Directive 2001/82/EC of the European Parliament and of the Council
of 6 November 2001
on the Community code relating to veterinary medicinal products
THE EUROPEAN PARLIAMENT AND THE COUNCIL OF THE EUROPEAN UNION,
Having regard to the Treaty establishing the European Community, and in particular Article 95 thereof,
Having regard to the proposal from the Commission,
Having regard to the opinion of the Economic and Social Committee(1),
Acting in accordance with the procedure laid down in Article 251 of the Treaty(2),
Whereas:
(1) Council Directive 81/851/EEC of 28 September 1981 on the approximation of the laws of the Member States relating to veterinary medicinal products(3), Council Directive 81/852/EEC of 28 September 1981 on the approximation of the laws of the Member States relating to analytical, pharmaco-toxicological and clinical standards and protocols in respect of the testing of veterinary medicinal products(4), Council Directive 90/677/EEC of 13 December 1990 extending the scope of Directive 81/851/EEC on the approximation of the laws of the Member States relating to veterinary medicinal products and laying down additional provisions for immunological veterinary medicinal products(5), and Council Directive 92/74/EEC of 22 September 1992 widening the scope of Directive 81/851/EEC on the approximation of provisions laid down by law, regulation or administrative action relating to veterinary medicinal products and laying down additional provisions on homeopathic veterinary medicinal products(6) have been frequently and substantially amended; in the interests of clarity and rationality, the said Directives should therefore be codified by assembling them in a single text.
(2) The primary purpose of any rules for the production and distribution of veterinary medicinal products must be the safeguarding of public health.
(3) However, this objective must be achieved by means which will not hinder the development of industry and trade in medicinal products within the Community.
(4) In so far as the Member States already have certain provisions laid down by law, regulation or administrative action governing veterinary medicinal products, such provisions differ in essential principles. This results in the hindering of trade in medicinal products within the Community, thereby directly affecting the functioning of the internal market.
(5) Such hindrances must, accordingly, be removed; whereas this entails approximation of the relevant provisions.
(6) It is necessary from the point of view of public health and the free movement of veterinary medicinal products for the competent authorities to have at their disposal all useful information on authorized veterinary medicinal products in the form of approved summaries of the characteristics of products.
(7) With the exception of those medicinal products which are subject to the centralised Community authorization procedure established by 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(7), a marketing authorization in one Member State ought to be recognized by the competent authority of the other Member States unless there are serious grounds for supposing that the authorization of the veterinary medicinal product concerned may present a risk to human or animal health, or to the environment; in the event of a disagreement between Member States about the quality, the safety or the efficacy of a medicinal product, a scientific evaluation of the matter should be undertaken at a Community level, lead to a single decision on the area of disagreement, binding on the Member States concerned. This Decision should be adopted by a rapid procedure ensuring close cooperation between the Commission and the Member States.
(8) For this purpose, a Committee for Veterinary Medicinal Products should be set up in accordance with the European Agency for the Evaluation of Medicinal Products laid down in the aforementioned Regulation (EEC) No 2309/93.
(9) This Directive is only one stage in the achievement of the aim of freedom of movement of veterinary medicinal products. However, for this purpose, new measures will prove necessary, in the light of experience gained - especially within the Committee for Veterinary Medicinal Products - for the removal of the remaining barriers to freedom of movement.
(10) Medicated feedingstuffs do not come within the scope of this Directive. However, it is necessary, for both public health and economic reasons, to prohibit the use of unauthorized medicinal products in the manufacture of medicated feedingstuffs.
(11) The concepts of harmfulness and therapeutic efficacy can be examined only in relation to one another and have only a relative significance, depending on the progress of scientific knowledge and the use for which the medicinal product is intended. The particulars and documents which must accompany an application for marketing authorization must demonstrate that potential hazards are outweighed by the benefits due to efficacy. Failing such demonstration, the application must be rejected.
(12) Marketing authorization should be refused where a medicinal product lacks therapeutic effect or where there is insufficient proof of such effect. The concept of therapeutic effect must be understood as being the effect promised by the manufacturers.
(13) Such marketing authorization should also be refused where the withdrawal period indicated is not long enough to eliminate health hazards arising from residues.
(14) Before an authorization to market an immunological veterinary medicinal product can be granted, the manufacturer must demonstrate his ability to attain batch-to-batch consistency.
(15) The competent authorities should also be empowered to prohibit the use of an immunological veterinary medicinal product when the immunological responses of the treated animal will interfere with a national or Community programme for the diagnosis, eradication or control of animal disease.
(16) It is desirable in the first instance to provide users of homeopathic medicinal products with a very clear indication of their homeopathic character and with sufficient guarantees of their quality and safety.
(17) The rules relating to the manufacture, control and inspection of homeopathic veterinary medicinal products must be harmonised to permit the circulation throughout the Community of medicinal products which are safe and of good quality.
(18) Having regard to the particular characteristics of these homeopathic veterinary medicinal products, such as the very low level of active principles they contain and the difficulty of applying to them the conventional statistical methods relating to clinical trials, it is desirable to provide a special, simplified registration procedure for those traditional homeopathic medicinal products which are placed on the market without therapeutic indications in a pharmaceutical form and dosage which do not present a risk for the animal.
(19) The usual rules governing the authorization to market veterinary medicinal products must be applied to homeopathic veterinary medicinal products marketed with therapeutic indications or in a form which may present risks which must be balanced against the desired therapeutic effect. Member States should be able to apply particular rules for the evaluation of the results of tests and trials intended to establish the safety and efficacy of these medicinal products for pet animals and exotic species, provided that they notify them to the Commission.
(20) In order to better protect human and animal health and avoid any unnecessary duplication of effort during the examination of application for a marketing authorization, Member States should systematically prepare assessment reports in respect of each veterinary medicinal product which is authorized by them, and exchange the reports upon request. Furthermore, a Member State should be able to suspend the examination of an application for authorization to place a veterinary medicinal product on the market which is currently under active consideration in another Member State with a view to recognizing the decision reached by the latter Member State.
(21) In order to facilitate the movement of veterinary medicinal products and to prevent the checks carried out in one Member State from being repeated in another, minimum requirements for manufacture and imports from third countries, and the grant of corresponding authorizations, should be applied to veterinary medicinal products.
(22) The quality of veterinary medicinal products manufactured within the Community should be guaranteed by requiring compliance with the principles of good manufacturing practice for medicinal products irrespective of the final destination of the medicinal products.
(23) Measures should also be taken to ensure that distributors of veterinary medicinal products are authorized by Member States and maintain adequate records.
(24) Standards and protocols for the performance of tests and trials on veterinary medicinal products are an effective means of control of these products and, hence, of protecting public health and can facilitate the movement of these products by laying down uniform rules applicable to tests and the compilation of dossiers, allowing the competent authorities to arrive at their decisions on the basis of uniform tests and by reference to uniform criteria, and therefore helping to obviate differences in evaluation.
(25) It is advisable to stipulate more precisely the cases in which the results of pharmacological and toxicological tests or clinical trials do not have to be provided with a view to obtaining authorization for a veterinary medicinal product which is essentially similar to an innovative product, while ensuring that innovative forms are not placed at a disadvantage. However, there are reasons of public policy for not repeating tests carried out on animals without overriding cause.
(26) Following the establishment of the internal market, specific controls to guarantee the quality of veterinary medicinal products imported from third countries can be waived only if appropriate arrangements have been made by the Community to ensure that the necessary controls are carried out in the exporting country.
(27) In order to ensure the continued safety of veterinary medicinal products in use, it is necessary to ensure that pharmacovigilance systems in the Community are continually adapted to take account of scientific and technical progress.
(28) For public health protection, relevant data on adverse effects in humans related to the use of veterinary medicines should be collected and evaluated.
(29) The pharmacovigilance systems should consider the available data on lack of efficacy.
(30) In addition, collection of information on adverse reactions due to off-label use, investigations of the validity of the withdrawal period and on potential environmental problems may contribute to improve regular monitoring of good usage of veterinary medicines.
(31) It is necessary to take account of changes arising as a result of international harmonisation of definitions, terminology and technological developments in the field of pharmacovigilance.
(32) The increasing use of electronic means of communication of information on adverse reactions to veterinary medicinal products marketed in the Community is intended to allow a single reporting point for adverse reactions, at the same time ensuring that this information is shared with the competent authorities in all Member States.
(33) It is the interest of the Community to ensure that the veterinary pharmacovigilance systems for centrally authorised medicinal products and those authorised by other procedures are consistent.
(34) Holders of marketing authorisations should be proactively responsible for ongoing pharmacovigilance of the veterinary medicinal products they place on the market.
(35) The measures necessary for the implementation of this Directive should be adopted in accordance with Council Decision 1999/468/EC of 28 June 1999 laying down the procedures for the exercise of implementing powers conferred on the Commission(8).
(36) In order to improve the protection of public health, it is necessary to specify that foodstuffs for human consumption may not be taken from animals which have been used in clinical trials of veterinary medicinal products unless a maximum residue limit has been laid down for residues of the veterinary medicinal product concerned in accordance with the provisions of Council 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 of animal origin(9).
(37) The Commission should be empowered to adopt the changes necessary in order to adapt Annex I to scientific and technical progress.
(38) This Directive should be without prejudice to the obligations of the Member States concerning the time-limits for transposition of the Directives set out in Annex II, Part B,
HAVE ADOPTED THIS DIRECTIVE:
TITLE I
DEFINITIONS
Article 1
For the purposes of this Directive, the following terms shall bear the following meanings:
1. Proprietary medicinal product: Any ready-prepared medicinal product placed on the market under a special name and in a special pack.
2. Veterinary medicinal product: Any substance or combination of substances presented for treating or preventing disease in animals.
Any substance or combination of substances which may be administered to animals with a view to making a medical diagnosis or to restoring, correcting or modifying physiological functions in animals is likewise considered a veterinary medicinal product.
3. Ready-made veterinary medicinal product: Any veterinary medicinal product prepared in advance which does not comply with the definition of proprietary medicinal products and which is marketed in a pharmaceutical form which may be used without further processing.
4. Substance: Any matter irrespective of origin which may be:
- human, e.g.
human blood and human blood products;
- animal, e.g.
micro-organisms, whole animals, parts of organs, animal secretions, toxins, extracts, blood products;
- vegetable, e.g.
micro-organisms, plants, parts of plants, vegetable secretions, extracts;
- chemical, e.g.
elements, naturally occurring chemical materials and chemical products obtained by chemical change or synthesis.
5. Pre-mix for medicated feedingstuffs: Any veterinary medicinal product prepared in advance with a view to the subsequent manufacture of medicated feedingstuffs.
6. Medicated feedingstuffs: Any mixture of a veterinary medicinal product or products and feed or feeds which is ready prepared for marketing and intended to be fed to animals without further processing, because of its curative or preventive properties or other properties as a medicinal product covered by point 2.
