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Community code relating to veterinary medicinal products

Community code relating to veterinary medicinal products

Outline of the Community (European Union) legislation about Community code relating to veterinary medicinal products

Topics

These categories group together and put in context the legislative and non-legislative initiatives which deal with the same topic.

Food safety > Animal health

Community code relating to veterinary medicinal products

Document or Iniciative

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 [See amending acts].

Summary

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.

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 (EU) No 470/2009 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 (EU) No 470/2009 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 years 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 (EU) No 470/2009);
  • 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 versionis of documentary value only.

This summary is for information only. It is not designed to interpret or replace the reference document, which remains the only binding legal text.

Authorisation and supervision of medicinal products – European Medicines Agency

Authorisation and supervision of medicinal products – European Medicines Agency

Outline of the Community (European Union) legislation about Authorisation and supervision of medicinal products – European Medicines Agency

Topics

These categories group together and put in context the legislative and non-legislative initiatives which deal with the same topic.

Internal market > Pharmaceutical and cosmetic products

Authorisation and supervision of medicinal products – European Medicines Agency

Document or Iniciative

Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency [See amending acts].

Summary

With this Regulation, the European Union (EU) develops and improves European procedures for the authorisation, supervision and pharmacovigilance of medicinal products for human and veterinary use. The Regulation also provides the legal basis for the European Medicines Agency, which was established in 1993.

AUTHORISATION OF MEDICINAL PRODUCTS

Scope

No medicinal product appearing in the Annex may be placed on the European market without prior authorisation from the EU. The centralised authorisation procedure will be compulsory for:

  • medicinal products derived from biotechnology;
  • advanced therapy medicinal products;
  • orphan medicinal products;
  • medicinal products containing an entirely new active substance for which the therapeutic indication is the treatment of acquired immune deficiency syndrome, cancer, neurodegenerative disorder or diabetes, auto-immune diseases and other immune dysfunctions and viral diseases.

The centralised authorisation procedure will be optional for:

  • other medicinal products containing a new active substance;
  • medicinal products which constitute a therapeutic, scientific or technical innovation or are of interest at Community level.

Immunological veterinary medicinal products for the treatment of animal diseases that are subject to Community prophylactic measures may also be granted such authorisation. Finally, generic medical products of reference medicinal products authorised by the EU may be subject to a decentralised authorisation procedure, provided that the harmonisation achieved at European level is maintained.

Authorisation of medicinal products for human use

The Committee for Medicinal Products for Human Use is part of the European Medicines Agency. It is responsible for drawing up the opinion of the Agency on any matter concerning the evaluation of medicinal products for human use.

Each application for authorisation must be accompanied by the particulars and documents referred to in Directive 2001/83/EC on the Community code relating to medicinal products for human use, and by the fee payable to the Agency. It should also contain a statement to the effect that clinical trials carried out outside the European Union meet the principles of good clinical practice and the ethical requirements of Directive 2001/20/EC on good clinical practice in the conduct of clinical trials on medicinal products for human use.

Each authorisation decision must be taken on the basis of scientific criteria concerning the quality, safety and efficacy of the medicinal product concerned. These three criteria make it possible to assess the risk-benefit balance of all medicinal products. The Committee verifies first of all that conditions for granting a marketing authorisation are satisfied. If this is not the case, the applicant is informed forthwith and he/she may give notice to the Agency within fifteen days that he/she wishes to request a re-examination of the opinion.

In general, the Committee must give its opinion within 210 days after receipt of the application. This analysis may involve a test being conducted on the medicinal product, its starting materials or its intermediate products and a specific inspection of the manufacturing site of the medicinal product concerned.

Within 15 days after receipt of the opinion, the Commission prepares a draft of the decision on the application which may contain the marketing authorisation. If this draft decision is not in accordance with the opinion of the Agency, the Commission annexes an explanation of the reasons for the differences, which is forwarded to Member States and the applicant. The Commission takes a final decision following a procedure of consultation of the Member States (comitology) within 15 days of the end of the procedure.

After verification of the particulars and documents submitted, the marketing authorisation may be refused if:

  • the applicant has not properly or sufficiently demonstrated the quality, safety or efficacy of the medicinal product;
  • the particulars provided are incorrect.

At the time of authorisation, or once the marketing authorisation has been issued, the Agency may recommend that the Commission impose an obligation to carry out:

  • a post-authorisation safety study;
  • a post-authorisation efficacy study.

These obligations are contained in the authorisation and in the risk management system.

