EXPLANATORY MEMORANDUM

1. CONTEXT OF THE PROPOSAL

Justification and objectives

Work on a European legal framework for veterinary medicinal products started in 1965 with the adoption of Directive 65/65/EEC,[1] which required that marketing authorisations be issued before such products could be placed on the market. Since then, numerous other directives and regulations have been adopted to extend and refine the rules, and a harmonised framework has gradually been established. In 2001, all the rules on production, marketing, distribution and use were consolidated in a veterinary medicines code (Directive 2001/82/EC);[2] this was followed by Regulation (EC) No 726/2004.[3] These two acts regulate the authorisation, manufacturing, marketing, distribution, pharmacovigilance and use of veterinary medicinal products over their lifetime. The annex to the Directive 2001/82/EC specifies the data to be submitted in applications for marketing authorisations. Among other things, the Regulation (EC) No 726/2004 lays down the EU procedures applying to medicinal products for human and veterinary use and establishes the European Medicines Agency (‘the Agency’).

In the course of the co-decision procedure for its proposal for a regulation on residue limits of pharmacological active substances in foodstuffs, the Commission submitted a declaration[4] recognising the importance of problems linked to the availability of veterinary medicinal products, the use of veterinary medicinal products in species for which they are not authorised, and disproportionate regulatory burden hampering innovation. The present proposal is the Commission’s follow-up to its declaration.

Stakeholders and Member States have expressed concern that the current legislation does not fully deliver a single market in veterinary medicinal products and fails to meet the Union’s needs as regards the regulation of medicines. In particular, the private and public sectors have indicated the following areas for improvement:

· regulatory burden;

· the lack of availability of veterinary medicinal products, especially for small markets such as that for bees; and

· the functioning of the internal market.

In this regard, it is important to recall that needs of the veterinary sector differ substantially from those of the human sector in relation to medicines. In particular, the drivers for investment for the human and the veterinary medicines markets are different. For example, in the veterinary sector there are many different animal species, which creates both a fragmented market and the need for major investments in order to extend the authorisation of medicines existing for one animal species to another. Moreover, the price-setting mechanisms in the veterinary sector follow a completely different logic. Consequently, prices for veterinary medicines are typically substantially lower than for medicinal products for human use. The size of the animal pharmaceutical industry is only a small fraction of the size of the pharmaceutical industry for human medicines. It is therefore considered appropriate to develop a regulatory framework addressing the characteristics and specificities of the veterinary sector, which cannot be considered as a model for the human medicines market.

The revision of Directive 2001/82/EC and other legislation on veterinary medicinal products is in line with the principles set out in the Commission’s 2013 and 2014 work programmes. The proposal seeks to put in place, while safeguarding public health, animal health, food safety and the environment, an up-to-date, proportionate body of legislation tailored to the specificities of the veterinary sector, aiming in particular to:

· increase the availability of veterinary medicinal products;

· reduce administrative burdens;

· stimulate competitiveness and innovation;

· improve the functioning of the internal market; and

· address the public health risk of antimicrobial resistance (AMR).

These objectives are not only complementary, but also interlinked, as innovation will provide new and better medicines to treat and prevent diseases in animals, while avoiding damage to the environment.

The spread of AMR is a major threat to public and animal health. In November 2011, the Commission launched a five-year action plan,[5] which seeks to mobilise all stakeholders in a joint effort to combat AMR; in particular, Action 2 in the plan aims to strengthen the regulatory framework for veterinary medicinal products. This proposal implements this action.

The Commission’s Communication on honeybee health[6] stresses the importance of proactively protecting bee health, while taking into account the particularities of beekeeping, and acknowledges the limited availability of medicines to treat the diseases that afflict bees. As regards measures to increase availability, the Communication refers to the revision of the legislation on veterinary medicinal products.

Legal basis

The legal bases for legislative measures on animal health, which are essential to public and animal health, environmental protection, trade and single market policy are:

– Article 114 of the Treaty on the Functioning of the European Union (TFEU), which provides for the establishment and functioning of the internal market and the approximation of relevant legal, regulatory and administrative provisions; and

– Article 168(4)(b) TFEU, which covers measures in the veterinary field directly aimed at protecting public health.

2. RESULTS OF CONSULTATIONS WITH THE INTERESTED PARTIES AND IMPACT ASSESSMENTS

Better regulation of veterinary pharmaceuticals: how to put in place a simpler legal framework, safeguarding public and animal health while increasing the competitiveness of companies, a public consultation on the key issues of the envisaged legal proposal, was launched on the Commission’s website on 13 April 2010 and was available through the interactive policy-making (IPM) tool until 15 July 2010.[7]

The consultation and a study, An assessment of the impact of the revision of veterinary pharmaceutical legislation, formed the basis of an impact assessment carried out for the Commission between November 2009 and June 2011.[8]

The Commission’s Impact Assessment Board (IAB) released its final opinion in September 2013.

3. LEGAL ELEMENTS OF THE PROPOSAL

Chapter I: Subject matter, scope and definitions

This part contains provisions on the scope of the Regulation. It also sets out clear definitions reflecting the proposed changes.

Chapter II: Marketing authorisations — general provisions and rules on applications

In the Union, only veterinary medicinal products that meet standards of safety, quality and efficacy are authorised. The proposal lays down rules for obtaining a marketing authorisation, specifying that the product in question can be marketed for the approved indications only. The indications are listed in the summary of product characteristics (SPC) included in the terms of the marketing authorisation. Those terms also contain a description of the product’s properties and the conditions attached to its use. Before a marketing authorisation can be granted for a veterinary medicinal product for food-producing species, the Commission has to establish a maximum residue limit for the pharmacologically active substance it contains.

An applicant has to provide certain details on the packaging and labelling of the medicine. The proposal introduces a major simplification of the rules by reducing the compulsory information and introducing harmonised pictograms and abbreviations. This should reduce translation and packaging costs and encourage multilingual packages and labelling. Member States will have a degree of flexibility as to the languages used.

In principle, applicants must prove the quality, safety and efficacy of the veterinary medicinal product. In exceptional circumstances (e.g. in emergencies) and where limited markets are concerned, however, temporary authorisation may be granted without comprehensive data in order to fill therapeutic gaps on the market.

This part of the proposal also includes provisions for generic applications. If a product meets the conditions for a generic veterinary medicinal product, the applicant is not required to prove safety and efficacy and the application will rely on the data provided for the reference product. The proposal contains a definition of generic veterinary medicinal products.

This part also regulates the ‘protection period’ applying to technical documentation submitted in order to obtain or amend a marketing authorisation. It addresses the characteristics and specificities of the veterinary sector. Experience has shown that the needs of the veterinary sector differ substantially from those of the human sector. Also the drivers for investment differ for the human and veterinary medicines market, for example in animal health there is more than one species, creating a fragmented market and necessitating major investments to add other animal species. Therefore, the provisions in this proposal to stimulate innovation cannot be considered as a model for the human medicines market. The protection arrangements prevent applicants for a generic product from referring to the documentation submitted for the reference product. Data provided to extend the generic product to another animal species should also be protected according to the same principle.

Extending the protection periods provided for in Directive 2001/82/EC should create incentives and stimulate innovation in the animal health sector. The current ten‑year period would be maintained for the initial marketing authorisation. In order to encourage industry to extend already authorised products to other species, a further 1 year would be added for any extension of the veterinary medicinal products to another species (up to a maximum of 18 years).

In order to encourage the animal health industry to develop products for minor species, increased protection will apply: 14 years for the initial marketing authorisation for a minor species, and 4 additional years for an extension to a minor species.

So as to secure data protection, any application for an extension must be submitted at least 3 years before expiry of the data protection period. This ensures that companies can place a generic product on the market immediately after expiry of the protection period for the reference product. Product developments for bee medicines will receive increased data protection because of the small size of the market for bee medicines and the lack of effective medicines to treat diseases in bees. The protection applying to environmental data would be the same as that for safety and efficacy data.

The results of clinical trials comprise much of the data required to demonstrate the quality, safety and efficacy of a product. A Union procedure for the authorisation of clinical trials is provided for (this is currently not harmonised).

It is important to safeguard the effectiveness of certain antimicrobials that are essential for the treatment of human infections. Therefore, it is proposed that the Commission be empowered to establish rules excluding or restricting the use of certain antimicrobials in the veterinary sector.

Chapter III: Procedures for granting marketing authorisations

Various marketing authorisation procedures are provided for:

· a centralised procedure, in which the Commission grants an authorisation;

· procedures in which Member States grant the authorisation:

· a national procedure;

· a mutual recognition procedure; and

· a decentralised procedure.

Regardless of whether the authorisation is obtained at Union or national level, the requirements for the safety, efficacy and quality of the product are the same. In all authorisation procedures, a key part of the assessment of an application is the benefit-risk analysis of a product.

The centralised procedure is mandatory for all veterinary medicinal products derived from biotechnology and optional with any other type of veterinary medicinal product. For products that are of interest in the majority of the Member States, access to the centralised procedure can lead to savings for the marketing authorisation holder.

