Veterinary Products [EU]

Table of Contents

Community code relating to veterinary medicinal products

The European Union has combined in a single act all current legal provisions on production, marketing, distribution and use of veterinary medicinal products.

Directive 2001/82/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to veterinary medicinal products

Summary

The Directive replaces and consolidates in a single act the following:

directive 81/851/EECon the general conditions for placing veterinary medicinal products on the market and subsequent amendments (90/676/EEC, 90/677/EEC, 92/74/EEC, 93/40/EEC and 2000/37/EEC);
directive 81/852/EECon the additional conditions for placing veterinary medicinal products on the market and subsequent amendments (87/20/EEC, 92/18/EEC, 1999/104/EEC).
These Directives and subsequent amendments to them are repealed.

The Community code relating to veterinary medicinal products will therefore include all the existing provisions governing the production, placing on the market, distribution and use of veterinary medicinal products.

The Directive is divided into eleven titles: definitions; scope; marketing; manufacture and imports; labelling and package insert; possession; wholesale distribution and dispensing; pharmacovigilance; supervision and sanctions; standing committee; general provisions and final measures.

Scope

The code will apply to all veterinary medicinal products, with the exception of:

medicated feedingstuffs;
inactivated immunological medicinal products which are manufactured from pathogens obtained from an animal from the same holding;
medicinal products prepared in a pharmacy in accordance with a “magistral” or “official” formula;
medicinal products based on radioactive isotopes;
certain additives incorporated into animal feeding stuffs.

To take better account of the emergence of new therapies, such as cell therapies, the definition of veterinary medicinal product was amended in 2004.

Marketing authorisation

No veterinary medicinal product (with the exception, under certain conditions, of those for aquarium fish, cage birds, homing pigeons, terrarium animals and small rodents) may be placed on the European Union (EU) market without a marketing authorisation. In exceptional cases, where required by the health situation or in the event of a serious disease epidemic, derogation from this principle may be permitted.

Medicinal products intended for food producing species may only be granted a marketing authorisation if the active substances they contain are listed in Regulation (EEC) No 2377/90 on residue limits of veterinary medicinal products in foodstuffs of animal origin . By way of derogation, medicinal products containing active substances not covered by these provisions may be authorised for equidae which are not intended for human consumption.

No veterinary medicinal product may be administered to animals unless a marketing authorisation has been issued, except for the purpose of product testing.

Where there is no medicinal product for a condition, Member States may exceptionally, in order to avoid causing unacceptable suffering to the animals concerned, permit the administration to non-food producing animals of:

veterinary medicinal products authorised for use for another condition or with another animal species;
medicinal products for human use;
veterinary medicinal products prepared extemporaneously.

Additional conditions apply where such medicinal products are administered to food-producing animals. In particular, the active substances in these medicinal products must be listed in Regulation (EEC) No 2377/90 and a minimum waiting time must be observed.

The authorisation is issued by the competent authority of the Member State concerned or, where the centralised procedure established by Regulation (EEC) No 726/2004 applies, by the European Agency for the Evaluation of Medicinal Products (“the Agency”). A marketing authorisation may only be granted to an applicant established in the EU.

Various particulars must be appended to the application for a marketing authorisation (composition and characteristics of the medicinal product, manufacturing method, therapeutic indications, contra-indications and adverse reactions, indication of the withdrawal period in order to limit the level of product residues in foodstuffs, control methods, results of toxicological and pharmacological tests and clinical trials, copy of any marketing authorisation or refusal of marketing authorisation issued in another Member State, etc.).

There are derogations to the requirement to provide certain information with the request for marketing authorisation, such as the law relating to the protection of industrial and commercial property. For example:

Applicants are not obliged to provide the results of safety tests, residue tests, pre-clinical trials and clinical trials if they can show that the medicinal product is a generic * of a medicinal product which has been authorised under this legislation for at least 8 months in the EU. Furthermore, a period of 10 years from the authorisation of the reference medicinal product * must be observed before a generic medicinal product can be marketed. This period is extended to 13 years in the case of medicinal products intended for certain species, particularly fish and bees;
Applicants are not obliged to provide the results of safety tests, residue tests, pre‑clinical trials or clinical trials if they can show that the active substances in the medicinal product have been in well-established veterinary use in the EU for at least 10 years, that their efficacy is recognised and that they demonstrate an acceptable level of safety.