7. Immunological veterinary medicinal product: A veterinary medicinal product administered to animals in order to produce active or passive immunity or to diagnose the state of immunity.
8. Homeopathic veterinary medicinal product: Any veterinary medicinal product prepared from products, substances or compositions called homeopathic stocks in accordance with a homeopathic manufacturing procedure described by the European Pharmacopoeia or, in the absence thereof, by the pharmacopoeias currently used officially in the Member States.
A homeopathic veterinary medicinal product may also contain a number of principles.
9. Withdrawal period: Period necessary between the last administration of the veterinary medicinal product to animals under normal conditions of use and the production of foodstuffs from such animals, in order to ensure that such foodstuffs do not contain residues in quantities in excess of the maximum limits laid down in application of Regulation (EEC) No 2377/90.
10. Adverse reaction: A reaction which is harmful and unintended and which occurs at doses normally used in animals for the prophylaxis, diagnosis or treatment of disease or the modification of physiological function.
11. Human adverse reaction: A reaction which is noxious and unintended and which occurs in a human being following exposure to a veterinary medicine.
12. Serious adverse reaction: An adverse reaction which results in death, is life-threatening, results in significant disability or incapacity, is a congenital anomaly/birth defect, or which results in permanent or prolonged signs in the animals treated.
13. Unexpected adverse reaction: An adverse reaction, the nature, severity or outcome of which is not consistent with the summary of the product characteristics.
14. Periodic safety update reports: The periodical reports containing the records referred to in Article 75.
15. Post-marketing surveillance studies: Pharmacoepidemiological study or a clinical trial carried out in accordance with the terms of the marketing authorization, conducted with the aim of identifying and investigating a safety hazard relating to an authorized veterinary medicinal product.
16. Off-label use: The use of a veterinary medicinal product that is not in accordance with the summary of the product characteristics, including the misuse and serious abuse of the product.
17. Wholesale dealing in veterinary medicinal products: Any activity which includes the purchase, sale, import, export, or any other commercial transaction in veterinary medicinal products, whether or not for profit, except for:
- the supply by a manufacturer of veterinary medicinal products manufactured by himself,
- retail supplies of veterinary medicinal products by persons entitled to carry out such supplies in accordance with Article 66.
18. Agency: European Agency for the Evaluation of Medicinal Products established by Regulation (EEC) No 2309/93.
19. Risk to human or animal health or the environment: Any risk relating to the quality, safety and efficacy of the veterinary medicinal product.
TITLE II
SCOPE
Article 2
The provisions of this Directive shall apply to veterinary medicinal products intended to be placed on the market inter alia in the form of medicinal products, ready-made veterinary medicinal products or pre-mixes for medicated feeedingstuffs.
Article 3
This Directive shall not apply to:
1. Medicated feedingstuffs as defined in Council Directive 90/167/EEC of 26 March 1990 laying down the conditions governing the preparation, placing on the market and use of medicated feedingstuffs in the Community(10);
However, medicated feedingstuffs may be prepared only from pre-mixes which have been authorized under this Directive;
2. Inactivated immunological veterinary medicinal products which are manufactured from pathogens and antigens obtained from an animal or animals from a holding and used for the treatment of that animal or the animals of that holding in the same locality;
3. Any medicinal product prepared in a pharmacy in accordance with a prescription for an individual animal (commonly known as the magistral formula);
4. Any medicinal product prepared in a pharmacy in accordance with the prescriptions of a pharmacopoeia and is intended to be supplied directly to the end-user (commonly known as the officinal formula);
5. Veterinary medicinal products based on radio-active isotopes;
6. Any additives covered by Council Directive 70/524/EEC of 23 November 1970 concerning additives in feedingstuffs(11), where they are incorporated in animal feedingstuffs and supplementary animal feedingstuffs in accordance with that Directive. Nevertheless, Member States may, when implementing Articles 10(1)(c) and(2) take acount of the medicinal products referred to in points 3 and 4 of the first paragraph.
Nonetheless, Member States may, when implementing Article 10(1)(c) and (2) take account of the medicinal products referred to in points 3 and 4 of the first paragraph.
Article 4
1. Member States may provide that this Directive shall not apply to non-inactivated immunological veterinary medicinal products which are manufactured from pathogens and antigens obtained from an animal or animals from a holding and used for the treatment of that animal or the animals of that holding in the same locality.
2. Member States may permit exemptions on their territory in respect of veterinary medicinal products intended solely for aquarium fish, cage birds, homing pigeons, terrarium animals and small rodents, from the provisions in Articles 5, 7 and 8, provided that such products do not contain substances the use of which requires veterinary control and that all possible measures have been taken to prevent unauthorized use of the products for other animals.
TITLE III
MARKETING
CHAPTER 1
Marketing authorization
Article 5
No veterinary medicinal product may be placed on the market of a Member State unless a marketing authorization has been issued by the competent authorities of that Member State in accordance with this Directive or a marketing authorization has been granted in accordance with Regulation (EEC) No 2309/93.
Article 6
In order that a veterinary medicinal product may be the subject of a marketing authorization for the purpose of administering it to food-producing animals, the active substances which it contains must be shown in Annexes I, II or III of Regulation (EEC) No 2377/90.
Article 7
Where the health situation so requires, a Member State may authorise the marketing or administration to animals of veterinary medicinal products which have been authorized by another Member State in accordance with this Directive.
Article 8
In the event of serious disease epidemic, Member States may provisionally allow the use of immunological veterinary medicinal products without an authorization for placing on the market, in the absence of a suitable medicinal product and after informing the Commission of the detailed conditions of use.
Article 9
No veterinary medicinal product may be administered to animals unless the marketing authorization has been issued, except for the tests of veterinary medicinal products referred to in Article 12(3)(j) which have been accepted by the competent national authorities, following notification or authorization, in accordance with the national rules in force.
Article 10
1. Where there is no authorized medicinal product for a condition, Member States may exceptionally, in particular in order to avoid causing unacceptable suffering to the animals concerned, permit the administration by a veterinarian or under his/her direct personal responsibility to an animal or to a small number of animals on a particular holding:
(a) of a veterinary medicinal product authorized in the Member State concerned under this Directive or under Regulation (EEC) No 2309/93 for use in another animal species, or for another condition in the same species; or
(b) if there is no product as referred to in point (a), of a medicinal product authorized for use in the Member State concerned in human beings in accordance with Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community Code relating to medicinal products for human use(12) or under Regulation (EEC) No 2309/93; or
(c) if there is no product as referred to in point (b) and within the limits of the law of the Member State concerned, of a veterinary medicinal product prepared extemporaneously by a person authorized to do so under national legislation in accordance with the terms of a veterinary prescription.
For the purposes of this paragraph, the phrase "an animal or a small number of animals on a particular holding" also covers pets, and shall be interpreted more flexibly for minor or exotic animal species which do not produce food.
2. The provisions of paragraph 1 shall apply provided that the medicinal product, where administered to food-producing animals, contains only substances to be found in a veterinary medicinal product authorized for such animals in the Member State concerned and that in the case of food-producing animals the veterinarian responsible specifies an appropriate withdrawal period.
Unless the medicinal product used indicates a withdrawal period for the species concerned, the specified withdrawal period shall not be less than:
>TABLE>
With regard to homeopathic veterinary medicinal products in which the level of active principles is equal to or less than one part per million, the withdrawal period referred to in the first and second subparagraphs is reduced to zero.
Article 11
When a veterinarian has recourse to the provisions of Article 10, he shall keep adequate records of the date of examination of the animals, details of the owner, the number of animals treated, the diagnosis, the medicinal products prescribed, the dosages administered, the duration of treatment and the withdrawal periods recommended, and make these records available for inspection by the competent authorities for a period of at least three years. This requirement may be extended by the Member States to non food-producing animals.
Article 12
1. For the purposes of obtaining a marketing authorization in respect of a veterinary medicinal product, other than under the procedure established by Regulation (EEC) No 2309/93, an application shall be lodged with the competent authority of the Member State concerned.
2. A marketing authorization may only be granted to an applicant established in the Community.
3. The following particulars and documents shall accompany an application in accordance with Annex I:
(a) name or business name and permanent address or registered place of business of the person responsible for placing the product on the market and, if different, of the manufacturer or manufacturers involved and of the sites of manufacture;
(b) name of the veterinary medicinal product (brand name, non-proprietary name, with or without a trademark, or name of the manufacturer or scientific name or formula, with or without a trademark, or the name of the manufacturer);
(c) qualitative and quantitative particulars of all the constituents of the veterinary medicinal product, using the usual terminology, but not empirical chemical formulae and giving the international non-proprietary name recommended by the World Health Organization, where such a name exists;
(d) description of the method of manufacture;
(e) therapeutic indications, contra indications and adverse reactions;
(f) dosage for the various species of animal for which the veterinary medicinal product is intended, its pharmaceutical form, method and route of administration and proposed shelf life;
(g) if applicable, explanations of the precautionary and safety measures to be taken when the product is stored, when it is administered to animals and when waste therefrom is disposed of, together with an indication of any potential risks the medicinal product might pose to the environment and the health of humans, animals or plants;
(h) indication of the withdrawal period. Where necessary, the applicant shall propose and justify a tolerance level for residues which may be accepted in foodstuffs without risk for the consumer, together with routine analysis methods which could be used by the competent authorities to trace residues;
(i) description of the control testing methods employed by the manufacturer (qualitative and quantitative analysis of the constituents and the finished product, specific tests e.g. sterility tests, test for the presence of pyrogens, for the presence of heavy metals, stability tests, biological and toxicity tests, tests on intermediate products);
(j) results of:
- physico-chemical, biological or microbiological tests,
- toxicological and pharmacological tests,
- clinical trials.
(k) a summary in accordance with Article 14 of the product characteristics, one or more specimens or mock-ups of the sales presentation of the veterinary medicinal product together with the package insert;
(l) a document showing that the manufacturer is authorized in his own country to produce veterinary medicinal products;
(m) copies of any marketing authorization obtained in another Member State or in a third country for the relevant veterinary medicinal product, together with a list of those Member States in which an application for authorization submitted in accordance with this Directive is under examination. Copies of the summary of the product characteristics proposed by the applicant in accordance with Article 14 or approved by the competent authority of the Member State in accordance with Article 25 and copies of the package insert proposed, details of any decision to refuse authorization, whether in the Community or a third country and the reasons for that decision.
This information shall be updated on a regular basis;
(n) in the case of medicinal products containing new active substances which are not mentioned in Annex I, II or III to Regulation (EEC) No 2377/90, a copy of the documents submitted to the Commission in accordance with Annex V to that Regulation.
