. In addition, the person responsible for placinga veterinary medi-cinal product on the market shall be required to maintain detailedrecords of all suspected adverse reactions occurringwithin or outsidethe Community which are reported to him. Unless other requirementshave been laid down as a condition of the granting of the marketingauthorization by the Community, these records shall be submitted to theAgency and Member States immediately upon request or at least everysix months duringthe first two years followingauthorization and once ayear for the followingthree years. Thereafter, the records shall besubmitted at five-yearly intervals together with the application ofrenewal of the authorization, or immediately upon request. Theserecords shall be accompanied by a scientific evaluation.
Article 45
Each Member State shall ensure that all suspected serious adverse
reactions occurringwithin their territory to a veterinary medicinalproduct authorized in accordance with the provisions of this Regulationwhich are brought to their attention are recorded and reported imme-diately to the Agency and the person responsible for placing the veter-inary medicinal product on the market, and in no case later than 15 daysfollowingthe receipt of the information.
The Agency shall inform the national pharmacovigilance systems.
Article 46
The Commission in consultation with the Agency, Member States, and
interested parties, shall draw up guidance on the collection, verificationand presentation of adverse reaction reports.
The Agency, in consultation with the Member States and the Commis-
sion, shall set up a data-processingnetwork for the rapid transmission ofdata between the competent Community authorities in the event of analert relatingto faulty manufacture, serious adverse reactions and otherpharmacovigilance data regarding veterinary medicinal productsmarketed in the Community.
Article 47
The Agency shall cooperate with international organizations concerned
with veterinary pharmacovigilance.
Article 48
Any amendment which may be necessary to update the provisions of
this Chapter to take account of scientific and technical progress shall beadopted in accordance with the provisions of Article 72.
TITLE IV
THE EUROPEAN AGENCY FOR THE EVALUATION OF MEDICINAL
PRODUCTS
CHAPTER 1
Tasks of the Agency
Article 49
A European Agency for the Evaluation of Medicinal Products is hereby
established.
The Ag ency shall be responsible for coordinatingthe existingscientific
resources put at its disposal by the competent authorities of the MemberStates for the evaluation and supervision of medicinal products.
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Article 50
1. The Agency shall comprise:
(a) the Committee for Proprietary Medicinal Products, which shall be
responsible for preparingthe opinion of the Ag ency on any questionrelatingto the evaluation of medicinal products for human use;
(b) the Committee for Veterinary Medicinal Products, which shall be
responsible for preparingthe opinion of the Ag ency on any questionrelatingto the evaluation of veterinary medicinal products;
(c) a Secretariat, which shall provide technical and administrative
support for the two Committees and ensure appropriate coordinationbetween them;
(d) an Executive Director, who shall exercise the responsibilities set out
in Article 55;
(e) a Management Board, which shall exercise the responsibilities set
out in Articles 56 and 57.
2. The Committee for Proprietary Medicinal Products and the
Committee for Veterinary Medicinal Products may each establishworkingparties and expert g roups.
3. The Committee for Proprietary Medicinal Products and the
Committee for Veterinary Medicinal Products may, if they consider itappropriate, seek guidance on important questions of a general scientificor ethical nature.
Article 51
In order to promote the protection of human and animal health and of
consumers of medicinal products throughout the Community, and inorder to promote the completion of the internal market through theadoption of uniform regulatory decisions based on scientific criteriaconcerningthe placingon the market and use of medicinal products, theobjectives of the Agency shall be to provide the Member States and theinstitutions of the Community with the best possible scientific advice onany question relatingto the evaluation of the quality, the safety, and theefficacy of medicinal products for human or veterinary use, which isreferred to it in accordance with the provisions of Community legisla-tion relatingto medicinal products.
