1993R2309 — EN — 05.06.2003 — 002.001 — 1
This document is meant purely as a documentation tool and the institutions do not assume any liability for its contents
►B COUNCILREGULATION(EEC)No2309/93
of22July1993
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 Medic-
inalProducts
(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
►M2Council Regulation (EC) No 807/2003 of 14 April 2003 L 122 36 16.5.2003
▼B
COUNCILREGULATION(EEC)No2309/93
of22July1993
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 Medic-
inalProducts
THE COUNCIL OF THE EUROPEAN COMMUNITIES,
Having regard to the Treaty establishing the European EconomicCommunity, and in particular Article 235 thereof,
Having regard to the proposal from the Commission (
1),
Having regard to the opinion of the European Parliament (2),
Having regard to the opinion of the Economic and Social
Committee (3),
WhereasCouncil Directive 87/22/EEC of 22 December 1986 on the
approximation of national measures relating to the placing on themarket of high-technology medicinal productsparticularly thos ederived from biotechnology (
4) has established a Community
mechanism for concertation, prior to any national decision relating to
a high-technology medicinal product, with a view to arriving at
uniform decisions throughout the Community; whereas this routeshould be followed, particularly in order to ensure the smooth func-tioning of the internal market in the pharmaceutical sector;
Whereasthe experience acquired asa res ult of Directive 87/22/EEC
has shown that it is necessary to establish a centralized Communityauthorization procedure for technologically advanced medicinalproducts, in particular those derived from biotechnology; whereas this
procedure should also be available to persons responsible for placing
on the market medicinal products containing new active substanceswhich are intended for use in human beings or in food-producinganimals;
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 efficacyof the medicinal product concerned to the exclusion of economic orother considerations; whereas, however, Member States should excep-
tionally be able to prohibit the use on their territory of medicinal
productsfor human us e which infringe objectively defined conceptsofpublic order or public morality; whereas, moreover, a veterinary medic-inal product may not be authorized by the Community if itsus e wouldcontravene the legal measures laid down by the Community within theframework of 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 approximation
of provisions laid down by law, regulation or administrative action
relating to 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 proprie-tary medicinal products(
6), and by Council Directive 75/318/EEC of
20 May 1975 on the approximation of the lawsof the Member States1993R2309 — EN — 05.06.2003 — 002.001 — 2
(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).
▼B
relating to analytical pharmaco-toxicological and clinical standards and
protocols in respect of the testing of 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 lawsof the Member Statesrelating toveterinary medicinal products(
2) and by Council Directive 81/852/EEC
of 28 September 1981 on the approximation of the lawsof the Member
Statesrelating to analytical, pharmaco-toxicological and clinical s tan-
dards and protocols in respect of the testing of 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 marketing authorizationbe granted by the Community by a rapid procedure ensuring close
cooperation between the Commission and Member States.
WhereasCouncil Directive 93/39/EEC of 14 June 1993 amending
Directive 65/65/EEC, 75/318/EEC and 75/319/EEC in respect ofmedicinal products(
4) hasprovided that in the event of a dis agreement
between Member Statesabout the quality, s afety or efficacy of a
medicinal product which isthe s ubject of the decentralized Community
authorization procedure, the matter should be resolved by a bindingCommunity decision following a scientific evaluation of the issuesinvolved within a European medicinal product evaluation agency;whereas similar provisions have been laid down in respect of veterinary
medicinal productsby Council Directive 93/40/EEC of 14 June 1993
amending Directives81/851/EEC and 81/852/EEC on the approxima-tion of the lawsof the Member Statesrelating to veterinary medicinalproducts(
5);
Whereasthe Community mus t be provided with the meansto undertake
a scientific evaluation of medicinal products which are presented for
authorization in accordance with the centralized Community proce-dures; whereas, furthermore, in order to achieve the effectiveharmonization of the administrative decisions taken by Member Statesin relation to individual medicinal productswhich are pres ented for
authorization in accordance with decentralized procedures, it is neces-
sary to provide the Community with the means of resolvingdisagreements between Member States about the quality, safety andefficacy of medicinal 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 institutionsand the Member Statesfor the exercis e of the powersconferred uponthem by Community legislation in the field of medicinal products in
relation to the authorization and supervision of medicinal products;
Whereas it is necessary to ensure close cooperation between the
Agency and scientists working within the Member States;
Whereas, therefore, the exclusive responsibility for preparing the
opinionsof the Agency on all mattersrelating to medicinal products
for human use should be entrusted to the Committee for ProprietaryMedicinal Productscreated by the Second Council Directive 75/319/1993R2309 — EN — 05.06.2003 — 002.001 — 3
(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 thisOfficial Journal.
(5) See page 31 of thisOfficial Journal.
▼B
CEE; whereas in respect of veterinary medicinal products this respon-
sibility should be entrusted to the Committee for Veterinary MedicinalProductscreated by Directive 81/851/EEC;
Whereas the establishment of the Agency will make it possible to rein-
force the scientific role and independence of these two Committees, inparticular through the establishment of a permanent technical and
administrative secretariat;
Whereas it is also necessary to make provisions for the supervision of
medicinal productswhich have been authorized by the Community, andin particular for the intensive monitoring of adverse reactions to those
medicinal productsthrough Community pharmacovigilance activitiesin
order to ensure the rapid withdrawal from the market of any medicinalproduct which presents an unacceptable level of risk under normalconditionsof us e;
Whereas the Commission, working in close cooperation with the
Agency, and after consultation with Member States, should also beentrusted with the task of coordinating the discharge of the varioussupervisory responsibilities of Member States and in particular theprovisions of information about medicinal products, monitoring the
respect of good manufacturing practices, good laboratory practices and
good clinical practices;
Whereas the Agency should also be responsible for coordinating the
activitiesof the Member Statesin the field of the monitoring of
adverse reactions to medicinal products (pharmacovigilance);
Whereas it is necessary to provide for the orderly introduction of
Community proceduresfor the authorization of medicinal productsalongside the national procedures of the Member States which have
already been extensively harmonized by Directives 65/65/EEC, 75/
319/EEC and 81/851/EEC; whereasit istherefore appropriate in thefirst instance to limit the obligation to use the new Community proce-dure to certain medicinal products; whereas the scope of theCommunity proceduress hould be reviewed in the light of experience
at the latest six years after the entry into force of this Regulation;
Whereas risks to the environment may be associated with medicinal
products containing or consisting of genetically modified organisms;whereas therefore it is necessary to provide for an environmental risk
assessment of such products similar to that provided for by Council
Directive 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;
Whereasthe Treaty doesnot 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:
TITLE1
DEFINITIONSANDSCOPE
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 Evalua-
tion 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 system1993R2309 — EN — 05.06.2003 — 002.001 — 4
(1) OJ No L 117, 8. 5. 1990, p. 15.