Article 13
1. By way of derogation from point (j) of Article 12(3), and without prejudice to the law relating to the protection of industrial and commercial property:
(a) the applicant shall not be required to provide the results of toxicological and pharmacological tests and clinical trials if he can demonstrate:
(i) either that the veterinary medicinal product is essentially similar to a medicinal product authorized in the Member State concerned by the application and that the marketing authorization holder has agreed that the toxicological, pharmacological and/or clinical references contained in the file on the original veterinary medicinal product may be used for the purpose of examining the application in question;
(ii) or that the constituent or constituents of the veterinary medicinal product have a well-established medicinal use, with recognized efficacy and an acceptable level of safety, by means of detailed references to scientific literature;
(iii) or that the veterinary medicinal product is essentially similar to a medicinal product which has been authorized within the Community, in accordance with Community provisions in force, for not less than six years and is marketed in the Member State for which the application is made; this period shall be extended to 10 years in the case of high-technology medicinal products having been authorized in pursuance of the procedure established by Article 2(5) of Council Directive 87/22/EEC(13). Furthermore, a Member State may also extend this period to 10 years by a single Decision covering all the medicinal products marketed in its territory where it considers this necessary in the interest of public health. Member States are at liberty not to apply the six-year period beyond the date of expiry of a patent protecting the original medicinal product;
(b) in the case of new veterinary medicinal products containing known constituents not hitherto used in combination for therapeutic purposes, the results of toxicological and pharmacological tests and of clinical trials relating to that combination must be provided, but it shall not be necessary to provide the relevant documentation for each individual constituent.
2. Annex I shall apply in like manner where, pursuant to point (a)(ii) of paragraph 1, references to published data are submitted.
Article 14
The summary of the product characteristics shall contain the following information:
1. Name of the veterinary medicinal products;
2. Qualitative and quantitative composition in terms of the active substances and constituents of the excipient, knowledge of which is essential for proper administration of the medicinal product; the international non-proprietary names recommended by the World Health Organization shall be used, where such names exist, or failing this, the usual non-proprietary name or chemical description;
3. Pharmaceutical form;
4. Pharmacological properties and, in so far as this information is useful for the therapeutic purposes, pharmacokinetic particulars;
5. Clinical particulars;
5.1 target species,
5.2 indications for use, specifying the target species,
5.3 contra-indications,
5.4 undesirable effects (frequency and seriousness),
5.5 special precautions for use,
5.6 use during pregnancy and lactation,
5.7 interaction with other medicaments and other forms of interaction,
5.8 posology and method of administration,
5.9 overdose (symptoms, emergency procedures, antidotes) (if necessary),
5.10 special warnings for each target species,
5.11 withdrawal periods,
5.12 special precautions to be taken by the person administering the medicinal product to animals;
6. Pharmaceutical particulars:
6.1 major incompatibilities,
6.2 shelf life, when necessary after reconstitution of the medicinal product or when the container is opened for the first time,
6.3 special precautions for storage,
6.4 nature and contents of container,
6.5 special precautions for the disposal of unused medicinal product or waste materials, if any;
7. Name or corporate name and address or registered place of business of the authorization holder.
Article 15
1. Member States shall make all necessary arrangements to ensure that the documents and particulars listed in Article 12(3)(h), (i), (j) and Article 13(1) are drafted by experts with the requisite technical or professional qualifications before being submitted to the competent authorities.
These documents and particulars shall be signed by the experts in question.
2. According to their particular qualifications, the role of the experts shall be:
(a) to carry out such work as falls within their particular discipline (analysis, pharmacology and similar experimental sciences, clinical trials) and to describe objectively the results obtained in both quantitative and qualitative terms;
(b) to describe their findings in accordance with Annex I and in particular to state:
(i) in the case of analysts, whether the medicinal product conforms with the stated composition, providing any reasons for the control testing methods which the manufacturer is to use;
(ii) in the case of pharmacologists and appropriately qualified specialists:
- the toxicity of the medicinal product and the pharmacological properties observed,
- whether, after administration of the veterinary medicinal product under normal conditions of use and observance of the recommended withdrawal period, foodstuffs obtained from the treated animals contain residues which might constitute a health hazard to the consumer;
(iii) in the case of clinicians, whether they have found in animals treated with the medicinal product effects corresponding to the information furnished by the manufacturer pursuant to Articles 12 and 13(1), whether the medicinal product is well tolerated, what dosage they recommend and what are the contra-indications and adverse reactions, if any;
(c) to give reasons for the use of the references to published data referred to in point (a)(ii) of Article 13(1).
3. The experts' detailed reports shall form part of the documentation which the applicant shall lodge with the competent authorities. A brief curriculum vitae of the expert shall be appended to each report.
CHAPTER 2
Particular provisions applicable to homeopathic veterinary medicinal products
Article 16
1. Member States shall ensure that homeopathic veterinary medicinal products manufactured and marketed within the Community are registered or authorized in accordance with the provisions of Articles 17(1) and (2), 18 and 19. Each Member State shall take due account of registrations and authorizations previously granted by another Member State.
2. A Member State may refrain from establishing a special, simplified registration procedure for the homeopathic veterinary medicinal products referred to in Article 17(1) and (2). A Member State applying this provision shall inform the Commission accordingly. The Member State concerned shall, by 31 December 1995 at the latest, allow use in its territory of homeopathic veterinary medicinal products registered by other Member States in accordance with Article 17(1) and (2) and Article 18.
Article 17
1. Only homeopathic veterinary medicinal products which satisfy all of the following conditions may be subject to authorization by means of a special, simplified registration procedure:
- they are intended for administration to pet animals or exotic species which are non food-producing,
- they are administered by a route described in the European Pharmacopoeia or, in absence thereof, by the pharmacopoeias currently used officially in the Member States,
- no specific therapeutic indication appears on the labelling of the veterinary medicinal product or in any information relating thereto,
- there is a sufficient degree of dilution to guarantee the safety of the medicinal product; in particular, the medicinal product may not contain either more than one part per 10000 of the mother tincture or more than 1/100th of the smallest dose used in allopathy with regard to active principles whose presence in an allopathic medicinal product results in the obligation to submit a veterinary prescription.
At the time of registration, Member States shall determine the classification for the dispensing of the medicinal product.
2. The criteria and rules of procedure provided for in Chapter 3, with the exception of Article 25, shall apply by analogy to the special, simplified registration procedure for homeopathic veterinary medicinal products referred to in paragraph 1, with the exception of the proof of therapeutic effect.
3. The proof of therapeutic effect shall not be required for homeopathic veterinary medicinal products registered in accordance with paragraph 1 of this Article or, where appropriate, admitted in accordance with Article 16(2).
Article 18
A special, simplified application for registration may cover a series of medicinal products derived from the same homeopathic stock or stocks. The following documents shall be included with the application in order to demonstrate, in particular, the pharmaceutical quality and the batch-to-batch homogeneity of the products concerned:
- scientific name or other name given in a pharmacopoeia of the homeopathic stock or stocks, together with a statement of the various routes of administration, pharmaceutical forms and degree of dilution to be registered,
- dossier describing how the homeopathic stock or stocks is/are obtained and controlled, and justifying its/their homeopathic nature, on the basis of an adequate bibliography; in the case of homeopathic veterinary medicinal products containing biological substances, a description of the measures taken to ensure the absence of pathogens,
- manufacturing and control file for each pharmaceutical form and a description of the method of dilution and potentiation,
- manufacturing authorization for the medicinal products concerned,
- copies of any registrations or authorizations obtained for the same medicinal products in other Member States,
- one or more specimens or mock-ups of the outer packaging and immediate packaging of the medicinal products to be registered,
- data concerning the stability of the medicinal product.
Article 19
1. Homeopathic veterinary medicinal products other than those referred to in Article 17(1) shall be authorized in accordance with the provisions of Articles 12 to 15 and Chapter 3.
2. A Member State may introduce or retain in its territory specific rules for the pharmacological and toxicological tests and clinical trials of homeopathic veterinary medicinal products intended for pet animals and exotic species which are non food-producing other than those referred to in Article 17(1), in accordance with the principles and characteristics of homeopathy as practised in that Member State.
In this case, the Member State concerned shall notify the Commission of the specific rules in force.
Article 20
This Chapter shall not apply to immunological homeopathic veterinary medicinal products.
The provisions of titles VI and VII shall apply to homeopathic veterinary medicinal products.
CHAPTER 3
Procedure for marketing authorization
Article 21
1. Member States shall take all appropriate measures to ensure that the procedure for granting an authorization to place a veterinary medicinal product on the market is completed within 210 days of the submission of a valid application.
2. Where a Member State notes that an application for authorization submitted is already under active examination in another Member State in respect of that veterinary medicinal product, the Member State concerned may decide to suspend the detailed examination of the application in order to await the assessment report prepared by the other Member State in accordance with Article 25(4).
The Member State concerned shall inform the other Member State and the applicant of its decision to suspend detailed examination of the application in question. As soon as it has completed the examination of the application and reached a decision, the other Member State shall forward a copy of its assessment report to the Member State concerned.
Article 22
Where a Member State is informed in accordance with Article 12(3)(m), that another Member State has authorized a veterinary medicinal product which is the subject of an application for authorization in the Member State concerned, that Member State shall forthwith request the authorities of the Member State which has granted the authorization to forward to it the assessment report referred to in Article 25(4).
Within 90 days of receipt of the assessment report, the Member State concerned shall either recognise the decision of the first Member State and the summary of the product characteristics as approved by it or, if it considers that there are grounds for supposing that the authorization of the veterinary medicinal product concerned may present a risk to human or animal health or the environment, it shall apply the procedures set out in Articles 33 to 38.
Article 23
In order to examine the application submitted pursuant to Articles 12 and 13(1), the competent authorities of the Member States:
1. shall check that the documentation submitted in support of the application complies with Articles 12 and 13(1) and, on the basis of the reports drawn up by the experts pursuant to Article 15(2) and (3), ascertain whether the conditions for the issue of the marketing authorization have been fulfilled;
2. may submit the medicinal product, its raw materials and if necessary intermediate products or other constituent materials for testing by a State laboratory or by a laboratory designated for that purpose, in order to ensure that the testing methods employed by the manufacturer and described in the application documents, in accordance with Article 12(3)(i), are satisfactory;
3. may, where appropriate, require the applicant to provide further information as regards the items listed in Articles 12 and 13(1). Where the competent authorities take this course of action, the time-limits specified in Article 21 shall be suspended until the further data required have been provided. Similarly, these time-limits shall be suspended for any period which the applicant may be given to provide oral or written explanations;
4. may require the applicant to submit substances in the quantities necessary to verify the analytical detection method proposed by the applicant in accordance with Article 12(3)(h) and to put it into effect as part of routine checks to reveal the presence of residues of the veterinary medicinal products concerned.
Article 24
Member States shall take all appropriate measures to ensure that:
(a) the competent authorities ascertain that the manufacturers and importers of veterinary medicinal products from third countries are able to manufacture them in compliance with the details supplied pursuant to Article 12(3)(d), and/or to carry out control tests in accordance with the methods described in the application documents under Article 12(3)(i);
(b) the competent authorities may authorize manufacturers and importers of veterinary medicinal products from third countries, where circumstances so justify, to have certain stages of manufacture and/or certain of the control tests referred to in (a) carried out by third parties; in such cases, checks by the competent authorities shall also be carried out in the establishments concerned.