The mutual recognition procedure applies for veterinary medicinal products already authorised in one Member State for which authorisation is requested in respect of two or more Member States. This procedure is based on the principle that a product authorised in one Member State should be recognised by another.

The decentralised procedure applies in cases where a medicine has not received a marketing authorisation in any Member State. It enables applicants to target their product to a limited group of Member States. After a marketing authorisation has been granted for the group of Member States in the original application, marketing authorisation holders can obtain an authorisation for additional Member States without repeated scientific assessment. This should mean that unnecessary duplication of work by competent authorities can be avoided, ease the rolling‑out of national marketing authorisations to other Member States and therefore increase the availability of veterinary medicinal products in the Union.

For the decentralised and mutual recognition procedures, an arbitration mechanism applies if a Member State cannot agree with the scientific assessment. If an applicant cannot agree with the outcome of a Member State’s assessment, it may request re-examination by the Agency. In such cases, the Agency will deliver a scientific opinion to the coordination group of Member States, which will act by consensus or by a majority of votes cast.

Currently, marketing authorisations have to be renewed every five years. The proposal provides for unlimited validity, which will reduce the regulatory burden.

Chapter IV: Post-marketing authorisation measures

This part establishes a single product database for all authorised veterinary medicinal products in the Union. Competent authorities will be obliged to upload data on national marketing authorisations. Having a readily accessible, up-to-date database of all authorised medicines will mean inter alia improved application of the provisions on the use of veterinary medicinal products outside the terms of the marketing authorisation, as veterinarians will be able to identify the products they need from other Member States.

Post-marketing authorisation measures include amending marketing authorisations and monitoring products after they have been on the market (pharmacovigilance). The terms of the authorisation may need to be amended where, for example, a change to the SPC is proposed. The provisions of Regulation (EC) No 1234/2008 should no longer apply to variations to veterinary medicinal products. The Regulation lays down a system for varying the terms of marketing authorisations that takes account of the level of risk involved. Only changes that substantially affect product safety or efficacy will still require prior authorisation by the competent authorities or the Commission before being implemented.

Veterinary medicinal products tend to have unintended effects when actually brought into use. Pharmacovigilance involves identifying adverse events and determining what action, if any, is required. The objective is to ensure the continuous safety of products once they are authorised. This proposal introduces a risk-based approach to pharmacovigilance whereby certain requirements that do not contribute effectively to public health, animal health or environmental protection (e.g. submitting periodic safety update reports) are relaxed. The Agency will manage a database of adverse events linked to medicines authorised in the Union. It will work together with competent authorities to monitor and evaluate collated data on adverse events linked to similar groups of veterinary medicinal products (signal management process).

Many SPCs of nationally authorised products may differ in some respects between Member States. As a result, dosage, uses and warnings may also differ. This lack of harmonisation could result in discrepancies between the SPCs of the originator and the generic product on the same national market. This part also seeks to harmonise the SPCs for products on the Union market that have been authorised at national level by means of a dual procedure:

· products considered low-risk will be subject to an administrative procedure; and

· products that are by nature more likely to present a risk to animal or public health or the environment will be scientifically re-assessed.

This harmonisation should increase the availability of products in the Union.

Member States or the Commission can request a re-evaluation of veterinary medicinal products available on the market on the grounds that they may pose a risk to animal or public health or the environment. Once this ‘Union referral procedure’ is triggered, the Agency adopts an opinion on the case and the Commission adopts a decision that will apply throughout the Union.

In addition, a system will be set up to record and report the use of antimicrobials. This is one of measures in the Commission’s AMR action plan.

Chapter V: Homeopathic veterinary medicinal products

This part lays down requirements and a simplified registration procedure for homeopathic veterinary medicinal products.

Chapter VI: Manufacturing, import and export

This part covers the procedure and requirements for obtaining an authorisation to manufacture, import or export veterinary medicinal products. It lays down the obligations of a manufacturing authorisation holder. These rules will ensure the quality of the medicine available on the Union market.

Chapter VII: Supply and use

This part covers the supply and use of veterinary medicinal products after a marketing authorisation has been granted. It imposes new restrictions on the supply of antimicrobial veterinary medicinal products and lays down rules on prescriptions and online sales of veterinary medicinal products.

In order to improve access to veterinary medicinal products in the Union, retailers should be allowed to sell products via the internet if they are authorised to supply them in the Member State in which the buyer is established. Online sales of veterinary medicinal products throughout the Union must be harmonised and ring-fenced, as falsified or substandard veterinary medicinal products represent a threat to public and animal health. Member States may impose conditions, for public health reasons, on supplying veterinary medicinal products to the public via the internet.

The provisions on the use of veterinary medicinal products for species or indications outside the terms of the marketing authorisation are improved as follows:

· the ranking system is abolished and more flexibility introduced, enabling veterinarians to choose the best available treatment for animals under their care;

· withdrawal periods are determined according to a multiplication factor system which takes account of relevant available information;

· specific provisions are included for the use of products in an aquatic environment in order to better protect the environment; and

· the Commission is empowered to exclude or restrict the use of certain antimicrobials.

Chapter VIII: Controls

Inspections by Member States’ competent authorities should ensure that the Union rules are complied with and enforced at national level. The Agency should coordinate the controls of veterinary medicinal products authorised by the centralised procedure. The key change is that the Commission will be able to check Member States’ inspection systems to ensure that the legislation is enforced consistently. This brings the arrangements for veterinary medicinal products into line with those in the food sector.

Chapter IX: Restrictions and sanctions

This part deals with Member State and Union-level measures to tackle risks to public or animal health or the environment. It provides for:

· a procedure for temporary safety restrictions; and

· suspending, withdrawing and varying marketing authorisations; or

· prohibiting the supply of veterinary medicinal products.

Chapter X: Regulatory network

This part regulates the Union regulatory network on veterinary medicinal products. Responsibility for veterinary medicinal products is shared between the Member States and the Commission. The fully fledged European network between the competent authorities of the Member States, the Agency and the Commission should ensure that:

· veterinary medicinal products are available on the Union market;

· they are properly evaluated before being authorised for use; and

· their safety and efficacy is constantly monitored.

This part of the proposal specifies the functioning and the tasks of the Agency’s Committee for Medicinal Products for Veterinary Use (CVMP) and the Coordination Group for Mutual Recognition and Decentralised Procedures (veterinary) (CMDv). The main changes are to clarify the remit of the CMDv, which will have more responsibility under the new arrangements and will take decisions by majority voting. These changes should improve the functioning of the network. The CVMP’s tasks are amended to reflect the proposed changes to marketing authorisation procedures and post‑marketing measures.

Chapter XI: Final provisions

This proposal repeals and replaces Directive 2001/82/EC. To give those affected sufficient time to adapt to the new legislation, the Regulation will apply as from two years after its publication.

Regulation (EC) No 726/2004 must be amended to take account of the fact that centralised marketing authorisation for veterinary medicinal products is being decoupled from that for medicines for humans. The amendments are proposed in a separate act accompanying this proposal.

4. BUDGETARY IMPLICATION

It is planned that the costs for the Agency for implementing and applying the new rules are entirely covered by fees charged to industry.

Therefore, the proposal is not expected to have any financial impact on the budget of the EU.

As set out in the legislative financial statement the additional resource needs for the European Medicines Agency are approximately 8 staff plus expenditure for meetings, translation, IT, etc.

The level of fees, their structure, modalities and exceptions will be set at a later stage by the Commission by way of implementing acts. This holds not only for the fees for new tasks for the Agency set out in this proposal, but for all fees in general.

5. OPTIONAL ELEMENTS

2014/0257 (COD)

Proposal for a

REGULATION OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL

on veterinary medicinal products

(Text with EEA relevance)

THE EUROPEAN PARLIAMENT AND THE COUNCIL OF THE EUROPEAN UNION,

Having regard to the Treaty on the Functioning of the European Union, and in particular Articles 114 and 168(4)(b) thereof,

Having regard to the proposal from the European Commission,

After transmission of the draft legislative act to the national Parliaments,

Having regard to the opinion of the European Economic and Social Committee[9],

Having regard to the opinion of the Committee of the Regions[10],

Acting in accordance with the ordinary legislative procedure,

Whereas:

(1) Directive 2001/82/EC of the European Parliament and of the Council[11] and Regulation (EC) No 726/2004 of the European Parliament and of the Council[12] constitute the Union regulatory framework for the placing on the market, manufacture, import, export, supply, pharmacovigilance, control and the use of veterinary medicinal products.

(2) In the light of the experience acquired and following the assessment by the Commission of the functioning of the market for veterinary medicinal products, the legal framework for veterinary medicinal products should be adapted to scientific progress, the current market conditions and economic reality.

(3) The legal framework should take into account the needs of the businesses in the veterinary pharmaceutical sector and trade in veterinary medicinal products within the Union. It should also integrate the major policy objectives set out in the Communication from the Commission of 3 March 2010 "Europe 2020 A Strategy for smart, sustainable and inclusive growth"[13].