The documents and particulars supplied to the competent authorities must be drafted by experts with the requisite qualifications and analyses must be carried out in accordance with the guidelines in Annex 1.

Particular provisions applicable to homeopathic veterinary medicinal products

Member States may apply a special simplified registration procedure to homeopathic veterinary medicinal products (including homeopathic veterinary medicinal products intended for food-producing animals), provided they meet the following criteria:

the route of administration must be that described in the pharmacopoeias currently used officially in the Member States;
no specific therapeutic indication must appear on the labelling or in any information relating to the medicinal product;
there is a sufficient degree of dilution to guarantee the safety of the medicinal product.

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

Member States may introduce or retain specific rules for the testing of homeopathic veterinary medicinal products intended for pet animals and exotic species which are non food-producing. In this case, they must notify the Commission of the specific rules in force.

Procedure for marketing authorisation

The marketing authorisation procedure must be completed within 210 days.

Any request for authorisation in more than one Member State must be made in accordance with the centralised authorisation procedure (see below “Authorisations in more than one Member State and mutual recognition”). Thus, Member States must refuse to examine authorisation requests where an initial request is already being examined in another Member State.

If a single request is made, the competent authority of the Member State where it is made:

must check the information sent by the applicant;
may submit the medicinal product to an official laboratory test and require the applicant to provide further information or substances for testing.

Member States must ensure that manufacturers and importers of veterinary medicinal products from third countries also comply with the Community provisions.

The competent authority must inform the applicant of its decision to issue a marketing authorisation and draw up an assessment report on the dossier. This report must be updated whenever new information becomes available concerning the quality, efficacy or safety of the product.

Exceptionally, and for objective and verifiable reasons, the marketing authorisation may be subject to certain obligations as regards labelling, packaging, notification, etc.

Holders of a marketing authorisation must make any changes needed to ensure that the product is always manufactured and checked by means of up-to-date and generally accepted scientific methods. These changes are subject to the approval of the competent authority of the Member State concerned.

Furthermore, holders must notify the competent authority of certain relevant information concerning the medicinal product (the dates on which marketing begins and ends, expected changes to information provided to users etc.).

In the event of changes to the terms of marketing authorisations, the Commission adopts provisions by means of an implementing Regulation.

The marketing authorisation is valid for a renewable period of five years. After this period, it may be renewed for an unlimited period unless the competent authority decides only to renew it for a further five years.

An authorisation ceases to be valid if:

the relevant product is not actually placed on the market within three years;
an authorised medicinal product is no longer actually present on the market for a period of three years.

Authorisation will be refused if it is established that:

the risk-benefit balance of the veterinary medicinal product is not favourable (safety criterion);
it has no therapeutic effect or there is insufficient proof of such effect (efficacy criterion);
its qualitative and quantitative composition is not as declared (quality criterion);
the withdrawal period recommended by the applicant is not long enough to ensure that the level of residue in foodstuffs is sufficiently low;
the labelling or package leaflet is not in compliance with the relevant legislation;
the product is offered for sale for a prohibited use;
it presents a risk for public, consumer or animal health.

Authorisations in more than one Member State and mutual recognition

Marketing authorisation in more than one Member State may be given in two ways: either an application for authorisation is made in several countries at the same time, or the holder of an authorisation asks for this authorisation to be recognised in other countries:

when the same application is made in more than one Member State, the dossier filed in each of the Member States concerned must be identical. This dossier should comply with the standard authorisation procedure (see “Procedure for marketing authorisation” above) and contain the list of countries in which the application is made. The applicant nominates one Member State to act as “reference Member State”. This Member State is given the task of preparing the assessment report for the medicinal product and a draft labelling leaflet within 120 days. It then sends these to the other Member States concerned which have 90 days in which to comment.
when a medicinal product has already been authorised, the holder of the authorisation asks the Member State (or one of the Member States if there are several) to send the assessment report, which has been updated if necessary, to the other Member States concerned. They then have 90 days in which to decide whether they recognise this authorisation.

