Proposal for a DIRECTIVE OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL amending Directive 2001/82/EC on the Community code relating to veterinary medicinal products

(presented by the Commission)

EXPLANATORY MEMORANDUM

I. General considerations

The Community provisions on the marketing of veterinary medicinal products are, for the most part, similar or identical to those concerning products for human medicine. No veterinary medicinal product may be marketed unless its quality, safety and efficacy have been demonstrated, and unless these guarantees are maintained when the product is actually placed on the market.

The veterinary sector nevertheless has a number of specific features.

First, it should be borne in mind that veterinary medicinal products for food-producing animals may be authorised only on terms that guarantee that the food will not be harmful for the consumer. The provisions governing the use of such medicinal products by practitioners and farmers notwithstanding, manufacturers must from the outset provide all the necessary information on residues of these products that may remain in items produced from animals that have been treated.

Second, the availability of certain medicinal products is a growing problem.

Thus, the animals that are to benefit from treatment - particularly farm animals - have a limited economic value, while all the costs of treatment or prevention must be borne by the owner. In addition, certain markets are restricted because of the number of species concerned, the size of the animal populations, the range of disorders, or differences in the regional situations.

II. Justification

A. Aims

1. In the light of experience with the operation of Community marketing procedures for medicinal products and the conclusions of the Commission report to the European Parliament and the Council (COM(2001)...), the Commission saw a need to adapt certain provisions of Regulation (EEC) No 2309/93 [1] laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Agency for the Evaluation of Medicinal Products (COM(2001) 404 final, European Parliament and Council Directive 2001/83/EC on the Community code relating to medicinal products for human use [2], and European Parliament and Council Directive 2001/82/EC on the Community code relating to veterinary medicinal products [3]. The revision of the latter is the subject of this proposal for amendments.

[1] OJ C

[2] OJ C

[3] OJ C

2. In so far as the general aims and the provisions on the authorisation and use of medicinal products in the Community are comparable in both the human and the animal health sectors - particularly as regards ensuring quality, safety and efficacy -this parallel approach should be maintained as far as possible, as regards both the general terminology and the system for assessing the quality, safety and efficacy of medicinal products as the basis for granting marketing authorisations. This also applies to the constant monitoring of the quality of the medicinal products manufactured by means of a quality-assurance system, a code of good manufacturing practice or inspections, and subsequent monitoring of the safety and efficacy of the products by means of a pharmacovigilance system.

The conclusions of the abovementioned Commission report and the reasons underlying the other proposals for revising pharmaceutical legislation are therefore directly applicable to these proposals for amendments in so far as they do not specifically concern veterinary products.

The recent adoption of the two Community codes relating to medicinal products for human and veterinary use also provides an excellent opportunity for improving and simplifying the general legislative framework and, where appropriate, amplifying or fine-tuning certain provisions on veterinary medicinal products to bring them into line with provisions that already exist for medical products for human use or proposed amendments to those provisions.

3. This proposal also is also intended to take account of the specific problem of the availability of veterinary medicinal products, as envisaged by the Commission in its Communication to the European Parliament and the Council of December 2000 [4]. The general aim is to adapt the regulatory framework to the specific features of the animal health sector in order to curtail or reverse the downward trend in the number of veterinary medicinal products available. There is a need, therefore, for a balanced response to the imperatives of animal health and well-being, particularly where food-producing animals are concerned, without prejudice to a high level of protection of the health of the final consumer.

[4] Communication from the Commission to the Council and the European Parliament of 5.12.2000 - Availability of veterinary medicinal products (COM(2000) 806 final).

4. Finally, outside the scope of this proposal, the Commission is continuing its reflections on the possibility of developing in parallel a policy analogous to the "orphan drugs for human use" scheme for veterinary medicinal products, by means of a specific legal instrument. The paths to be explored should seek in particular to define indirect incentives to promote the development of new veterinary medicinal products specific to these abandoned market segments (reduced registration fees, technical assistance from the Agency, longer exclusive market rights, and others). Direct incentives could also be considered (financial contributions to R&D, reimbursement of certain investments on granting of marketing authorisation, voluntary co-financing by associations of breeders of the species concerned, etc.) But the Commission considers that if such a proposal should see the light of day, the scope and the ways and means of its application will need to be precisely identified.

B. Legal basis and procedure

The legal basis for the proposal is Article 95 and Article 152.4(b) of the Treaty. Article 95, which specifically prescribes use of the co-decision procedure described in Article 251, is the legal basis for achieving the aims set out in Article 14 of the Treaty, which include the free movement of goods - in this case veterinary medicinal products. While taking account of the fact that any regulations on the manufacture and distribution of medicinal products, including veterinary medicinal products, must be fundamentally aimed at safeguarding public health, this aim must be achieved by means that do not impede the manufacture and free movement of medicinal products within Community. Since the Amsterdam Treaty came into force, all legislative provisions adopted by the European Parliament and the Council - except for directives adopted on the basis of executive powers vested in the Commission - and aimed at aligning the provisions on medicinal products have been adopted on the basis of that Article, since the differences between the national legislative, regulatory and administrative provisions on medicinal products tend to hinder intra-Community trade and therefore directly affect the operation of the internal market. The intervention of the Community legislator is therefore justified with a view to preventing or eliminating these obstacles. Furthermore, Article 152.4(b) mentions henceforth explicitly the measures having as direct objective public heath protection in the veterinary and phytosanitary sectors. The present proposal contains a number of measures in the veterinary field having as an objective public heath protection. The adoption procedure referred to in this Article is the same as the one referred to in Article 95; thus, it is wise to add this Article as a legal basis.

III. Detailed contents of the proposal

(To improve readability, the Articles quoted here are those contained in Directive 2001/82/EC as amended by this proposal).

A. Definitions, scope, general terminology

1. It is proposed that use of the term "proprietary medicinal product" [spécialité pharmaceutique] be discontinued, since it is no longer used in the legislative provisions and there have been difficulties in defining precisely how it should be interpreted. Use of the term "Ready-made veterinary medicinal product" [médicament vétérinaire préfabriqué], defined by reference to "proprietary medicinal product", has therefore also been discontinued (Article 1).

It is proposed that the scope of the directive should be clarified and in particular that it should be specified that the granting of a marketing authorisation or any directly associated arrangement is relevant only once a medicinal product has begun to be manufactured industrially (Article 2(1)). Nevertheless, it should be made clear that, for reasons of both animal and public health, officinal or magistral veterinary preparations made up in a pharmacy should be subject to the provisions of the directive regarding prescription, dispensing, possession and administration to animals (Article 3(1)).

2. The definition of a veterinary medicinal product has been adapted in order to ensure that the directive applies to certain products that must meet the requirements of quality, safety and efficacy. This adaptation only makes it possible not to extend the concept of medicinal product to new types of treatment, such a cell therapy, but also to clarify the status of certain more traditional products, such as those used for extracorporeal dialysis, even if these products are not at present of comparable importance in both veterinary and human medicine.

3. The additions to the definitions of the terms "adverse reaction", and the inclusion of new definitions (Article 1), particularly of "veterinary prescription", "name of medicinal product", "non-proprietary name", "strength", "immediate packaging", "outer packaging", "labelling" or "package leaflet" are in line with the definitions for medicinal products for human use.

The definition "withdrawal period" has also been revised in order to highlight its principal purpose, i.e. protecting the public, when used correctly in a veterinary context (Article 1).

4. The possible dual use of certain products - as a pharmaceutical product or veterinary hygiene product, for example - has led to differences in interpretation and the adoption of different regulatory approaches in the various Member States. It proposed, therefore, that in such circumstances the legislation affording the highest degree of protection for animal and human health, i.e. that covering veterinary medicinal products, should apply in cases of uncertainty (Article 2(2)).

5. Finally, this proposed revision provides an opportunity to harmonise and simplify, and to correct certain terminology that is regarded as obsolete or inappropriate for the field. It mainly concerns references to the evaluation criteria - i.e. quality, safety and efficacy - or introducing the idea of weighing benefits against risks, which is central to the system of marketing authorisation for medicinal products.

B. Marketing authorisations: general provisions and procedures

1. The general provisions on applying for a marketing authorisation, assessing applications, granting marketing authorisation, and the respective responsibilities of the competent authorities and the holder of the authorisation do not depend on the type medicinal product in question - i.e. whether it is for veterinary or human use. The justification and proposed amendments are therefore complementary to those relating to Regulation (EEC) No 2309/93 (COM(2000)...), or similar, if not strictly identical, to those relating to the legislation on medicinal products for human use (COM(2001)...).