(4) Experience has shown that the needs of the veterinary sector differ substantially from those of the human sector in relation to medicines. In particular, the drivers for investment for the human and the veterinary medicines markets are different. For example, in the veterinary sector there are many different animal species, which creates both a fragmented market and the need for major investments in order to extend the authorisation of medicines existing for one animal species to another. Moreover, the price-setting mechanisms in the veterinary sector follow a completely different logic. Consequently, prices for veterinary medicines are typically substantially lower than for medicinal products for human use. The size of the animal pharmaceutical industry is only a small fraction of the size of the pharmaceutical industry for human medicines.It is therefore appropriate to develop a regulatory framework addressing the characteristics and specificities of the veterinary sector, which cannot be considered as a model for the human medicines market.

(5) The provisions of this act aim to reduce administrative burden, enhance the internal market and increase the availability of veterinary medicinal products, while guaranteeing the highest level of public and animal health and environmental protection.

(6) Animals may suffer from a broad range of diseases which can be prevented or treated. The impact of animal diseases and the measures necessary to control them can be devastating for individual animals, animal populations, animal keepers and the economy. Animal diseases transmissible to humans may also have a significant impact on public health. Therefore sufficient and effective veterinary medicinal products should be available in the Union in order to ensure high standards of animal and public health, and for the development of the agriculture and aquaculture sectors.

(7) This Regulation should set high standards of quality, safety and efficacy for veterinary medicinal products in order to meet common concerns as regards the protection of public and animal health. At the same time, this Regulation should harmonise the rules for the authorisation of veterinary medicinal products and the placing of them on the Union market.

(8) With a view to harmonising the internal market for veterinary medicinal products in the Union and improving their free movement, rules should be established concerning the procedures for authorisation of such products that ensure the same conditions for all applications and a transparent framework for all interested parties.

(9) The scope of the mandatory use of a centralised authorisation procedure under which the authorisations are valid throughout the Union should cover inter alia products containing new active substances and products which contain or consist of engineered tissues or cells. At the same time, in order to ensure the widest possible availability of veterinary medicinal products in the Union, the centralised authorisation procedure should be extended to allow for applications for authorisations under that procedure to be submitted for any veterinary medicinal product, including for generics of nationally authorised veterinary medicinal products.

(10) The national procedure for authorising veterinary medicinal products should be maintained because of varying needs in different geographical areas of the Union as well as the business models of small and medium sized enterprises (SMEs). It should be ensured that marketing authorisations granted in one Member State are recognised in other Member States.

(11) In order to help applicants, and in particular SMEs, to comply with the requirements of this Regulation, Member States should provide advice to the applicants, for example by establishing helpdesks. This advice should be provided in addition to the operational guidance documents and other advice and assistance provided by the European Medicines Agency.

(12) In order to avoid unnecessary administrative and financial burdens for applicants and competent authorities, a full in-depth assessment of an application for the authorisation of a veterinary medicinal product should be carried out only once. It is appropriate therefore to lay down special procedures for the mutual recognition of national authorisations.

(13) Moreover, rules should be established under the mutual recognition procedure to resolve any disagreements between competent authorities in a coordination group of the Member States without undue delay.

(14) Where a Member State or the Commission considers that there are reasons to believe that a veterinary medicinal product may present a potential serious risk to human or animal health or to the environment, a scientific evaluation of the product should be undertaken at Union level, leading to a single decision on the area of disagreement, binding on the Member States concerned, being taken on the basis of an overall benefit-risk assessment.

(15) No veterinary medicinal product should be allowed to be placed on the market or used in the Union unless it has been authorised, and its quality, safety and efficacy have been demonstrated.

(16) Where a veterinary medicinal product is intended for food-producing animal species, a marketing authorisation should only be granted if the pharmacologically active substances which the product contains are allowed in accordance with Commission Regulation (EU) No 37/2010[14] for the species for which the veterinary medicinal product is intended.

(17) However, there may be situations where no suitable authorised veterinary medicinal product is available. In those situations, by way of exception, veterinarians should be allowed to prescribe other medicinal products to the animals under their responsibility in conformity with strict rules and in the interest of animal health or animal welfare only. In case of food-producing animals, veterinarians should ensure that an appropriate withdrawal period is prescribed, so that harmful residues of those medicinal products do not enter the food chain.

(18) Member States should be able to allow exceptional use of veterinary medicinal products without a marketing authorisation where it is necessary to respond to Union listed diseases and where the health situation in a Member State so requires.

(19) Taking into account the need for simple rules on changes to the marketing authorisations of veterinary medicinal products, only changes that may affect animal health, public health or the environment should require a scientific assessment.

(20) Directive 2010/63/EU of the European Parliament and of the Council[15] lays down provisions on the protection of animals used for scientific purposes based on the principles of replacement, reduction and refinement. Clinical trials for veterinary medicinal products are exempted from that Directive. The design and performance of clinical trials, which provide essential information on the safety and efficacy of a veterinary medicinal product, should be such as to provide the most satisfactory results whilst using the minimum number of animals, the procedures should be the least likely to cause pain, suffering or distress to animals and should take into account the principles established by Directive 2010/63/EU.

(21) The principles of replacement, reduction and refinement concerning the care and use of live animals for scientific purposes should therefore be taken into account during the design and performance of clinical trials.

(22) It is recognised that improved access to information contributes to public awareness, gives the public the opportunity to express its observations and enables authorities to take due account of those observations. Regulation (EC) No 1049/2001 of the European Parliament and of the Council[16] gives the fullest possible effect to the right of public access to documents and lays down the general principles and limits on such access. The European Medicines Agency should therefore give the widest possible access to the documents carefully balancing the right for information with existing data protection requirements. Certain public and private interests, such as regarding the protection of personal data, or the protection of commercially confidential information, should be protected by way of exceptions in accordance with Regulation (EC) No 1049/2001.

(23) Companies have less interest in developing veterinary medicinal products for markets of a limited size. In order to promote the availability of veterinary medicinal products within the Union for those markets, in some cases it should be possible to grant marketing authorisations without a complete application dossier having been submitted, on the basis of a benefit-risk assessment of the situation and, where necessary, subject to specific obligations. In particular, this should be possible in the case of veterinary medicinal products for use in minor species or for the treatment or prevention of diseases that occur infrequently or in limited geographical areas.

(24) Environmental risk assessments should be mandatory for all new applications for a marketing authorisation and should consist of two phases. In the first phase the extent of environmental exposure of the product, its active substances and other constituent should be estimated, while in the second phase the effects of the active residue should be assessed.

(25) Tests, pre-clinical studies and clinical trials represent a major investment for companies which they need to make in order to submit the necessary data with the application for a marketing authorisation or to establish a maximum residue limit for pharmaceutical active substances in the veterinary medicinal product. That investment should be protected in order to stimulate research and innovation, so that it is ensured the necessary veterinary medicinal products are available in the Union. For that reason data submitted to a competent authority or the Agency should be protected against use by other applicants. That protection should, however, be limited in time in order to allow competition.

(26) Certain particulars and documents that are normally to be submitted with an application for a marketing authorisation should not be required if a veterinary medicinal product is a generic medicinal product of a veterinary medicinal product that is authorised or has been authorised in the Union.

(27) It is recognised that the potential effect of a product on the environment may depend on the volume used and the resulting amount of the pharmaceutical substance that may reach the environment. Therefore, where there is evidence that a constituent of a medicinal product for which a generic application for a marketing authorisation is submitted is a hazard for the environment, it is appropriate to require data on the potential effect on the environment in order to safeguard the environment. In such cases applicants should endeavour to join efforts in generating such data in order to reduce costs and to reduce testing on vertebrate animals.

(28) The protection of technical documentation should be applied to new veterinary medicinal products, as well as to data developed for supporting innovations of products with or referring to an existing marketing authorisation, for example in the case of extending use of an existing product to an additional animal species. In this case the variation or marketing authorisation application may refer partly to data submitted in a former marketing authorisation or variation applications, and should include new data specifically developed to support the required innovation of the existing product.

(29) Differences in the manufacturing process of biological products or a change in the excipient used may lead to differences in the generic product characteristics. In an application for generic biological veterinary medicinal product the bioequivalence should be demonstrated in order to ensure, based on the existing knowledge, that quality, safety and efficacy are similar.

(30) In order to avoid unnecessary administrative and financial burdens both for the competent authorities and for the pharmaceutical industry, as a general rule a marketing authorisation for a veterinary medicinal product should be granted for an unlimited period of time. Conditions for renewing the approval of a marketing authorisation should be imposed only exceptionally and should be duly justified.

(31) It is recognised that, in some cases, a scientific risk assessment alone cannot provide all the information on which a risk management decision should be based, and other relevant factors should be taken into account including societal, economical, ethical, environmental and welfare factors and the feasibility of controls.

(32) In certain circumstances where a significant animal or public health concern exists but scientific uncertainty persists, appropriate measures can be adopted taking into account Article 5(7) of the WTO Agreement on the Application of Sanitary and Phytosanitary Measures which has been interpreted for the Union in the Communication from the Commission on the precautionary principle[17]. In such circumstances, Member States or the Commission should seek to obtain additional information necessary for a more objective assessment of the particular concern and should review the measure accordingly within a reasonable period of time.

