Product Authorisation [EU]

Authorisation and supervision of medicinal products

European Medicines Agency

This Regulation improves the operation of the authorisation procedures for the placing of medicinal products on the market in the Community and amends certain administrative aspects of the European Medicines Agency. Thanks to these measures, all innovative and safe pharmaceutical products will be placed on the European market as soon as possible.

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].

With this Regulation, the European Union (EU) develops and improves the Community 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.

Scope

No medicinal product appearing in the Annex may be placed on the Community market without prior authorisation from the Community. 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 Community may be subject to a decentralised authorisation procedure, provided that the harmonisation achieved at Community 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 in accordance with, and within 15 days after 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.

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 Community 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 marketing authorisation is valid throughout the Community for five years. It may be renewed after five years and thus become valid for an unlimited period except when an additional five-year renewal is necessary. Authorised veterinary medicinal products are entered in the Community Register of Medicinal Products.

The refusal of a Community marketing authorisation constitutes a prohibition on the placing on the market of the medicinal product throughout the Community. 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 AND PHARMACOVIGILANCE

Given the emergence of new treatments and the increase in the size of the market to be monitored following the recent enlargements of the European Union, there is a need to improve some of the existing procedures and to make the pharmacovigilance and market surveillance system more efficient.

Supervision

The Regulation provides for increased market surveillance by reinforcing monitoring procedures. When the medicinal product has been manufactured in the Community, 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 to take account of technical and scientific progress in accordance with Directives 2001/83/EC and 2001/82/EC. 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.

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.

Pharmacovigilance

This Regulation expands the criteria for reporting adverse reactions. The Agency must receive all relevant information about suspected adverse reactions to authorised medicinal products. Where appropriate, the competent committees draw up opinions on the measures necessary, including amendments to the marketing authorisation. The holder of the marketing authorisation ensures that all suspected serious adverse reactions occurring within the Community or in a third country which are brought to his/her attention are recorded and reported promptly to Member States within the territory of which the incident occurred. Similarly, all Member States must ensure that all suspected serious adverse reactions occurring within their territory are recorded and reported to the Agency and the marketing authorisation holder.

The Regulation also makes provision for:

• increasing the frequency of the periodic safety update reports following the initial placing of the product on the Community market; the frequency then tails off gradually;
• extending the use of a guide containing the information collected;
• setting up a network for the electronic transmission of information to the authorities in the event of an alert relating to faulty manufacture or serious adverse reactions.

EMA

The European Medicines Agency is made up of different committees, including the Committee for Medicinal Products for Human Use, the Paediatric Committee, the Committee on Herbal Medicinal Products, the Committee for Advanced Therapies, a secretariat, an Executive Director 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 Community 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 Community marketing authorisation procedures and the scientific resources put at its disposal by Member States for the evaluation, supervision and pharmacovigilance of medicinal products;
• keeping, and transmitting on request, assessment reports and information on authorised medicinal products;
• disseminating information on adverse reactions to medicinal products authorised in the Community, by means of a database permanently accessible to all Member States;
• 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 Community and fees paid by undertakings for obtaining and maintaining Community marketing authorisations and for other services provided by the Agency. Provisions have been adopted to establish the circumstances in which SMEs may pay reduced fees, defer payment of the fee, or receive administrative assistance.

REFERENCES

Act	Entry into force – Date of expiry	Deadline for transposition in the Member States	Official Journal
Regulation (EC) No 726/2004 [adoption: codecision COD/2002/0252]	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 of 31.3.2009
Regulation (EC) No 470/2009	6.7.2009	–	OJ L 152 of 16.6.2009