To this end, the Agency shall undertake the following tasks within its
Committees:
(a) the coordination of the scientific evaluation of the quality, safety
and efficacy of medicinal products which are subject to Communitymarketingauthorization procedures;
(b) the transmission of assessment reports, summaries of product char-
acteristics, labels and package leaflets or inserts for these medicinalproducts;
(c) the coordination of the supervision, under practical conditions of
use, of medicinal products which have been authorized within theCommunity and the provision of advice on the measures necessaryto ensure the safe and effective use of these products, in particularby evaluatingand makingavailable throug h a database informationon adverse reactions to the medicinal products in question (pharma-covigilance);
(d) advisingon the maximum limits for residues of veterinary medi-
cinal products which may be accepted in foodstuffs of animal originin accordance with Regulation (EEC) No 2377/90.
(e) coordinatingthe verification of compliance with the principles of
good manufacturing practice, good laboratory practice and goodclinical practice;
(f) upon request, providingtechnical and scientific support for steps to
improve cooperation between the Community, its Member States,international organizations and third countries on scientific andtechnical issues relatingto the evaluation of medicinal products;
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(g ) recordingthe status of marketingauthorizations for medicinal prod-
ucts granted in accordance with Community procedures;
(h) providingtechnical assistance for the maintenance of a database on
medicinal products which is available for public use;
(i) assistingthe Community and Member States in the provision of
information to health care professionals and the general publicabout medicinal products which have been evaluated within theAgency;
(j) where necessary, advisingcompanies on the conduct of the various
tests and trials necessary to demonstrate the quality, safety andefficacy of medicinal products.
Article 52
1. The Committee for Proprietary Medicinal Products and the
Committee for Veterinary Medicinal Products shall each consist of twomembers nominated by each Member State for a term of three yearswhich shall be renewable. They shall be chosen by reason of their roleand experience in the evaluation of medicinal products for human andveterinary use as appropriate and shall represent their competent author-ities.
The Executive Director of the Agency or his representative and repre-
sentatives of the Commission shall be entitled to attend all meetings ofthe Committees, their workingparties and expert g roups.
Members of each Committee may arrange to be accompanied by
experts.
2. In addition to their task of providingobjective scientific opinions
to the Community and Member States on the questions which arereferred to them, the members of each Committee shall ensure that thereis appropriate coordination between the tasks of the Agency and thework of competent national authorities, includingthe consultativebodies concerned with the marketingauthorization.
3. The members of the Committees and the experts responsible for
evaluatingmedicinal products shall rely on the scientific assessment andresources available to the national marketingauthorization bodies. EachMember State shall monitor the scientific level of the evaluation carriedout and supervise the activities of members of the Committees and theexperts it nominates, but shall refrain from giving them any instructionwhich is incompatible with the tasks incumbent upon them.
4. When preparingthe opinion, each Committee shall use its best
endeavours to reach a scientific consensus. If such a consensus cannotbe reached, the opinion shall consist of the position of the majority ofmembers and may, at the request of those concerned, include thedivergent positions with their grounds.
Article 53
1. Where, in accordance with the provisions of this Regulation, the
Committee for Proprietary Medicinal Products or the Committee forVeterinary Medicinal Products is required to evaluate a medicinalproduct, the Committee shall appoint one of its members to act asrapporteur for the coordination of the evaluation, takinginto considera-tion any proposal from the applicant for the choice of a rapporteur. TheCommittee may appoint a second member to act as co-rapporteur.
The Committee shall ensure that all its members undertake the role of
rapporteur or co-rapporteur.
2. Member States shall transmit to the Agency a list of experts with
proven experience in the assessment of medicinal products who wouldbe available to serve on workingparties or expert g roups of theCommittee for Proprietary Medicinal Products or the Committee forVeterinary Medicinal Products, together with an indication of theirqualifications and specific areas of expertise.
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This list shall be updated as necessary.
3. The provision of services by rapporteurs or experts shall be
governed by a written contract between the Agency and the personconcerned, or where appropriate between the Agency and his employer.The person concerned, or his employer, shall be remunerated in accord-ance with a fixed scale of fees to be included in the financial arrange-ments established by the Management Board.
4. On a proposal from the Committee for Proprietary Medicinal
Products or the Committee for Veterinary Medicinal Products, theAgency may also avail itself of the services of rapporteurs or experts forthe discharge of other specific responsibilities of the Agency.
Article 54
1. The membership of the Committee for Proprietary Medicinal
Products and the Committee for Veterinary Medicinal Products shall bemade public. When each appointment is published, the professionalqualifications of each member shall be specified.