2. The same is true of the general provisions on the scope of the authorisation and the responsibility of the holder (Article 5), and the additional details on the concept of generics and Community harmonisation (ten years) of the period of administrative protection of data (Article 13(1), (2) and (3)), "bibliographical applications" (Article 13a), fixed combinations (Article 13b), or applications submitted with the consent of the holder (Article 13c). The amendments also introduce the possibility of testing a generic before the end of the period of exclusivity without thereby infringing the law on the protection of industrial and commercial property (Article 13(6)).

3. Similarly, Chapters 3 and 4 of Title III, on the marketing-authorisation procedure and the mutual-recognition or decentralised authorisation procedures have been adapted in exactly the same way as the corresponding chapters of the Community code relating to medicinal products for human use. Particular attention should be draw to the proposals concerning the coordination of deadlines for the various procedures (Articles 21 and 32), authorisation on specific conditions (Article 26), the discontinuation of the five-yearly renewal of the authorisation and the expiry clauses (Article 28), or the transparency of the assessment process (Article 25(3) and (4)). For the decentralised procedure, it is proposed to set up a coordination group on the mutual recognition of veterinary medicinal products, thus formalising an existing process of cooperation between the Member States (Article 31), to clarify operation on the basis of whether or not an authorisation already exists in a Member State (Article 32), and to make the initiation of the arbitration procedure automatic in all cases of dispute between the competent authorities in the Member States (Article 33). The provisions on arbitration have been clarified, particularly with a view to protecting the position of the applicant or the marketing authorisation holder more effectively (Article 36). It is also proposed to speed up certain stages in the procedure for obtaining the opinion of the committee and completing the decision-making process (Article 38), and it is intended to establish a system for the gradual harmonisation of summaries of characteristics of products for veterinary medicinal products that have been authorised by the Member States for more than ten years (Article 34(2)), and to introduce the possibility of the Agency giving an opinion on certain parts of the marketing authorisation if the question at issue concerns more than one product or a therapeutic class (Article 35(2)).

4. It is also proposed to adapt, while taking account of the specific features of veterinary medicinal products, certain provisions regarding the contents of the file accompanying an application for marketing authorisation and the summary of product characteristics (Articles 12, 14, 15). These adaptations will not change the essence of the existing provisions, but will be more concerned with gearing certain provisions with sometimes outdated wording to the administrative, scientific or technical realities of the applications. Thus, the erstwhile "expert reports" will continue to exist, but under the name "detailed and critical summaries", particularly in so far as most of the scientists involved in drafting the reports will be associated to a greater or lesser extent with the applicant. It is also proposed that it should be clearly stated that these summaries form an integral part of the application file. Withdrawal periods are also indicated in the interests of improved protection for the final consumer (Article 14(5.11)).

C. Marketing authorisations: proposals specific to the veterinary sector

1. Obviously, the general principle of authorising the marketing of a veterinary medicinal product before it can be used is not being questioned.

Nevertheless, a number of adjustments have been proposed to permit derogations from the authorisation requirement, either for certain "new" categories of pets, such as dwarf rabbits or ferrets (Article 4(2)), or for the use of a medicinal product on animals subject to compulsory specific health provisions with a view to export to non-member countries or import into the Community. This proposal particularly concerns certain sport animals taking part in international competitions (e.g. horses), or certain valuable productive livestock, which must be vaccinated against infectious diseases that are endemic in certain non-member countries (Article 8(2)). The directive has also been brought into line with other Community provisions in order to enable the Commission to permit the use of immunological veterinary medicinal products without a marketing authorisation in cases of serious epizootic diseases if no suitable medicinal products are available (Article 8(1)). This provision also contributes to improving the consistency of Community measures to combat certain animal diseases, and particularly concerns alignment with the Commission's proposal for amending Regulation (EEC) No 2309/93 in order to permit authorisation through a centralised procedure for immunological veterinary medicinal products for such diseases. It has also been found necessary to introduce derogations from the need to conduct field trials for these medicinal products (Article 13d).

2. If no authorised medicinal product is available for a given species or disorder, it is proposed that the use of other products be made more straightforward. The aim is to help solve the problem of the availability of certain veterinary medicinal products and the intention is to differentiate the provisions regarding pets or animals kept in zoos or circuses (Article 10) more clearly from those on food-producing animals (Article 11).

In the former case, it is intended to retain the system whereby either another veterinary medicinal product, a medicinal product for human use, or a product prepared extemporaneously must be used in that order of priority ("cascade"). However, this possibility will henceforth be open directly to practitioners on their own direct responsibility. It is also proposed to eliminate all associated administrative formalities - particularly the recording of the use of such products - in so far as such provisions do not affect the level of consumer protection.

In the case of food-producing animals, it proposed to keep veterinary practice under administrative supervision, thus enabling the Member States to opt for the use of a veterinary medicinal product authorised in another Member State. This provision must be supplemented by ad hoc import and inspection measures. The measures aimed at protecting consumers have been retained (withdrawal period, registration of use) and clarified (inclusion of the substance in Annex I, II or III to Regulation (EEC) No 2377/90, existence of maximum residue limits for at least one species).

Regarding horses, given the specific ways in which those are used, It is proposed to allow the use of a substance which does not have any maximal residue limit, under the only condition that the animal in question is excluded from the nutritional chain (Article 10 (2)). This implies that many of these are treated in a way comparable to company animals, and this in an unalterable way. The definition of an arbitrary six-month waiting period, provided for in the Commission Decision 2000/68/EC concerning the passport of horses [5], could only be justified under limited and exceptional circumstances. The Commission considers that such a possibility should not become the general rule in the Community, not only in order to take into consideration the direct protection of European citizens consuming horse meat, but also in order to ensure the general coherence of consumer protection measures within the framework of the use of veterinary medicinal products on all animal species. The equidae remain as such food producing species at European level.

[5] OJ C

3. In addition to the measures concerning the use of products without authorisation for the species or indication concerned, it is also proposed that economic incentives be introduced to encourage the pharmaceutical industry to place veterinary medicinal products on the market without delay.

The main amendment is a proposal to increase the period of administrative data protection in some cases and hence provide for a more attractive return on investment for an economic operator (Article 13(4) and (5)):

- The ten-year protection period would be extended by one year for any extension of the authorisation to another food-producing animal (up to a maximum of three more years for three or more species), provided that such an extension is obtained within three years of the granting of the original authorisation. A measure of this kind would encourage the industry to extend the authorisation of a new medicinal product for a species representing a major economic sector very swiftly to other species representing a smaller market.

- It is also proposed that the period of general protection for medicinal products for bees and fish should be 13 years instead of 10, because of the specific characteristics of these species and the general veterinary treatment procedures that necessitate specific developments on the part of manufacturers.

It is also proposed that the protection should at the same time cover the data contained in the file submitted for the establishment of maximum residue limits as required under Regulation (EEC) No 2377/90 and in the application for authorisation (Article 13(a)(1) and (2)), and to strengthen the legal links between the procedures for fixing maximum residue limits and the granting of a marketing authorisation (Article 6, Article 12(1)). It is also intended to grant a period of three years of specific protection for a medicinal product containing of substance of which use has been well established in a species for not less than ten years, but for which the marketing authorisation has been obtained for a "new" species by a holder other than the holder of the original authorisation. This protection would, however, be granted only if the new holder had also been the applicant for the establishment of maximum residue limits for the new species and had provided the evidence of the efficacy of the medicinal product in this new species (Article 13(a)(3)).

4. In view of the problem of availability of veterinary medicinal products and in particular the difficulties encountered by manufacturers (see the abovementioned Commission report COM (2001)...), it is proposed that the obligations and the division of responsibilities between the applicant for or the marketing authorisation holder for a veterinary medicinal product and the competent authorities in the Member States should be clarified. This mainly concerns the implementation of general checks of the quality of foodstuffs and the residues of chemical substances in connection with the misuse of authorised medicinal products, the use of prohibited substances, or contamination of foodstuffs by pollutants.

Scientific studies to back up a file of maximum residue limits or a file of a marketing authorisation will mean that the applicants will have to develop methods for determining the concentration of active substances and any active metabolites in certain tissues or types of foodstuff of animal origin. Nevertheless, the aims of studies of this kind and the experimental conditions under which they are conducted are not the same as those of the control laboratories responsible for monitoring any residues of chemicals that might be present in foodstuffs in general. Consequently, the control laboratories will as a rule need to develop their own methods.There is a need to review the provisions on the analytical methods to be used to determine the amounts of residues, particularly as the expression "routine analysis method" has given rise to many questions of interpretation (Article 12(3)(h), (i), and (j). The obligation of the applicant to demonstrate the quality and reliability of the scientific information presented in his/her file and to provide a validated dosage method has not been changed. This provision has even been strengthened by the introduction of the possibility of checking whether the method is satisfactory in the light of the aims of the application (Article 23(3)). It is also proposed that the provisions on the monitoring of residues should be strengthened and in particular that the task of the competent authorities should be simplified if specific needs are involved. The marketing authorisation holder should therefore, on request by the competent authorities, supply the reference substances needed for the control. It is also intended that the authorisation-holder should provide the reference laboratory with technical support if it has to use the analytical method described in the authorisation file but encounters practical difficulties (Article 27(2)).