(33) Antimicrobial resistance to human and veterinary medicinal products is a growing health problem in the Union and worldwide. Many of the antimicrobials used in animals are also used in humans. Some of those antimicrobials are critical for preventing or treating life-threatening infections in humans. In order to fight antimicrobial resistance a number of measures should be taken. It needs to be ensured that appropriate warnings and guidance are included on the labels of veterinary antimicrobials. Use not covered by the terms of the marketing authorisation of certain new or critically important antimicrobials for humans should be restricted in the veterinary sector. The rules for advertising veterinary antimicrobials should be tightened, and the authorisation requirements should sufficiently address the risks and benefits of antimicrobial veterinary medicinal products.

(34) It is necessary to mitigate the risk of development of antimicrobial resistance to human and veterinary medicinal products. Therefore, an application for an antimicrobial veterinary medicinal product should contain information about the potential risks that use of the product may lead to the development of antimicrobial resistance in humans or animals or in organisms associated with them. In order to ensure a high level of public and animal health, veterinary antimicrobials should only be authorised following a careful scientific benefit-risk assessment. If necessary, conditions should be laid down in the marketing authorisation in order to restrict the use of the product. This should include restrictions on the use of the veterinary medicinal product not in accordance with the terms of the marketing authorisation, in particular the summary of product characteristics of the veterinary medicinal product.

(35) The combined use of several antimicrobial active substances may represent a particular risk with respect to the development of antimicrobial resistance. Combinations of antimicrobial substances should therefore only be authorised where evidence is provided that the benefit-risk balance of the combination is favourable.

(36) The development of new antimicrobials has not kept pace with the increase of resistance to existing antimicrobials. Given the limited innovation in developing new antimicrobials it is essential that the efficacy of existing antimicrobials is maintained for as long as possible. The use of antimicrobials in veterinary medicinal products may accelerate the emergence and spread of resistant micro-organisms and may compromise the effective use of the already limited number of existing antimicrobials to treat human infections. Therefore the misuse of antimicrobials should not be allowed.

(37) In order to preserve as long as possible the efficacy of certain antimicrobials in the treatment of infections in humans, it may be necessary to reserve those antimicrobials for humans only. Therefore it should be possible to decide that certain antimicrobials, following the scientific recommendations of the Agency, should not be available on the market in the veterinary sector.

(38) If an antimicrobial is administered and used incorrectly, this presents a risk to public or animal health. Therefore antimicrobial veterinary medicinal products should only be available on veterinary prescription. Persons having the right to prescribe have a key role in ensuring prudent use of antimicrobials and consequently they should not be influenced, directly or indirectly, by economic incentives when prescribing those products. Therefore the supply of veterinary antimicrobials by those health professionals should be restricted to the amount required for treatment of the animals under their care.

(39) It is important to consider the international dimension of the development of antimicrobial resistance when assessing the benefit-risk balance of certain veterinary antimicrobials in the Union. Any measure restricting the use of those products may affect the trade of products of animal origin or the competitiveness of certain animal production sectors in the Union. Moreover, antimicrobial resistant organisms can spread to humans and animals in the Union through consumption of products of animal origin imported from third countries, from direct contact with animals or humans in third countries or by other means. Therefore, measures restricting the use of veterinary antimicrobials in the Union should be based on scientific advice and should be considered in the context of cooperation with third countries and international organisations addressing antimicrobial resistance in order the ensure consistency with their activities and policies.

(40) There is still a lack of sufficiently detailed and comparable data at Union level to determine the trends and identify possible risk factors that could lead to the development of measures to limit the risk from antimicrobial resistance and to monitor the effect of measures already introduced. Therefore it is important to collect data on the sales and use of antimicrobials in animals, data on the use of antimicrobials in humans and data on antimicrobial resistant organisms found in animals, humans and food. To ensure that the information collected can be used effectively, appropriate rules should be laid down concerning the collection and the exchange of data. The Member States should be responsible for collecting data on the use of antimicrobials under the coordination of the Agency.

(41) The majority of the veterinary medicinal products on the market have been authorised under national procedures. The lack of harmonisation of summary of product characteristics for veterinary medicinal products authorised nationally in more than one Member State creates additional and unnecessary barriers for the circulation of veterinary medicinal products within the Union. It is necessary to harmonise those summaries of product characteristics. In order to avoid unnecessary costs and burdens for the Member States, the Commission and the pharmaceutical industry, and in order to increase the availability of veterinary medicinal products as fast as possible, it should be possible to harmonise summaries of the products characteristics for certain veterinary medicinal products in accordance with an administrative procedure, while taking on board the risk to public and animal health and to the environment. This harmonisation exercise should cover veterinary medicinal products authorised before 2004.[18].

(42) In order to reduce administrative burden and maximise the availability of veterinary medicinal products in the Member States, simplified rules should be laid down as to how their packaging and labelling are to be presented. The textual information provided should be reduced and, if possible, replaced by pictograms and abbreviations. Pictograms and abbreviations should be standardised across the Union. Care should be taken so that those rules do not jeopardise public and animal health and environmental safety.

(43) In addition, Member States should be empowered to choose the language of the text used in the packaging and labelling of veterinary medicinal products authorised in their territory. The package leaflet, however, should be provided in the official language or languages of the Member State.

(44) With a view to increasing availability of veterinary medicinal products in the Union it should be possible to grant more than one marketing authorisation for a specific veterinary medicinal product to the same marketing authorisation holder in the same Member State. In that case all product-related characteristics of the product and data in support of the applications for the product should be identical. However, multiple applications for a specific product should not be used to circumvent the principles of mutual recognition, and therefore this type of applications in different Member States should take place inside the procedural framework for mutual recognition.

(45) Pharmacovigilance rules are necessary for the protection of public and animal health and the environment. Collection of information on adverse events should contribute to the good usage of veterinary medicinal products.

(46) In the light of the experience acquired it has become clear that it is necessary to take measures to improve the operation of the pharmacovigilance system. It should integrate and monitor data at Union level. It is the interest of the Union to ensure that the veterinary pharmacovigilance systems for all authorised veterinary medicinal products are consistent. At the same time, it is necessary to take account of changes arising as a result of international harmonisation of definitions, terminology and technological developments in the field of pharmacovigilance.

(47) Holders of marketing authorisations should be responsible for continuously carrying out pharmacovigilance of the veterinary medicinal products they place on the market. They should collect reports on adverse events relating to their products, including those concerning use outside the terms of the granted marketing authorisation.

(48) It is necessary to increase the shared use of resources between authorities, and to enhance efficiency of the pharmacovigilance system. Data collected should be uploaded to a single reporting point to ensure that the information is shared. The competent authorities should use those data to ensure the continuous safety and efficacy of the veterinary medicinal products that are on the market.

(49) It is necessary, in specific cases, or from a public health and animal health perspective, to complement the safety and efficacy data available at the time of authorisation with additional information following the placing of the product on the market. Therefore the obligation to conduct post-authorisation studies should be imposed on the marketing authorisation holder.

(50) A pharmacovigilance database at Union level should be established to record and integrate information of adverse events for all veterinary medicinal products authorised in the Union. That database should improve detection of adverse events and should allow and facilitate the pharmacovigilance surveillance and work-sharing between the competent authorities.

(51) It is necessary to exercise control over the entire chain of distribution of veterinary medicinal products, from manufacture or import into the Union through supply to the end-user. Veterinary medicinal products from third countries should comply with the same requirements which apply to products manufactured in the Union, or with requirements which are recognised to be at least equivalent thereto.

(52) In order to facilitate the movement of veterinary medicinal products and to prevent checks carried out in one Member State being repeated in others, minimum requirements should be applied to veterinary medicinal products manufactured in or imported from third countries.

(53) The quality of veterinary medicinal products manufactured within the Union should be guaranteed by requiring compliance with the principles of good manufacturing practice for medicinal products irrespective of the final destination of the medicinal products.

(54) Companies should be in possession of an authorisation to be able to wholesale or retail veterinary medicinal products, so as to guarantee that such medicines are appropriately stored, transported and handled. It should be the responsibility of the Member States to ensure that those conditions are met. Those authorisations should be valid throughout the Union.

(55) In order to ensure transparency, a database should be established at Union level for the purposes of publishing a list of wholesale distributors who have been found to comply with applicable Union legislation following an inspection by the competent authorities of a Member State.

(56) The conditions governing the supply of veterinary medicinal products to the public should be harmonised in the Union. Veterinary medicinal products should only be supplied by persons authorised to do so by the Member State where they are established. At the same time, in order to improve access to veterinary medicinal products in the Union, retailers that are authorised to supply veterinary medicinal products by the competent authority in the Member State where they are established should be allowed to sell prescription and non-prescription veterinary medicinal products via the Internet to buyers in other Member States.

(57) The illegal sale of veterinary medicinal products to the public via the Internet may represent a threat to public and animal health, as falsified or substandard medicines may reach the public in this way. It is necessary to address this threat. Account should be taken of the fact that specific conditions for supply of medicinal products to the public have not been harmonised at Union level and, therefore, Member States may impose conditions for supplying medicinal products to the public within the limits of the Treaty.