2. Members of the Management Board, Committee members, rappor-
teurs and experts shall not have financial or other interests in thepharmaceutical industry which could affect their impartiality. Allindirect interests which could relate to this industry shall be entered in aregister held by the Agency which the public may consult.
Article 55
1. The Executive Director shall be appointed by the Management
Board, on a proposal from the Commission, for a period of five years,which shall be renewable.
2. The Executive Director shall be the legal representative of the
Agency. He shall be responsible:
— for the day-to-day administration of the Agency,— for the provision of appropriate technical support for the Committee
for Proprietary Medicinal Products and the Committee for Veter-inary Medicinal Products, and their workingparties and expertgroups,
— for ensuringthat the time limits laid down in Community leg islation
for the adoption of opinions by the Agency are respected,
— for ensuringappropriate coordination between the Committee for
Proprietary Medicinal Products and the Committee for VeterinaryMedicinal Products,
— for the preparation of the statement of revenue and expenditure and
the execution of the budget of the Agency,
— for all staff matters.
3. Each year, the Executive Director shall submit to the Management
Board for approval, while makinga distinction between the Ag ency’sactivities concerningmedicinal products for human use and thoseconcerningveterinary medicinal products:
— a draft report coveringthe activities of the Ag ency in the previous
year, includinginformation about the number of applications eval-uated within the Agency, the time taken for the completion of theevaluation and the medicinal products authorized, rejected or with-drawn,
— a draft programme of work for the coming year,— the draft annual accounts for the previous year,— the draft budget for the coming year.
4. The Executive Director shall approve all financial expenditure of
the Agency.
Article 56
1. The Management Board shall consist of two representatives from
each Member State, two representatives of the Commission and tworepresentatives appointed by the European Parliament. One repres-
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entative shall have specific responsibilities relatingto medicinal prod-
ucts for human use and one relatingto veterinary medicinal products.
Each representative may arrange to be replaced by an alternate.2. The term of office of the representatives shall be three years. It
shall be renewable.
3. The Management Board shall elect its Chairman for a term of
three years and shall adopt its rules of procedure.
Decisions of the Management Board shall be adopted by a majority of
two-thirds of its members.
4. The Executive Director shall provide the Secretariat of the
Management Board.
5. Before 31 January each year, the Management Board shall adopt
the general report on the activities of the Agency for the previous yearand its programme of work for the coming year and forward them to theMember States, the Commission, the Council and the European Parlia-ment.
CHAPTER 2
Financial provisions
Article 57
1. The revenues of the Agency shall consist of a contribution from
the Community, and the fees paid by undertakings for obtaining andmaintaininga Community marketingauthorization and for otherservices provided by the Agency.
2. The expenditure of the Agency shall include the staff, adminis-
trative, infrastructure and operational expenses and expenses resultingfrom contracts entered into with third parties.
3. By 15 February each year at the latest, the Director shall draw up
a preliminary draft budget covering the operational expenditure and theprogramme of work anticipated for the following financial year, andshall forward this preliminary draft to the Management Board togetherwith an establishment plan.
4. Revenue and expenditure shall be in balance.5. The Management Board shall adopt the draft budget and forward
it to the Commission which on that basis shall establish the relevantestimates in the preliminary draft general budget of the EuropeanCommunities, which it shall put before the Council pursuant to Article203 of the Treaty.
6. The Management Board shall adopt the Agency’s final budget
before the beg inningof the financial year, adjustingit where necessaryto the Community subsidy and the Agency’s other resources.
7. The Director shall implement the Agency’s budget.8. Monitoringof the commitment and payment of all the Ag ency’s
expenditure and of the establishment and recovery of all the Agency’srevenue shall be carried out by the financial controller appointed by theManagement Board.
9. By 31 March each year at the latest, the Director shall forward to
the Commission, the Management Board and the Court of Auditors theaccounts for all the Agency’s revenue and expenditure in respect of theprecedingfinancial year.
The Court of Auditors shall examine them in accordance with Article
206a of the Treaty.
