The draft Directive contains the term "biogenerics", which is only vaguely defined. It proposes that, for drugs manufactured by biotechnology, the same substance manufactured by another biotech manufacturing process should not be considered a simple copy. This implies that the applicant would not be able to use the clinical originator clinical evaluation dossier and would therefore have to provide specific tests (preclinical studies, but also clinical trials).

Many drug manufacturing processes might be poorly reproducible, even from one batch to another (extraction from natural products, fermentation processes, etc.), or suffer from problems with residues (e.g. vaccine manufacturing).

But experience shows that new trials, with necessarily small populations and short follow-up, cannot prove that two versions of the same drug manufactured with different methods are identical or different. The results are always the same: the two versions have similar risk-benefit ratios and can be used for the same purposes.

Possible differences linked to the manufacturing process may only emerge after many years of use by large numbers of patients. For example, different manufacturing processes are suspected of being behind differences between epoetin preparations in terms of adverse effects such as erythroblastopenia, but this remains to be confirmed, and a further, small clinical trial would not have provided any relevant information.

Obliging biotech generics manufacturers to conduct new trials with falsely reassuring results would simply offer excessive protection to manufacturers of originator drugs. It would also imply the ethically questionable enrolment of patients who would derive no extra therapeutic benefit, and such trials would be a waste of financial and human resources.

What is needed is better post-marketing surveillance of adverse effects (of both generics and originator drugs) in order to detect possible differences linked to the manufacturing process and to protect the patients concerned. Active, prospective pharmacovigilance would help determine if certain types of generics warrant special assessment because of problems inherent in their manufacturing process. There are no sound data in this area, and it is thus premature to legislate.

©Medicines in Europe Forum 15 October 2003