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
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