10. The Management Board shall give a discharge to the Director in
respect of the implementation of the budget.
11. After the Court of Auditors has delivered its opinion, the
Management Board shall adopt the internal financial provisions speci-
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fying, in particular, the detailed rules for establishing and implementingthe Agency’s budget.
Article 58
The structure and the amount of the fees referred to in Article 57 (1)
shall be established by the Council actingunder the conditions providedfor by the Treaty on a proposal from the Commission, followingconsul-tation of organizations representing the interests of the pharmaceuticalindustry at Community level.
CHAPTER 3
General provisions governing the Agency
Article 59
The Agency shall have legal personality. In all Member States it shall
benefit from the widest powers granted by law to legal persons. Inparticular it may acquire and dispose of real property and chattels andinstitute legal proceedings.
Article 60
1. The contractual liability of the Agency shall be governed by the
law applicable to the contract in question. The Court of Justice of theEuropean Communities shall have jurisdiction to give judgmentpursuant to any arbitration clause contained in a contract concluded bythe Agency.
2. In the case of non-contractual liability, the Agency shall, in
accordance with the general principles common to the laws of theMember States, make good any damage caused by it or its servants inthe performance of their duties.
The Court of Justice shall have jurisdiction in any dispute relatingto
compensation for such damages.
3. The personal liability of its servants towards the Agency shall be
governed by the relevant conditions applying to the staff of the Agency.
Article 61
The Protocol on the Privileges and Immunities of the European
Communities shall apply to the Agency.
Article 62
The staff of the Agency shall be subject to the rules and regulations
applicable to officials and other staff of the European Communities.
In respect of its staff, the Agency shall exercise the powers which have
been devolved to the appointingauthority.
The Management Board, in agreement with the Commission, shall
adopt the necessary implementingprovisions.
Article 63
Members of the Management Board, members of Committees, and
officials and other servants of the Agency shall be required, even aftertheir duties have ceased, not to disclose information of the kind coveredby the obligation of professional secrecy.
Article 64
The Commission may, in agreement with the Management Board and
the relevant Committee, invite representatives of international organ-izations with interests in the harmonization of regulations applicable tomedicinal products to participate as observers in the work of theAgency.
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Article 65
The Management Board shall, in agreement with the Commission,
develop appropriate contacts between the Agency and the representa-tives of the industry, consumers and patients and the health professions.
Article 66
The Agency shall take up its responsibilities on 1 January 1995.
TITLE V
GENERAL AND FINAL PROVISIONS
Article 67
All decisions to grant, refuse, vary, suspend, withdraw or revoke a
marketingauthorization which are taken in accordance with this Reg u-lation shall state in detail the reasons on which they are based. Suchdecisions shall be notified to the party concerned.
Article 68
1. An authorization to place on the market a medicinal product
comingwithin the scope of this Reg ulation shall not be refused, varied,suspended, withdrawn or revoked except on the grounds set out in thisRegulation.
2. An authorization to place on the market a medicinal product
coming within the scope of this Regulation shall not be granted,refused, varied, suspended, withdrawn or revoked except in accordancewith the procedures set out in this Regulation.
Article 69
Without prejudice to Article 68, and without prejudice to the Protocol
on the Privileges and Immunities of the European Communities, eachMember State shall determine the penalties to be applied for theinfringement of the provisions of this Regulation. The penalties must besufficient to promote compliance with those measures.
Member States shall forthwith inform the Commission of the institution
of any infringement proceedings.
Article 70
Additives covered by Council Directive 70/524/EEC of 23 November
1970 concerningadditives in feeding stuffs(
1), where they are intended
to be administered to animals in accordance with that Directive, shallnot be considered as veterinary medicinal products for the purposes ofthis Regulation.
Within three years of the entry into force of this Regulation the
Commission shall produce a report on whether the level of harmon-ization achieved by this Regulation and by Council Directive 90/167/EEC of 26 March 1990 layingdown the conditions g overningthepreparation, placingon the market and use of medicated feeding stuffs inthe Community (
2) is equivalent to that provided for in Council
Directive 70/524/EEC, accompanied if necessary by the proposals tomodify the status of the coccidiostats and other medicinal substancescovered by that Directive.