The marketing authorisation is valid for five years and may be renewed. Once it has been renewed, the marketing authorisation is valid for an unlimited period unless the Commission once again opts for a validity of five years.

Authorisation of medicinal products for veterinary use

The Committee for Medicinal Products for Veterinary Use is part of the Agency. It has sole responsibility for preparing the Agency’s opinions on all questions concerning the evaluation of veterinary medicinal products.

Most of the above considerations apply in this field, subject to adjustments relating to certain technical or scientific characteristics.

The marketing authorisation may be refused if:

  • the applicant has not properly or sufficiently demonstrated the quality, safety or efficacy of the medicinal product;
  • the product is presented for a use prohibited under European law;
  • the health and welfare of animals or consumer safety are not sufficiently taken into account in the case of zootechnical veterinary medicines and performance enhancers;
  • the withdrawal period indicated by the applicant is not long enough to ensure that foodstuffs obtained from treated animals do not contain residues which might constitute a health hazard for the consumer.

For both categories of medicinal products, if the products marketed are of major therapeutic interest, the applicant can request an accelerated assessment procedure.

The refusal of an EU marketing authorisation constitutes a prohibition on the placing on the market of the medicinal product throughout the EU. Any marketing authorisation which is not followed by the actual placing of the medicinal product on the market for three consecutive years ceases to be valid.

SUPERVISION OF MEDICINAL PRODUCTS (PHARMACOVIGILANCE)

Pharmacovigilance rules are necessary in order to protect public health and to prevent, detect and assess the undesirable effects of medicinal products for human use placed on the EU market, insofar as the safety profile of medicinal products can only be fully appreciated after products have been marketed. In the light of the knowledge obtained and following an assessment by the Commission of the EU pharmacovigilance system, it transpired that measures to improve the European pharmacovigilance system were required.

The Regulation provides for increased market surveillance by reinforcing monitoring procedures. When the medicinal product has been manufactured in the EU, the supervisory authorities are the competent authorities of the Member States which granted the manufacturing authorisation. In the case of medicinal products imported from third countries, the competent authorities are those that granted the import authorisation. These must inform the Committee for Medicinal Products and the Commission of all instances where the manufacturer or importer fails to fulfil the obligations laid down.

The holder of a marketing authorisation for a medicinal product for human or veterinary use is obliged to make any variations that may be required taking account of the manufacturing methods and of technical and scientific progress in accordance with Directives 2001/83/EC and 2001/82/EC.

The holder must also ensure that the medicinal product is manufactured and monitored according to generally accepted scientific methods. He/she must supply to the Agency, to the Commission and to the Member States any new information which might entail the variation of the particulars or documents they have obtained. He/she must also relay any prohibition or restriction imposed in countries in which the medicinal product is marketed, as well as any other information which might influence the evaluation of the benefits and risks of the medicinal product. The holder of the marketing authorisation must also forward the results of clinical trials or other studies. This information must be updated regularly on the basis of recent scientific knowledge.

When there are serious differences of opinion between Member States with respect to whether the holder of a marketing authorisation, a manufacturer or an importer satisfies the requirements set in Directives 2001/83/EC and 2001/82/EC, the Commission may request a new inspection of the marketing authorisation holder, the manufacturer or the importer.

Where urgent action is essential to protect human health or the environment, a Member State may suspend the use in its territory of an authorised medicinal product.

Risk management

The holders of marketing authorisations issued prior to 2 July 2012 are not obliged to implement a risk management system for each medicinal product.

However, the Agency may nevertheless impose upon the holder of a marketing authorisation an obligation to implement such a system if it detects risks that might modify the risk-benefit balance of an authorised medicinal product.

Obligations incumbent upon holders of marketing authorisations, Member States, the Agency and the Commission apply to safety notices concerning medicinal products for human use.

The Agency must draw up and update a list of medicinal products that are to be the subject of further monitoring. This list must give:

  • the name of and active substances contained in medicinal products authorised in the EU if such medicinal products contain a new active substance which, until 1 January 2011, was not contained in any medicinal product authorised in the Union;
  • the name of and active substances contained in any biological medicinal product authorised after 1 January 2011.

EudraVigilance database

The Agency has set up the EudraVigilance database, the aim of which is to collate pharmacovigilance information relating to medicinal products authorised in the EU and to make such information accessible to the competent authorities.

EudraVigilance collects information relating to the undesirable effects on humans arising following use, whether compliant or not, of medicinal products, or those which come to light during post-authorisation studies. On the basis of this information, the Agency prepares an annual report which is sent to the Commission, the European Parliament and the Council.