5. It is also intended to revise the general provision on total exclusion from human consumption of foodstuffs from animals used for testing medicinal products if maximum residues limits have not been established in accordance with Regulation (EEC) No 2377/90, since this provision is a major obstacle to the development of new medicinal products for food-producing animals. The existing provision impedes the development of a new veterinary medicinal product for several years - even to the point of discouraging pharmaceutical companies from developing innovative medicinal products for major markets.

The example of new medicinal products for dairy cows may serve as an illustration: unless it carries out trials outside the Community, it becomes extremely difficult for a pharmaceutical company and the experts responsible for conducting field trials to find a farmer who will agree to having an animal from his/her herd included in a clinical study of a new veterinary medicinal product if this means that it will not be possible to use the animal for milk production again.

The number of productive livestock used in testing veterinary medicinal products is small compared with the number of animals likely to be treated with a medicinal product outside the authorised use, if only because of the "cascade" provisions described in C.2). Testing of new medicinal products also necessitates close veterinary observation of the animals and major monitoring work on the part of the person responsible for the test. These measures do not compare with the normal conditions of use of an authorised medicinal product in productive livestock. The Commission therefore considers that consumer protection would not be affected in these particular circumstances by abolishing the obligation for the prior establishment of maximum residue limits, since this measure is accompanied by the introduction of a sufficiently long withdrawal period (Article 95).

6. It is proposed that the provisions on homeopathic veterinary medicinal products should be adapted to the current situation. Since no use has been made of the possibility for a Member State to refrain from establishing a simplified registration system for homeopathic medicinal products meeting certain criteria, it is proposed that it should be abolished (Article 16).

Also, particularly in view of the developments in biological agriculture and the special place of homeopathic medicinal products in that context, it is proposed that the simplified registration system should be extended to veterinary medicinal products intended for food-producing species. This does not, however, affect the provisions on consumer protection (Article 17(1), Article 18). It is also proposed, under certain conditions, to authorise the Commission, if appropriate, to adapt the degree of dilution in the light of new scientific knowledge (Article 17(1)). It is necessary, therefore, to adapt the provisions on labelling and the package leaflet accompanying homeopathic veterinary medicinal products (Article 64).

D. Provisions aimed at improving the monitoring of the quality of medicinal products.

1. Monitoring the general quality of medicinal products depends partly on the system of granting marketing authorisations on the basis of a prior assessment of the information submitted by the applicant, including all pharmaceutical documentation. It also depends on constant subsequent monitoring of the quality of the products manufactured and sold, and their conformity with the specifications laid down in the authorisation.

Quality guarantees are based essentially on a system of quality assurance, including compliance with good manufacturing practice, and monitoring of conformity with all the provisions by the competent authorities - mainly by means of inspections. These general measures are applicable to both medicinal products for human use and veterinary medicinal products.

2. The Commission must therefore pursue the same objectives in the field of veterinary medicinal products and propose similar amendments to those made to the legislation on medicinal products for human use (COM(2000)...). However, account must be taken not only of consumer protection and the completion of the internal market, but also of the international dimension of the pharmaceutical sector (particularly mutual recognition agreements with third countries).

3. The Commission therefore finds it necessary, at this stage, to strengthen the provisions on inspection, in conjunction with the European Pharmacopoeia where appropriate (Article 80(1) and (4)), to step up Community coordination by introducing certificates of good manufacturing practice, and to set up a Community register containing the relevant information (Article 80(5), (6) and (7)). The latter measure is in a consistent manner supplemented by the establishment of Community system of data on manufacturing authorisations (Article 44(4)). All this is also intended to facilitate mutual recognition within the system. It is proposed, however, to introduce a procedure for settling any disputes concerning the outcome of an inspection (Article 90). This improvement of Community harmonisation goes hand-in-hand with a total harmonisation of the criteria to be met by the qualified person responsible for the quality of manufacturing (Articles 53 and 54).

It is also intended to increase the quality guarantees by extending good manufacturing practice (Article 50(f)) to the starting materials used as active substances in veterinary medicinal products. This means that this term must be clearly defined and that there must be procedures for revising the definition in the light of technical progress (Article 50a). The practical provisions have been adapted accordingly, both for the adoption of specific detailed guidelines (Article 51) and for the inspection system (Article 80(1)). It also appears necessary to clarify the provisions on monitoring the quality of imported products, since even if they had originally been manufactured in the Community, the competent authorities will not be able to ensure that all the specifications, particularly those concerning storage conditions for medicinal products, have been respected outside the Community (Article 55).

4. In the field of immunological veterinary medicinal products, the existing legislation stipulates that the Community provisions on quality assurance in connection with manufacturing authorisations, good manufacturing practice and inspections may be supplemented by a system of "official release" of each batch of the product after manufacture, after control by an "official" laboratory designated for this purpose by the competent authorities of the Member State. In these circumstances, the "official batch release" of a batch of vaccine would have to be the subject of mutual recognition.

Since this measure was introduced at Community level (1990), along the lines of long-established practices in some Member States, significant progress has been made in quality and consistency in the manufacturing of vaccines. Furthermore, in view of the number and diversity of immunological products in the veterinary sector, the national laboratories do not necessarily have the means for re-control of the batches that have already been checked by the manufacturers, and only some Member States use the "official release" procedure. Finally, the system of mutual recognition does not operate ideally, mainly because the Member States do not necessarily carry out all the conformity controls provided for in the authorisation file - hence the discrepancies in the Community-level validity of the "official release".

The Commission therefore proposes reviewing this arrangement, partly by restricting the scope for official release of batches to certain types of immunological veterinary medicinal products, i.e. live vaccines or immunological medicinal products for diseases covered by Community measures, which would mean particular responsibility for the competent authorities. It is also proposed to define the obligations on pharmaceutical companies and the competent authorities under these circumstances, particularly as regards the tests that need to be done by official control laboratories (Article 82). These proposed amendments are without prejudice to the possibility of requiring copies of any certificates describing the controls conducted by the holder, or to having medicinal products placed on the market controlled by the official laboratory at any time.

E. Labelling and package leaflet

The provisions on labelling of medicinal products and the accompanying package leaflet have not been amended substantially. The terminological improvements in connection with the introduction of the new definitions notwithstanding, it is proposed that certain provisions aimed at improving information for users should be strengthened.

The labelling and the package leaflet must be approved by the competent authorities and conform to the summary of the characteristics of the product (Article 58(1), Article 61(2)). The labelling of veterinary medicinal product and the accompanying package leaflet consequently also become important elements in the application for a marketing authorisation and the decision taken by the competent authorities (Article 25(2), Article 30(e), Article 32(2), (3), (4) and (5), Article 33 (1), Article 36).

A number of amendments have also been proposed in the general interests of users (Article 58(1)(e); Article 61(1) and (2)(a) and (b) while taking account of certain elements of flexibility, including some for medicinal products that are covered by a centralised marketing authorisation under Regulation (EEC) No 2309/93 (Article 58(5)).

It is also proposed that the information on use in food-producing animals - in this case, the withdrawal period (Article 58(1)(g) and (l) should be strengthened. This goes hand-in-hand with a proposal to strengthen the measures relating to the prescription procedures for medicinal products of this kind (Article 67). It is proposed that in future all medicinal products for food-producing animals (including, for example, those for which the withdrawal period is nil) should be available only on veterinary prescription.

F. Possession, distribution and dispensing

In addition to the abovementioned provision on the prescribing of medicinal products for food-producing animals, it is proposed that the provisions on emergency recall of medicinal products from the market should be amplified, as the case may be by including wholesale distributors (Article 65(4)).

Even if the provisions on the traceability of the distribution circuits for veterinary medicinal products from the manufacturer to the final user have not been amended - indeed they have been strengthened by the fact that the range of prescription-only medicinal products has been extended. It is, however, proposed that retail sale should be simplified for those for which no prescription is required, by abolishing the obligation to keep detailed documentation (Article 66(2)).