▼B
of 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 the
marketing authorization those therapeutic indications and pack sizes
which will be covered by their social security organizations.
Article 2
The definitionslaid down in Article 1 of Directive 65/65/EEC and
those laid down in Article 1 (2) of Directive 81/851/EEC shall applyfor the purposes of this Regulation.
The person responsible for placing the 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 marketing author-
ization hasbeen granted by the Community in accordance with theprovisions of this Regulation.
2. The person responsible for placing on 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 the
Community in accordance with the provisions of this Regulation.
3. Before entry into force of thisRegulation and after cons ultation
of the Committee for Proprietary Medicinal Products, Parts A and Bof the Annex as regards medicinal products for human use shall be re-examined in the light of scientific and technical progress with a view tomaking any amendments necessary which will be adopted under the
procedure laid down in Article 72.
4. Before entry into force of thisRegulation and after cons ultation
of the Committee for Veterinary Medicinal Products, Parts A and B ofthe Annex asregardsveterinary medicinal productss hall be re-exam-ined in the light of scientific and technical progress with a view tomaking any amendments necessary which will be adopted under the
procedure laid down in Article 72.
5. The proceduresreferred to in paragraphs3 and 4 s hall continue to
apply after entry into force of thisRegulation.
Article 4
1. In order to obtain the authorization referred to in Article 3, the
person responsible for placing a 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
under Title IV.
2. The Community shall issue and supervise marketing authoriza-
tionsfor medicinal productsfor human us e in accordance with Title II.
3. The Community shall issue and supervise marketing authoriza-
tionsfor veterinary medicinal productsin accordance with Title III.
TITLEII
AUTHORIZATION AND SUPERVISION OF MEDICINAL
PRODUCTSFORHUMANUSE
CHAPTER 1
Submission and examination of applications — authorizations —
renewalofauthorization
Article 5
The Committee for Proprietary Medicinal Products established by
Article 8 of Directive 75/319/EEC, in thisTitle referred to as‘theCommittee’, shall be responsible for formulating the opinion of the1993R2309 — EN — 05.06.2003 — 002.001 — 5
▼B
Agency on any question concerning the admissibility of the files
submitted in accordance with the centralized procedure, the granting,variation, suspension or withdrawal of an authorization to place a
medicinal product for human use on the market arising in accordance
with the 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 documents
referred to in Articles4 and 4a of Directive 65/65/EEC, in the Annex
to Directive 75/318/EEC and in Article 2 of Directive 75/319/EEC.
2. In the case of a medicinal product containing or consisting of
genetically modified organisms within the meaning of Article 2 (1)and (2) of Directive 90/220/EEC, the application must also be accom-
panied by:
— a copy of any written consent or consents of the competent autho-
ritiesto the deliberate releas e into the environment of the
genetically modified organisms for research and development
purposes where provided for by Part B of Directive 90/220/EEC,
— the complete technical dossier supplying the information requested
in AnnexesII and III to Directive 90/220/EEC and the environ-mental risk assessment resulting from this information; the resultsof any investigations performed for the purposes of research ordevelopment.
Articles11 to 18 of Directive 90/220/EEC s hall not apply to medicinal
products for human use containing or consisting of genetically modi-fied organisms.
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 daysof the receipt of a valid application.
In the case of a medicinal product containing or consisting of geneti-
cally modified organisms, the opinion of the Committee shall respect
the environmental safety requirements laid down by Directive 90/220/
EEC to ensure that all appropriate measures are taken to avoid adverseeffectson human health and the environment which might aris e fromthe deliberate release or placing on the market of genetically modifiedorganisms. During the process of evaluating applications for marketingauthorizations for products containing or consisting of genetically
modified organisms, necessary consultations will be held by the rappor-
teur with the bodiess et up the Community or the Member Statesinaccordance 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
the form in which applicationsfor authorization are to be pres ented.
Article 7
In order to prepare itsopinion, the Committee:
(a) shall verify that the particulars and documents submitted in accor-
dance with Article 6 comply with the requirementsof Directives
65/65/EEC, 75/318/EEC and 75/319/EEC, and examine whether
the conditions 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 starting materials and, ifneed be, itsintermediate productsor other cons tituent materialsinorder 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
particularsaccompanying the application within a s pecific timelimit. Where the Committee availsits elf of thisopinion, the timelimit laid down in Article 6 shall be suspended until such time as1993R2309 — EN — 05.06.2003 — 002.001 — 6
▼B
the 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.
Article 8
1. Upon receipt of a written request from the Committee, a Member
State shall forward the information establishing that the manufacturer
of a medicinal product or the importer from a third country isable tomanufacture the medicinal product concerned and/or carry out thenecessary control tests in accordance with the particulars and docu-ments supplied pursuant to Article 6.
2. Where it considers it necessary in order to complete its examina-
tion of an application, the Committee may require the applicant to
submit to a specific inspection of the manufacturing site of the medic-inal 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-cationsand who may, if need be, be accompanied by a rapporteur or
expert appointed by the Committee.
Article 9
1. Where the opinion of the Committee isthat:
— the application does not satisfy the criteria for authorization set out
in thisRegulation, or
— the summary of the product characteristics proposed by the appli-
cant in accordance with Article 6 should be amended, or
— the labelling or package leaflet of the product isnot in compliance
with Council Directive 92/27/EEC of 31 March 1992 on the label-ling of medicinal productsfor human us e and on package
leaflets(
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 groundsfor hisappeal to the Agency within 60 daysof receiptof the opinion. Within 60 daysof the receipt of the groundsfor appeal,the Committee shall consider whether its opinion should be revised,
and the conclusions reached on the appeal shall be annexed to the
assessment report referred to in paragraph 2.
2. Within 30 daysof itsadoption, the Agency s hall 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 stating the reasons for its
conclusions.
3. In the event of an opinion in favour of granting the relevant
authorization to place the medicinal product concerned on the market,the following documentss hall 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) details of any conditions or restrictions which should be imposed
on the supply or use of the medicinal product concerned, includingthe conditionsunder which the medicinal product may be madeavailable to patients, having regard to the criteria laid down inCouncil Directive 92/26/EEC of 31 March 1992 concerning the
classification for the supply of medicinal products for human
use (
2), without prejudice to the provisions in Article 3 (4) of that
Directive;1993R2309 — EN — 05.06.2003 — 002.001 — 7
(1) OJ No L 113, 30. 4. 1992, p. 8.
(2) OJ No L 113, 30. 4. 1992, p. 5.