(58) When examining the compatibility with Union law of the conditions for the supply of medicinal products, the Court of Justice of the European Union has recognised, in the context on medicinal products for human use, the very particular nature of medicinal products whose therapeutic effects distinguish them substantially from other goods. The Court of Justice has also held that health and life of humans rank foremost among the assets and interests protected by the Treaty and that it is for Member States to determine the level of protection which they wish to afford to public health and the way in which that level has to be achieved. Since that level may vary from one Member State to another, Member States must be allowed some discretion as regards the conditions for the supply on their territory of medicinal products to the public. Therefore Member States should be able to subject the supply of medicinal products offered for sale at a distance by means of information society services to conditions justified by the protection of public health. Such conditions should not unduly restrict the functioning of the internal market.

(59) In order to ensure high standards and safety of the veterinary medicinal products offered for sale at a distance, the public should be assisted in identifying websites which are legally offering such medicinal products. A common logo should be established, which is recognisable throughout the Union, while allowing for the identification of the Member State where the person offering veterinary medicinal products for sale at a distance is established. The Commission should develop the design for such a logo. Websites offering veterinary medicinal products for sale at a distance to the public should be linked to the website of the competent authority concerned. The websites of the competent authorities of Member States, as well as that of the European Medicines Agency, should give an explanation of the use of the logo. All those websites should be linked in order to provide comprehensive information to the public.

(60) Collection systems for the take-back of unused or expired veterinary medicinal products should continue to be in place in the Member States in order to control any risk that such products might raise with regard to the protection of animal, human health or the environment.

(61) Advertising, even on non-prescription medicinal products, could affect public and animal health and distort competition. Therefore, advertising of veterinary medicinal products should satisfy certain criteria. Persons qualified to prescribe or supply can properly evaluate the information available in advertising because of their knowledge, training and experience in animal health. The advertising of veterinary medicinal products to persons who cannot properly appreciate the risk associated with their use may lead to medicine misuse or overconsumption which is liable to harm public or animal health, or the environment.

(62) Where medicinal products are authorised within a Member State and have been prescribed in that Member State by a member of a regulated animal health profession for an individual animal or group of animals, it should in principle be possible for that veterinary prescription to be recognised and for the medicinal product to be dispensed in another Member State. The removal of regulatory and administrative barriers to such recognition should not affect any professional or ethical duty for dispensing professionals to refuse to dispense the medicine stated in the prescription.

(63) The implementation of the principle of recognition of prescriptions should be facilitated by the adoption of a standard prescription, listing the essential information necessary to ensure the safe and efficacious use of the product. Nothing should prevent Member States from having further elements in their prescriptions, as long as this does not prevent prescriptions from other Member States from being recognised.

(64) Information on veterinary medicinal products is essential in order to enable health professionals, authorities and undertakings to make informed decisions. A key aspect is the creation of a European database that should collate information on marketing authorisations granted in the Union. The database should enhance overall transparency, streamline and facilitate the flow of information between authorities and prevent multiple reporting requirements.

(65) The verification of compliance with the legal requirements through controls is of fundamental importance to ensure that the objectives of the Regulation are effectively achieved across the Union. Therefore the competent authorities of the Member States should have the power to perform inspections at all stages of production, distribution and use of veterinary medicinal products. In order to preserve the effectiveness of the inspections, authorities should have the possibility to perform unannounced inspections.

(66) The frequency of controls should be established by the competent authorities having regard to the risk and to the level of compliance expected in the different situations. This approach should allow authorities to allocate resources where the risk is the highest. In some cases, however, controls should be performed irrespective of the level of risk or expected non-compliance, for example prior to granting manufacturing authorisations.

(67) In certain cases failures in Member States’ control system can substantially hinder the achievement of the objectives of this Regulation and may lead to the emergence of risks to public and animal health and the environment. To ensure a harmonised approach to inspections throughout the Union, the Commission should be able to carry out audits in the Member States to verify the functioning of national control systems.

(68) In order to ensure transparency, impartiality and consistency in the level of enforcement activities by Member States, it is necessary for Member States to set up an appropriate framework for penalties with a view to imposing effective, proportionate and dissuasive penalties for non-compliance, as non-compliance can result in damage to animal and public health and the environment.

(69) At the same time, the power to adopt acts in accordance with Article 290 of the Treaty should be delegated to the Commission in respect of laying down the procedure for investigating the infringements and the imposition of fines to the holders of marketing authorisations granted under this Regulation, the maximum amounts of these penalties as well as the conditions and methods for their collection.

(70) Companies and authorities are frequently confronted with the need to distinguish between veterinary medicinal products, feed additives, biocidal products and other products. In order to avoid inconsistencies in the treatment of such products, to increase legal certainty, and to facilitate the decision process by Member States, a coordination group of Member States should be established, and among other tasks it should provide on a case-by-case basis a recommendation whether a product falls within the definition of a veterinary medicinal product. In order to ensure legal certainty the Commission may decide whether a specific product is a veterinary medicinal product.

(71) Having regard to the special characteristics of homeopathic veterinary medicinal products, especially the constituents of these products, it is desirable to establish a special, simplified registration procedure and to provide specific provisions for labelling for certain homeopathic veterinary medicinal products which are placed on the market without therapeutic indications. Immunological homeopathic products cannot follow the simplified registration procedure as immunologicals may initiate a response at a high dilution rate. The quality aspect of a homeopathic medicinal product is independent of its use so no specific provisions should apply with regard to the necessary quality requirements and rules.

(72) In order to follow the scientific developments of the sector, the power to adopt acts in accordance with Article 290 of the Treaty should be delegated to the Commission in respect of amending the rules on designation of homeopathic veterinary medicinal products for which registration procedure should be allowed.

(73) In order to protect public health, animal health and the environment, the activities and tasks attributed to the Agency in this Regulation should be adequately funded. Those activities, services and tasks should be funded through fees charged to enterprises. Those fees, however, should not affect the right of Member States to charge fees for activities and tasks at national level.

(74) In order to ensure that annexes to this Regulation are adapted to the technical and scientific developments, the power to adopt acts in accordance with Article 290 of the Treaty should be delegated to the Commission.

(75) In order to adapt this Regulation to the scientific developments of the sector, the power to adopt acts in accordance with Article 290 of the Treaty should be delegated to the Commission in respect of the use of a product outside the terms of the granted marketing authorisation, in particular regarding establishing a list of antimicrobial veterinary medicinal products for which such use should be prohibited.

(76) In order to adapt this Regulation to the scientific developments of the sector, the power to adopt acts in accordance with Article 290 of the Treaty should be delegated to the Commission in respect of amending the list of groups of veterinary medicinal products for which the centralised authorisation procedure shall be compulsory.

(77) In order to adapt this Regulation to the scientific developments of the sector, the power to adopt acts in accordance with Article 290 of the Treaty should be delegated to the Commission in respect of establishing detailed rules on the principles for the refusal or restriction of marketing authorisations of antimicrobial veterinary medicinal products, in particular with a view to preserving the efficacy of certain active substances in treating infections in humans.

(78) In order to exercise its supervisory powers effectively, the power to adopt acts in accordance with Article 290 of the Treaty should be delegated to the Commission in respect of laying down the procedure for investigating the infringements and the imposition of fines or periodic penalty payments to the holders of marketing authorisations granted under this Regulation, the maximum amounts of these penalties as well as the conditions and methods for their collection.

(79) In order to introduce harmonised standards within the Union for the methods of gathering data on the use of antimicrobials and the methods of transferring of these data to the Commission, the power to adopt acts in accordance with Article 290 of the Treaty should be delegated to the Commission in respect of establishing rules on these methods.

(80) In order to ensure uniform conditions for the implementation of this Regulation, implementing powers should be conferred on the Commission. Those powers should be exercised in accordance with Regulation (EU) No 182/2011 of the European Parliament and of the Council[19].

(81) Taking into account the main changes that should be made to the existing rules, and aiming to improve the functioning of the internal market, a regulation is the appropriate legal instrument to replace Directive 2001/82/EC in order to lay down clear, detailed and directly applicable rules. Moreover, a regulation ensures that legal requirements are implemented at the same time and in a harmonised manner throughout the Union.

(82) Since the objectives of this Regulation, namely to establish rules on veterinary medicinal products ensuring the protection of human and animal health and the environment as well as the functioning of the internal market, cannot be sufficiently achieved by the Member States, but can rather, by reason of its effects, be better achieved at Union level, the Union may adopt measures, in accordance with the principle of subsidiarity as set out in Article 5 of the Treaty on European Union. In accordance with the principle of proportionality, as set out in that Article, this Regulation does not go beyond what is necessary in order to achieve those objectives,

HAVE ADOPTED THIS REGULATION:

Chapter I Subject matter, scope and definitions

Article 1 Subject matter

This Regulation lays down rules for the placing on the market, manufacture, import, export, supply, pharmacovigilance, control and use of veterinary medicinal products.