Article 25
1. When the marketing authorization is issued, the holder shall be informed by the competent authorities of the Member State concerned, of the summary of the product characteristics as approved by it.
2. The competent authorities shall take all necessary measures to ensure that the information given in the summary is in conformity with that accepted when the marketing authorization is issued or subsequently.
3. The competent authorities shall forward to the Agency a copy of the authorization together with the summary of the product characteristics.
4. The competent authorities shall draw up an assessment report and comments on the dossier as regards the results of the analytical and pharmacotoxicological tests and the clinical trials of the veterinary medicinal product concerned. The assessment report shall be updated whenever new information becomes available which is of importance for the evaluation of the quality, safety or efficacy of the veterinary medicinal product concerned.
Article 26
1. The marketing authorization may require the holder to indicate on the container and/or the outer wrapping and the package insert, where the latter is required, other particulars essential for safety or health protection, including any special precautions relating to use and any other warnings resulting from the clinical and pharmacological trials prescribed in Articles 12(3)(j) and 13(1) or from experience gained during the use of the veterinary medicinal product once it has been marketed.
2. The authorization may also require the inclusion of a tracer substance in the veterinary medicinal product.
3. In exceptional circumstances, and following consultation with the applicant, an authorization may be granted subject to certain specific obligations, and subject to annual review, including:
- the carrying out of further studies following the granting of authorization,
- the notification of adverse reactions to the veterinary medicinal product.
These exceptional decisions may only be adopted for objective and verifiable reasons.
Article 27
1. After a marketing authorization has been issued, the holder must, in respect of the manufacturing methods and control methods provided for in Article 12(3)(d) and (i), take account of scientific and technical progress and introduce any changes that may be required to enable that veterinary medicinal product to be manufactured and checked by means of generally accepted scientific methods.
These changes shall be subject to the approval of the competent authorities of the Member State concerned.
2. Upon request from the competent authorities, the marketing authorization holder shall also review the analytical detection methods provided for in Article 12(3)(h) and propose any changes which may be necessary to take account of scientific and technical progress.
3. The marketing authorization holder shall forthwith inform the competent authorities of any new information which might entail the amendment of the particulars and documents referred to in Articles 12 and 13(1) or of the approved summary of the product characteristics. In particular, he shall forthwith inform the competent authorities of any prohibition or restriction imposed by the competent authorities of any country in which the veterinary medicinal product is marketed and of any serious unexpected adverse effect occurring in the animals concerned or human beings.
4. The marketing authorization holder shall be required to maintain records of all adverse reactions observed in animals or human beings. The records so established shall be kept at least five years and shall be made available to the competent authorities upon request.
5. The marketing authorization holder shall immediately inform the competent authorities, with a view to authorization, of any alteration he proposes to make to the particulars and documents referred to in Articles 12 and 13(1).
Article 28
Authorization shall be valid for five years and shall be renewable for five-year periods, on application by the holder at least three months before the expiry date and after consideration of a dossier updating the information previously submitted.
Article 29
The granting of authorization shall not diminish the general legal liability of the manufacturer and, where appropriate, of the authorization holder.
Article 30
The marketing authorization shall be withheld if examination of the documents and particulars listed in Articles 12 and 13(1) establishes that:
(a) the veterinary medical product is harmful under the conditions of use stated at the time of application for authorization; or
(b) has no therapeutic effect or the applicant has not provided sufficient proof of such effect as regards the species of animal which is to be treated; or
(c) its qualitative or quantitative composition is not as stated; or
(d) the withdrawal period recommended by the applicant is not long enough to ensure that foodstuffs obtained from the treated animal do not contain residues which might constitute a health hazard to the consumer, or is insufficiently substantiated; or
(e) the veterinary medicinal product is offered for sale for a use prohibited under other Community provisions.
However, pending Community rules, the competent authorities may refuse to grant authorization for a veterinary medicinal product where such action is necessary for the protection of public health, consumer or animal health.
Authorization shall also be withheld if the application documents submitted to the competent authorities do not comply with Articles 12, 13(1) and 15.
CHAPTER 4
Mutual recognition of authorizations
Article 31
1. In order to facilitate the adoption of common decisions by Member States on the authorization of veterinary medicinal products on the basis of the scientific criteria of quality, safety and efficacy, and to achieve thereby the free movement of veterinary medicinal products within the Community, a Committee for Veterinary Medicinal Products, hereinafter referred to as "the Committee", is hereby set up. The Committee shall be part of the Agency.
2. In addition to the other responsibilities conferred upon it by Community law, the Committee shall examine any question relating to the granting, variation, suspension or withdrawal of marketing authorization which is submitted to it in accordance with the provisions of this Directive. It shall also examine any question relating to tests of veterinary medicinal products.
3. The Committee shall adopt its own rules of procedure.
Article 32
1. Before submitting an application for mutual recognition of marketing authorizations, the holder of the authorization shall inform the Member State which granted the authorization on which the application is based (hereinafter: the reference Member State) that an application is to be made in accordance with this Directive and shall notify it of any additions to the original dossier; that Member State may require the applicant to provide it with all the particulars and documents necessary to enable it to check that the dossiers filed are identical.
In addition, the holder of the authorization shall request the reference Member State which granted the initial authorization to prepare an assessment report in respect of the veterinary medicinal product concerned, or, if necessary, to update it. That Member State shall prepare it within 90 days of receipt of the request.
At the same time as the application is submitted in accordance with paragraph 2 the reference Member Sate which granted the initial authorization shall forward the assessment report to the Member State or Member States concerned by the application.
2. In order to obtain the recognition according to the procedure laid down in this Chapter in one or more of the Member States of a marketing authorization issued by a Member State, the holder of the authorization shall submit an application to the competent authority of the Member State or Member States concerned, together with the information and particulars referred to in Articles 12, 13(1), 14 and 25. He shall testify that the dossier is identical to that accepted by the reference Member State, or shall identify any additions or amendments it may contain. In the latter case, he shall certify that the summary of the product characteristics proposed by him in accordance with Article 14 is identical to that accepted by the reference Member State in accordance with Article 25. Moreover, he shall certify that all the dossiers filed as part of this procedure are identical.
3. The holder of the marketing authorization shall transmit the application to the Agency, inform it of the Member States concerned and of the dates of submission of the application and send it a copy of the authorization granted by the reference Member State. He shall also send the Agency copies of any such authorization which may have been granted by the other Member States in respect of the veterinary medicinal product concerned, and shall indicate whether any application for authorization is currently under consideration in any Member State.
4. Save in the exceptional case provided for in Article 33(1), each Member State shall recognise the marketing authorization granted by the reference Member State within 90 days of receipt of the application and the assessment report. It shall inform the reference Member State, the other Member States concerned by the application, the Agency, and the holder of the authorization for placing the product on the market.
Article 33
1. Where a Member State considers that there are grounds for supposing that the marketing authorization of the veterinary medicinal product concerned may present a risk to human or animal health or the environment, it shall forthwith inform the applicant, the reference Member State, any other Member States concerned by the application and the Agency. The Member State shall state its reason in detail and shall indicate what action may be necessary to correct any defect in the application.
2. All the Member States concerned shall use their best endeavours to reach agreement on the action to be taken in respect of the application. They shall provide the applicant with the opportunity to make his point of view known orally or in writing. However, if the Member States have not reached agreement within the time-limit referred to in Article 32(4) they shall forthwith refer the matter to the Agency, for referral to the Committee, for the application of the procedure laid down in Article 36.
3. Within the time-limit referred to in Article 32(4), the Member States concerned shall provide the Committee with a detailed statement of the matters on which they have been unable to reach agreement and the reasons for their disagreement. The applicant shall be provided with a copy of this information.
4. As soon as he is informed that the matter has been referred to the Committee, the applicant shall forthwith forward to the Committee a copy of the information and particulars referred to in Article 32(2).
Article 34
If several applications submitted in accordance with Articles 12, 13(1) and 14 have been made for marketing authorization for a particular veterinary medicinal product and Member States have adopted divergent decisions concerning the authorization of that veterinary medicinal product, or suspension or withdrawal of that authorization, a Member State, or the Commission, or the marketing authorization holder may refer the matter to the Committee for application of the procedure laid down in Article 36.
The Member State concerned, the marketing authorization holder or the Commission shall clearly identify the question which is referred to the Committee for consideration and, if appropriate, shall inform the aforementioned holder thereof.
The Member States and the marketing authorization holder shall forward to the Committee all available information relating to the matter in question.
Article 35
The Member States or the Commission or the applicant or holder of the marketing authorization may, in specific cases where the interests of the Community are involved, refer the matter to the Committee for the application of the procedure laid down in Article 36 before reaching a decision on a request for a marketing authorization or on the suspension or withdrawal of an authorization, or on any other variations to the terms of a marketing authorization which appears necessary, in particular to take account of the information collected in accordance with Title VII.
The Member State concerned or the Commission shall clearly identify the question which is referred to the Committee for consideration and shall inform the marketing authorization holder.
The Member States and the holder shall forward to the Committee all available information relating to the matter in question.
Article 36
1. When reference is made to the procedure described in this Article, the Committee shall consider the matter concerned and issue a reasoned opinion within 90 days of the date on which the matter was referred to it.
However, in cases submitted to the Committee in accordance with Articles 34 and 35, this period may be extended by 90 days.
In case of urgency, on a proposal from its Chairman, the Committee may agree to a shorter deadline.
2. In order to consider the matter, the Committee may appoint one of its members to act as rapporteur. The Committee may also appoint individual experts to advise it on specific questions. When appointing experts, the Committee shall define their tasks and specify the time-limit for the completion of these tasks.
3. In the cases referred to in Articles 33 and 34, before issuing its opinion, the Committee shall provide the marketing authorization holder with an opportunity to present written or oral explanations.
In the case referred to in Article 35, the marketing authorization holder may be asked to explain himself orally or in writing.
If it considers it appropriate, the Committee may invite any other person to provide information relating to the matter before it.
The Committee may suspend the time-limit referred to in paragraph 1 in order to allow the marketing authorization holder to prepare explanations.
4. The Agency shall forthwith inform the marketing authorization holder where the opinion of the Committee is that:
- the application does not satisfy the criteria for authorization, or
- the summary of the product characteristics proposed by the applicant in accordance with Article 14 should be amended, or
- the authorization should be granted subject to conditions, with regard to conditions considered essential for the safe and effective use of the veterinary medicinal product including pharmacovigilance, or
- a marketing authorization should be suspended, varied or withdrawn.