The Agency takes the following measures concerning medicinal products for human use that have been authorised by means of the centralised procedure:

  • monitoring the results of measures to minimise the risks outlined in risk management plans;
  • assessment of updates to risk management systems;
  • monitoring information contained in the EudraVigilance database.

Cooperation

The Agency collaborates with the World Health Organization (WHO) as regards pharmacovigilance, as well as with the European Monitoring Centre for Drugs and Drug Addiction.

It collaborates with the Member States on the international harmonisation and standardisation of technical measures related to pharmacovigilance.

PROVISIONS CONCERNING THE EUROPEAN MEDICINES AGENCY

The European Medicines Agency is made up of different committees, including the Committee for Medicinal Products for Human Use, the Pharmacovigilance Risk Assessment Advisory Committee, the Paediatric Committee, the Committee on Herbal Medicinal Products, the Committee for Advanced Therapies, a secretariat and a Management Board. Each Member State appoints one member and one alternate of the Management Board and one member and one alternate to the Committees. The members of each Committee may be accompanied by experts in specific scientific or technical fields.

The Agency is specifically responsible for:

  • providing the Member States and the EU institutions with the best possible scientific advice on any question relating to the evaluation of the quality, safety and efficacy of medicinal products for human or veterinary use which are referred to it;
  • coordinating the scientific evaluation of the quality, safety and efficacy of medicinal products which are subject to European marketing authorisation procedures and the scientific resources put at its disposal by Member States for the evaluation, supervision and pharmacovigilance of medicinal products;
  • coordinating the supervision of medicinal products for human use which have been authorised in the EU;
  • keeping, and transmitting on request, assessment reports and information on authorised medicinal products;
  • collecting and disseminating information on potential adverse reactions to medicinal products for human use authorised in the EU, by means of a database permanently accessible to all Member States;
  • assisting Member States with the rapid communication of information to health-care professionals;
  • creating a database on medicinal products which is accessible to the general public;
  • advising on the maximum limits for residues of veterinary medicinal products and biocidal products used in animal husbandry which may be accepted in foodstuffs of animal origin.

Each committee establishes a standing working party with the sole remit of providing scientific advice to businesses, particularly small and medium-sized enterprises (SMEs), during the research stage and when developing new therapies. The objective is to stimulate pharmaceutical research in Europe, and thus allow patients to benefit earlier from more effective medicinal products.

The Agency’s revenue consists of a contribution from the EU and fees paid by undertakings for obtaining and maintaining EU marketing authorisations and for other services provided by the Agency. SMEs may pay reduced fees, defer payment of the fee, or receive administrative assistance under certain conditions.

References

Act Entry into force Deadline for transposition in the Member States Official Journal

Regulation (EC) No 726/2004

20.5.2004

OJ L 136, 30.4.2004

Amending act(s) Entry into force Deadline for transposition in the Member States Official Journal

Regulation (EC) No 1901/2006

26.1.2007

OJ L 378, 27.12.2006

Regulation (EC) No 1394/2007

3.12.2007

OJ L 324, 10.12.2007

Regulation (EC) No 219/2009

20.4.2009

OJ L 87, 31.3.2009

Regulation (EC) No 470/2009

6.7.2009

OJ L 152, 16.6.2009

Regulation (EU) No 1235/2010

1.1.2011 (applicable from 2.7.2012)

OJ L 348, 31.12.2010

Subsequent amendments and corrections to Regulation (EC) No 726/2004 have been incorporated in the basic text. This consolidated version  has a purely documentary value”.

Related Acts

Commission Regulation (EC) No 658/2007 of 14 June 2007 concerning financial penalties for infringement of certain obligations in connection with marketing authorisations granted under Regulation (EC) No 726/2004 of the European Parliament and of the Council [Official Journal L 155 of 15 June 2007].

This Regulation lays down rules concerning the application of financial penalties to the holders of marketing authorisations who infringe certain obligations. It provides for two types of financial penalties: fines and periodic penalty payments.

Commission Regulation (EC) No 507/2006 of 29 March 2006 on the conditional marketing authorisation for medicinal products for human use falling within the scope of Regulation (EC) No 726/2004 of the European Parliament and of the Council [Official Journal L 92 of 30 March 2006].

Commission Regulation (EC) No 2049/2005 of 15 December 2005 laying down, pursuant to Regulation (EC) No 726/2004 of the European Parliament and of the Council, rules regarding the payment of fees to, and the receipt of administrative assistance from, the European Medicines Agency by micro, small and medium-sized enterprises [Official Journal L 329 of 16 December 2005].