▼B
(c) the draft text of the labelling and package leaflet proposed by the
applicant, presented in accordance with Directive 92/27/EEC,without prejudice to the provisions of Article 7 (2) of that Direc-
tive;
(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,taking account of Community law.
In the event of a draft decision which envisages the granting of
marketing authorization, the documentsreferred 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 detailed
explanation 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 rulesof procedure of the Committee referred to in Article 73
shall be adjusted to take account of the tasks incumbent upon it inaccordance with thisRegulation.
These adjustments shall involve the following:
— except in cases referred to in the third subparagraph of paragraph 1,
the opinion of the Standing Committee shall be obtained in writing,
— each Member State isallowed at leas t 28 daysto forward written
observations on the draft decision to the Commission,
— each Member State isable to require in writing that the draft deci-
sion be discussed by the Standing Committee, giving its reasons indetail.
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 to
the 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 authori-
zation provided for in Article 3 shall be refused if, after verification ofthe information and particularss ubmitted in accordance with Article 6,it appearsthat the quality, the s afety or the efficacy of the medicinalproduct have not been adequately or sufficiently demonstrated by the
applicant.
Authorization shall likewise be refused if the particulars and documents
provided by the applicant in accordance with Article 6 are incorrect orif the labelling and package leafletspropos ed by the applicant are notin accordance with Directive 92/27/EEC.
Article 12
1. Without prejudice to Article 6 of Directive 65/65/EEC, a
marketing authorization which hasbeen granted in accordance withthe procedure laid down in thisRegulation s hall be valid throughoutthe Community. It shall confer the same rights and obligations in each1993R2309 — EN — 05.06.2003 — 002.001 — 8
▼B
of the Member Statesasa marketing authorization granted by that
Member State in accordance with Article 3 of Directive 65/65/EEC.
The authorized medicinal productss hall be entered in the Community
Register of Medicinal Products and shall be given a number which
must appear on the packaging.
2. The refusal of a Community marketing authorization shall consti-
tute a prohibition on the placing on the market of the medicinal productconcerned throughout the Community.
3. Notification of marketing authorization shall be published in the
Official Journal of the European Communities , quoting in 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 Productsand the reas onsfor its
opinion 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 a
dossier containing up-to-date information on pharmacovigilance.
2. In exceptional circumstances and following consultation 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 veri-
fiable reasons and must be based on one of the causes mentioned in
Part 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 productswhich have been authorized by the Commu-
nity in accordance with the provisions of this Regulation shall benefit
from the 10-year period of protection referred to in point 8 of the
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 Statesof the manufacturer or, whereapplicable, of the person responsible for placing the medicinal product
on the market.
CHAPTER 2
Supervisionandsanctions
Article 15
1. After an authorization has been issued in accordance with this
Regulation, the person responsible for placing the medicinal producton the market shall, in respect of the methods of production and controlprovided for in points4 and 7 of the s econd paragraph of Article 4 of
Directive 65/65/EEC, take account of technical and scientific progress
and make any amendmentsthat may be required to enable the medic-inal productsto be manufactured and checked by meansof generallyaccepted scientific methods. The aforementioned person must applyfor approval for these amendments in accordance with this Regulation.
2. The person responsible for placing the medicinal product on the
market shall forthwith inform the Agency, the Commission and theMember Statesof any new information which might entail the amend-ment of the particularsand documentsreferred to in Articles6 or 9 orin the approved summary of the product characteristics. In particularthe aforementioned person shall forthwith inform the Agency, the1993R2309 — EN — 05.06.2003 — 002.001 — 9
▼B
Commission and the Member States of any prohibition or restriction
imposed by the competent authorities of any country in which themedicinal product isplaced on the market and of any other new info-
mation which might influence the evaluation of the benefitsand ris ks
of the medicinal product concerned.
3. If the person responsible for placing the 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 the
Agency.
4. The Commission shall, in consultation with the Agency, adopt
appropriate arrangementsfor the examination of variationsto the termsof a marketing authorization.
These arrangements shall include a notification system or administra-
tive proceduresconcerning minor variationsand define precis ely theconcept of ‘a minor variation’.
These arrangements shall be adopted by the Commission in the form of
an implementing Regulation 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 the
Member State or Member Stateswhich 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
Member Statesin which the controlsreferred to in Article 22 (1) (b)of Directive 75/319/EEC are carried out unless appropriate arrange-mentshave been made between the Community and the exportingcountry to ensure that those controls are carried out in the exporting
country and that the manufacturer appliess tandardsof good manufac-
turing practice at least equivalent to those laid down by theCommunity.
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 placing themedicinal product on the market or the manufacturer or importer from
third countries satisfies the requirements laid down in Chapter IV of
Directive 75/319/EEC and for exercising supervision 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-
encesof opinionsbetween Member Statesasto whether the pers on
responsible for placing the medicinal product on the market or a manu-facturer or importer established within the Community is satisfying therequirements 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 the
aforementioned person, the manufacturer or the importer; the inspector
in question may be accompanied by an inspector from a Member Statewhich isnot party to the dis pute and/or by a rapporteur or expert nomi-nated by the Committee.
3. Subject to any arrangementswhich may have been concluded
between the Community and third countriesin accordance with thesecond subparagraph of Article 16, the Commission may, upon receiptof a reasoned request from a Member State, the Committee for Proprie-tary Medicinal Products, or on its own initiative, require amanufacturer established in a third country to submit to an inspection.1993R2309 — EN — 05.06.2003 — 002.001 — 10
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The inspection shall be undertaken by appropriately qualified inspec-
torsfrom the Member States , who may, if appropriate, beaccompanied by a rapporteur or expert nominated by the Committee.
The report of the inspectors shall be made available to the Commis-
sion, the Member States and the Committee for Proprietary MedicinalProducts.
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 countriesisno longer fulfilling the obligationslaid down in Chapter IV of Directive 75/319/EEC, they shall forthwithinform the Committee and the Commission, stating their reasons in
detail and indicating the 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 of
Directive 75/319/EEC should be applied in respect of the medicinalproduct concerned or where the Committee for Proprietary MedicinalProductshasdelivered 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 shall
request the opinion of the Committee within a time limit which it shall
determine having regard to the urgency of the matter. Whenever prac-ticable, the person responsible for placing the 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 hasinvoked the provis ionsof para-
graph 4, the time limit provided for in Article 73 shall be reduced to
15 calendar days.
4. Where urgent action is essential to protect human or animal
health or the environment, a Member State may suspend the use on
itsterritory of a medicinal product which hasbeen authorized in accor-dance with this Regulation. It shall inform the Commission and theother Member Statesno later than the following working day of thereasons for its action. The Commission shall immediately consider the
reasons given by the Member State in accordance with paragraph 2 and
shall initiate the procedure provided for in paragraph 3.