Within 15 days of the receipt of the opinion, the holder may notify the Agency in writing of his intention to appeal. In that case, he shall forward the detailed grounds for appeal to the Agency within 60 days of receipt of the opinion. Within 60 days of receipt of the grounds for 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 5.
5. Within 30 days of its adoption, the Agency shall forward the final opinion of the Committee to the Member States, the Commission and the marketing authorization holder together with a report describing the assessment of the veterinary medicinal product and the reasons for its conclusions.
In the event of an opinion in favour of granting or maintaining an authorization to place the veterinary medicinal product concerned on the market, the following documents shall be annexed to the opinion:
(a) a draft summary of the product characteristics, as referred to in Article 14; where necessary this will reflect differences in the veterinary conditions pertaining in the Member States;
(b) any conditions affecting the authorization within the meaning of paragraph 4.
Article 37
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 into account Community law.
In the event of a draft decision which envisages the granting of marketing authorization, the documents referred to in Article 36(5)(2), (a) and (b) 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.
Article 38
1. A final decision on the application shall be adopted in accordance with the procedure referred to in Article 89(2).
2. The rules of procedure of the Standing Committee set up by Article 89(1) shall be adjusted to take account of the tasks incumbent upon it in accordance with this Chapter.
These adjustments shall involve the following:
- except in cases referred to in the third paragraph of Article 37, the opinion of the Standing Committee shall be obtained in writing,
- each Member State is allowed at least 28 days to forward written observations on the draft decision of the Commission,
- each Member State is able to require in writing that the draft decision be discussed by the Standing Committee, giving its reasons in detail.
Where, in the opinion of the Commission, the written observations of a Member State raise important new questions of a scientific or technical nature 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 referred to in Article 89(2).
3. A decision as referred to in paragraph 1 shall be addressed to the Member States concerned by the matter and communicated to the marketing authorization holder. The Member States shall either grant or withdraw marketing authorization, or vary the terms of a marketing authorization as necessary to comply with the decision within 30 days of its notification. They shall inform the Commission and the Agency thereof.
Article 39
1. Any application by the marketing authorization holder to vary a marketing authorization which has been granted in accordance with the provisions of this Chapter shall be submitted to all the Member States which have previously authorized the veterinary medicinal product concerned.
The Commission shall, in consultation with the Agency, adopt appropriate arrangements for the examination of variations to the terms of a marketing authorization.
These arrangements shall include a notification system or administration procedures concerning minor variations and define precisely the concept of "a minor variation".
These arrangements shall be adopted by the Commission in the form of an implementing regulation in accordance with the procedure referred to in Article 89(2).
2. In case of arbitration submitted to the Commission, the procedure laid down in Articles 36, 37 and 38 shall apply by analogy to variations made to marketing authorizations.
Article 40
1. Where a Member State considers that the variation of the terms of a marketing authorization which has been granted in accordance with the provisions of this Chapter or its suspension or withdrawal is necessary for the protection of human or animal health or the environment, the Member State concerned shall forthwith refer the matter to the Agency for the application of the procedures laid down in Articles 36, 37 and 38.
2. Without prejudice to the provisions of Article 35, in exceptional cases, where urgent action is essential to protect human or animal health or the environment, until a definitive decision is adopted, a Member State may suspend the marketing and the use of the veterinary medicinal product concerned on its territory. It shall inform the Commission and the other Member States no later than the following working day of the reasons for its action.
Article 41
Articles 39 and 40 shall apply by analogy to veterinary medicinal products authorized by Member States following an opinion of the Committee given in accordance with Article 4 of Directive 87/22/EEC before 1 January 1995.
Article 42
1. The Agency shall publish an annual report on the operation of the procedures laid down in this Chapter and shall forward it to the European Parliament and the Council for information.
2. By 1 January 2001, the Commission shall publish a detailed review of the operation of the procedures laid down in this Chapter and shall propose any amendments which may be necessary to improve these procedures.
The Council shall decide, under the conditions provided for in the Treaty, on the Commission proposal within one year of its submission.
Article 43
The provisions of Articles 31 to 38 shall not apply to homeopathic veterinary medicinal products referred to in Article 19(2).
TITLE IV
MANUFACTURE AND IMPORTS
Article 44
1. Member States shall take all appropriate measures to ensure that the manufacture of veterinary medicinal products in their territory is subject to the holding of an authorization. This manufacturing authorization shall likewise be required for veterinary medicinal products intended for export.
2. The authorization referred to in paragraph 1 shall be required both for total and partial manufacture and for the various processes of dividing up, packaging or presentation.
However, such authorization shall not be required for preparation, dividing up, changes in packaging or presentation where these processes are carried out solely for retail supply by pharmacists in dispensing pharmacies or by persons legally authorized in the Member States to carry out such processes.
3. The authorization referred to in paragraph 1 shall also be required for imports from third countries into a Member State; this Title and Article 83 shall apply to such imports in the same way as to manufacture.
Member States shall take all appropriate measures to ensure that veterinary medicinal products brought into their territory from a third country and destined for another Member State are accompanied by a copy of the authorization referred to in paragraph 1.
Article 45
In order to obtain the manufacturing authorization, the applicant shall meet at least the following requirements:
(a) he shall specify the veterinary medicinal products and pharmaceutical forms which are to be manufactured or imported and also the place where they are to be manufactured and/or controlled;
(b) he shall have at his disposal, for the manufacture or import of the above, suitable and sufficient premises, technical equipment and control facilities complying with the legal requirements which the Member State concerned lays down as regards both manufacture and control and the storage of products, in accordance with Article 24;
(c) he shall have at his disposal the services of at least one qualified person within the meaning of Article 52.
The applicant shall provide particulars in his application to establish his compliance with the above requirements.
Article 46
1. The competent authority of the Member State shall not issue the manufacturing authorization until it has established the accuracy of the particulars supplied pursuant to Article 45 by means of an inquiry carried out by its representatives.
2. In order to ensure that the requirements referred to in Article 45 are complied with, authorization may be made conditional on the fulfilment of certain obligations imposed either when authorization is granted or at a later date.
3. The authorization shall apply only to the premises specified in the application and to the veterinary medicinal products and pharmaceutical forms specified in that application.
Article 47
The Member States shall take all appropriate measures to ensure that the time taken for the procedure for granting the manufacturing authorization does not exceed 90 days from the day on which the competent authority receives the application.
Article 48
If the holder of the manufacturing authorization requests a change in any of the particulars referred to in Article 45, first paragraph, (a) and (b), the time taken for the procedure relating to this request shall not exceed 30 days. In exceptional cases, this period of time may be extended to 90 days.
Article 49
The competent authority of the Member States may require from the applicant further information concerning both the particulars supplied pursuant to Article 45 and the qualified person referred to in Article 52; where the competent authority concerned exercises this right, application of the time-limits referred to in Articles 47 and 48 shall be suspended until the additional data required have been supplied.
Article 50
The holder of a manufacturing authorization shall at least be obliged to:
(a) have at his disposal the services of staff complying with the legal requirements existing in the Member State concerned as regards both manufacture and controls;
(b) dispose of the authorized veterinary medicinal products only in accordance with the legislation of the Member States concerned;
(c) give prior notice to the competent authority of any changes which he may wish to make to any of the particulars supplied pursuant to Article 45; the competent authority shall, in any event, be immediately informed if the qualified person referred to in Article 52 is replaced unexpectedly;
(d) allow the representatives of the competent authority of the Member State concerned access to his premises at any time;
(e) enable the qualified person referred to in Article 52 to carry out his duties, particularly by placing at his disposal all the necessary facilities;
(f) comply with the principles and the guidelines of good manufacturing practice for medicinal products laid down by Community law;
(g) keep detailed records of all veterinary medicinal products supplied by him, including samples, in accordance with the laws of the countries of destination. The following information at least shall be recorded in respect of each transaction, whether or not it is made for payment:
- date,
- name of the veterinary medicinal product,
- quantity supplied,
- name and address of the recipient,
- batch number.
These records shall be available for inspection by the competent authorities for a period of at least three years.
Article 51
The principles and guidelines of good manufacturing practice for veterinary medicinal products referred to in Article 50(f) shall be adopted in the form of a Directive addressed to the Member States in accordance with the procedure referred to in Article 89(2).
Detailed guidelines shall be published by the Commission and revised as appropriate to take account of scientific and technical progress.
Article 52
1. Member States shall take all appropriate measures to ensure that the holder of the manufacturing authorization has permanently and continuously at his disposal the services of at least one qualified person who fulfils the conditions laid down in Article 53 and is responsible, in particular, for carrying out the duties specified in Article 55.
2. If he personally fulfils the conditions laid down in Article 53, the holder of the authorization may himself assume the responsibility referred to in paragraph 1.
Article 53
1. Member States shall ensure that the qualified person referred to in Article 52 fulfils the minimum conditions of qualification set out in paragraphs 2 and 3.
2. The qualified person shall be in possession of a diploma, certificate or other evidence of formal qualifications awarded on completion of a university course of study, or a course recognized as equivalent by the Member State concerned, extending over a period of at least four years of theoretical and practical study in one of the following scientific disciplines: pharmacy, medicine, veterinary science, chemistry, pharmaceutical chemistry and technology, biology.
However, the minimum duration of the university course may be three and a half years where the course is followed by a period of theoretical and practical training of at least one year and includes a training period of at least six months in a pharmacy open to the public, corroborated by an examination at university level.
Where two university or recognized equivalent courses coexist in a Member State and where one of these extends over four years and the other over three years, the diploma, certificate or other evidence of formal qualifications awarded on completion of the three-year university course or its recognized equivalent shall be considered to fulfil the condition of duration referred to in the first subparagraph in so far as the diplomas, certificates or other evidence of formal qualifications awarded on completion of both courses are recognized as equivalent by the State in question.
The course shall include theoretical and practical tuition bearing upon at least the following basic subjects:
- experimental physics,
- general and inorganic chemistry,
- organic chemistry,
- analytical chemistry,
- pharmaceutical chemistry, including analysis of medicinal products,
- general and applied biochemistry (medical),
- physiology,
- microbiology,
- pharmacology,
- pharmaceutical technology,
- toxicology,
- pharmacognosy (study of the composition and effects of the active principles of natural substances of plant and animal origin).
Tuition in these subjects should be so balanced as to enable the person concerned to fulfil the obligations specified in Article 55.
In so far as certain diplomas, certificates or other evidence of formal qualifications mentioned in this paragraph do not fulfil the criteria laid down above, the competent authority of the Member State shall ensure that the person concerned provides evidence that he has, in the subjects involved, the knowledge required for the manufacture and control of veterinary medicinal products.
3. The qualified person shall have acquired practical experience over at least two years, in one or more undertakings which are authorized manufacturers, in the activities of qualitative analysis of medicinal products, of quantitative analysis of active substances and of the testing and checking necessary to ensure the quality of veterinary medicinal products.
The duration of practical experience may be reduced by one year where a university course lasts for at least five years and by a year and a half where the course lasts for at least six years.