If there is disagreement between one of the Member States concerned and the reference Member State, particularly if one of them considers that the medicinal product poses a risk for human or animal health or for the environment, a conciliation procedure is organised between the Member States concerned. They have 60 days in which to reach an agreement. If no solution has been found by this deadline, the matter is referred to the Committee for Medicinal Products for Veterinary Use. This Committee then has 60 days (which can be extended by up to 90 days) in which to issue a reasoned opinion.

The applicant is entitled to appeal against the Committee’s opinion.

The Member States, the Commission and the holder of the marketing authorisation are notified by the Agency of the Committee’s final opinion.

The Commission takes a final decision on the application under the “regulatory procedure”. It is assisted by the Standing Committee on Veterinary Medicinal Products for the Adaptation to Technical Progress of the Directives on the Removal of Technical Barriers to Trade in the Veterinary Medicinal Products Sector (“the Standing Committee”).

In specific cases where the interests of the Community are involved, the application may be sent directly to the Committee for Medicinal Products for Veterinary Use.

Any application to vary a marketing authorisation must be submitted to all the Member States which have previously authorised the product concerned. In the event of disagreement, the Member States may institute a conciliation procedure (as described above).

Where a Member State considers that alteration, suspension or withdrawal of an authorisation is necessary to protect human or animal health or the environment, it shall forthwith refer the matter to the Agency for application of the conciliation procedure described above.
Pending a final decision, a Member State may, in exceptional and urgent cases, suspend the marketing and use of a veterinary medicinal product.

The Agency will publish an annual report on the application of the mutual recognition procedures. At least every ten years, the Commission must present a detailed report on the procedures, where necessary suggesting changes.

Manufacture and import

The Member States must make subject to the holding of an authorisation:

total or partial manufacture of the veterinary medicinal products and the various processes of dividing up, packaging or presentation (unless these processes are carried out by pharmacists for retail supply);
importing of veterinary medicinal products.

Applicants for manufacturing or import authorisations must have suitable premises and equipment and at least one qualified person (as defined in the Directive).

Before issuing the manufacturing or import authorisation, the competent authority of the Member State concerned must establish the accuracy of the particulars supplied by the applicant.

The authorisation granting procedure must not exceed 90 days (30 days for applications to amend an authorisation). This deadline may be suspended where the applicant has been asked to supply further information.

The holder of an authorisation is bound by certain obligations concerning staff, information, controls and premises and must keep detailed records of all veterinary medicinal products supplied by him. These records, and the holders’ premises, must be accessible to the competent authorities. He must also comply with the principles and guidelines of good manufacturing practices for medicinal products laid down in Directive 91/412/EEC.

The Commission (or, where applicable, the Council) is to adopt guidelines of good manufacturing practice for veterinary medicinal products.

Labelling and package leaflet

The containers and outer packages of veterinary medicinal products must carry specific information, viz.:

the name and composition of the product;
the manufacturer’s batch number and the marketing authorisation number;
the name or corporate name and address of the market authorisation holder or the manufacturer;
the species of animal for which the product is intended;
the withdrawal period for medicinal products for food-producing animals;
the expiry date;
any special precautions;
the words “For animal treatment only”.

In the case of ampoules, certain information on the outer packaging must also be given on the ampoules themselves. Where there is no outer packaging, all the particulars must be shown on the container.

The packaging of the veterinary medicinal product must contain an insert carrying the same information as on the packaging.

Non-observance of these labelling and package insert requirements may lead to the suspension or withdrawal of the marketing authorisation.

The labelling and package inserts of homeopathic veterinary medicinal products must be marked with the words “homeopathic veterinary medicinal product without approved therapeutic indications” and:

the scientific name of the stocks and the degree of dilution;
the name and address of the marketing authorisation holder;
the method of administration;
the expiry date;
the pharmaceutical form and capacity;
any special precautions;
target species;
the manufacturer’s batch number and registration number.