5. A Member State which has adopted the suspensive measures
referred to in paragraph 4 may maintain them in force until such timeasa definitive decis ion hasbeen reached in accordance with the proce-dure laid 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 pharmacov-
igilance systems established in accordance with Article 29a of
Directive 75/319/EEC, shall receive all relevant information aboutsuspected adverse reactions to medicinal products which have beenauthorized by the Community in accordance with thisRegulation. Ifnecessary the Committee may, in accordance with Article 5, formulateopinions on the measures necessary to ensure the safe and effective use1993R2309 — EN — 05.06.2003 — 002.001 — 11
▼B
of such medicinal products. These measures shall be adopted in accor-
dance with the procedure laid down in Article 18.
The person responsible for placing the medicinal product on the market
and the competent authorities of the Member States shall ensure that allrelevant information about suspected adverse reactions to medicinal
productsauthorized in accordance with thisRegulation are brought to
the attention of the Agency in accordance with the provisions of thisRegulation.
Article 21
The person responsible for the placing on the market of a medicinal
product authorized by the Community in accordance with the provi-sions of this Regulation shall have permanently and continuously at
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 medical represen-
tatives, is collected, evaluated and collated so that it may be
accessed at a single point within the Community;
(b) the preparation of the reportsreferred to in Article 22 for the
competent authoritiesof the Member Statesand the Agency inaccordance with the requirementsof thisRegulation;
(c) ensuring that any request from the competent authorities 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 the volumeof sales or prescriptions for the medicinal product concerned.
Article 22
1. The person responsible for placing the medicinal product on the
market shall ensure that all suspected serious adverse reactions occur-ring within the Community to a medicinal product authorized in
accordance with the provisions of this Regulation which are brought
to his attention by a health care professional, are recorded and reportedimmediately to the Member Statesin whos e territory the incidentoccurred, and in no case later than 15 days following the receipt ofthe information.
The person responsible for placing the medicinal product on the market
shall ensure that all suspected serious unexpected adverse reactionsoccurring in the territory of a third country, are reported immediatelyto Member Statesand the Agency and in no cas e later than 15 days
following the receipt of the information.
The arrangements for the reporting of suspected unexpected adverse
reactions which are not serious, whether arising in the Community or
in a third country, shall be adopted in accordance with Article 26.
2. In addition, the person responsible for placing the medicinal
product on the market shall be required to maintain detailed records
of all suspected adverse reactions occurring within or outside the
Community which are reported to him by a health care professional.Unless other requirements have been laid down as a condition of thegranting of the marketing authorization by the Community, theserecords shall be submitted to the Agency and Member States immedi-
ately upon request or at least every six months during the first two
yearsfollowing authorization and once a year for the following threeyears. 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 ascientific evaluation.1993R2309 — EN — 05.06.2003 — 002.001 — 12
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Article 23
Each Member State shall ensure that all suspected serious adverse reac-
tionsoccurring within their territory to a medicinal product authorizedin accordance with the provisions of this Regulation which are brought
to their attention are recorded and reported immediately to the Agency
and the person responsible for placing the medicinal product on themarket, and in no case later than 15 days following the receipt of theinformation.
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-processing network for the rapid transmissionof data between the competent Community authoritiesin the event ofan alert relating to faulty manufacture, serious adverse reactions and
other pharmacovigilance data regarding medicinal productsmarketed
in the Community.
Article 25
The Agency shall collaborate with the World Health Organization on
international pharmacovigilance and shall take the necessary steps to
submit promptly to the World Health Organization appropriate and
adequate information regarding the measures taken in the Communitywhich may have a bearing on 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 shallbe adopted in accordance with the provisions of Article 72.
TITLEIII
AUTHORIZATION AND SUPERVISION OF VETERINARY
MEDICINALPRODUCTS
CHAPTER 1
Submission and examination of applications — authorization —
reneval ofauthorization
Article 27
The Committee for Veterinary Medicinal Products established by
Article 16 of Directive 81/851/EEC, in thisTitle referred to as‘the
Committee’, shall be responsible for formulating the opinion of the
Agency 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 aveterinary medicinal product on the market arising in accordance withthe provisions of this Title and pharmacovigilance.
Article 28
1. An application for authorization for a veterinary medicinal
product must be accompanied by the particulars and documentsreferred to in Articles5, 5a and 7 of Directive 81/851/EEC.
2. In the case of a veterinary medicinal product containing or
consisting of genetically modified organisms within the meaning of1993R2309 — EN — 05.06.2003 — 002.001 — 13
▼B
Article 2 (1) and (2) of Directive 90/220/EEC, the application must
also be accompanied by:
— a copy of any written consent or consents of the competent autho-
ritiesto the deliberate releas e into the environment of thegenetically modified organisms for research and developmentpurposes where provided for in Part B of Directive 90/220/EEC,
— the complete technical dossier supplying the information requested
in AnnexesII and III to Directive 90/220/EEC and the environ-mental risk assessment resulting from this information; the results
of any investigations performed for the purposes of research or
development.
Articles11 to 18 of Directive 90/220/EEC s hall not apply to veterinary
medicinal products containing or consisting of genetically 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 daysof the receipt of a valid application.
In the case of a veterinary medicinal product containing or consisting
of 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 mightarise from the deliberate release into the environment or placing on
the market of genetically modified organisms. During the process of
evaluating applicationsfor marketing authorizationsfor veterinarymedicinal products containing or consisting of genetically modifiedorganisms, necessary consultations shall be held by the rapporteurwith the bodiess et up by 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 onthe form in which applicationsfor authorization are to be pres ented.
Article 29
In order to prepare itsopinion, the Committee:
(a) shall verify that the particulars and documents submitted in accor-
dance with Article 28 comply with the requirementsof Directives81/851/EEC and 81/852/EEC and examine whether the conditionsspecified in this Regulation for issuing a marketing authorizationare satisfied;
(b) may ask for a State laboratory or a laboratory designated for this
purpose to test the veterinary medicinal product, its starting mate-rialsand, if need be, itsintermediate productsor other cons tituentmaterialsin order to ens ure that the control methodsemployed by
the manufacturer and described in the application documents are
satisfactory;
(c) may request a State laboratory or laboratory designated for this
purpose to verify, using samples provided by the applicant, that
the analytical detection method proposed by the applicant in accor-
dance with point 8 of the second paragraph of Article 5 ofDirective 81/851/EEC is suitable for use in routine checks to revealthe presence 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 laying
down a Community procedure for the establishment of maximum
residue limits of veterinary medicinal products in foodstuffs ofanimal origin (
1);1993R2309 — EN — 05.06.2003 — 002.001 — 14
(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).
