France: Implementation of Directive 2004/27/EC on the Community Code relating to medicinal products for human use into French law

29 May 2007

Paule Drouault-Gardrat, Juliette Peterka

Directive 2004/27 dated 31 March 2004 amending Directive 2001/83 on the Community Code relating to medicinal products had to be implemented into French national law by 30 October 2005. Some provisions of Directive 2004/27 were partially implemented into the French Public Health Code by Law No. 2004-810 of 13 August 2004, Law No. 2004-806 of 9 August 2004 and Decree No. 2005-156 of 18 February 2005. Following Law No. 2007-248 of 26 February 2007, Directive 2004/27 has now been almost fully implemented into the French Public Health Code. The key new provisions introduced by Law 2007-248 are described below.

Law No. 2007-248 harmonises the definition of medicinal product to be identical to that used in Directive 2004/27. Article L.5111-1 of the French Public Health Code also specifies that, in case of doubt, where a product falls within the definition of a medicinal product and of other products, the product may be considered as a medicinal product.

Moreover, the Law clarifies the definition of a “generic medicinal product”. It refers to “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. A proprietary medicinal product can only be qualified as reference medicinal product if its marketing authorisation (MA) has been granted on the basis of a dossier containing all necessary data which are sufficient as such for its evaluation. The different salts, esters, ethers, isomers, mixtures of isomers, complexes or derivatives of an active substance shall be regarded to be the same active substance, unless they differ significantly in properties with regard to safety and/or efficacy. In such cases, additional information providing proof of the safety and efficacy of the various salts, esters or derivatives of an authorised active substance must be supplied by the applicant.” This definition is almost identical to the large definition provided by the Directive. Only the mention of the full dossier of the reference product has been added.

Law No. 2007-248 also introduces into the French Public Health Code definitions of “biological medicinal product” and “similar biological medicinal product” which are not, as such, defined in Directive 2004/27. A “biological medicinal product” is defined as any medicinal product whose active substance is produced from a biological source or is extracted from it and whose quality characterisation and determination require a combination of physicochemical and biological tests as well as the knowledge of its manufacturing process and of its control (Article L.5121-1 14° of the French Public Health Code).

A “similar biological product” is defined as any biological medicinal product with the same qualitative and quantitative composition in active substance and with the same pharmaceutical form as a reference biological medicinal product but which does not meet the conditions to be considered as a generic medicinal product owing to, in particular, differences relating to the variability of the raw materials or differences in manufacturing processes and requiring supplementary pre-clinical and clinical data with respect to conditions stated by way of regulation (Article L.5121-1 15° of the French Public Health Code). According to the French definition, a similar biological medicinal product cannot be substituted for the reference medicinal product. Indeed, similar biological medicinal products will not be registered in the Directory of Generics, which is a requirement to authorise substitution by pharmacists.

With regards the new data exclusivity period, the so-called “8+2+1” rule, Law No. 2007-248 provides in new Article L. 5121-10-1 that the generic product cannot be commercialised before the expiration of a period of 10 years after the grant of the initial marketing authorisation (“MA”) of the reference product. This Article also implements the additional one year protection for new therapeutic indications that, during the scientific evaluation prior to their authorisation, are held to bring a significant clinical benefit in comparison with existing therapies. Nevertheless, the first eight year period has not yet been implemented into the French Public Health Code. It will probably be implemented by the Implementing Decree that is currently being prepared.

The legal status of the MA is modified in order to reinforce medicinal products’ sanitary safety. A MA has to be delivered when a medicinal product is either “prepared industrially” or, following Law 2007-248, “manufactured by a method involving an industrial process”.

Renewal procedures have also been modified and once renewed, the MA shall be valid for an unlimited period unless the French Agency for Sanitary Safety of Health Products (“AFSSAPS”) decides to proceed with one additional five-year renewal on justified grounds relating to pharmacovigilance. Article 24 of Directive 2004/27 also provides that “any authorisation which within three years of its granting is not followed by the actual placing on the market of the authorised product in the authorising MemberState shall cease to be valid. When an authorised product previously placed on the market in the authorising MemberStateis no longer actually present on the market for a period of three consecutive years, the authorisation for that product shall cease to be valid”. These provisions will be implemented by the Implementing Decree.

Regarding the new provisions of advertising, Law No. 2007-248 specifies that advertising of medicinal products to the general public shall now be prohibited when they have to be used with the intervention of a medical practitioner for diagnostic purposes or for the prescription or monitoring of treatment.

With regards to professionals’ responsibility, Article L.3110-3 of French Public Health Code now extends the liability exoneration of health professionals, when the Minister of Health authorises, to face a serious health threat, the use of medicinal products outside the conditions stated in the MA, to medicinal products manufacturers and MA holders.

As mentioned above, the main provisions of Directive 2004/27 have now been implemented into French law. The Implementing Decree, currently in preparation, will complete the implementation of Directive 2004/27, for example, in relation to MA renewal and data exclusivity.

Finally, Law 2007-248 authorises the Government to make Orders to implement (i) Directive 2002/98 on “standards of quality and safety for the collection, testing, processing, storage and distribution of human blood and blood components”; (ii) Directive 2003/15 on cosmetic products; (iii) Directive 2004/23 on “standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells”; (iv) Directive 2004/24 on traditional herbal medicinal products; and (v) Directive 2004/28 on veterinary medicinal products. The first Order No. 2007-613 partially implementing these Directives was published on 26 April 2007. It contains measures on medicinal products for human use, dietetic foods, insecticides and miticides, dangerous chemical substances and preparations, and criminal offences. It will be followed by other Orders to complete the implementation the above mentioned Directives.