Residues of veterinary medicinal products in foodstuffs of animal origin

Residues of veterinary medicinal products in foodstuffs of animal origin

Outline of the Community (European Union) legislation about Residues of veterinary medicinal products in foodstuffs of animal origin

Topics

These categories group together and put in context the legislative and non-legislative initiatives which deal with the same topic.

Internal market > Pharmaceutical and cosmetic products

Residues of veterinary medicinal products in foodstuffs of animal origin

Document or Iniciative

Regulation (EC) No 470/2009 of the European Parliament and of the Council of 6 May 2009 laying down Community procedures for the establishment of residue limits of pharmacologically active substances in foodstuffs of animal origin, repealing Council Regulation (EEC) No 2377/90 and amending Directive 2001/82/EC of the European Parliament and of the Council and Regulation (EC) No 726/2004 of the European Parliament and of the Council (Text with EEA relevance).

Summary

This Regulation aims at defining the rules and procedures to be applied when setting maximum residue limits for medicinal products in foodstuffs of animal origin in order to guarantee food safety.

Scope

This Regulation establishes on the one hand the maximum concentration of a residue of a pharmacologically active substance which may be permitted in foodstuffs of animal origin and on the other defines the level of residues of medicinal products for which a maximum limit has not yet been set.

Active principles of biological origin used in immunological veterinary medicinal products and substances covered by the Regulation on contaminants in foodstuffs for human consumption are excluded from its scope.

Maximum residue limits

Substances intended for use in veterinary medicinal products

The European Medicines Agency issues an opinion on any application relating to a pharmacologically active substance intended for use in veterinary medicinal products. This opinion consists of a scientific risk assessment and risk management recommendations. The Agency ensures that the final opinion of the Committee is given within 210 days.

Other substances requiring an opinion from the Agency

The European Commission or Member States may submit to the Agency a request for an opinion on maximum residue limits in the following cases:

  • the use of the substance in question is authorised in a third country but has not been subject to an application for the establishment of a maximum residue limit by the Agency;
  • the substance in question is contained in a medicinal product but has not been subject to an application for the establishment of a maximum residue limit by the Agency.

The Agency shall ensure that the opinion of the Committee concerning a relevant request from the European Commission or Member States is given within 210 days.

Once the opinions have been published, the Commission, in consultation with the Agency, Member States and interested parties, shall adopt the following measures:

  • methodological principles to be applied following the risk assessment and recommendations described above;
  • rules concerning the use of a maximum residue limit for medicinal products.

Classification

The Commission classifies the pharmacologically active substances which have already been subject to an opinion from the Agency. This classification includes a list of pharmacologically active substances and the therapeutic classes to which they belong, as well as the following:

  • a maximum residue limit;
  • a provisional maximum residue limit (for a period not exceeding five years);
  • the absence of the need to establish a maximum residue limit;
  • a prohibition on the administration of a substance.

A maximum residue limit may be provided if scientific data is incomplete, as long as the substance does not constitute a hazard to human health. It is presupposed that the residues do not constitute a hazard to the health of individuals.

It is possible to obtain an emergency authorisation for a veterinary medicinal product or biocide product by making an application to the Agency to carry out an accelerated procedure for the assessment of the maximum residue limit. The Agency shall ensure that the final opinion of the Committee is given within 120 days.

Reference points for action

The Commission can establish reference points for action for residues of pharmacologically active substances which are not classified.

Reference points for action are established in consultation with official control laboratories in accordance with a method corresponding to Community requirements.

A request for a risk assessment may be sent to the European Food Safety Authority (EFSA) in order to determine whether the reference points for action are adequate.

Various provisions

The Agency consults Community reference laboratories using analytical methods which are appropriate for analysing residues. The aim of this consultation is also to achieve harmonised controls in order to provide information on the methods used during the authorisation procedure for official control laboratories.

When placed on the market, foodstuffs of animal origin which contain residues of medicinal products at a level exceeding the limit established by this Regulation or containing an unclassified substance are not considered as complying with the legislation.

This Regulation repeals Regulation (EC) No 2377/90. The Commission includes pharmacologically active substances and their classification from Regulation (EC) No 2377/90 in Annexes I to IV.

References

Act Entry into force Deadline for transposition in the Member States Official Journal
Regulation (EC) No 470/2009

6.7.2009

OJ L 152 of 16.6.2009

Related Acts

Commission Regulation (EU) No 37/2010 of 22 December 2009 on pharmacologically active substances and their classification regarding maximum residue limits in foodstuffs of animal origin [Official Journal L 15 of 20.1.2010].