The special conditions on a possible ban on manufacturing, possessing or selling certain immunological veterinary medicinal products are extended to the marketing authorisation according to a decentralised procedure (Article 71(2), in conjunction with Article 33(1) second subparagraph), in order to take account of the proposal for "automatic" initiation of the arbitration procedure.

G. Pharmacovigilance

The pharmacovigilance procedures have been strengthened (Articles 72-78) along the lines of the proposals in connection with the centralised procedure and more generally those on medicinal products for human use, particularly in conjunction with the proposal to abolish the five-yearly renewal of the authorisation. It is intended to strengthen the general information network, particularly by electronic means and to increase the frequency with which the periodical safety update reports are to be submitted. One of the aims is to enable the Commission to ask the Member States to take temporary measures with immediate effect, if emergency action is needed.

2001/0254 (COD)

Proposal for a DIRECTIVE OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL amending Directive 2001/82/EC on the Community code relating to veterinary medicinal products

(Text with EEA relevance)

THE EUROPEAN PARLIAMENT AND THE COUNCIL OF THE EUROPEAN UNION,

Having regard to the Treaty establishing the European Community, and in particular Article 95 and point (b) of Article152(4) thereof,

Having regard to the proposal of the Commission [6],

[6] OJ C

Having regard to the opinion of the Economic and Social Committee [7],

[7] OJ C

Having regard to the opinion of the Committee of the Regions [8],

[8] OJ C

Acting in accordance with the procedure referred to in Article 251 of the Treaty [9],

[9] OJ C

Whereas:

(1) Directive 2001/82/EC of the European Parliament and of the Council of 23 October 2001 on the Community code relating to veterinary medicinal products [10], in the interests of clarity and rationalisation, has codified and combined in a single text the texts of Community legislation on veterinary medicinal products.

[10] OJ C

(2) Community legislation constitutes an important stage in the achievement of the objective of free movement of veterinary medicinal products. However, new measures prove necessary in the light of the experience gained, particularly in the Committee for veterinary medicinal products, with a view to eliminating the remaining obstacles to free movement.

(3) It is therefore necessary to align the national laws, regulations and administrative provisions which contain differences with regard to the basic principles in order to promote the operation of the internal market.

(4) Any regulations on the production and distribution of veterinary medicinal products should be essentially aimed at safeguarding public health. The legislation on marketing authorisations for veterinary medicinal products, and the criteria governing the grant of authorisations, are such as to strengthen the protection of public health within the meaning of point (b) of Article 152(4) of the Treaty, as inserted by the Treaty of Amsterdam. That aim should, however, be achieved by means that will not impede the development of the pharmaceuticals industry or trade in medicinal products within the Community.

(5) Article 71 of Council Regulation (EEC) No 2309/93 of 22 July 1993 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Agency for the Evaluation of Medicinal Products [11] provides that, within six years of its entry into force, the Commission is required to publish a general report on the experience acquired as a result of the operation of the marketing authorisation procedures laid down in that Regulation and in other Community legal provisions

[11] OJ L 214, 24.8.1993, p. 1; Regulation as amended by Commission Regulation (EC) No 649/98 (OJ L 88, 24.3.1998, p. 7).

(6) In the light of the Commission's report [12] on the experience gained, it has proved necessary to improve the operation of the marketing authorisation procedures for medicinal products in the Community.

[12] COM(2001)....final.

(7) Particularly as a result of scientific and technical progress in the field of animal health, the definitions and scope of Directive 2001/82/EC should be clarified in order to ensure a high level of requirements as to the quality, safety and efficacy of veterinary medicinal products. In order to take account, both of the emergence of new therapies and of the growing number of so-called "borderline" products between the medicinal product sector and other sectors, the definition of medicinal product should be modified so as to avoid any doubt as to the applicable legislation when a product, whilst fully falling within the definition of a medicinal product, may also fall within the definition of other regulated products. Also, taking into account the characteristics of the pharmaceutical legislation, it is proposed that such legislation is to apply. It is also worth taking advantage of this opportunity to improve the consistency of the terminology of pharmaceutical legislation.

(8) The veterinary medicinal products sector has a number of very specific features. Veterinary medicinal products for food-producing animals may be authorised only on conditions that guarantee that the foodstuffs produced will be harmless to consumers as regards any residues of medicinal products.

(9) The costs of research and development to meet increased requirements as regards the quality, safety and efficacy of veterinary medicinal products are leading to a gradual reduction in the range of products authorised for the species and indications representing smaller market sectors.

(10) The provisions of Directive 2001/82/EC also need, therefore, to be adapted to the specific features of the sector, particularly to meet the health and welfare of food-producing animals on terms that guarantee a high level of consumer protection, and in a context that provides adequate economic interest for the veterinary medicinal products industry.

(11) In certain circumstances, particularly where new types of pets are concerned, the need to obtain a marketing authorisation for a veterinary medicinal product in accordance with Community provisions is clearly unjustified. Moreover, the absence of authorisation to market an immunological product in the Community should not be an obstacle to international movements of certain live animals for which binding health measures have to be taken for this purpose. The provisions on the authorisation or use of such medicinal products to take account of measures to combat certain infectious animal diseases at Community level also need to be adapted.

(12) An assessment of the operation of the procedures for the granting of market authorisation has revealed the need to revise, in particular, the mutual recognition procedure in order to increase the scope for cooperation between Member States. This cooperation process should be formalised by setting up a coordination group and defining its role in settling disagreements, in the context of a revised decentralised procedure.

(13) Except in special circumstances, marketing authorisations should be granted for an unlimited period and, in parallel, the procedures for monitoring products actually being marketed should be strengthened.

(14) In the veterinary sector, if no medicinal product has been authorised for a given species or a given disorder, the use of other existing products should be made a straightforward matter, but without prejudice to consumer health in the case of medicinal products intended for administration to food-producing animals.

(15) There is also a need to stimulate the interest of the veterinary pharmaceuticals industry in certain market segments in order to encourage the development of new veterinary medicinal products. The period of administrative data-protection vis-à-vis generics needs to be harmonised and extended, subject to certainconditions.

(16) There is also a need to clarify the obligations of, and division of responsibilities between, the applicant for or marketing authorisation holder of a veterinary medicinal product and the competent authorities in charge of monitoring the quality of foodstuffs, particularly through compliance with the provisions on the use of these medicinal products. In addition, in order to facilitate the testing of new medicinal products while guaranteeing a high level of protection for consumers, sufficiently long withdrawal periods should be laid down for foodstuffs that might be produced by the animals involved in the tests.

(17) Without prejudice to the provisions aimed at guaranteeing consumer protection, the specific characteristics of homeopathic veterinary medicinal products, and particularly their use in ecological farming, should be taken into account by establishing a simplified procedure for registration on terms defined in advance.

(18) In order to increase the information available to users and to improve consumer protection in the case of food-producing animals, the provisions on the labelling of veterinary medicinal products and the accompanying package leaflet should also bestrengthened. The requirement that a veterinary medicinal product may only be dispensed after a veterinary prescription has been made out should also be extended to all medicinal products for food-producing animals. The administrative procedures for supplying medicinal products for pets should, on the other hand, be simplified.

(19) The quality of the veterinary medicinal products manufactured or available in the Community should be guaranteed by requiring that the active substances they contain have been produced in accordance with good manufacturing practice. The Community provisions on inspections also need to be strengthened, and a Community register established containing the results of these inspections. The arrangements for the official release of batches of certain immunological medicinal products should be reviewed in order to take account of the improvement of the general system for monitoring the quality of medicinal products and to reflect technical and scientific progress, and also in order to make mutual recognition fully effective.

(20) The monitoring of the efficacy and safety of the veterinary medicinal products on the market should be improved by stepping up pharmacovigilance measures, particularly where the validity of marketing authorisations is no longer compulsorily limited to five years. The frequency with which the periodical safety update reports are submitted should be increased, there should be an operational network for the exchange of electronic data and, where appropriate, the competent authorities should be enabled to take temporary emergency measures.

(21) Since most of the measures necessary for the implementation of this Directive are measures of individual scope, use should be made of the advisory procedure provided for in Article 3 of Council Decision 1999/468/EC of 28 June 1999 laying down the procedures for the exercise of implementing powers conferred on the Commission [13], or ofthe management procedure under Article 4 thereof. As regards general scope within the meaning of Article 2 of the Decision, those measures should be adopted by use of the regulatory procedure provided for in Article 5 thereof.

[13] OJ L 184, 17.7.1999, p. 23.