▼B
(d) may, where appropriate, request the applicant to supplement the
particularsaccompanying the application within a s pecific timelimit. Where the Committee availsits elf of thisoption, the time
limit laid down in Article 28 shall be suspended until such time
as the supplementary information requested has been provided.Likewise, this time limit shall be suspended for the time allowedto the applicant to prepare oral or written explanations.
Article 30
1. Upon receipt of a written request from the Committee, a Member
State shall forward the information establishing that the manufacturer
of a veterinary medicinal product or the importer from a third country
isable to manufacture the veterinary medicinal product concerned and/or carry out the necessary control tests in accordance with the particu-lars and documents supplied pursuant to Article 28.
2. Where it considers it necessary in order to complete its examini-
nation of an application, the Committee may require the applicant tosubmit to a specific inspection of the manufacturing site of the veter-inary medicinal product concerned. The inspection, which shall becompleted within the time limit referred to in Article 28, shall be
undertaken by inspectors from the Member State who possess the
appropriate qualificationsand who may, if need be, be accompaniedby a rapporteur or expert appointed by the Committee.
Article 31
1. Where the opinion of the Committee isthat:
— the application does not satisfy the criteria for authorization set out
in thisRegulation,
or
— the summary of the product characteristics proposed by the appli-
cant in accordance with Article 28 should be amended,
or
— the labelling or package 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 the
Agency that he wishes to appeal. In that case he shall forward thedetailed groundsfor hisappeal to the Agency within 60 daysof receiptof the opinion. Within 60 daysof the receipt of the groundsfor appeal,the Committee shall consider whether its opinion should be revised,and the reasons for the conclusion reached on the appeal shall be
annexed to the assessment report referred to in paragraph 2.
2. Within 30 daysof itsadoption, the Agency s hall forward the final
opinion of the Committee to the Commission, the Member States and
the applicant together with a report describing the assessment of the
veterinary medicinal product by the Committee and stating the reasonsfor its conclusions.
3. In the event of an opinion in favour of granting the relevant
authorization to market the veterinary medicinal product, the following
documentss hall 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 will
reflect differencesin the veterinary conditionspertaining in theMember States;
(b) in the case of a veterinary medicinal product intended for adminis-
tration to food-producing animals, a statement of the maximumresidue level which may be accepted by the Community in accor-dance with Regulation (EEC) No 2377/90;1993R2309 — EN — 05.06.2003 — 002.001 — 15
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(c) details of any conditions or restrictions which should be imposed
on the supply or use of the veterinary medicinal product concerned,including the conditionsunder which the veterinary medicinal
product may be made available to users, in accordance with the
criteria laid down in Directive 81/851/EEC;
(d) the draft text of the labelling and package insert proposed by the
applicant, presented in accordance with Directive 81/851/EEC;
(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,taking account of Community law.
In the event of a draft decision which envisages the granting of
marketing authorization, the documentsreferred 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 rulesof procedure of the Committee referred to in Article 73
shall be adjusted to take account of the tasks incumbent upon it inaccordance with thisRegulation.
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
in writing,
— each Member State isallowed at leas t 28 daysto forward written
observations on the draft decision to the Commission,
— each Member State isable to require in writing that the draft deci-
sion be discussed by the Standing Committee giving its reasons indetail.
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, the
Chairman shall suspend the procedure and refer the application back to
the 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 authori-
zation provided for in Article 3 shall be refused if, after verification of
the information and particularss ubmitted in accordance with Article
28, it appearsthat:
1. the veterinary medicinal product isharmful under the conditionsof
use stated at the time of the application for authorization, has notherapeutic effect or the applicant hasnot provided s ufficient proofof such effect as regards the species of animal which is to be
treated, or itsqualitative and quantitative compos ition isnot as
stated;
2. the withdrawal period recommended by the applicant isnot long
enough to ensure that foodstuffs obtained from treated animals do1993R2309 — EN — 05.06.2003 — 002.001 — 16
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not contain residues which might constitute a health hazard for the
consumer 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 labelling and package inserts proposed by the applicant are not in
accordance with Chapter VII of Directive 81/851/EEC.
Article 34
1. Without prejudice to Article 4 of Council Directive 90/677/EEC
of 13 December 1990 extending the scope of Directive 81/851/EECon the approximation of the lawsof the Member Statesrelating toveterinary medicinal products(
1), and laying down additional provi-
sions for immunological veterinary medicinal products, a marketingauthorization which hasbeen granted in accordance with the procedure
laid down in thisRegulation s hall apply throughout the Community. It
shall confer the same rights and obligations in each of the MemberStatesasa marketing authorization granted by that Member State inaccordance with Article 4 of Directive 81/851/EEC.
The authorized veterinary medicinal productss hall be entered in the
Community Register of Medicinal Products and shall be given a
number which must appear on the packaging.
2. The refusal of a Community marketing authorization shall consti-
tute a prohibition on the placing on the market of the veterinarymedicinal product concerned throughout the Community.
3. Notification of marketing authorization shall be published in the
Official Journal of the European Communities , quoting in 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 by
the Committee for Veterinary Medicinal Productsand the reas onsforitsopinion in favour of granting authorization, after deletion of anyinformation 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 a
dossier containing up-to-date information on pharmacovigilance.
2. In exceptional circumstances and following consultations 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 productswhich have been authorized by the
Community in accordance with the provisions of this Regulation shall
benefit 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 Statesof the manufacturer or, whereapplicable, of the person responsible for placing the veterinary medic-inal product on the market.1993R2309 — EN — 05.06.2003 — 002.001 — 17
(1) OJ No L 373, 31. 12. 1990, p. 26.
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CHAPTER 2
Supervisionandsanctions
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 productionand control provided for in points4 and 9 of the s econd paragraph ofArticle 5 of Directive 81/851/EEC, take account of technical and scien-tific progress and make changes that may be required to enable the
veterinary medicinal product to be manufactured and checked by
means of generally accepted scientific methods. The aforementionedperson must apply for approval for these changes in accordance withthisRegulation.
Upon a request from the Commission, the person responsible for
placing the veterinary medicinal product on the market shall alsoreview the analytical detection methodsprovided for in point 8 of the
second paragraph of Article 5 of Directive 81/851/EEC and propose
any changes which may be necessary to take account of technical andscientific progress.
2. The person responsible for placing the 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 particularsand documentsreferred to in Articles
28 and 31 or in the approved summary of the product characteristics. In
particular the aforementioned person shall forthwith inform theAgency, the Commission and the Member States of any prohibition orrestriction imposed by the competent authorities of any country inwhich the veterinary medicinal product ismarketed and of any othernew information which might influence the evaluation of the benefits
and risks of the veterinary medicinal product concerned.
3. If the person responsible for placing the 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 arrangementsfor the examination of variationsto the termsof a marketing authorization.