Article 2 Scope

1. This Regulation shall apply to veterinary medicinal products prepared industrially or by a method involving an industrial process and intended to be placed on the market.

2. In addition to the products referred to in paragraph 1, Chapter VI shall also apply to active substances, intermediate products and excipients used as starting materials in veterinary medicinal products.

3. In addition to the products referred to in paragraph 1, Chapter VII shall also apply to:

(a) substances that have anabolic, anti-infectious, anti-parasitic, anti-inflammatory, hormonal or psychotropic properties and that may be used in animals;

(b) veterinary medicinal products prepared in a pharmacy in accordance with a veterinary prescription for an individual animal or a small group of animals (‘magistral formula’);

(c) veterinary medicinal products prepared in a pharmacy in accordance with the directions of a pharmacopoeia and intended to be supplied directly to the end-user (‘officinal formula’).

4. This Regulation shall not apply to:

(a) 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 those animals in the same locality;

(b) veterinary medicinal products containing autologous or allogeneic cells or tissues that have not been subjected to an industrial process;

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

(d) feed additives as defined in Regulation (EC) No 1831/2003 of the European Parliament and of the Council[20];

(e) veterinary medicinal products intended for research and development.

Article 3 Conflict of laws

1. Where a veterinary medicinal product referred to in Article 2(1) also falls within the scope of Regulation (EU) No 528/2012 of the European Parliament and of the Council[21] or Regulation (EC) No 1831/2003 of the European Parliament and of the Council, and there is a conflict between the provisions of this Regulation and the provisions of Regulation (EU) No 528/2012 or Regulation (EC) No 1831/2003, the provisions of this Regulation shall prevail.

2. The Commission may, by means of implementing acts, adopt decisions on whether a specific product or group of products is to be considered as a veterinary medicinal product. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 145(2).

Article 4 Definitions

For the purposes of this Regulation, the following definitions shall apply:

(1) ‘veterinary medicinal product’ means any substance or combination of substances which fulfils at least one of the following conditions:

(a) it is presented as having properties for treating or preventing disease in animals;

(b) its purpose is to be used in or administered to animals with a view to restoring, correcting or modifying physiological functions by exerting a pharmacological, immunological or metabolic action, or to making a medical diagnosis;

(c) its purpose is to be used for euthanasia of animals;

(2) ‘substance’ means any matter of the following origin:

(a) human,

(b) animal,

(c) vegetable,

(d) chemical;

(3) ‘immunological veterinary medicinal product’ means a veterinary medicinal product consisting of vaccines, toxins, sera or allergen products and intended to be administered to an animal in order to produce active or passive immunity or to diagnose its state of immunity;

(4) ‘biological veterinary medicinal product’ means a veterinary medicinal product an active substance of which is a biological substance;

(5) ‘biological substance’ means a substance that is produced by or extracted from a biological source and that needs for its characterisation and the determination of its quality a combination of physico-chemical-biological testing, together with knowledge of the production process and its control;

(6) ‘generic veterinary medicinal product’ means a veterinary medicinal product which has the same qualitative and quantitative composition of active substances and the same pharmaceutical form as the reference medicinal product, and with regard to which appropriate bioavailability studies have demonstrated a bioequivalence with the reference veterinary medicinal product;

(7) ‘homeopathic veterinary medicinal product’ means a veterinary medicinal product prepared from homeopathic stocks in accordance with a homeopathic manufacturing procedure described by the European Pharmacopoeia or, in the absence thereof, by the pharmacopoeias used officially in Member States;

(8) ‘antimicrobial resistance’ means the ability of microorganisms to survive or to grow in the presence of a concentration of an antimicrobial agent which is usually sufficient to inhibit or kill microorganisms of the same species;

(9) ‘clinical trial’ means a study which aims to examine under field conditions the safety or efficacy of a veterinary medicinal product or both under normal conditions of animal husbandry or as part of normal veterinary practice for the purpose of obtaining a marketing authorisation or a change thereof;

(10) ‘pre-clinical study’ means a study not covered by the definition of clinical trial which aims to investigate the safety or efficacy of a veterinary medicinal product for the purpose of obtaining a marketing authorisation or a change thereof;

(11) ‘benefit-risk balance’ means an evaluation of the positive effects of the veterinary medicinal product in relation to the following risks relating to the use of that product:

(a) any risk relating to the quality, safety and efficacy of the veterinary medicinal products as regards animal or human health;

(b) any risk of undesirable effects on the environment;

(c) any risk relating to the development of antimicrobial resistance;

(12) ‘common name’ means the international non-proprietary name recommended by the World Health Organisation for a veterinary medicinal product, or, if one does not exist, the name generally used;

(13) ‘strength’ means the content of active substances in a veterinary medicinal product, expressed quantitatively per dosage unit, per unit of volume or per unit of weight according to the pharmaceutical form;

(14) ‘competent authority’ means an authority designated by a Member State in accordance with Article 136;

(15) ‘labelling’ means information on the immediate packaging or the outer packaging;

(16) ‘outer packaging’ means packaging in which is placed the immediate packaging;

(17) ‘immediate packaging’ means the container or any other form of packaging that is in direct contact with the veterinary medicinal product;

(18) ‘package leaflet’ means a documentation leaflet on a veterinary medicinal product which contains information to ensure its safe and efficacious use;

(19) ‘letter of access’ means an original document, signed by the data owner or its representative, which states that the data may be used for the benefit of a third party by the competent authorities, the Agency or the Commission for the purposes of this Regulation;

(20) ‘limited market’ means a market for one of the following product types:

(a) veterinary medicinal products for the treatment or prevention of diseases that occur infrequently or in limited geographical areas;

(b) veterinary medicinal products for animal species other than cattle, sheep, pigs, chickens, dogs and cats;

(21) ‘pharmacovigilance’ means the process of monitoring and investigating adverse events;

(22) ‘pharmacovigilance system master file’ means a detailed description of the pharmacovigilance system used by the marketing authorisation holder with respect to one or more authorised veterinary medicinal products;

(23) ‘control’ means any task performed by a competent authority, including inspections, for the verification of compliance with this Regulation;

(24) ‘veterinary prescription‘ means any prescription for a veterinary medicinal product issued by a professional person qualified to do so in accordance with applicable national law;

(25) ‘withdrawal period’ means the minimum period between the last administration of a veterinary medicinal product to an animal and the production of foodstuffs from that animal which under normal conditions of use is necessary to ensure that such foodstuffs do not contain residues in quantities harmful to public health;

(26) ‘making available on the market’ means any supply of a veterinary medicinal product for distribution, consumption or use on the Union market in the course of a commercial activity, whether in return for payment or free of charge;

(27) ‘placing on the market’ means the first making available of a veterinary medicinal product on the Union market.

Chapter II Marketing authorisations – general provisions and rules on applications

Section 1 General provisions

Article 5 Marketing authorisations

1. A veterinary medicinal product shall be placed on the market only when a marketing authorisation has been granted in respect of the product by a competent authority in accordance with Articles 44, 46 or 48 or by the Commission in accordance with Article 40.

2. A marketing authorisation for a veterinary medicinal product shall be valid for an unlimited period of time.

3. Decisions to grant, refuse, suspend, withdraw or vary a marketing authorisation shall be made public.

4. Applicants for marketing authorisations and marketing authorisation holders shall be established in the Union.

Article 6 Submission of applications for marketing authorisations

1. Applications shall be submitted to the competent authority where they concern the granting of marketing authorisations in accordance with any of the following procedures:

(a) the national procedure laid down in Articles 42, 43 and 44;

(b) the decentralised procedure laid down in Articles 45 and 46;

(c) the mutual recognition procedure laid down in Articles 47 and 48.

2. Applications for the granting of marketing authorisations in accordance with the centralised marketing authorisation procedure laid down in Articles 38 to 41 shall be submitted to the European Medicines Agency (‘the Agency’) established by Regulation (EC) No 726/2004.

3. Applications shall be submitted electronically. For applications submitted in accordance with the centralised marketing authorisation procedure, the formats made available by the Agency shall be used.

4. The applicant shall be responsible for the accuracy of the documents and data submitted.

5. Within 15 days of receipt of the application, the competent authority or the Agency shall notify the applicant of whether all data required in accordance with Article 7 have been presented.

6. Where the competent authority or the Agency considers that the application is incomplete, it shall inform the applicant accordingly and shall set a time limit for submitting the missing information.

Section 2 Dossier requirements

Article 7 Data to be submitted with the application

1. An application for a marketing authorisation shall contain the following information:

(a) the administrative information set out in Annex I;

(b) technical documentation satisfying the requirements set out in Annex II;

(c) the information to be provided in the immediate packaging, outer packaging and the package leaflet in accordance with Articles 9 to 14.

2. Where the application concerns an antimicrobial veterinary medicinal product, the following shall be submitted in addition to the information listed in paragraph 1:

(a) documentation on the direct or indirect risks to public or animal health of use of the antimicrobial veterinary medicinal product in animals,

(b) information about risk mitigation measures to limit antimicrobial resistance development related to the use of veterinary medicinal product.