Possession, wholesale distribution and dispensing

Wholesale distribution of veterinary medicinal products is subject to the holding of an authorisation. The authorisation granting procedure must take no longer than 90 days.

In order to obtain an authorisation for distribution, the applicant must have suitable staff, premises and equipment.

The holder of the authorisation shall have an emergency plan which makes it possible to recall the product.

The holder of the authorisation must keep detailed records of each incoming or outgoing transaction. These records must be kept available for inspection by the competent authorities for at least three years.

The same requirement to keep detailed records applies to retailers. Member States must ensure that retail supply is carried out only by persons permitted to do so under their national legislation.

A prescription is required for dispensing to the public certain medicinal products specified in the Directive:

products subject to official (international or European) restrictions;
medicinal products for food-producing animals;
products in respect of which special precautions must be taken to avoid risks to animals, humans or the environment;
products which require a precise prior diagnosis or which may interfere with diagnosis or therapeutic measures;
official formulae * intended for food-producing animals;
new veterinary medicinal products containing active substances which have been authorised for less than five years.

Specific obligations apply to the possession of and keeping of records on medicinal products with anabolic, anti-infectious, anti-parasitic, anti-inflammatory, hormonal or psychotropic properties.

Under certain conditions, veterinarians providing services in another Member State can take with them small quantities of ready-made veterinary medicinal products (other than immunological products) even if they are not authorised for use in the Member State concerned.

Member States may prohibit the manufacture, import, possession, sale, supply or use of immunological medicinal products if they can show that:

the use of these products will interfere with a national disease eradication programme; or
the disease for which the medicinal product is intended is largely absent from their country.

Pharmacovigilance

Member States are expected to encourage the reporting of adverse effects to the competent authorities.

They must establish a pharmacovigilance system to collect all useful information on veterinary medicinal products, with particular reference to adverse reactions in animals. This information is to be collated with data on consumption and on the misuse or serious abuse of veterinary medicinal products.

The marketing authorisation holder must appoint an appropriately qualified person responsible for pharmacovigilance. This person must be resident in the European Union and is responsible for managing an information system on adverse reactions and for providing information to the competent authorities.

The authorisation holder must:

report any suspected serious adverse reaction to the competent authority (within 15 days);
keep detailed records on any other adverse reaction. These records must be submitted to the competent authorities at regular intervals.

Member States must ensure that reports of suspected adverse reactions are brought to the attention of the Agency and the authorisation holder (within 15 days).

The Commission is to draw up guidelines on the adverse reaction notification system.

Where, on the basis of an adverse reaction report, the competent authority of a Member State considers that a marketing authorisation should be altered, suspended or withdrawn, it must forthwith inform the Agency and the authorisation holder. In the event of urgency, the competent authority may suspend the marketing of the veterinary medicinal product concerned.

Monitoring and sanctions

The competent authority may inspect manufacturing and trading establishments and laboratories to ensure that the legal requirements are complied with, including those of manufacturers established in a third country.

Following such an inspection, the officials representing the competent authority report on whether the principles of good manufacturing practice are being complied with. The manufacturers concerned are informed of the content of such reports.

Holders of marketing authorisations for immunological medicinal products must ensure that representative samples are available for tests. Member States may, if they consider it necessary, require these samples to be submitted to an approved laboratory for testing before being placed on the market.

The competent authorities of the Member States shall suspend or withdraw marketing authorisation when it is clear that:

the product proves to be very harmful;
it lacks therapeutic efficacy;
its qualitative and quantitative composition is not as declared;
the recommended withdrawal period is inadequate;
the product is offered for sale for a prohibited use;
the information given is incorrect;
the required tests have not been carried out.

The marketing authorisation may also be suspended, withdrawn or amended where:

certain necessary changes have not been made to the information in the product dossier;
new information has not been communicated to the competent authorities.