These arrangements shall include a notification system or administra-
tive proceduresconcerning minor variationsand define precis ely theconcept of ‘a minor variation’.
These arrangements shall be adopted by the Commission in the form of
an implementing Regulation in accordance with the procedure laid
down in Article 72.
Article 38
In the case of veterinary medicinal products manufactured within the
Community, the supervisory authorities shall be the competent authori-
tiesof the Member State or Member Stateswhich have granted the
manufacturing authorization 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 Statesin which the controlsreferred to in Article 30 (1)
(b) of Directive 81/851/EEC are carried out unless appropriate arrange-
mentshave been made between the Community and the exportingcountry to ensure that those controls are carried out in the exportingcountry and that the manufacturer appliess tandardsof good manufac-turing practice at least equivalent to those laid down by theCommunity.1993R2309 — EN — 05.06.2003 — 002.001 — 18
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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 placing the
veterinary medicinal product on the market, or manufacturer or
importer from third countries satisfies the requirements laid down inChapter V of Directive 81/851/EEC and for exercising supervisionover such persons 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-
encesof opinion between Member Statesasto whether the pers onresponsible for placing the veterinary medicinal product on the marketor a manufacturer or importer established within the Community issatisfying the requirements referred to in paragraph 1, the Commission
may, after consultation with the Member States concerned, request an
inspector 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 isnot party to the dis pute and/or by a rapporteuror expert nominated by the Committee.
3. Subject to any arrangementswhich may have been concluded
between the Community and third countriesin accordance with thesecond paragraph of Article 38, the Commission may, upon receipt ofa reasoned 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 inspection
shall be undertaken by appropriately qualified inspectors from the
Member States, who may, if appropriate, be accompanied by a rappor-teur or expert nominated by the Committee. The report of theinspectors shall be made available to the Commission, the MemberStatesand the Committee 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 or
importer from third countriesisno longer fulfilling the obligations
laid down in Chapter V of Directive 81/851/EEC, they shall forthwithinform the Committee and the Commission, stating their reasons indetail and indicating the 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 Direc-
tive 81/851/EEC should be applied in respect of the veterinary
medicinal product concerned or where the Committee for VeterinaryMedicinal Productshasdelivered an opinion to that effect in accor-dance with Article 42.
2. The Commission shall in consultation with the Agency forthwith
examine the reasons advanced by the Member State concerned. It shall
request 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 placing the 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 in
Article 32.
However, where a Member State hasinvoked the provis ionsof para-
graph 4, the time limit provided for in Article 73 shall be reduced to15 calendar days.
4. Where urgent action is essential to protect human or animal
health or the environment, a Member State may suspend the use on1993R2309 — EN — 05.06.2003 — 002.001 — 19
▼B
itsterritory of a veterinary medicinal product which hasbeen author-
ized in accordance with thisRegulation. It s hall inform theCommission and the other Member States no later than the following
working day of the reasons for its action. The Commission shall imme-
diately consider the reasons given by the Member State in accordancewith paragraph 2 and shall initiate the procedure provided for in para-graph 3.
5. A Member State which has adopted the suspensive measures
referred to in paragraph 4 may maintain them in force until such timeasa definitive decis ion hasbeen reached in accordance with the proce-dure laid down in paragraph 3.
6. The Agency shall, upon request, inform any person concerned of
the final decision.
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 pharmacov-
igilance systems established in accordance with Article 42a of
Directive 81/851/EEC, shall receive all relevant information about
suspected adverse reactions to veterinary medicinal products whichhave been authorized by the Community in accordance with thisRegu-lation. If necessary the Committee may, in accordance with Article 27,formulate opinions on the measures necessary to ensure the safe and
effective use of such veterinary medicinal products. These measures
shall be adopted in accordance with the procedure laid down in Article40.
The person responsible for placing the veterinary medicinal product on
the market and the competent authoritiesof the Member Statess hall
ensure that all relevant information about suspected adverse reactions
to veterinary medicinal productsauthorized in accordance with thisRegulation are brought to the attention of the Agency in accordancewith the provisions of this Regulation.
Article 43
The person responsible for the placing on the market of a veterinary
medicinal product authorized by the Community in accordance withthe provisions of this Regulation shall have permanently and continu-ously at his disposal an appropriately qualified person responsible forpharmacovigilance.
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 representatives
is collected, evaluated and collated so that it may be accessed at a
single point within the Community;
(b) the preparation of the reportsreferred to in Article 44 for the
competent authoritiesof the Member Statesand the Agency in
accordance with the requirementsof thisRegulation;
(c) ensuring that 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, including the provision of information aboutthe volume of sales or prescriptions for the veterinary medicinalproduct concerned.1993R2309 — EN — 05.06.2003 — 002.001 — 20
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Article 44
1. The person responsible for placing a veterinary medicinal product
on the market shall ensure that all suspected serious adverse reactions
occurring within the Community to a veterinary medicinal product
authorized in accordance with the provisions of this Regulation whichare brought to hisattention are recorded and reported immediately tothe Member Statesin whos e territory the incident occurred, and in nocase later than 15 days following the receipt of the information.
The aforementioned person shall ensure that all suspected serious unex-
pected adverse reactions occurring in the territory of a third country,
are reported immediately to the Member Statesand the Agency and in
no case later than 15 days following the receipt of the information.
The arrangements for the reporting of suspected unexpected adverse
reactions which are not serious, whether arising in the Community orin a third country, shall be adopted in accordance with Article 48.
2. In addition, the person responsible for placing a veterinary medic-
inal product on the market shall be required to maintain detailed
records of all suspected adverse reactions occurring within or outside
the Community which are reported to him. Unless other requirementshave been laid down asa condition of the granting of the marketingauthorization by the Community, these records shall be submitted tothe Agency and Member States immediately upon request or at leastevery six months during the first two years following authorization
and once a year for the following three years. Thereafter, the records
shall be submitted at five-yearly intervals together with the applicationof renewal 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 reac-
tionsoccurring within their territory to a veterinary medicinal productauthorized in accordance with the provisions of this Regulation which
are brought to their attention are recorded and reported immediately to
the Agency and the person responsible for placing the veterinarymedicinal product on the market, and in no case later than 15 daysfollowing the 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-processing network for the rapid transmission
of data between the competent Community authoritiesin the event of
an alert relating to faulty manufacture, serious adverse reactions andother pharmacovigilance 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 shallbe adopted in accordance with the provisions of Article 72.1993R2309 — EN — 05.06.2003 — 002.001 — 21
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TITLEIV
THE EUROPEAN AGENCY FOR THE EVALUATION OF
MEDICINALPRODUCTS
CHAPTER 1
TasksoftheAgency
Article 49
A European Agency for the Evaluation of Medicinal Productsishereby
established.