3. Where the application concerns a veterinary medicinal product intended for food-producing target species and containing pharmacologically active substances that are not listed in Table 1 of the Annex to Regulation (EU) No 37/2010 for the animal species in question, a document certifying that a valid application for the establishment of maximum residue limits has been submitted to the Agency in accordance with Regulation (EC) No 470/2009 of the European Parliament and of the Council[22] shall be submitted in addition to the information listed in paragraph 1.

4. Paragraph 3 shall not apply to veterinary medicinal products intended for animals of the equidae family that have been declared as not being intended for slaughter for human consumption in accordance with Commission Regulation (EC) 504/2008[23] and the active substances contained in those veterinary medicinal products are not listed in Table 2 of the Annex to Regulation (EU) No 37/2010.

5. Where the application concerns a veterinary medicinal product containing or consisting of genetically modified organisms within the meaning of Article 2 of Directive 2001/18/EC of the European Parliament and of the Council[24] the application shall in addition to the documents listed in paragraph 1 be accompanied by:

(a) a copy of the written consent of the competent authorities to the deliberate release into the environment of the genetically modified organisms for research and development purposes, as provided for in Part B of Directive 2001/18/EC;

(b) the complete technical file supplying the information required under Annexes III and IV to Directive 2001/18/EC;

(c) the environmental risk assessment in accordance with the principles set out in Annex II to Directive 2001/18/EC; and

(d) the results of any investigations performed for the purposes of research or development.

6. Where the application is submitted in accordance with the national procedure laid down in Articles 42, 43 and 44, the applicant shall, in addition to the information listed in paragraph 1, submit a declaration stating that he has not submitted an application for a marketing authorisation for the veterinary medicinal product in another Member State.

7. The Commission shall be empowered to adopt delegated acts in accordance with Article 146 in order to amend Annexes I and II to adapt the information and documentation requirements to technical and scientific progress.

Section 3 Clinical trials

Article 8 Approval of clinical trials

1. An application for the approval of a clinical trial shall be submitted to a competent authority of the Member State in which the clinical trial is to take place.

2. Approvals of clinical trials shall be granted on condition that food-producing animals used in the clinical trials or their produce do not enter the human food chain unless:

(a) the tested product is a veterinary medicinal product authorised for the food-producing species used in the clinical trial, and the withdrawal period set out in the summary of the product characteristics is respected, or

(b) the tested product is an authorised veterinary medicinal product for target species other than the food-producing species used in the clinical trial and the withdrawal period set out in accordance with Article 117 is respected.

3. The competent authority shall issue a decision on the approval of a clinical trial within 60 days after the receipt of an application. Where the competent authority has not notified the applicant of its decision within that time limit, the clinical trial shall be considered to have been approved.

4. The clinical trials referred to in paragraph 1 shall be carried out taking due account of the standards set by the international guidelines on good clinical practice of the International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products.

5. Results of clinical trials shall be submitted with the application for a marketing authorisation for the purposes of providing the documentation referred to in Article 7(1)(b).

6. Data stemming from clinical trials conducted outside the Union may be taken into consideration for the assessment of an application for a marketing authorisation only if those trials were designed, implemented and reported in accordance with the standards set by the international guidelines on good clinical practice of the International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products.

Section 4 Labelling and package leaflet

Article 9 Labelling of the immediate packaging of veterinary medicinal products

1. The immediate packaging of a veterinary medicinal product shall contain only the following information:

(a) the name of the veterinary medicinal product, followed by its strength and pharmaceutical form;

(b) a statement of the active substances expressed qualitatively and quantitatively per unit or according to the form of administration for a particular volume or weight, using their common names;

(c) the batch number, preceded by the word "Lot";

(d) the name or corporate name or logo name of the marketing authorisation holder;

(e) the target species;

(f) the expiry date, in the format: "mm/yyyy", preceded by the abbreviation "Exp.";

(g) special storage precautions, if any.

2. The information listed in paragraph 1 shall appear in easily legible and clearly comprehensible characters, or, where appropriate, abbreviations or pictograms common throughout the Union.

Article 10 Labelling of the outer packaging of veterinary medicinal products

1. The outer packaging of a veterinary medicinal product shall contain only the following information:

(a) the information listed in Article 9(1);

(b) the contents by weight, volume or number of immediate packaging units of the veterinary medicinal product;

(c) warning that the veterinary medicinal product must be kept out of the sight and reach of children;

(d) warning that the veterinary medicinal product is for animal treatment only;

(e) recommendation to read the package leaflet;

(f) requirement to use take-back schemes for veterinary medicinal products for the disposal of unused veterinary medicinal products or waste materials derived from the use of such products and, if appropriate, additional precautions as regarding hazardous waste disposal of unused veterinary medicinal products or waste materials derived from the use of such products;

(g) in case of homeopathic veterinary medicinal products, the statement "homeopathic veterinary medicinal product".

2. The information listed in paragraph 1 shall appear in easily legible and clearly comprehensible characters, or, where appropriate, abbreviations or pictograms common throughout the Union.

3. Where there is no outer packaging, all the particulars listed in paragraph 1 shall appear on the immediate packaging.

Article 11 Labelling of small immediate packaging units of veterinary medicinal products

By way of derogation from Article 9, small immediate packaging units shall contain only the following information:

(a) the name of veterinary medicinal product;

(b) the quantitative particulars of the active substances;

(c) the batch number, preceded by the word "Lot";

(d) the expiry date, in the format: "mm/yyyy", preceded by the abbreviation "Exp.".

Article 12 Package leaflet of veterinary medicinal products

1. The package leaflet shall be available for each veterinary medicinal product and shall contain at least the following information:

(a) the name or corporate name and permanent address or registered place of business of the marketing authorisation holder and of the manufacturer and, where applicable, of the representative of the marketing authorisation holder;

(b) the name of the veterinary medicinal product or, where applicable, a list of the names of the veterinary medicinal product, as authorised in different Member States;

(c) the strength and pharmaceutical form of the veterinary medicinal product;

(d) the target species, the dosage for each species, the method and route of administration and advice on correct administration, if necessary;

(e) the therapeutic indications;

(f) the contra-indications and adverse events in so far as this information is necessary for the use of the veterinary medicinal product;

(g) the withdrawal period, even if this is nil, in the event that the target species are food-producing animals;

(h) special storage precautions, if any;

(i) information essential for safety or health protection, including any special precautions relating to use and any other warnings;

(j) requirement to use take-back schemes for veterinary medicinal products for the disposal of unused veterinary medicinal products or waste materials derived from the use of such products and, if appropriate, additional precautions regarding hazardous waste disposal of unused veterinary medicinal products or waste materials derived from the use of such products;

(k) the marketing authorisation number;

(l) in case of generic veterinary medicinal products, the statement ‘generic veterinary medicinal product’;

(m) in case of homeopathic veterinary medicinal products, the statement "homeopathic veterinary medicinal product".

2. The package leaflet may bear additional information concerning distribution, possession or any necessary precaution in conformity with the marketing authorisation, provided that the information is not promotional. This additional information shall appear in the package leaflet clearly separated from the information referred to in paragraph 1.

3. The package leaflet shall be written and designed to be clear and understandable, in terms that are comprehensible to the general public.

Article 13 Package leaflet of homeopathic veterinary medicinal products

By way of derogation from Article 12(1), the package leaflet for homeopathic veterinary medicinal products registered in accordance with Articles 89 to 90 shall contain only the following information:

(a) the scientific name of the stock or stocks followed by the degree of dilution, using the symbols of the European Pharmacopoeia or, in the absence thereof, of the pharmacopoeias currently used officially in Member States;

(b) name and address of the marketing authorisation holder and, where appropriate, of the manufacturer;

(c) method of administration and, if necessary, route;

(d) the expiry date, in the format "mm/yyyy", preceded by the abbreviation "Exp.";

(e) pharmaceutical form;

(f) special storage precautions, if any;

(g) target species;

(h) a special warning if necessary for the medicinal product;

(i) the batch number, preceded by the word "Lot";

(j) registration number;

(k) withdrawal period, if applicable.

(l) the statement "homeopathic veterinary medicinal product".

Article 14 Languages

1. The language or languages of the information on the labelling shall be determined by Member State where the veterinary medicinal product is made available on the market.

2. Member States shall communicate the languages determined by them for the purpose of paragraph 1 to the Commission. The Commission shall make this information public.

3. Veterinary medicinal products may be labelled in several languages.

Article 15 Abbreviations and pictograms common throughout the Union

The Commission shall, by means of implementing acts, adopt a list of the abbreviations and pictograms common throughout the Union to be used for the purposes of Article 9(2) and Article 10(2). Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 145(2).

Section 5 Dossier requirements for generic, combination and hybrid veterinary medicinal products and for applications based on informed consent and bibliographic data

Article 16 Generic veterinary medicinal products

1. By way of derogation from Article 7(1)(b), an application for a marketing authorisation for a generic veterinary medicinal products shall not contain the documentation on safety and efficacy if all the following conditions are fulfilled:

(a) the application satisfies the requirements set out in Annex III;

(b) the applicant can demonstrate that the application concerns a generic veterinary medicinal product of a veterinary medicinal product which has been authorised by a Member State or by the Commission, and the period of protection of the technical documentation in respect of that reference veterinary medicinal product laid down in Articles 34 and 35 has elapsed or is due to elapse in less than 2 years (‘reference veterinary medicinal product’);

(c) documentation referred to in Article 7(1)(b) is available for the reference veterinary medicinal product to the competent authority or to the Agency.