Article 54
1. A person engaging, in a Member State, in the activities of the person referred to in Article 52 at the date on which Directive 81/851/EEC became applicable, without complying with the provisions of Article 53 shall be eligible to continue to engage in those activities in the State concerned.
2. The holder of a diploma, certificate or other evidence of formal qualifications awarded on completion of a university course - or a course recognized as equivalent by the Member State concerned - in a scientific discipline allowing him to engage in the activities of the person referred to in Article 52 in accordance with the laws of that State may - if he began his course prior to 9 October 1981 - be considered as qualified to carry out in that State the duties of the person referred to in Article 52, provided that he has previously engaged in the following activities for at least two years before 9 October 1991 in one or more undertakings with a manufacturing authorization; production supervision and/or qualitative and quantitative analysis of active substances, and the necessary testing and checking under the direct authority of a person as referred to in Article 52 to ensure the quality of veterinary medicinal products.
If the person concerned has acquired the practical experience referred to in the first subparagraph before 9 October 1971, a further one year's practical experience in accordance with the conditions referred to in the first subparagraph shall be completed by him immediately before he engages in such activities.
Article 55
1. Member States shall take all appropriate measures to ensure that the qualified person referred to in Article 52 is, without prejudice to his relationship with the holder of the manufacturing authorization, responsible, in the context of the procedures referred to in Article 56, for ensuring that:
(a) in the case of veterinary medicinal products manufactured within the Member State concerned, each batch of veterinary medicinal products has been manufactured and checked in compliance with the laws in force in that Member State and in accordance with the requirements of the marketing authorization;
(b) in the case of veterinary medicinal products coming from third countries, each production batch imported has undergone in the importing Member State a full qualitative analysis, a quantitative analysis of at least all the active substances and all the other tests or checks necessary to ensure the quality of veterinary medicinal products in accordance with the requirements of the marketing authorization.
Batches of veterinary medicinal products which have undergone such controls in a Member State shall be exempt from the above controls if they are placed on the market in another Member State, accompanied by the control reports signed by the qualified person.
2. In the case of veterinary medicinal products imported from a third country, where appropriate arrangements have been made by the Community with the exporting country to ensure that the manufacturer of the veterinary medicinal product applies standards of good manufacturing practice at least equivalent to those laid down by the Community and to ensure that the controls referred to under point (b) of the first subparagraph of paragraph 1 have been carried out in the exporting country, the qualified person may be relieved of responsibility for carrying out those controls.
3. In all cases, and particularly where the veterinary medicinal products are released for sale, the qualified person shall certify, in a register or equivalent document provided for the purpose, that each production batch satisfies the provisions of this Article; the said register or equivalent document shall be kept up to date as operations are carried out and shall remain at the disposal of the representatives of the competent authority for the period specified in the provisions of the Member State concerned and, in any event, for at least five years.
Article 56
Member States shall ensure that the obligations of qualified persons referred to in Article 52 are fulfilled, either by means of appropriate administrative measures or by making such persons subject to a professional code of conduct.
Member States may provide for the temporary suspension of such a person upon the commencement of administrative or disciplinary proceedings against him for failure to fulfil his obligations.
Article 57
The provisions of this Title shall apply to homeopathic veterinary medicinal products.
TITLE V
LABELLING AND PACKAGE INSERT
Article 58
1. The following information, which shall conform with the particulars and documents provided pursuant to Articles 12 and 13(1) and be approved by the competent authorities, shall appear in legible characters on containers and outer packages of medicinal products:
(a) Name of the veterinary medicinal product, which may be a brand name or a non-proprietary name accompanied by a trade mark or the name of the manufacturer, or a scientific name or formula, with or without a trade mark, or the name of the manufacturer.
Where the special name of a medicinal product containing only one active substance is a brand name, this name must be accompanied in legible characters by the international non-propriety name recommended by the World Health Organization, where such name exists or, where no such name exists, by the usual non-proprietary name;
(b) A statement of the active substances expressed qualitatively and quantitatively per dosage unit or according to the form of administration for a particular volume or weight, using the international non-proprietary names recommended by the World Health Organization, where such names exist or, where no such names exist, the usual non-proprietary names;
(c) Manufacturer's batch number;
(d) Marketing authorization number;
(e) Name or corporate name and permanent address or registered place of business of the marketing authorization holder and of the manufacturer, if different;
(f) The species of animal for which the veterinary medicinal product is intended; the method and route of administration;
(g) The withdrawal period, even if nil, in the case of veterinary medicinal products administered to food-producing animals;
(h) Expiry date, in plain language;
(i) Special storage precautions, if any;
(j) Special precautions for disposal of unused medicinal products or waste material from medicinal products, if any;
(k) Particulars required to be indicated pursuant to Article 26(1), if any;
(l) The words "For animal treatment only".
2. The pharmaceutical form and the contents by weight, volume or number of dose-units need only be shown on the outer package.
3. The provisions of Part 1, A of Annex I, in so far as they concern the qualitative and quantitative composition of veterinary medicinal products in respect of active substances, shall apply to the particulars provided for in paragraph 1(b).
4. The particulars mentioned in paragraph 1(f) to (l) shall appear on the outer package and on the container of the medicinal products in the language or languages of the country in which they are placed on the market.
Article 59
1. As regards ampoules, the particulars listed in the first paragraph of Article 58(1) shall be given on the outer package. On the containers, however, only the following particulars shall be necessary:
- name of veterinary medicinal product,
- quantity of the active substances,
- route of administration,
- manufacturer's batch number,
- date of expiry,
- the words "For animal treatment only".
2. As regards small single-dose containers, other than ampoules, on which it is impossible to give the particulars mentioned in paragraph 1, the requirements of Article 58(1), (2) and (3), shall apply only to the outer package.
3. The particulars mentioned in the third and sixth indents of paragraph 1 shall appear on the outer package and on the container of the medicinal products in the language or languages of the country in which they are placed on the market.
Article 60
Where there is no outer package, all the particulars which should feature on such a package pursuant to the Articles 58 and 59 shall be shown on the container.
Article 61
1. The inclusion of a package insert in the packaging of veterinary medicinal products shall be obligatory unless all the information required by this Article can be conveyed on the container and the external packaging. Member States shall take all appropriate measures to ensure that the insert relates solely to the veterinary medicinal product with which it is included. The insert shall be in the official language or languages of the Member State in which the medicinal product is marketed.
2. The package insert shall contain at least the following information, which shall conform to the particulars and documents provided pursuant to Articles 12 and 13(1) and be approved by the competent authorities:
(a) name or corporate name and permanent address or registered place of business of the marketing authorization holder and of the manufacturer, if different;
(b) name of the veterinary medicinal product and a statement of its active substances expressed qualitatively and quantitatively;
The international non-proprietary names recommended by the World Health Organization shall be used wherever they exist;
(c) the therapeutic indications;
(d) contra-indications and adverse reactions in so far as these particulars are necessary for the use of the veterinary medicinal product;
(e) the species of animal for which the veterinary medicinal product is intended, the dosage for each species, the method and route of administration and advice on correct administration, if necessary;
(f) the withdrawal period, even if this is nil, in the case of veterinary medicinal products administered to food-producing animals;
(g) special storage precautions, if any;
(h) particulars required to be indicated pursuant to Article 26(1), if any;
(i) special precautions for the disposal of unused medicinal products or waste materials from medicinal products, if any.
3. The particulars referred to in paragraph 2 shall appear in the language or languages of the country in which the product is marketed. The other information shall be clearly separate from such particulars.
Article 62
Where the provisions of this Title are not observed and a formal notice addressed to the person concerned has been ineffectual, the competent authorities of the Member States may suspend or withdraw marketing authorization.
Article 63
The requirements of Member States concerning conditions of supply to the public, the marking of prices on medicinal products for veterinary use and industrial property rights shall not be affected by the provisions of this Title.
Article 64
1. Without prejudice to paragraph 2, homeopathic veterinary medicinal products shall be labelled in accordance with the provisions of this title and identified by the inclusion on their labels, in clearly legible form, of the words "homeopathic medicinal product for veterinary use".
2. In addition to the clear mention of the words "homeopathic veterinary medicinal product without approved therapeutic indications", the labelling and, where appropriate, package insert for the homeopathic veterinary medicinal products referred to in Article 17(1) shall bear the following information and no other information:
- the scientific name of the stock or stocks followed by the degree of dilution, using the symbols of the pharmacopoeia used in accordance with point 8 of Article 1,
- name and address of the marketing authorization holder and, where appropriate, of the manufacturer,
- method of administration and, if necessary, route,
- expiry date, in clear terms (month, year),
- pharmaceutical form,
- contents of the sales presentation,
- special storage precautions, if any,
- target species,
- a special warning if necessary for the medicinal product,
- manufacturer's batch number,
- registration number.
TITLE VI
POSSESSION, WHOLESALE DISTRIBUTION AND DISPENSING OF VETERINARY MEDICINAL PRODUCTS
Article 65
1. Member States shall take all appropriate measures to ensure that wholesale distribution of veterinary medicinal products is subject to the holding of an authorization and to ensure that the time taken for the procedure for granting this authorization does not exceed 90 days from the date on which the competent authority receives the application.
Member States may exclude supplies of small quantities of veterinary medicinal products from one retailer to another from the scope of the definition of wholesale distribution.
2. In order to obtain the authorization for distribution, the applicant shall have at his disposal technically competent staff and suitable and sufficient premises complying with the requirements laid down in the Member State concerned as regards the storage and handling of veterinary medicinal products.
3. The holder of the authorization for distribution shall be required to keep detailed records. The following minimum information shall be recorded in respect of each incoming or outgoing transaction:
(a) date;
(b) precise identity of the veterinary medicinal product;
(c) manufacturer's batch number, expiry date;
(d) quantity received or supplied;
(e) name and address of the supplier or recipient.
At least once a year a detailed audit shall be carried out to compare incoming and outgoing medicinal supplies with supplies currently held in stock, any discrepancies being recorded.
These records shall be available for inspection by the competent authorities for a period of at least three years.
4. Member States shall take all appropriate measures to ensure that wholesalers supply veterinary medicinal products only to persons permitted to carry out retail activities in accordance with Article 66, or to other persons who are lawfully permitted to receive veterinary medicinal products from wholesalers.
Article 66
1. Member States shall take all appropriate measures to ensure that the retail supply of veterinary medicinal products is conducted only by persons who are permitted to carry out such operations by the legislation of the Member State concerned.
2. Any person permitted under paragraph 1 to sell veterinary medicinal products shall be required to keep detailed records. The following information shall be recorded in respect of each incoming or outgoing transaction:
(a) date;
(b) precise identity of the veterinary medicinal product;
(c) manufacturer's batch number;
(d) quantity received or supplied;
(e) name and address of the supplier or recipient;
(f) where relevant, name and address of the prescribing veterinarian and a copy of the prescription.