(22) Directive 2001/82/EC should be amended accordingly,

HAVE ADOPTED THIS DIRECTIVE:

Article 1

Directive 2001/82/EC is amended as follows:

(1) The first citation is replaced by the following:

"Having regard to the Treaty establishing the European Community, and in particular Article 95 and point (b) of Article 152(4) thereof,"

(2) Article 1 is amended as follows:

(a) Point (1) is deleted.

(b) Point (2) is replaced by the following:

"2. Veterinary medicinal product

Any substance or combination of substances

(a) presented for treating or preventing disease in animals.

(b) capable of use in animals with a view to making a medical diagnosis or to restoring, correcting or modifying physiological functions in animals."

(c) Point (3) is deleted.

(d) Points (9) and (10) are replaced by the following:

"9. Withdrawal period

Period necessary between the last administration of the veterinary medicinal product to animals, under normal conditions of use and in accordance with good veterinary practice, and the production of foodstuffs from such animals, in order to protect public health, by ensuring [follow on] that such foodstuffs do not contain residues in quantities in excess of the maximum residue limits of active substances laid down in Annex I or III to Regulation (EEC) No 2377/90.

10. Adverse reaction:

A reaction to a veterinary medical product which is harmful and unintended and which occurs at doses normally used in animals for the prophylaxis, diagnosis or treatment of disease or to restore, correct or modify a physiological function."

(e) The following points (20) to (27) are added:

"(20) Veterinary prescription

Any prescription for veterinary medicinal products issued by a professional person qualified to do so.

(21) Name of veterinary medicinal product

The name, which may be either an invented name which is not liable to confusion with the common name, or a common or scientific name accompanied by a trade mark or the name of the marketing authorisation holder. .

(22) Non-proprietary name

The international name recommended by the World Health Organisation or, failing this, the common name.

(23) Strength

The content of active substances, expressed as quantity per unit, per unit volume or per unit weight, depending on how the product is presented.

(24) Immediate packaging

The container or any other form of packaging that is in direct contact with the medicinal product.

(25) Outer packaging

The packaging into which the immediate packaging is placed.

(26) Labelling

The words printed on the outside or immediate packaging.

(27) Package leaflet

The leaflet containing information for the user that accompanies the medicinal product."

(3) Articles 2 and 3 are replaced by the following:

"Article 2

1. The provisions of this Directive shall apply to veterinary medicinal products including pre-mixes for medicated feeding stuffs intended to be placed on the market in the Member States and prepared industrially or by a method involving an industrial process.

2. The provisions of this Directive shall apply whenever a substance or composition of substances corresponds to the definition of a medicinal product, even if the substance or composition of substances is also falling within the field of application of other Community legislation.

Article 3

1. This Directive shall not apply to:

(a) medicated feedingstuffs as defined in Council Directive 90/167/EEC*.

(b) 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;

(c) veterinary medicinal products based on radio-active isotopes;

(d) any additives covered by Council Directive 70/524/EEC** where they are incorporated in animal feedingstuffs and supplementary animal feedingstuffs in accordance with that Directive.

However, medicated feedingstuffs under point (a) may be prepared only from pre-mixes which have been authorised under this Directive.

2. Except for the provisions on possession, prescription, dispensing and administration of veterinary medicinal products, this Directive shall not apply to:

(a) any medicinal product prepared in a pharmacy in accordance with a prescription for an individual animal, commonly known as the magistral formula;

(b) any medicinal product prepared in a pharmacy in accordance with the prescriptions of a pharmacopoeia and intended to be supplied directly to the end-user, commonly known as the officinal formula.

* OJ L 92, 7.4.1990, p. 42.

** OJ L 270, 14.12.1970, p. 1."

(4) Article 4(2) is replaced by the following:

"2. Member States may permit exemptions on their territory in respect of veterinary medicinal products intended solely for aquarium fish, ornamental birds, homing pigeons, terrarium animals, small rodents, and ferrets and rabbits kept exclusively as pets from the provisions in Articles 5 to 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 unauthorised use of the products for other animals."

(5) Articles 5 and 6 are replaced by the following:

"Article 5

1. No veterinary medicinal product may be placed on the market of a Member State unless a marketing authorisation has been issued by the competent authorities of that Member State in accordance with this Directive or a marketing authorisation has been granted in accordance with Regulation (EEC) No 2309/93.

The various strengths, pharmaceutical forms, administration routes, presentations and any amendment under Article 39 must be authorised under the first subparagraph and shall be considered part of the same authorisation.

2. The holder of the marketing authorisation shall be responsible for the marketing of the medicinal product.

Article 6

1. In order that a veterinary medicinal product may be the subject of a marketing authorisation for the purpose of administering it to one or more food-producing species, the pharmacologically active substances which it contains must be shown in Annexes I, II or III to Regulation (EEC) No 2377/90.

2. If it is justified by an amendment to the Annexes to Regulation (EEC) No 2377/90, the holder of the marketing authorisation or, where appropriate, the competent authorities shall take all necessary measures for amending or withdrawing the marketing authorisation within 60 days of the date on which the amendment to the Annexes to Regulation (EEC) No 2377/90 was published in the Official Journal of the European Communities."

(6) Article 8 is replaced by the following:

"Article 8

In the event of serious epizootic diseases, Member States may provisionally allow the use of immunological veterinary medicinal products without an authorisation for placing on the market, in the absence of a suitable medicinal product and after informing the Commission of the detailed conditions of use.

The Commission may avail itself of the option set out in the first paragraph when explicit provision is made for that option under Community rules concerning certain serious epizootic diseases.

If an animal is being imported from, or exported to, a third country and is thereby subject to specific binding health rules, a Member State may permit the use, for the animal in question, of a immunological veterinary medicinal product that is not covered by a marketing authorisation in the Member State in question but is authorised under the legislation of the third country. Member States shall take all appropriate measures concerning the supervision of the importation and the use of such immunological products."

(7) Articles 10 to 13 are replaced by the following:

"Article 10

1. If there is no authorised medicinal product in a Member State for a condition affecting a species of pet animal or animals kept in zoos or circuses, the veterinarian may, particularly in order to avoid causing unacceptable suffering to the animal concerned, under his/her personal responsibility, treat the animal(s) with:

(a) a veterinary medicinal product authorised in the Member State concerned under this Directive or under Regulation (EEC) No 2309/93 for use with another animal species, or for another condition in the same species; or

(b) if there is no product as referred to in point (a), a medicinal product authorised for human use in the Member State concerned in accordance with Directive 2001/83/EC of the European Parliament and of the Council* 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, a veterinary medicinal product prepared extemporaneously by a person authorised to do so under national legislation in accordance with the terms of a veterinary prescription.

2. By way of derogation from Article 11, the provisions of paragraph 1 shall also apply to the treatment by a veterinarian of an animal belonging to the equidae family provided that it has been declared, under Commission Decision 93/623/EEC**, as never having been intended for the production of foodstuffs.

3. By way of derogation from Article 11, and in accordance with the procedure referred to in Article 89(2), the Commission shall establish a list of veterinary medicinal products essential for the treatment of equidae and for which the withdrawal period shall be not less than six months according to the control mechanisms laid down in Decision 93/623/EEC**.

* OJ L

** OJ L 298, 3. 12. 1993, p. 45.

Article 11

1. Where there is no authorised medicinal product for a condition affecting a food-producing species, Member States shall, particularly 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 authorised in the Member State concerned under this Directive or under Regulation (EEC) No 2309/93 for use with another animal species, or for another condition in the same species; or

(b) if there is no product as referred to in point (a),

(i) either, of a medicinal product authorised for use in the Member State concerned with human beings in accordance with Directive 2001/83/EC or under Regulation (EEC) No 2309/93, or

(ii) (ii) of a veterinary medicinal product authorised in another Member State in accordance with this Directive for use in the same species for the condition in question or for another condition; or

(c) if the product or products as referred to in point (b) is/are not available and within the limits of the law of the Member State concerned, of a veterinary medicinal product prepared extemporaneously by a person authorised to do so under national legislation in accordance with the terms of a veterinary prescription.

2. Paragraph 1 shall apply provided that pharmacologically active substances included in the medicinal product are listed in Annex I, II or III to Regulation (EEC) No 2377/90, and that the veterinarian 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:

(a) 7 days for eggs;

(b) 7 days for milk;

(c) 28 days for meat from poultry and mammals including fat and offal;

(d) 500 degree-days for fish meat.

3. When a veterinarian has recourse to the provisions of paragraphs 1 and 2 of this Article, he/she 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 doses 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 five years.

4. Without prejudice to the other provisions of this Directive, Member States shall take all necessary measures concerning the import, distribution and dispensing of and information on the medicinal products which they permit for administration to food-producing animals in accordance with paragraph 1(b)(ii) of this Article.