2. For the purpose of this Section, where the active substance consists of salts, esters, ethers, isomers and mixtures of isomers, complexes or derivatives differing from the active substance used in the reference veterinary medicinal product, it shall be considered to be the same active substance as that used in the reference veterinary medicinal product, unless it differs significantly in respect of properties with regard to safety or efficacy. Where it differs significantly in respect of those properties, the applicant shall submit additional information in order to prove the safety and/or efficacy of the various salts, esters or derivatives of the authorised active substance of the reference veterinary medicinal product.

3. Where the reference veterinary medicinal product was not authorised in the Member State in which the application for the generic medicinal product is submitted, or the application is submitted in accordance with Article 38(3) where the reference medicinal product was authorised in a Member State, the applicant shall indicate in its application the Member State in which the reference veterinary medicinal product has been authorised.

4. The competent authority or the Agency may request information on the reference veterinary medicinal product from the competent authority of the Member State where it was authorised. Such information shall be transmitted to the requestor within 30 days of receipt of the request.

5. The summary of the product characteristics of the generic veterinary medicinal product shall be identical to that of the reference veterinary medicinal product. However, that requirement shall not apply to those parts of the summary of the product characteristics of the reference veterinary medicinal product that refer to indications or pharmaceutical forms which are still covered by patent law at the time when the generic veterinary medicinal product is authorised.

6. A competent authority or the Agency may require the applicant to provide safety data concerning the potential risks posed by the generic veterinary medicinal product to the environment in case the marketing authorisation for the reference veterinary medicinal product was granted before 20 July 2000 or in case the second phase environmental risk assessment was required for the reference veterinary medicinal product.

7. The Commission shall be empowered to adopt delegated acts in accordance with Article 146 concerning amendments to Annex III in order to adapt the requirements to technical and scientific progress.

Article 17 Combination veterinary medicinal products

By way of derogation from Article 7(1)(b) an application for a marketing authorisation for a veterinary medicinal product containing a combination of active substances that have each already been used in authorised veterinary medicinal products, but have not hitherto been authorised in that combination (‘combination veterinary medicinal product’) shall satisfy the following criteria:

(a) the application satisfies the requirements set out in Annex III;

(b) the applicant can demonstrate that the veterinary medicinal product is a combination of reference veterinary medicinal products as referred to in Article 16(1)(b);

(c) documentation referred to in Article 7(1)(b) is available for the reference veterinary medicinal products to the competent authority or to the Agency;

(d) documentation on the safety of that combination is provided.

Article 18 Hybrid veterinary medicinal products

1. By way of derogation from Article 16(1), the results of appropriate pre-clinical studies and clinical trials shall be required when the product does not meet all the characteristics of a generic veterinary medicinal product because:

(a) there are changes in the active substance(s), therapeutic indications, strength, pharmaceutical form or route of administration of the generic veterinary medicinal product compared to the reference veterinary medicinal product, or

(b) bioavailability studies cannot be used to demonstrate bioequivalence with the reference veterinary medicinal product, or

(c) there are differences relating to raw materials or in manufacturing processes of the biological veterinary medicinal product and the reference biological veterinary medicinal product.

2. The pre-clinical studies or clinical trials may be conducted with batches of reference products manufactured in the Union or in third countries.

When the batches are manufactured in third countries, the applicant shall demonstrate by state of the art analytical tests that the two reference products are so highly similar that they can substitute to each other in the clinical trials.

Article 19 Application based on informed consent

By way of derogation from Article 16(1)(b), an applicant for a marketing authorisation for a generic veterinary medicinal product shall not be required to provide the documentation on safety and efficacy if he demonstrates in the form of a letter of access that he is allowed to use the documentation on safety and efficacy referred to in Article 7(1)(b) which is available for the reference veterinary medicinal product.

Article 20 Application based on bibliographic data

1. By way of derogation from Article 7(1)(b), the applicant shall not be required to provide the documentation referred to therein if he demonstrates that the active substances of the veterinary medicinal product have been in well-established veterinary use within the Union for at least 10 years, that their efficacy is documented and that they provide an acceptable level of safety.

2. The application shall satisfy the requirements set out in Annex III.

Section 6 Dossier requirements for applications for limited market and in exceptional circumstances

Article 21 Reduced data requirements for applications for limited markets

1. By way of derogation from Article 7(1)(b), a marketing authorisation for a veterinary medicinal product intended for a limited market shall be granted although the quality and/or efficacy documentation required in accordance with Annex II has not been provided, if all the following conditions are met:

(a) the benefit of the immediate availability on the market of the veterinary medicinal product to the animal or public health outweighs the risk inherent in the fact that certain documentation has not been provided;

(b) the applicant provides the evidence that the veterinary medicinal product is intended for a limited market.

2. By way of derogation from Article 5(2), a marketing authorisation for a limited market shall be granted for a period of 3 years.

3. Where a medicinal product has been granted a marketing authorisation in accordance with this Article, the summary of product characteristics shall clearly state that only a limited assessment of quality and/or efficacy has been conducted due to the lack of comprehensive efficacy and/or quality data.

Article 22 Data requirements for applications in exceptional circumstances

1. By way of derogation from Article 7(1)(b), in exceptional circumstances related to animal or public health, where the applicant has demonstrated that for objective, verifiable reasons he is unable to provide the quality, safety and/or efficacy documentation required in accordance with Part 1, Part 2 and Part 3 of Annex II, a marketing authorisation may be granted subject to any of the following:

(a) a requirement to introduce conditions or restrictions, in particular concerning the safety of the veterinary medicinal product;

(b) a requirement to notify the competent authorities of any incident relating to the use of the veterinary medicinal product;

(c) a requirement to conduct post-authorisation studies.

2. By way of derogation from Article 5(2), a marketing authorisation in exceptional circumstances shall be granted for a period of 1 year.

3. Where a medicinal product has been granted a marketing authorisation in accordance with this Article, the summary of product characteristics shall clearly state that only a limited assessment of quality, safety and/or efficacy has been conducted due to the lack of comprehensive quality, safety and/or efficacy data.

Section 7 Examination of applications and granting of marketing authorisations

Article 23 Examination of applications

1. The competent authority or the Agency to which the application has been submitted in accordance with Article 6 shall:

(a) verify that the documentation submitted complies with the requirements laid down in Article 7(1) and is satisfactory for granting a marketing authorisation;

(b) assess the veterinary medicinal product regarding the quality, safety and efficacy documentation provided.

2. During the process of assessing applications for marketing authorisations for veterinary medicinal products containing or consisting of genetically modified organisms as referred to in Article 7(5), the necessary consultations shall be held by the Agency with the bodies set up by the Union or Member States in accordance with Directive 2001/18/EC.

Article 24 Requests to laboratories in the course of the examination of applications

1. The competent authority or the Agency examining the application may require an applicant to provide samples of the veterinary medicinal product to the Union reference laboratory, an Official Medicines Control Laboratory or a laboratory that a Member State has designated for that purpose to:

(a) test the veterinary medicinal product, its starting materials and if necessary intermediate products or other constituent materials in order to ensure that the control methods employed by the manufacturer and described in the application documents are satisfactory;

(b) verify, using samples provided by the applicant, that the analytical detection method proposed by the applicant for the purposes of safety tests and residue tests is satisfactory and suitable for use to reveal the presence of residue levels, particularly those exceeding the maximum residue level of the pharmacologically active substance established by the Commission in accordance with Regulation (EC) No 470/2009 and Commission Decision 2002/657/EC[25].

2. The time limits laid down in Articles 40, 44, 46 and 48 shall be suspended until the samples requested in accordance with paragraph 1 have been provided.

Article 25 Information on manufacturers

The competent authority shall ascertain that the manufacturers of veterinary medicinal products from third countries are able to manufacture the veterinary medicinal product concerned and/or carry out control tests in accordance with the methods described in the documentation submitted in support of the application in accordance with Article 7(1).

Article 26 Information to the applicant

The competent authority or the Agency to which the application has been submitted in accordance with Article 6 shall inform the applicant if the documentation submitted in support of the application is insufficient. The competent authority or the Agency shall request the applicant to provide the documentation within a given deadline. In such case the time limits laid down in Articles 40, 44, 46 and 48 shall be suspended until the deadline has elapsed.

Article 27 Withdrawal of applications

1. An applicant may withdraw his application for marketing authorisation submitted to a competent authority or the Agency at any time before the decision referred to in Article 31 or 32 has been taken.

2. If an applicant withdraws his application for marketing authorisation submitted to a competent authority or the Agency before the assessment of the application as referred to in Article 23 has been completed, the applicant shall communicate its reasons for doing so to the competent authority or the Agency to which the application