Member States must take all necessary measures to ensure that supply of a veterinary medicinal product is prohibited in the following cases:

the product proves to be very harmful;
it lacks therapeutic efficacy;
its qualitative and quantitative composition is not as declared;
the recommended withdrawal period is inadequate;
the required tests have not been carried out.

The manufacturing authorisation is withdrawn if the requirements valid at the time of application (suitable premises and equipment and at least one qualified person as defined in the Directive) are no longer met.

Member States must take measures to encourage veterinarians or other professionals concerned to report any adverse reaction to medicinal products to the competent authorities.

General provisions

The competent authorities in the Member States are bound by a mutual information obligation. Where there is a serious difference in opinion in respect of a report drawn up following an inspection, the Member States concerned must inform the Commission. The Commission may then ask for a new inspection.

Member States must ensure that the Agency is informed of all decisions concerning marketing authorisations applications.

Marketing authorisation holders must notify the Member States forthwith of any action taken to withdraw or suspend the marketing of a veterinary medicinal product. The Member States are responsible for ensuring that this information is brought to the attention of the Agency and, in the case of products exported to third countries, to the relevant international organisations.

The general mutual information obligation also applies to homeopathic medicinal products.

At the request of a manufacturer or exporter of veterinary medicinal products or of an importing country, Member States will certify that the manufacturer in question holds an authorisation.

Decisions to grant or revoke a marketing authorisation shall be made publicly available.

Member States will not permit foodstuffs for human consumption to be taken from test animals, unless:

maximum residue limits have been established (in accordance with Regulation (EC) No 2377/90);
a minimum withdrawal period has been established.

Member States shall set up appropriate collection systems for veterinary medicinal products that are unused or expired.

Two annexes are attached to the Community code:

Annex I on the requirements and analytical protocol, safety tests, pre-clinical and clinical, for tests of veterinary medicinal products;
Annex II listing the Directives repealed by this Directive, together with their successive amended versions.

Background

In November 2001, the Commission presented an important revision of Community legislation on pharmaceutical products. This “legislative package”, which was adopted in March 2004, consists of three instruments:

a regulation amending Community procedures for the authorisation, supervision and pharmacovigilance of medicinal products for human and veterinary use and establishing a European Medicines Agency;
a directive amending the Community code relating to medicinal products for human use;
a directive amending the Community code relating to veterinary medicinal products, which is the subject of this factsheet.

Key terms

· Generic medicinal product: a medicinal product which has the same qualitative and quantitative composition in active substances and the same pharmaceutical form as the reference medicinal product, and whose bioequivalence with the reference medicinal product has been demonstrated by appropriate bioavailability studies.

· Reference medicinal product: a medicinal product authorised in accordance with these regulations;

· Official formulae: medicinal products prepared in a pharmacy in accordance with the prescriptions of a pharmacopoeia and intended to be supplied directly to the end-user

REFERENCES

Act	Entry into force	Deadline for transposition in the Member States	Official Journal
Directive 2001/82/EC	18.12.2001	–	OJ L 311 of 28.11.2001

Amending act(s)	Entry into force	Deadline for transposition in the Member States	Official Journal
Directive 2004/28/EC	30.4.2004	30.10.2005	OJ L 136 of 30.4.2004
Directive 2009/53/EC	20.7.2009	20.1.2009	OJ L 168 of 30.6.2009
Regulation No 470/2009/EC	6.7.2009	–	OJ L 152 of 16.6.2009
Regulation No 596/2009/EC	7.8.2009	–	OJ L 188 of 18.7.2009

The successive amendments and corrigenda to Directive 2001/82/EC have been incorporated into the basic text. This consolidated version is of documentary value only.

AMENDMENT OF ANNEXES

Annex I – Chemical, pharmaceutical and analytical standards, safety and residue tests, pre-clinical and clinical trials in respect of testing of veterinary medicinal products
Directive 2009/9/EC [Official Journal L 44 of 14.2.2009].

RELATED ACTS

Commission Regulation (EC) No 1234/2008 of 24 November 2008 concerning the examination of variations to the terms of marketing authorisations for medicinal products for human use and veterinary medicinal products (Text with EEA relevance).