At least once a year a detailed audit shall be carried out, and incoming and outgoing veterinary medicinal products shall be reconciled with products currently held in stock, any discrepancies being recorded.
These records shall be available for inspection by the competent authorities for a period of three years.
3. Member States may limit the number of detailed documenting requirements referred to in paragraph 2. However, these requirements shall always be applied in case of veterinary medicinal products which are intended for administration to food-producing animals and which are available only on veterinary prescription or in respect of which a withdrawal period must be observed.
4. Not later that 1 January 1992, Member States shall communicate to the Commission a list of the veterinary medicinal products which are available without prescription.
After having taken note of the communication from the Member States, the Commission shall examine whether suitable measures should be proposed for drawing up a Community list of such medicinal products.
Article 67
Without prejudice to stricter Community or national rules relating to dispensing veterinary medicinal products and to protect human and animal health, a prescription shall be required for dispensing to the public the following veterinary medicinal products;
(a) those products subject to official restrictions on supply or use, such as:
- the restrictions resulting from the implementation of the relevant United Nations conventions on narcotic and psychotropic substances,
- the restrictions on the use of veterinary medicinal products resulting from Community law;
(b) those products in respect of which special precautions must be taken by the veterinarian in order to avoid any unnecessary risk to:
- the target species,
- the person administering the products to the animal,
- the consumer of foodstuffs obtained from the treated animal,
- the environment;
(c) those products intended for treatments or pathological processes which require a precise prior diagnosis or the use of which may cause effects which impede or interfere with subsequent diagnostic or therapeutic measures;
(d) magistral formulae intended for animals.
In addition, a prescription shall be required for new veterinary medicinal products containing an active substance which has been authorized for use in a veterinary medicinal product for less than five years unless, having regard to the information and particulars provided by the applicant, or experience acquired in the practical use of the veterinary medicinal product, the competent authorities are satisfied that none of the criteria referred to in (a) to (d) of the first paragraph apply.
Article 68
1. Member States shall take all measures necessary to ensure that only persons empowered under their national legislation in force possess or have under their control veterinary medicinal products or substances which may be used as veterinary medicinal products that have anabolic, anti-infectious, anti-parasitic, anti-inflammatory, hormonal or psychotropic properties.
2. Member States shall maintain a register of manufacturers and dealers permitted to be in possession of active substances which may be used in the manufacture of veterinary medicinal products having the properties referred to in paragraph 1. Such persons must maintain detailed records of all dealings in substances which may be used in the manufacture of veterinary medicinal products and keep these records available for inspection by the competent authorities for a period of at least three years.
3. Any amendments to be made to the list of substances referred to in paragraph 1 shall be adopted in accordance with the procedure referred to in Article 89(2).
Article 69
Member States shall ensure that the owners or keepers of food-producing animals can provide proof of purchase, possession and administration of veterinary medicinal products containing the substances set out in Article 68; Member States may extend the scope of this obligation to other veterinary medicinal products.
In particular, Member States may require the maintenance of a record giving at least the following information:
(a) date;
(b) name of the veterinary medicinal product;
(c) quantity;
(d) name and address of the supplier of the medicinal product;
(e) identification of the animals treated.
Article 70
Notwithstanding Articles 9 and 67, Member States shall ensure that veterinarians providing services in another Member State can take with them and administer to animals small quantities of ready-made veterinary medicinal products not exceeding daily requirements other than immunological veterinary medicinal products which are not authorized for use in the Member State in which the services are provided (hereinafter: host Member State), providing that the following conditions are satisfied:
(a) the authorization to place the product on the market provided for in Articles 5, 7 and 8 has been issued by the competent authorities of the Member State in which the veterinarian is established;
(b) the veterinary medicinal products are transported by the veterinarian in the original manufacturer's packaging;
(c) the veterinary medicinal products intended for administration to food-producing animals have the same qualitative and quantitative composition in terms of active substances as the medicinal products authorized in accordance with Articles 5, 7 and 8 in the host Member State;
(d) the veterinarian providing services in another Member State acquaints himself with the good veterinary practices applied in that Member State and ensures that the withdrawal period specified on the labelling of the veterinary medicinal product concerned is complied with, unless he could reasonably be expected to know that a longer withdrawal period should be specified to comply with these good veterinary practices;
(e) the veterinarian shall not furnish any veterinary medicinal product to the owner or keeper of the animals treated in the host Member State unless this is permissible on the basis of the rules of the host Member State; in this case he shall, however, supply only in relation to animals under his care and only the minimum quantities of veterinary medicinal product necessary to complete the treatment of animals concerned on that occasion;
(f) the veterinarian shall be required to keep detailed records of the animals treated, the diagnosis, the veterinary medicinal products administered, the dosage administered, the duration of treatment and the withdrawal period applied. These records shall be available for inspection by the competent authorities of the host Member State for a period of at least three years;
(g) the overall range and quantity of veterinary medicinal products carried by the veterinarian shall not exceed that generally required for the daily needs of good veterinary practice.
Article 71
1. In the absence of specific Community legislation concerning the use of immunological veterinary medicinal products for the eradication or control of animal disease, a Member State may, in accordance with its national legislation, prohibit the manufacture, import, possession, sale, supply and/or use of immunological veterinary medicinal products on the whole or part of its territory if it is established that:
(a) the administration of the product to animals will interfere with the implementation of a national programme for the diagnosis, control or eradication of animal disease, or will cause difficulties in certifying the absence of contamination in live animals or in foodstuffs or other products obtained from treated animals;
(b) the disease to which the product is intended to confer immunity is largely absent from the territory in question.
2. The competent authorities of the Member States shall inform the Commission of all instances in which the provisions of paragraph 1 are applied.
TITLE VII
PHARMACOVIGILANCE
Article 72
1. Member States shall take all appropriate measures to encourage the reporting to the competent authorities of suspected adverse reactions to veterinary medicinal products.
2. The Member States may impose specific requirements on veterinary practitioners and other health care professionals in respect of the reporting of suspected serious or unexpected adverse reactions and human adverse reactions, in particular where such reporting is a condition of the marketing authorization.
Article 73
In order to ensure the adoption of appropriate regulatory decisions concerning the veterinary medicinal products authorised within the Community, having regard to information obtained about suspected adverse reactions to veterinary medicinal products under normal conditions of use, the Member States shall establish a veterinary pharmacovigilance system. This system shall be used to collect information useful in the surveillance of veterinary medicinal products, with particular reference to adverse reactions in animals and in human beings related to the use of veterinary medicinal products, and to evaluate such information scientifically.
Such information shall be collated with available data on the sale and prescription of veterinary medicinal products.
This system also takes into account any available information related to the lack of expected efficacy, off-label use, investigations of the validity of the withdrawal period and on potential environmental problems, arising from the use of the product, interpreted in accordance with the Commission guidelines referred to in Article 77(1), which may have an impact on the evaluation of their benefits and risks.
Article 74
The marketing authorization holder shall have permanently and continuously at his disposal an appropriately qualified person responsible for pharmacovigilance.
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 are reported to the personnel of the company, including its representatives, is collected and collated in order to be accessible at least at one point within the Community;
(b) the preparation for the competent authorities of the reports referred to in Article 75, in such form as may be laid down by those authorities, in accordance with the guidance referred to in Article 77(1);
(c) ensuring that any request from the competent authorities for the provision of additional information necessary for the evaluation of the benefits and risks afforded by a veterinary medicinal product is answered fully and promptly, including the provision of information about the volume of sales or prescriptions of the veterinary medicinal product concerned;
(d) the provision to the competent authorities, of any other information relevant to the evaluation of the benefits and risks afforded by a veterinary medicinal product, including appropriate information on post-marketing surveillance studies.
Article 75
1. The marketing authorization holder shall be required to maintain detailed records of all suspected adverse reactions occurring either in the Community or in a third country.
2. The marketing authorization holder shall be required to record and to report all suspected serious adverse reactions and human adverse reactions related to the use of veterinary medicinal products, of which he can reasonably be expected to have knowledge, or which are brought to his attention, immediately to the competent authority of the Member State in whose territory the incident occurred, and in no case later than 15 calendar days following the receipt of the information.
3. The marketing authorization holder shall ensure that the suspected serious and unexpected adverse reactions and human adverse reactions, occurring in the territory of a third country, are reported immediately in accordance with the guidance referred to in Article 77(1), so that they are available to the Agency and to the competent authorities in the Member State(s) where the veterinary medicinal product is authorized, and in no case later than 15 calendar days following the receipt of the information.
4. In the case of veterinary medicinal products which have been considered within the scope of Directive 87/22/EEC, or which have benefited from the procedures of mutual recognition under Articles 21, 22 and 32(4) of this Directive and veterinary medicinal products for which there has been a referral to the procedures under Articles 36, 37 and 38 of this Directive, the marketing authorisation holder shall additionally ensure that all suspected serious adverse reactions and human adverse reactions, occurring in the Community, are reported in the format and at intervals to be agreed with the reference Member State or a competent authority designated as reference Member State, in such a way so as to be accessible to the reference Member State.
5. Unless other requirements have been laid down as condition of the granting of authorization, records of all adverse reactions shall be submitted to the competent authorities in the form of a periodic safety update report, either immediately upon request or periodically as follows: six monthly for the first two years after authorization, annually for the subsequent two years, and at the same time of the first renewal. Thereafter, the periodic safety update reports shall be submitted at five-yearly intervals together with the application for renewal of the authorization. The periodic safety update report shall include a scientific evaluation of the benefits and risks afforded by the veterinary medicinal product.
6. Following the granting of a marketing authorization, the marketing authorization holder may request the amendment of the periods referred to in this Article according to the procedure laid down by the Commission Regulation (EC) No 541/95(14), if applicable.
Article 76
1. The Agency, in collaboration with the Member States and the Commission shall set up a data-processing network to facilitate the exchange of pharmacovigilance information regarding medicinal products marketed in the Community.
2. Making use of the network foreseen in the first paragraph, Member States shall ensure that reports of suspected serious adverse reactions and human adverse reactions, in accordance with the guidance referred to in Article 77(1), that have taken place on their territory are immediately made available to the Agency and the other Member States, and in any case within 15 calendar days of their notification, at the latest.
3. The Member States shall ensure that reports of suspected serious adverse reactions and human adverse reactions, that have taken place on their territory are immediately made available to the marketing authorisation holder, and in any case within 15 calendar days of their notification at the latest.
Article 77
1. In order to facilitate the exchange of information about pharmacovigilance within the Community, the Commission, in consultation with the Agency, Member States and the interested parties, shall draw up guidance on the collection, verification and presentation of adverse reaction reports, including technical requirements for electronic exchange of veterinary pharmacovigilance information in accordance with internationally agreed terminology.
This guidance shall be published in Volume 9 of the Rules governing medicinal products in the European Community and shall take account of international harmonisation work carried out in the field of pharmacovigilance.