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.

In the case of veterinary medical products intended for one or more food-producing species, whose pharmacologically active substances have not yet been included, for the species in question, in Annexes I, II or III to Regulation (EEC) No 2377/90, a marketing authorisation may not be applied for until after a valid application has been made for the establishment of maximum residue limits in accordance with that Regulation. At least six months shall elapse between a valid application for the establishment of maximum residue limits and an application for marketing authorisation.

2. A marketing authorization may only be granted to an applicant established in the Community.

3. The application for marketing authorisation shall include all the administrative information and scientific documentation necessary for demonstrating the quality, safety and efficacy of the veterinary medical product in question. The file shall be submitted in accordance with Annex I and shall contain, in particular, the following information:

(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 veterinary medicinal product;

(c) qualitative and quantitative particulars of all the constituents of the veterinary medicinal product;

(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 in the case of medicinal products intended for food-producing species;

(i) description of the testing methods employed by the manufacturer;

(j) results of:

- pharmaceutical (physico-chemical, biological or microbiological) tests;

- safety tests and residue tests;

- - pre-clinical and clinical trials;

(k) a summary in accordance with Article 14 of the product characteristics, a mock-up of the immediate packaging and the outer packaging of the veterinary medicinal product, together with the package leaflet, in accordance with Articles 58 to 61;

(l) a document showing that the manufacturer is authorised 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; all this information shall be updated on a regular basis.

(n) in the case of veterinary medical products intended for one or more food-producing species and containing one or more pharmacologically active substances not yet included, for the species in question, in Annexes I, II or III to Regulation (EEC) No 2377/90 on maximum residue limits of veterinary medicinal products, a document certifying that a valid application for the establishment of maximum residue limits has been submitted to the Agency in accordance with the aforementioned Regulation.

The documents and particulars relating to the results of the tests referred to in point (j) of the first subparagraph shall be accompanied by detailed and critical summaries, drawn up as specified in Article 15.

Article 13

1. By way of derogation from point (j) of the first subparagraph of Article 12(3), and without prejudice to the law relating to the protection of industrial and commercial property, the applicant shall not be required to provide the results of the safety and residue tests or of the pre-clinical and clinical trials if he/she can demonstrate that the medicinal product is a generic of a reference medicinal product authorised within the meaning of Article 5 for not less than ten years in a Member State or the Community.

However, the ten-year period provided for in the first subparagraph is extended to 13 years in the case of veterinary medicinal products for fish or bees.

2. For the purposes of this Article:

(a) reference medicinal product shall mean a product authorised within the meaning of Article 5 in accordance with the provisions of Article 12;

(b) generic medicinal product shall mean a medicinal product which has the same qualitative and quantitative composition in terms of active substances, the same pharmaceutical form, and whose bioequivalence with the reference medicinal product has been demonstrated by means of appropriate bioavailability tests. Bioavailability tests may not be required of the applicant if he/she can demonstrate that the medicinal product meets the criteria set out in Annex I.

3. The first subparagraph of paragraph 1 shall not apply in the event of a change in the active substance or substances, the therapeutic indications, the strength, the pharmaceutical form, the route of administration or the dose vis-à-vis the reference medicinal product, and the results of appropriate safety and residue tests studies and pre-clinical and clinical trials shall be provided.

4. In the case of veterinary medicinal products intended for one or more food-producing species and containing a new active substance that has not been authorised in the Community by [date] the ten-year period provided for in the first subparagraph of paragraph 1 shall be extended by one year for each extension of the marketing authorisation to another food-producing species, if it is authorised within the three years following the granting of the initial marketing authorisation.

The extension of one, two or three years of further data protection also applies to any initial marketing authorisation relative to two, three or four food-producing species, respectively.

This period cannot, however, exceed a total of 13 years, for a marketing authorisation for four or more food-producing species.

The extension of the ten-year period to 11, 12, or 13 years shall be granted only if the marketing authorisation holder had also been at the origin of the maximum residue limits established for the species covered by the authorisation.

5. Conducting the necessary tests and trial with a view to application of paragraphs 1 to 4 to a generic medicinal product shall not be regarded as contrary to patent related rights and to complementary protection certificates for those medicinal products."

(8) The following Articles 13a to 13d are inserted:

"Article 13a

1. By way of derogation from point (j) of the first subparagraph of Article 12(3), and without prejudice to the law on the protection of industrial and commercial property, the applicant shall not be required to provide the results of the safety and residue tests or of the pre-clinical and clinical trials if he/she can demonstrate that the active substance(s) of the veterinary medicinal product are of well-established veterinary use for not less than ten years in the Community, with recognised efficacy and an acceptable level of safety in accordance with the conditions set out in Annex I. In that event the applicant shall provide appropriate scientific documentation.

2. The assessment report published by the Agency following the evaluation of an application for the establishment of maximum residue limits in accordance with Regulation (EEC) No 2377/90 may be used in an appropriate manner as literature, particularly for the safety tests.

3. If an applicant makes use of scientific literature in order to obtain authorisation for a food-producing species, and submits, in respect of the same medicinal product and with a view to obtaining authorisation for another food-producing species, new residue studies in accordance with Regulation (EEC) No 2377/90, together with furtherclinical trials, it shall not be permissible for a third party to use such studies or such trials pursuant to Article 13, for a period of three years from the grant of the authorisation for which they were carried out.

Article 13b

1. In the case of new veterinary medicinal products containing active substances used in the composition of authorised veterinary medicinal products but not hitherto used in combination for therapeutic purposes, the results of safety and residue tests and of pre-clinical and clinical trials relating to that combination shall be provided, but it shall not be necessary to provide the documentation relating to each individual active substance.

Article 13c

After marketing authorisation has been granted, the marketing authorisation holder may allow use to be made of the pharmaceutical, safety and residues, pre-clinical and clinical documentation contained in the file for the veterinary medicinal product with a view to examining a subsequent application for a veterinary medicinal product having the same qualitative and quantitative composition in active substances and the same pharmaceutical form..

Article 13d

By way of derogation from point (j) of the first subparagraph of Article 12(3),and in exceptional circumstances with respect to immunological veterinary medicinal products, the applicant shall not be required to provide the results of certain field trials on the target species if these trials cannot be carried out for duly substantiated reasons, in particular on account of other Community provisions."

(9) Articles 14 and 15 are replaced by the following:

"Article 14

The summary of the product characteristics shall contain the following information:

(1) Name of the veterinary medicinal product followed by the strength and the pharmaceutical form;

(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 common name or chemical description will be used;

(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. special warnings for each target species;

5.5 special precautions for use, including special precautions to be taken by the person administering the medicinal product to the animals;

5.6 adverse reactions (frequency and seriousness);

5.7 use during pregnancy, lactation or lay;

5.8 interaction with other medicaments and other forms of interaction;

5.9 amounts to be administered and administration route;

5.10 overdose (symptoms, emergency procedures, antidotes) (if necessary);

5.11 withdrawal periods (expressed in hours or days) for the various foodstuffs, including those for which the withdrawal period is zero.

(6) Pharmaceutical particulars:

6.1 incompatibilities;

6.2 shelf life, when necessary after reconstitution of the medicinal product or when the immediate packaging is opened for the first time;.

6.3 special precautions for storage,

6.4 nature and composition of immediate packaging;

6.5 special precautions, including those pertaining to the environment, for the disposal of unused medicinal products or waste materials derived from the use of these products, if any.

(7) Name, or corporate name, and permanent address or registered place of business of the marketing authorisation holder.

Article 15

1. Applicants shall ensure that the detailed and critical summaries referred to in the second subparagraph of Article 12(3) are drafted and signed by persons with the requisite technical or professional qualifications, set out in a brief curriculum vitae, before being submitted to the competent authorities.

2. Persons with the technical or professional qualifications, referred to in paragraph 1, shall justify any use made of the scientific literature referred to in Article 13a(1) in accordance with the conditions set out in Annex I.

3. A brief curriculum vitae of the persons referred to in paragraph 1 shall be appended to the detailed critical summaries."

(10) Article 16 is replaced by the following:

"Article 16

1. Member States shall ensure that homeopathic veterinary medicinal products manufactured and marketed within the Community are registered or authorised in accordance with the provisions of Article 17(1) and (2), and Articles 18 and 19.

2. Member States shall establish a simplified registration procedure for the homeopathic veterinary medicinal products referred to in Article 17."

