DRUG E VALUATION Thérapie 2008 Juillet-Août; 63 (4): 311–319 DOI: 10.2515/therapie:2008047 c  2008 Société Française de Pharmacologie et de Thérapeutique Generics and Substitution Modalities: Proposed Methods for the Evaluation of Equivalence, Traceability and Pharmacovigilance Reporting Véronique Lamarque 1 , Louis Merle 2 , Jean Paul Demarez 3 and the participants in Round Table N ◦ 7, Giens XXIII ⋆ 1 Direction Évaluation Santé, Sécurité et Gestion du Risque, Pfizer, Paris, France 2 Hôpital Dupuytren, Service de Pharmacologie et Toxicologie, Limoges, France 3 Direction Sécurité Médicament, Pierre Fabre Médicament, Boulogne, France Text received 18 July 2008 ; accepted 30 July 2008 Keywords: generic drugs; biosimilars drugs; traceability; pharmacovigilance; substitution Abstract – The use of generics results in savings for the budget of the health insurance, and no player of health could question seriously the principle. The generic drug of a reference medicinal product defines itself as a drug having the same qualitative and quantitative composition in active ingredients, the same dosage form and the bioequivalence with this reference medicinal product was demonstrated by appropriate studies of bioavailability. It is the right to switch granted to the pharmacists in 1999 that is at the origin of the real development of these specialities on the French pharmaceutical market. Nevertheless, about 10 years later, it seems that the system in place does not offer all the necessary securities with regard to the Pharmacovigilance, notably for the products with narrow therapeutic margin. By strengthening and/or by completing the role played by the health care professionals and the public institutions concerned, it is highly possible to improve the robustness of the system. Also, the recent arrival in Europe of the biosimilars, similar molecules but not bioequivalent to biological products cause an even more tricky specific situation, than that of the generics because of their nature, of the difficulty to manufacture them and of the risk of immunogenicity. If the substitution is not permitted in several European countries including France, the other issues can appear especially in case of interchangeability requiring also, the reinforcement of certain measures. The various aspects are described in this article with concrete proposals on how the current system can be made safer, both for the generics and the biosimilars. 1. Introduction Since they were first authorised in 1995, and particularly since the right to substitution was made legal in 1999, generic drugs, which are considered to be bioequivalent to their reference medicinal product, have increased in the French pharmaceuticals market, giving a key role to the retail pharmacist. Today in 2008, more than 10 years after they were first introduced, are there phar- macovigilance issues related to these medicinal products? This ar- ticle deals with the different aspects of this question and makes concrete proposals on how the current system can be made safer. ⋆ For a list of participants, see the end of the article. More recently, in 2006, the first biosimilar drugs appeared on the European market. These molecules are similar, but not bioe- quivalent, to biological products and the problems related to them are all the more complex because of their nature, since they are difficult to produce and highly dependant on the manufacturing processes, with even the slightest change notably in the proteins synthesised having the potential to induce immunogenicity. The first biosimilar products have just been launched on the market. Their substitution is not permitted either in France [1] or a number of other European countries but the situation is more ambiguous in other member states. At the present time, it is only possible to put forward warnings on this topic. Article published by EDP Sciences