2. For the interpretation of the definitions referred to in Article 1 points 10 to 16 and principles outlined in this title, the marketing authorisation holder and the competent authorities shall refer to the detailed guidance referred to in paragraph 1.
Article 78
1. Where, as a result of the evaluation of veterinary pharmacovigilance data, a Member State considers that a marketing authorization should be suspended, withdrawn or varied to restrict the indications or availability, amend the posology, add a contraindication or add a new precautionary measure, it shall forthwith inform the Agency, the other Member States and the marketing authorization holder.
2. In case of urgency, the Member State concerned may suspend the marketing authorization of a veterinary medicinal product, provided the Agency, the Commission and the other Member States are informed at the latest on the following working day.
Article 79
Any amendments which may be necessary to update the provisions of Articles 72 to 78 to take account of scientific and technical progress shall be adopted in accordance with the procedure referred to in Article 89(2).
TITLE VIII
SUPERVISION AND SANCTIONS
Article 80
1. The competent authority of the Member State concerned shall ensure by means of repeated inspection that the legal requirements relating to veterinary medicinal products are complied with.
Such inspections shall be carried out by authorized representatives of the competent authority who shall be empowered to:
(a) inspect manufacturing or trading establishments and any laboratories entrusted by the holder of the manufacturing authorization, with the task of carrying out control tests pursuant to Article 24;
(b) take samples;
(c) examine any documents relating to the object of the inspection, subject to current provisions in the Member States from 9 October 1981 which place restrictions on these powers with regard to the description of the manufacturing method.
2. Member States shall take all appropriate measures to ensure that the manufacturing processess used in the manufacture of immunological veterinary medicinal products are completely validated and batch-to-batch consistency is ensured.
3. The officials representing the competent authority shall report after each of the inspections mentioned in the first paragraph on whether the manufacturer complies with the principles and guidelines of good manufacturing practice referred to in Article 51. The inspected manufacturer shall be informed of the content of such reports.
Article 81
1. Member States shall take all appropriate measures to ensure that the marketing authorization holder and, where appropriate, the holder of the manufacturing authorization furnish proof of the control tests carried out on the veterinary medical product and/or on the constituents and intermediate products of the manufacturing process, in accordance with the methods laid down for the purposes of marketing authorization.
2. For the purposes of implementing paragraph 1, Member States may require the marketing authorization holder for immunological veterinary medicinal products to submit to the competent authorities copies of all the control reports signed by the qualified person in accordance with Article 55.
The marketing authorization holder for immunological veterinary medicinal products shall ensure that an adequate number of representative samples of each batch of veterinary medical products is held in stock at least up to the expiry date, and provide samples promptly to the competent authorities on request.
Article 82
1. Where it considers it necessary, a Member State may require the marketing authorization holder for immunological products to submit samples from the batches of the bulk and/or medical product for examination by a State laboratory or an approved laboratory before entry into circulation.
In the case of a batch manufactured in another Member State, examined by the competent authority of another Member State and declared to be in conformity with national specifications, such a control may be carried out only after the control reports of the batch in question have been examined, after the Commission has been informed, and where the difference in veterinary conditions between the two Member States concerned justifies it.
2. Except where the Commission has been informed that a longer period is necessary to complete the analyses, Member States shall ensure that any such examination is completed within 60 days of receipt of the samples. The marketing authorization holder shall be notified of the results of the examination within the same time-limit.
3. Before 1 January 1992, the Member States shall notify the Commission of the immunological veterinary medicinal products subject to compulsory official control before being placed on the market.
Article 83
1. The competent authorities of the Member States shall suspend or withdraw marketing authorization when it is clear that:
(a) the veterinary medicinal product proves to be harmful under the conditions of use stated at the time of application for authorization or subsequently;
(b) the veterinary medicinal product does not have any therapeutic effect on the species of animal for which the treatment is intended;
(c) its qualitative and quantitative composition is not as stated;
(d) the recommended withdrawal period is inadequate to ensure that foodstuffs obtained from the treated animal do not contain residues which might constitute a health hazard to the consumer;
(e) the veterinary medicinal product is offered for sale for a use which is prohibited by other community provisions.
However, pending Community rules, the competent authorities may refuse to grant authorization for a veterinary medicinal product where such action is necessary for the protection of public, consumer or animal health;
(f) the information given in the application documents pursuant to Article 12, 13(1) and 27 is incorrect;
(g) the control tests referred to in Article 81(1) have not been carried out;
(h) the obligation referred to in Article 26(2) has not been fulfilled.
2. Authorization may be suspended, or withdrawn where it is established that:
(a) the particulars supporting the application, as provided for in Articles 12 and 13(1), have not been amended in accordance with Article 27(1) and (5);
(b) any new information as referred to in Article 27(3) has not been communicated to the competent authorities.
Article 84
1. Without prejudice to Article 83, Member States shall take all necessary measures to ensure that supply of a veterinary medicinal product is prohibited and that the medicinal product concerned is withdrawn form the market where:
(a) it is clear that the veterinary medicinal product is harmful under the conditions of use stated at the time of the application for authorization or subsequently, pursuant to Article 27(5);
(b) the veterinary medicinal product has no therapeutic effect on the species of animal for which the treatment was intended;
(c) the qualitative and quantitative composition of the veterinary medicinal product is not as stated;
(d) the recommended withdrawal period is inadequate to ensure that foodstuffs obtained from the treated animal do not contain residues which might constitute a health hazard to the consumer;
(e) the control tests referred to in Article 81(1) have not been carried out, or any other requirement or obligation relating to the grant of the manufacturing authorization referred to in Article 44(1) has not been complied with.
2. The competent authority may confine the prohibition on supply and withdrawal from the market solely to the contested production batches.
Article 85
1. The competent authority of a Member State shall suspend or withdraw the manufacturing authorization for a category of preparations or for all preparations if any of the requirements laid down in Article 45 are no longer met.
2. The competent authority of a Member State may, in addition to the measures provided for in Article 84, either suspend manufacture or imports of veterinary medicinal products from third countries or suspend or withdraw the manufacturing authorization for a category of preparations or for all preparations in the event of non-compliance with the provisions regarding manufacture or imports from third countries.
Article 86
The provisions of this Title shall apply to homeopathic veterinary medicinal products.
Article 87
Member States shall take appropriate measures to encourage veterinarians and other professionals concerned to report to the competent authorities any adverse reaction of veterinary medicinal products.
TITLE IX
STANDING COMMITTEE
Article 88
Any changes which are necessary in order to adapt Annex I to take account of technical progress shall be adopted in accordance with the procedure referred to in Article 89(2).
Article 89
1. The Commission shall be assisted by a Standing Committee on Veterinary Medicinal Products for the Adaptation to Technical Progress of the Directives on the Removal of Technical Barriers to Trade in the Veterinary Medicinal Products Sector, (hereinafter referred to as the "Standing Committee".
2. Where reference is made to this paragraph, Articles 5 and 7 of Decision 1999/468/EC shall apply, having regard to the provisions of Article 8 thereof.
The period provided for in Article 5(6) of Decision 1999/468/EC shall be set at three months.
3. The Standing Committee shall adopt its rules of procedure.
TITLE X
GENERAL PROVISIONS
Article 90
Member States shall take all measures necessary to ensure that the competent authorities concerned communicate the appropriate information to each other, in particular regarding compliance with the requirements adopted for manufacturing authorization, or for authorization to place products on the market.
Upon reasoned request, Member States shall forthwith communicate the reports referred to in Article 80(3) to the competent authorities of another Member State. If, after considering the reports, the Member State receiving the reports considers that it cannot accept the conclusions reached by the competent authority of the Member State in which the report was established, it shall inform the competent authorities concerned of its reasons and may request further information. The Member States concerned shall attempt to reach agreement. If necessary, in the event of serious differences of opinion, one of the Member States concerned shall inform the Commission.
Article 91
1. Each Member State shall take all appropriate measures to ensure that the Agency is informed immediately of decisions granting marketing authorization and of all decisions refusing or withdrawing marketing authorization, cancelling a decision refusing or withdrawing marketing authorization, prohibiting supply or withdrawing a product from the market, together with the reasons on which such decisions are based.
2. The marketing authorization holder shall be obliged to notify the Member States forthwith of any action taken by him to suspend the marketing of a veterinary medicinal product or to withdraw a product from the market, together with the reasons for such action if it concerns the effectiveness of the veterinary medicinal product or the protection of public health. Member States shall ensure that this information is brought to the attention of the Agency.
3. Member States shall ensure that appropriate information about actions taken pursuant to paragraphs 1 and 2 which may affect the protection of health in third countries is forthwith brought to the attention of the relevant international organizations, with a copy to the Agency.
Article 92
Member States shall communicate to each other all the information necessary to guarantee the quality and safety of homeopathic veterinary medicinal products manufactured and marketed within the Community, and in particular the information referred to in Articles 90 and 91.
Article 93
1. At the request of the manufacturer or exporter of veterinary medicinal products, or the authorities of an importing third country, Member States shall certify that such manufacturer is in possession of the manufacturing authorization. When issuing such certificates, Member States shall comply with the following conditions:
(a) they shall have regard to the prevailing administrative arrangements of the World Health Organization;
(b) for veterinary medicinal products intended for export which are already authorized in their territory, they shall supply the summary of the product characteristics as approved in accordance with Article 25 or, in the absence thereof, an equivalent document.
2. Where the manufacturer is not in possession of an authorization to place the product on the market, he shall provide the authorities responsible for establishing the certificate referred to in the first paragraph with a declaration explaining why such authorization is not available.
Article 94
Any decision referred to in this Directive, taken by the competent authorities of the Member States, may only be taken on the grounds set out in this Directive and shall state in detail the reasons on which it is based.
Such a decision shall be notified to the party concerned who shall at the same time be informed of the remedies available to him under current legislation and the time allowed for seeking such remedies.
Marketing authorizations and revocations of such authorizations shall be published by each Member State in its official gazette.
Article 95
The Member States shall not permit foodstuffs for human consumption to be taken from test animals unless maximum residue limits have been established by the Community in accordance with the provisions of Regulation (EEC) No 2377/90 and an appropriate withdrawal period has been established to ensure that this maximum limit will not be exceeded in the foodstuffs.
TITLE XI
FINAL MEASURES
Article 96
Directives 81/851/EEC, 81/852/EEC, 90/677/EEC and 92/74/EEC referred to in Annex II, Part A are repealed, without prejudice to the obligations of the Member States in respect of the deadline for transposition laid down in Annex II, Part B.
The reference made to the said Repealed Directives shall be construed as references to this Directive and should be read in accordance with the correlation table set out in Annex III.
Article 97
This Directive enters into force on the 20th day following that of its publication in the Official Journal of the European Communities.
Article 98
This Directive is addressed to the Member States.
Done at Brussels, 6 November 2001.