The Agency shall be responsible for coordinating the existing scientific
resources put at its disposal by the competent authorities of theMember States for the evaluation and supervision of medicinal
products.
Article 50
1. The Agency shall comprise:
(a) the Committee for Proprietary Medicinal Products, which shall be
responsible for preparing the opinion of the Agency on any ques-tion relating to the evaluation of medicinal productsfor human us e;
(b) the Committee for Veterinary Medicinal Products, which shall be
responsible for preparing the opinion of the Agency on any ques-tion relating to the evaluation of veterinary medicinal products;
(c) a Secretariat, which shall provide technical and administrative
support for the two Committees and ensure appropriate coordina-tion between 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 Articles56 and 57.
2. The Committee for Proprietary Medicinal Productsand the
Committee for Veterinary Medicinal Products may each establishworking partiesand expert groups .
3. The Committee for Proprietary Medicinal Productsand the
Committee for Veterinary Medicinal Productsmay, if they cons ider it
appropriate, seek guidance on important questions of a general scien-
tific or 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 criteria
concerning the placing on the market and use of medicinal products,
the objectivesof the Agency s hall be to provide the Member Statesand the institutions of the Community with the best possible scientificadvice on any question relating to the evaluation of the quality, thesafety, and the efficacy of medicinal products for human or veterinaryuse, which is referred to it in accordance with the provisions of
Community legislation relating to 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 productswhich are s ubject to Commu-
nity marketing authorization procedures;
(b) the transmission of assessment reports, summaries of product char-
acteristics, labels and package leaflets or inserts for these medicinalproducts;1993R2309 — EN — 05.06.2003 — 002.001 — 22
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(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 necessary
to ensure the safe and effective use of these products, in particular
by evaluating and making available through a database informationon adverse reactions to the medicinal products in question (pharma-covigilance);
(d) advising on the maximum limits for residues of veterinary medic-
inal productswhich may be accepted in foods tuffsof animal originin accordance with Regulation (EEC) No 2377/90.
(e) coordinating the verification of compliance with the principlesof
good manufacturing practice, good laboratory practice and goodclinical practice;
(f) upon request, providing technical and scientific support for steps to
improve cooperation between the Community, itsMember States ,international organizationsand third countrieson s cientific andtechnical issues relating to the evaluation of medicinal products;
(g) recording the status of marketing authorizations for medicinal
productsgranted in accordance with Community procedures ;
(h) providing technical assistance for the maintenance of a database on
medicinal productswhich isavailable for public us e;
(i) assisting the Community and Member States in the provision of
information to health care professionals and the general public
about medicinal productswhich have been evaluated within theAgency;
(j) where necessary, advising companies on the conduct of the various
tests and trials necessary to demonstrate the quality, safety and effi-cacy of medicinal products.
Article 52
1. The Committee for Proprietary Medicinal Productsand the
Committee for Veterinary Medicinal Products shall each consist oftwo membersnominated by each Member State for a term of three
years which shall be renewable. They shall be chosen by reason of
their role and experience in the evaluation of medicinal productsforhuman and veterinary use as appropriate and shall represent theircompetent authorities.
The Executive Director of the Agency or hisrepres entative and repre-
sentatives of the Commission shall be entitled to attend all meetings of
the Committees, their working parties and expert groups.
Membersof each Committee may arrange to be accompanied by
experts.
2. In addition to their task of providing objective scientific opinions
to the Community and Member Stateson the ques tionswhich are
referred to them, the members of each Committee shall ensure thatthere isappropriate coordination between the tas ksof the Agency andthe work of competent national authorities, including the consultativebodiesconcerned with the marketing authorization.
3. The members of the Committees and the experts responsible for
evaluating medicinal products shall rely on the scientific assessment
and resources available to the national marketing authorization bodies.Each Member State shall monitor the scientific level of the evaluationcarried out and supervise the activities of members of the Committeesand the experts it nominates, but shall refrain from giving them any
instruction which is incompatible with the tasks incumbent upon them.
4. When preparing the 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 the diver-gent positions with their grounds.1993R2309 — EN — 05.06.2003 — 002.001 — 23
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Article 53
1. Where, in accordance with the provisions of this Regulation, the
Committee for Proprietary Medicinal Productsor the Committee forVeterinary Medicinal Productsisrequired to evaluate a medicinalproduct, the Committee shall appoint one of its members to act asrapporteur for the coordination of the evaluation, taking into considera-
tion any proposal from the applicant for the choice of a rapporteur. The
Committee 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 working parties or expert groups of theCommittee for Proprietary Medicinal Productsor the Committee for
Veterinary Medicinal Products, together with an indication of their
qualifications and specific areas of expertise.
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 hisemployer.The person concerned, or his employer, shall be remunerated in accor-
dance with a fixed scale of fees to be included in the financial
arrangements established by the Management Board.
4. On a proposal from the Committee for Proprietary Medicinal
Productsor the Committee for Veterinary Medicinal Products , the
Agency may also avail itself of the services of rapporteurs or experts
for the discharge of other specific responsibilities of the Agency.
Article 54
1. The membership of the Committee for Proprietary Medicinal
Productsand the Committee for Veterinary Medicinal Productss hallbe made public. When each appointment is published, the professionalqualifications of each member shall be specified.
2. Membersof the Management Board, Committee members ,
rapporteurs and experts shall not have financial or other interests inthe pharmaceutical industry which could affect their impartiality. Allindirect interests which could relate to this industry shall be entered ina register 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 Productsand the Committee for Veter-
inary Medicinal Products, and their working parties and expertgroups,
— for ensuring that the time limits laid down in Community legisla-
tion for the adoption of opinionsby the Agency are res pected,
— for ensuring appropriate coordination between the Committee for
Proprietary Medicinal Productsand 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 Manage-
ment Board for approval, while making a distinction between the1993R2309 — EN — 05.06.2003 — 002.001 — 24
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Agency'sactivitiesconcerning medicinal productsfor human us e and
those concerning veterinary medicinal products:
— a draft report covering the activitiesof the Agency in the previous
year, including information about the number of applicationsevalu-
ated within the Agency, the time taken for the completion of theevaluation and the medicinal productsauthorized, rejected or with-drawn,
— a draft programme of work for the coming year,
— the draft annual accountsfor the previousyear,
— 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 two
representatives appointed by the European Parliament. One representa-
tive shall have specific responsibilities relating to medicinal productsfor human use and one relating to 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 yearsand s hall adopt itsrulesof procedure.
Decisions of the Management Board shall be adopted by a majority of
two-thirdsof itsmembers .