The Council shall decide on the Commission proposal no later than one
year after their submission.
(1) OJ No L 270, 14. 12. 1970, p. 1. Directive last amended by Commission
Directive 92/64/EEC (OJ No L 221, 6. 8. 1992, p. 51).
(2) OJ No L 92, 7. 4. 1990, p. 42.
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Article 71
Within six years of the entry into force of this Regulation, the Commis-
sion shall publish a general report on the experience acquired as a resultof the operation of the procedures laid down in this Regulation, inChapter III of Directive 75/319/EEC and in Chapter IV of Directive81/851/EEC.
Article 72
Where the procedure laid down in this Article is to be followed the
Commission shall be assisted by:
— the StandingCommittee on Medicinal Products for Human Use, in
the case of matters relatingto medicinal products for human use,
— the StandingCommittee on Veterinary Medicinal Products, in the
case of matters relatingto veterinary medicinal products.
The representative of the Commission shall submit to the Committee a
draft of the measures to be taken. The Committee shall deliver itsopinion on the draft within a time limit which the Chairman may laydown accordingto the urg ency of the matter. The opinion shall bedelivered by the majority laid down in Article 148 (2) of the Treaty inthe case of decisions which the Council is required to adopt on aproposal from the Commission. The votes of the representatives of theMember States within the Committee shall be weighted in the mannerset out in that Article. The Chairman shall not vote.
The Commission shall adopt the measures envisaged if they are in
accordance with the opinion of the Committee.
If the measures envisaged are not in accordance with the opinion of the
Committee, or if no opinion is delivered, the Commission shall, withoutdelay, submit to the Council a proposal relatingto the measures to betaken. The Council shall act by a qualified majority.
If on the expiry of a period of three months from the date of referral to
the Council, the Council has not acted, the proposed measures shall beadopted by the Commission.
Article 73
Where the procedure laid down in this Article is to be followed the
Commission shall be assisted by:
— the StandingCommittee on Medicinal Products for Human Use, in
the case of matters relatingto medicinal products for human use,
— the StandingCommittee on Veterinary Medicinal Products, in the
case of matters relatingto veterinary medicinal products.
The representative of the Commission shall submit to the Committee a
draft of the measures to be taken. The Committee shall deliver itsopinion on the draft within a time limit which the Chairman may laydown accordingto the urg ency of the matter. The opinion shall bedelivered by the majority laid down in Article 148 (2) of the Treaty inthe case of decisions which the Council is required to adopt on aproposal from the Commission. The votes of the representatives of theMember States within the Committee shall be weighted in the mannerset out in that Article. The Chairman shall not vote.
The Commission shall adopt the measures envisaged if they are in
accordance with the opinion of the Committee.
If the measures envisaged are not in accordance with the opinion of the
Committee, or if no opinion is delivered, the Commission shall, withoutdelay, submit to the Council a proposal relatingto the measures to betaken. The Council shall act by a qualified majority.
If on the expiry of a period of three months from the date of referral to
the Council, the Council has not acted, the proposed measures shall beadopted by the Commission, save where the Council has decidedagainst the said measures by a simple majority.
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Article 74
This Regulation shall enter into force on the day following the decision
taken by the competent authorities on the headquarters of the Agency.
Subject to the first subparagraph Titles I, II, III and V shall enter into
force on 1 January 1995.
This Regulation shall be binding in its entirety and directly applicable in
all Member States.
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ANNEX
PART A
Medicinal products developed by means of one of the followingbiotechnolog ical
processes:
— recombinant DNA technology,— controlled expression of genes coding for biologically active proteins in
prokaryotes and eukaryotes includingtransformed mammalian cells,
— hybridoma and monoclonal antibody methods.
Veterinary medicinal products, includingthose not derived from biotechnolog y,
intended primarily for use as performance enhancers in order to promote thegrowth of treated animals or to increase yields from treated animals.
PART B
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 astwo-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 intendedfor human use.
▼
M1
Veterinary medicinal products containinga new active substance which, on thedate of entry into force of this Regulation, was not authorised by any MemberState for use in animals.