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Authorisation and supervision of medicinal products - European Medicines Agency

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Authorisation and supervision of medicinal products - European Medicines Agency

This Regulation establishes the operation of European authorisation procedures for the placing of medicinal products on the market in the European Union (EU) and amends certain administrative rules applying to the European Medicines Agency. These measures aim to ensure that all innovative and safe pharmaceutical products are placed on the European market as soon as possible.

ACT

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 sets 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 is 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.

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 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, measures to improve the European pharmacovigilance system were required on several occasions.

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.

In addition, if the medicinal product is no longer to be sold in a Member State, either temporarily or permanently, the marketing authorisation holder must notify the European Medicines Agency. Except in exceptional circumstances, this notification must be provided at the latest two months before the interruption to the sale of the product is due to take place.

The holder must also immediately notify the Agency of any action taken to suspend sale of a medicinal product, withdraw a product from the market, request the withdrawal of the marketing authorisation or to not request renewal, indicating the reasons for this action. This also applies should the action take place in a third country.

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 a series of medicinal products, among them:

  • 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;
  • any biological medicinal product authorised after 1 January 2011.

Regarding medicinal products appearing on the list, the summary of product characteristics and the instructions must feature the following statement: this medicinal product is undergoing additional assessment. This statement must be preceded by a black symbol and followed by an explanation.

The list must include an electronic link to product information and the summary of the risk management plan.

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 and providing advice on the necessary measures to ensure that said medicinal products are safely and efficiently used, in particular by coordinating the evaluation and implementation of pharmacovigilance requirements and pharmacovigilance systems;
  • 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.

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

Regulation (EU) No 1027/2012

4.12.2012 (applicable from 5.6.2013, except certain provisions which will be applicable from 4.12.2012)

-

OJ L 316, 14.11.2012

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 Implementing Regulation (EU) No 198/2013 on the selection of a symbol for the purpose of identifying medicinal products for human use that are subject to additional monitoring [Official Journal L 65 of 8.3.2013].

The Regulation stipulates the characteristics of the black symbol designed for easy identification of medicinal products that are subject to additional monitoring for reasons of their specific safety profile. The selection made is an inverted equilateral black triangle. For medicinal products subject to additional monitoring and whose marketing authorisation was granted before 1 September 2013, this symbol must be included in the summary of product characteristics and the package leaflet, by 31 December 2013 at the latest. Medicinal products packaged and labelled before 1 January 2014 which do not include the symbol in the package leaflet may continue to be placed on the market and used until stocks are exhausted.

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].

Last updated: 11.11.2013

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