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 activitiesof the Agency for the previousyearand itsprogramme of work for the coming year and forward them tothe Member States, the Commission, the Council and the EuropeanParliament.
CHAPTER 2
Financial provisions
Article 57
1. The revenues of the Agency shall consist of a contribution from
the Community, and the feespaid by undertakingsfor obtaining and
maintaining a Community marketing authorization and for otherservices provided by the Agency.
2. The expenditure of the Agency shall include the staff, administra-
tive, infrastructure and operational expenses and expenses resultingfrom contractsentered 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.1993R2309 — EN — 05.06.2003 — 002.001 — 25
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6. The Management Board shall adopt the Agency's final budget
before the beginning of the financial year, adjusting it where necessaryto the Community subsidy and the Agency's other resources.
7. The Director shall implement the Agency's budget.
8. Monitoring of the commitment and payment of all the Agency's
expenditure and of the establishment and recovery of all the Agency's
revenue 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 theaccountsfor all the Agency'srevenue and expenditure in res pect of thepreceding financial year.
The Court of Auditorss hall 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 Auditorshasdelivered itsopinion, the
Management Board shall adopt the internal financial provisions speci-fying, in particular, the detailed rules for establishing and implementingthe Agency'sbudget.
Article 58
The structure and the amount of the fees referred to in Article 57 (1)
shall be established by the Council acting under the conditions
provided for by the Treaty on a proposal from the Commission,
following consultation of organizations representing the interests ofthe pharmaceutical industry at Community level.
CHAPTER 3
General provisionsgoverningtheAgency
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 judgment
pursuant to any arbitration clause contained in a contract concluded
by the Agency.
2. In the case of non-contractual liability, the Agency shall, in
accordance with the general principlescommon to the lawsof the
Member States, make good any damage caused by it or its servants in
the performance of their duties.
The Court of Justice shall have jurisdiction in any dispute relating to
compensation for such damages.
3. The personal liability of its servants towards the Agency shall be
governed by the relevant conditionsapplying to the s taff of theAgency.
Article 61
The Protocol on the Privilegesand Immunitiesof the European
Communitiess hall apply to the Agency.1993R2309 — EN — 05.06.2003 — 002.001 — 26
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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 appointing authority.
The Management Board, in agreement with the Commission, shall
adopt the necessary implementing provisions.
Article 63
Membersof the Management Board, membersof Committees , and offi-
cials and other servants of the Agency shall be required, even after
their duties have ceased, not to disclose information of the kindcovered by the obligation of professional secrecy.
Article 64
The Commission may, in agreement with the Management Board and
the relevant Committee, invite representatives of international organiza-tionswith interes tsin the harmonization of regulationsapplicable to
medicinal productsto participate asobs erversin the work of the
Agency.
Article 65
The Management Board shall, in agreement with the Commission,
develop appropriate contactsbetween the Agency and the repres enta-tives of the industry, consumers and patients and the health professions.
Article 66
The Agency shall take up its responsibilities on 1 January 1995.
TITLEV
GENERALANDFINALPROVISIONS
Article 67
All decisions to grant, refuse, vary, suspend, withdraw or revoke a
marketing authorization which are taken in accordance with thisRegu-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
coming within the scope of this Regulation shall not be refused, varied,
suspended, withdrawn or revoked except on the grounds set out in this
Regulation.
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 proceduress et out in thisRegulation.
Article 69
Without prejudice to Article 68, and without prejudice to the Protocol
on the Privilegesand Immunitiesof the European Communities , eachMember State shall determine the penalties to be applied for the infrin-
gement of the provisions of this Regulation. The penalties must be
sufficient to promote compliance with those measures.
Member States shall forthwith inform the Commission of the institution
of any infringement proceedings.1993R2309 — EN — 05.06.2003 — 002.001 — 27
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Article 70
Additivescovered by Council Directive 70/524/EEC of 23 November
1970 concerning additivesin feedings tuffs(1), where they are intended
to be administered to animals in accordance with that Directive, shall
not be considered as veterinary medicinal products for the purposes of
thisRegulation.
Within three yearsof the entry into force of thisRegulation the
Commission shall produce a report on whether the level of harmoniza-tion achieved by thisRegulation and by Council Directive 90/167/EECof 26 March 1990 laying down the conditionsgoverning the prepara-tion, placing on the market and use of medicated feedingstuffs in the
Community (
2) isequivalent to that provided for in Council Directive
70/524/EEC, accompanied if necessary by the proposals to modify thestatus of the coccidiostats and other medicinal substances covered bythat Directive.
The Council shall decide on the Commission proposal no later than one
year after their submission.
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 aresult of the operation of the procedures laid down in this Regulation,
in Chapter III of Directive 75/319/EEC and in Chapter IV of Directive
81/851/EEC.
Article 72
1. The Commission shall be assisted by:
— the Standing Committee on Medicinal Productsfor Human Us e, in
the case of matters relating to medicinal products for human use,and
— the Standing Committee on Veterinary Medicinal Products, in the
case of matters relating to veterinary medicinal products.
2. Where reference ismade to thisArticle, Articles5 and 7 of Deci-
sion 1999/468/EC (
3) shall apply.
The period laid down in Article 5(6) of Decision 1999/468/EC shall be
set at three months.
3. The committeess hall adopt their rulesof procedure.
Article 73
1. The Commission shall be assisted by:
— the Standing Committee on Medicinal Productsfor Human Us e, in
the case of matters relating to medicinal products for human use,
and
— the Standing Committee on Veterinary Medicinal Products, in the
case of matters relating to veterinary medicinal products.
2. Where reference ismade to thisArticle, Article 5 and 7 of Deci-
sion 1999/468/EC shall apply.
The period laid down in Article 5(6) of Decision 1999/468/EC shall be
set at three months.1993R2309 — EN — 05.06.2003 — 002.001 — 28
(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.
(3) OJ L 184, 17.7.1999, p. 23.▼M2
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Article 74
This Regulation shall enter into force on the day following the decision
taken by the competent authoritieson the headquartersof the Agency.
Subject to the first subparagraph Titles I, II, III and V shall enter into
force on 1 January 1995.
ThisRegulation s hall be binding in itsentirety and directly applicable
in all Member States.1993R2309 — EN — 05.06.2003 — 002.001 — 29
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ANNEX
PART A
Medicinal productsdeveloped by meansof one of the following biotechnolo-
gical 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.
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 productspres ented 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 productsderived from human blood or human plas ma.
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,
wasnot authorized by any Member State for us e in a medicinal product
intended for human use.
Veterinary medicinal products containing a new active substance which, on the
date of entry into force of thisRegulation, wasnot authoris ed by any Member
State for use in animals.1993R2309 — EN — 05.06.2003 — 002.001 — 30
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