(11) Article 17 is amended as follows:

(a) Paragraph 1 is replaced by the following:

"1. Without prejudice to the provisions of Regulation (EEC) No 2377/90 on the establishment of maximum residue limits of pharmacologically active substances intended for food-producing animals, only homeopathic veterinary medicinal products which satisfy all of the following conditions may be subject to a special, simplified registration procedure:

(a) 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;

(b) no specific therapeutic indication appears on the labelling of the veterinary medicinal product or in any information relating thereto;

(c) there is a sufficient degree of dilution to guarantee the safety of the medicinal product; in particular, the medicinal product shall not contain either more than one part per 10 000 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.

If it appears justified in the light of new scientific evidence, the Commission may adapt points (b) and (c) of the first subparagraph in accordance with the procedure referred to in Article 89(2).

At the time of registration, Member States shall determine the classification for the dispensing of the medicinal product."

(b) Paragraph 3 is deleted.

(12) Article 18 is amended as follows:

(a) The sixth indent is replaced by the following:

"- one or more mock-ups of the outer packaging and immediate packaging of the medicinal products to be registered,"

(b) The following eighth indent is added:

"- proposed withdrawal period together with all requisite justification."

(13) Article 19 is replaced by the following:

"Article 19

1. Homeopathic veterinary medicinal products other than those referred to in Article 17(1) shall be authorised in accordance with the provisions of Articles 12 to 14.

2. A Member State may introduce or retain on its territory specific rules for the safety tests and pre-clinical and clinical trials of homeopathic veterinary medicinal products intended for pet species and non-food-producing exotic species 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."

(14) Articles 21, 22 and 23 are replaced by the following:

"Article 21

1. Member States shall take all appropriate measures to ensure that the procedure for granting an authorisation to place a veterinary medicinal product on the market is completed within 150 days of the submission of a valid application, including 120 days for drawing up the assessment report and the summary of product characteristics.

With a view to the grant of a marketing authorisation for a veterinary medicinal product in two or more Member States, applications shall be submitted in accordance with Articles 31 to 43.

2. Where a Member State notes that an application for authorisation of a given veterinary medical product submitted is already being examined in another Member State, the Member State concerned shall decline to assess the application and shall inform the applicant that the procedure described in Articles 31 to 43 applies.

Article 22

Where a Member State is informed, in accordance with point (m) of Article 12(3), that another Member State has authorised a veterinary medicinal product which is the subject of an application for authorisation in the Member State concerned, that Member State shall reject the application unless it has been submitted in compliance with Articles 31 to 43."

Article 23

In order to examine the application submitted pursuant to Articles 12 to 13d, the competent authorities of the Member States:

1. shall check that the documentation submitted in support of the application complies with Articles 12 to 13d and ascertain whether the conditions for the issue of the marketing authorisation 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 point (i) of Article 12(3), are satisfactory;

3. may similarly check, in particular through consultation of a national or Community reference laboratory, that the analytical method used for detecting residues presented by the applicant in accordance with the second subparagraph of Article 12(3) is satisfactory;

4. may, where appropriate, require the applicant to provide further information as regards the items listed in Articles 12 to 13d. 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."

(15) In Article 25, paragraphs 2, 3 and 4 are replaced by the following:

"2. The competent authorities shall take all necessary measures to ensure that the information concerning the veterinary medicinal product, and in particular the labelling and package leaflet, is in conformity with that approved in the summary of product characteristics when the marketing authorisation is issued or subsequently.

3. The competent authorities shall make available to any interested person a copy of the marketing authorisation together with the summary of product characteristics.

4. The competent authorities shall draw up an assessment report and comments on the dossier as regards the results of the pharmaceutical, safety and residue tests and the pre-clinical and 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.

At the request of any interested person, the competent authorities shall make available the assessment report and its reasons for the opinion after deleting any information of commercially confidential nature."

(16) Article 26 is amended as follows:

(a) Paragraph 1 is replaced by the following:

"1. The marketing authorisation may require the holder to indicate on the immediate packaging and/or the outer wrapping and the package leaflet, 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 point (j) of the first subparagraph of Article 12(3) and in Articles 13 to 13d or from experience gained during the use of the veterinary medicinal product once it has been marketed."

(b) Paragraph 2 is deleted.

(c) Paragraph 3 is replaced by the following:

"3. In exceptional circumstances, and following consultation with the applicant, an authorisation may be granted under specific conditions, which shall be reviewed annually. Continuation of the initial authorisation may be linked to the review of these conditions.

Such authorisations may be granted only for objective and verifiable reasons."

(17) Article 27 is amended as follows:

(a) Paragraphs 2 and 3 are replaced by the following:

"2. The competent authority may require the applicant or the marketing authorisation holder to provide sufficient quantities of the substances to enable controls to be made on the identification of the presence of residues of the veterinary medicinal products in question.

Upon request from the competent authorities, the marketing authorisation holder shall provide his/her technical expertise to facilitate the implementation of the analytical method for detecting residues of the veterinary medicinal products in the national reference laboratory designated under Council Directive 96/23/EC*.

3. In order to allow the continuous evaluation of the relation between the benefits and the risks, the marketing authorisation holder shall also forthwith forward to the competent authorities any new information which might entail the amendment of the contents of the file or of the approved summary of product characteristics. In particular, he/she 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 or of any rejection of an application for authorisation submitted in a third country.

* OJ L 125, 23.5.1996, p. 10."

(c) Paragraph 4 is deleted.

(d) Paragraph 5 is replaced by the following:

"5. The marketing authorisation holder shall immediately inform the competent authorities, with a view to authorisation, of any alteration which he/she proposes to make to the particulars and documents referred to in Articles 12 to 13d."

(18) Article 28 is replaced by the following:

"Article 28

1. Without prejudice to paragraphs 2 and 3, the authorisation shall be valid for an unlimited period.

2. Any authorisation that is not followed within two years of its issue by the actual marketing of the authorised veterinary medicinal product in the authorising Member State shall cease to be valid.

3. When an authorised veterinary medicinal product previously placed on the market in the authorising Member State is no longer actually present on the market in that Member State for a period of two consecutive years, the authorisation shall cease to be valid."

(19) Article 30 is replaced by the following:

"Article 30

The marketing authorisation shall be withheld if the file submitted to the competent authorities does not comply with the provisions of Articles 12 to 13d and Article 15.

The authorisation shall also be withheld if examination of the documents and particulars listed in Articles 12 and 13(1) establishes that:

(a) the benefit/risk assessment of the veterinary medicinal product is, under the authorised conditions of use, unfavourable; when the application concerns a veterinary medicinal product for zootechnical use, particular regard being had to the benefits for animal health and welfare and to the safety and health benefits for the consumer; or

(b) the product 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 labelling or the package leaflet proposed by the applicant does not comply with this Directive;

(f) the veterinary medicinal product is offered for sale for a use prohibited under other Community provisions.

However, when a Community legislative framework is in the course of being adopted, the competent authority may refuse authorisation 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."

(20) The title of Chapter 4 is replaced by the following:

"Chapter 4 Mutual recognition procedure and decentralised procedure"

(21) Articles 31 to 35 are replaced by the following:

"Article 31

1. A coordination group is set up for the examination of any question relating to marketing authorisation of a veterinary medicinal product in two or more Member States in accordance with the procedures laid down in this Chapter. The Agency shall provide the secretariat for this group.

2. The group shall be composed of one representative per Member State appointed for a renewable period of three years. Members of the group may arrange to be accompanied by experts.

3. The coordination group shall draw up its own rules of procedure, which shall enter into force after a favourable opinion of the Commission.

Article 32

1. With a view towards the grant of a marketing authorisation for a veterinary medicinal product in two or more Member States, the applicant shall submit an application referring to an identical dossier in those Member States. The dossier shall contain all the administrative information and scientific and technical documentation described in Articles 12 to 14. The documents submitted shall include a list of the Member States concerned by the application.

The applicant shall request one Member State to act as reference Member State and to prepare an assessment report in respect of the veterinary medical product according to paragraphs 2 or 3.

Where appropriate, the assessment report shall contain an evaluation for the purposes of Article 13(4) or (5) or Article 13a(3).

2. If the veterinary medicinal product has already received authorisation by the time of application, the Member State(s) concerned shall recognise the marketing authorisation granted by the reference Member State. To this end, the marketing authorisation holder shall request the reference Member State either to prepare an assessment report in respect of the veterinary medicinal product or, if necessary, to update any existing assessment report. The reference Member State shall prepare or update the assessment report within 60 days of receipt of a valid application. The assessment report together with the approved summary of product characteristics, labelling and package leaflet shall be forwarded to the Member State(s) concerned and the applicant.

