Commission directive 2003/63/EC
of 25 June 2003
amending Directive 2001/83/EC of the European Parliament and of the Council on the Community code relating to medicinal products for human use
(Text with EEA relevance)
THE COMMISSION OF THE EUROPEAN COMMUNITIES,
Having regard to the Treaty establishing the European Community,
Having regard to Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating medicinal products for human use(1), as last amended by Directive 2002/98/EC(2), and in particular Article 120 thereof,
Whereas:
(1) Every medicinal product for human use that is to be placed on the European Community market must be granted a marketing authorisation delivered by a competent authority. With the view to obtaining a marketing authorisation, an application dossier containing particulars and documents relating to the results of tests and trials carried out on this medicinal product must be submitted.
(2) The detailed scientific and technical requirements of Annex I to Directive 2001/83/EC need to be adapted to take account of scientific and technical progress and in particular of a large set of new requirements resulting from recent legislation. The presentation and content of the marketing authorisation application dossier have to be improved in order to facilitate the assessment and the better use of certain parts of the dossier which are common to several medicinal products.
(3) Within the framework of the International Conference on Harmonisation (ICH) a consensus was reached in 2000 to provide a harmonised format and terminology for a Common Technical Document through which a homogeneous organisation and presentation of a marketing authorisation application dossier for human medicinal products could be achieved. Standardised marketing authorisation dossier requirements should therefore be introduced in order to implement the Common Technical Document without delay.
(4) The standardised marketing authorisation dossier requirements (harmonised format) should be applicable to any type of medicinal product for human use, regardless of the procedure for the granting of the marketing authorisation. Some medicinal products present, however, such specific features that all the requirements cannot be fulfilled. To take account of these particular situations, a simplified dossier presentation should be provided for.
(5) The safety of biological medicinal products relies on rigorous control of their starting materials. Requirements for the suitability of human donors and the testing of donations of starting materials for plasma-derived medicinal products are laid down by Directive 2002/98/EC setting standards of quality and safety for the collection, testing, processing, storage and distribution of human blood and blood components and amending Directive 2001/83/EC. Article 109 of Directive 2001/83/EC has been amended. Plasma-derived medicinal products per se are biological medicinal products, the manufacture of which is based on the careful handling of human plasma as a starting material. To take account of the fact that the same plasma material is used in most cases for several medicinal products and, as a result, that a substantial part of the marketing authorisation dossier may be common to a great number of other dossiers for totally different plasma-derived medicinal products, it is appropriate to establish a new system aimed at simplifying procedures for both the approval of and subsequent changes to human plasma-derived medicinal products. To this end the concept of a plasma master file (PMF) should be introduced, in particular in order to allow the pooling of national expertise and through the coordination by the EMEA of a single evaluation. A PMF should serve as a stand-alone document, which is separate from the marketing authorisation dossier and through which a harmonised control of the relevant information regarding starting material used for the manufacture of plasma-derived medicinal products could be achieved. The PMF system should consist of a two-step assessment: first, an assessment of the PMF carried out at Community level, the result of which, i.e. a certificate of compliance with the Community legislation for each PMF, must be taken into account by any national competent authority, preventing them of any subsequent reassessment; second, an assessment of the finished plasma-derived medicinal product containing the modified part of the PMF (the two essential parts of the content, plasma origin and plasma quality-safety). This should remain the task of the competent authority that granted the marketing authorisation for the plasma-derived medicinal product.
(6) In the case of vaccines for human use, the same antigen may be common to several medicinal products (vaccines) and any change to that particular antigen, ipso facto, may impact, therefore, on several vaccines authorised by different procedures. In order to simplify the existing procedures for the assessment of such vaccines, both for the granting of a first marketing authorisation and for subsequent changes to it due to modifications to the manufacturing process and testing of individual antigens involved in combined vaccines, a new system based on the concept of a vaccine antigen master file (VAMF) should be introduced. This VAMF will allow the pooling of national expertise, and through the coordination by the EMEA, a single evaluation of the concerned vaccine antigen. The VAMF should serve as a stand-alone part of the marketing authorisation dossier and provide all relevant information of a biological and chemical nature related to one specific antigen, which constitutes one of the active substances of one or several combined vaccines.
(7) The VAMF system should consist of a two-step assessment: first, an assessment of the VAMF carried out at Community level, the result of which, i.e. a certificate of compliance with the Community legislation for each VAMF, must be taken into account by any national competent authority, preventing them from any subsequent reassessment; second, an assessment of the finished medicinal product (combined vaccine) containing the modified antigen which is the task of the competent authority that granted the combined vaccine marketing authorisation.
(8) Herbal medicinal products differ substantially from conventional medicinal products in so far as they are intrinsically associated with the very particular notion of herbal substances and herbal preparations. It is therefore appropriate to determine specific requirements in respect of these products with regard to the standardised marketing authorisation requirements.
(9) The treatment of various acquired and inherited pathological dysfunctions in humans calls upon novel concept-based approaches based on the development of biotechnology techniques. The latter involve the use of advanced therapy medicinal products based on processes focused on various gene-transfer-produced bio-molecules (gene therapy medicinal products) and manipulated or processed cells (cell therapy medicinal products) as active substances.
(10) In so far as they achieve their essential action through metabolic, physiological and immunological means to restore, correct or modify physiological functions in humans, these novel complex therapeutic products representing a new category of biological medicinal products in the sense of Articles 1 and 2 of Directive 2001/83/EC. The general principles already applicable to these products should be specified from a scientific and technical point of view and the specific requirements with regard to the standardised marketing authorisation requirements should be determined.
(11) Directive 2001/83/EC should be amended accordingly.
(12) The measures provided for in this Directive are in accordance with the opinion of the Standing Committee for Medicinal Products for Human Use,
HAS ADOPTED THIS DIRECTIVE:
Article 1
Directive 2001/83/EC is amended as follows:
a) in the second paragraph of Article 22 the words "Part 4 (G)" are replaced by the following:"Part II, point 6";
b) Annex I is replaced by the text in the Annex to this Directive.
Article 2
Member States shall bring into force the laws, regulations and administrative provisions necessary to comply with this Directive by 31 October 2003 at the latest. They shall forthwith inform the Commission thereof.
When Member States adopt those provisions, they shall contain a reference to this Directive or be accompanied by such a reference on the occasion of their official publication. Member States shall determine how such reference is to be made.
This Directive is applicable as from 1 July 2003.
Article 3
This Directive shall enter into force on the third day following that of its publication in the Official Journal of the European Union.
Article 4
This Directive is addressed to the Member States.
Done at Brussels, 25 June 2003.