3. If the veterinary medicinal product has not received authorisation by the time of application, the applicant shall request the reference Member State to prepare a draft assessment report and drafts of the summary of product characteristics, labelling and package leaflet. The reference Member State shall prepare these drafts within 120 days of the receipt of a valid application and shall send them to the concerned Member States and the applicant.

4. Within 90 days of receipt of the documents referred to in paragraphs 2 and 3, the Member States concerned shall approve the assessment report, the summary of product characteristics, the labelling and the package leaflet and inform the reference Member State to this effect.

The reference Member State shall ascertain the agreement, close the procedure and inform the applicant accordingly.

5. Each Member State where an application following paragraph 1 has been submitted shall adopt a decision in conformity with the approved assessment report, summary of product characteristics, labelling and package leaflet within 30 days of acknowledgement of the agreement.

Article 33

1. If a Member State cannot, within the period allowed in Article 32(4), agree with the assessment report, summary of product characteristics, labelling and package leaflet on grounds of a potential serious risk to human or animal health or the environment, a detailed statement of the reasons shall be provided to the reference Member State, the other Member States concerned and the applicant. The points of disagreement shall be referred without delay to the coordination group.

If a Member State to which an application has been submitted invokes the reasons referred to in Article 71(1), it shall no longer be regarded as a Member State concerned by this Chapter.

2. Within the coordination group, all the Member States referred to in Paragraph 1 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/her point of view known orally or in writing. If, within 60 days of the communication of the reasons for disagreement to the coordination group the Member States reach an agreement, the reference Member State shall confirm the agreement, close the procedure and inform the applicant accordingly. Article 31(5) shall apply.

3. If within the period of 60 days the Member States fail to reach an agreement, the Agency shall be immediately informed with a view to application of the procedure laid down in Article 36. The Agency shall be provided with a detailed description of the matters on which agreement could not be reached and the reasons for the disagreement. The applicant shall be provided with a copy of this information.

4. As soon as the applicant has been informed that the matter has been referred to the Agency, he/she shall forthwith forward to the Committee a copy of the information and particulars referred to in the first subparagraph of Article 32(1).

5. In the case referred to in paragraph 3, the Member States that have approved the assessment report, summary of product characteristics, labelling and package leaflet of the reference Member State may, on request by the applicant, grant a marketing authorisation for the veterinary medicinal product without waiting for the outcome of the procedure laid down in Article 36. In that case, the authorisation granted shall be without prejudice to the outcome of that procedure.

Article 34

1. If two or more applications submitted in accordance with Articles 12 to 14 have been made for marketing authorisation for a particular veterinary medicinal product and Member States have adopted divergent decisions concerning the authorisation of that veterinary medicinal product, or suspension or withdrawal of authorisation, a Member State, or the Commission, or the marketing-authorisation holder may refer the matter to the Agency for application of the procedure laid down in Article 36.

2. With a view to promoting the harmonisation of veterinary medicinal products authorised for not less than ten years in the Community, and to strengthen the efficiency of the provisions of Article 11, the Member States shall send to the coordination group, no later than [date], a list of veterinary medicinal products for which a harmonised summary of product characteristics should beprepared.

The coordination group shall agree on a list of medicinal products, on the basis of proposals sent by the Member States, and shall forward this list to the Commission.

The medicinal products in this list are subject to the provisions in paragraph 1 following a timetable established in cooperation with the Agency.

The Commission, acting in collaboration with the Agency, and taking into consideration the views of the interested parties, shall agree the final list.

Article 35

1. The Member States or the Commission or the applicant or holder of the marketing authorisation 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 authorisation or on the suspension or withdrawal of an authorisation, or on any other variations to the terms of a marketing authorisation which appear necessary, so as to take account in particular 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 applicant or the marketing authorisation holder.

The Member State and the applicant or the marketing authorisation holder shall forward to the Committee all available information relating to the matter in question.

2. Where the referral to the Committee concerns a range of medicinal products or a therapeutic class, the Agency may limit the procedure to specific parts of the authorisation.

In that case, Article 39 shall apply to those medicinal products only if they are covered by the marketing authorisation procedure referred to in this Chapter."

(22) Article 36 is amended as follows:

(a) Paragraph 1 is replaced by the following:

"1. When reference is made to the procedure laid down in this Article, the Committee shall consider the matter concerned and shall issue a reasoned opinion within sixty 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 the Committee for a further period of up to 90 days, taking into account the views of the marketing authorisation holders concerned.

In an emergency, and on a proposal from its Chairman, the Committee may agree to a shorter deadline."

(b) Paragraph 3 is replaced by the following:

"3. Before issuing its opinion, the Committee shall provide the applicant or the marketing authorisation holder with an opportunity to present written or oral explanations.

The opinion of the Committee shall include the draft summary of product characteristics and the drafts of the labelling and package leaflet.

If it considers 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 applicant or the marketing authorisation holder to prepare the explanations."

(c) Paragraph 4 is amended as follows:

(i) The introductory wording of the first subparagraph is replaced by the following:

"The Agency shall forthwith inform the applicant or the marketing authorisation holder of the opinion of the Committee if:"

(ii) The second indent of the first subparagraph is replaced by the following:

"- the summary of product characteristics proposed by the applicant or the marketing authorisation holder in accordance with Article 14 should be amended."

(iii) The second subparagraph is replaced by the following:

"Within 15 days of receipt of the opinion, the applicant or the marketing authorisation holder may notify the Agency in writing of his/her intention to appeal. In that case, he/she 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 reconsider its opinion in accordance with the second subparagraph of Article 53(1) of Regulation (EEC) No 2309/93. The conclusions reached on appeal shall be annexed to the assessment report referred to in paragraph 5."

(d) Paragraph 5 is amended as follows:

(i) The first subparagraph is replaced by the following:

"Within 30 days of its adoption, the Agency shall forward the final opinion of the Committee to the Member States, to the Commission and the applicant or the marketing authorisation holder together with a report describing the assessment of the veterinary medicinal product and the reasons for its conclusions."

(ii) In the second subparagraph, the following point (c) is added:

"(c) the drafts of the labelling and package leaflet"

(23) Article 37 is amended as follows:

(a) The second subparagraph is replaced by the following:

"In the event of a draft decision which envisages the granting of marketing authorisation, the documents referred to in the second subparagraph of Article 36(5) , shall be annexed."

(b) The fourth subparagraph is replaced by the following:

"The draft decision shall be forwarded to the Member States and the applicant or marketing authorisation holder."

(24) Article 38 is amended as follows:

(a) Paragraph 1 is replaced by the following:

"1 The Commission shall adopt a final decision in accordance with the procedure referred to in Article 89(3), where the draft decision is in conformity with the Agency's opinion.

2. The Commission shall adopt a final decision in accordance with the procedure referred to in Article 89(4), where the draft decision is not in conformity with the Agency's opinion."

(b) In paragraph 2, the second and third indents are replaced by the following:

"- each Member State shall be allowed at least fifteen days to forward written observations on the draft decision of the Commission. However, if the Decision is urgent, the President may set a shorter deadline in the light of the urgency.

- each Member State may require in writing that the draft decision be discussed by the Standing Committee in plenary session, giving its reasons in detail."

(c) Paragraph 3 is replaced by the following:

"3. A decision as referred to in paragraph 1 shall be addressed to all the Member States and communicated to the marketing authorisation holder or the applicant for information. The concerned Member States and the reference Member State shall either grant or withdraw marketing authorisation, or vary the terms of a marketing authorisation as necessary to comply with the decision within 30 days of its notification and shall refer to it. They shall inform the Commission and the Agency thereof."

(25) In Article 39, the third subparagraph of paragraph 1 is deleted.

(26) In Article 42, paragraph 2 is replaced by the following:

"2. The Commission shall publish, no later than [date], a report on experience gained on the basis of the procedures provided for in this chapter and shall propose any amendments necessary to improve the procedures."

(27) Article 43 is replaced by the following:

"Article 43

The provisions of Article 33(3), (4) and (5) and Articles 34 to 38 shall not apply to the homeopathic veterinary medicinal products referred to in Article 17.

The provisions of Articles 32 to 38 shall not apply to the homeopathic veterinary medicinal products referred to in Article 19(2)."

(28) In Article 44, the following paragraph 4 is added:

"4. The Member State shall forward to the Agency a copy of the manufacturing authorisations referred to in paragraph 1. On the basis of this information the Agency shall compile a database."

(29) In Article 50, point (f) is replaced by the following:

"(f) comply with the principles and the guidelines on good manufacturing practice for medicinal products and use as starting materials only active substances that have been manufactured in accordance with the detailed guidelines on good manufacturing practice for starting materials."

(30) The following Article 50a is inserted:

"Article 50a

1.