The hot-button issue is how much pre-clinical and clinical
data a
generics manufacturer should have to collect to document that a
follow-on product is equivalent to a drug from an innovator firm.
Although pharmacokinetic (PK) testing may be sufficient to document
bioequivalence and therapeutic equivalence for small molecules,
pharmaceutical companies maintain that more data from clinical trials
are necessary to ensure the safety and efficacy of protein products.
Innovators acknowledge that full product characterization is critical
for documenting sameness, but that clinical trials and documented
compliance with good manufacturing practices (GMPs) also are needed for
a manufacturer to bring a follow-on biologic to market. At the February
workshop, Amgen noted that it plans to conduct fairly large clinical
trials for its products undergoing manufacturing process changes to
ensure that a change in cell line does not produce adverse reactions or
other safety problems.
The European Medicines Agency (EMEA) appears to agree with the
innovator position. Even though some Eastern European generics firms
have produced and marketed equivalent biotech therapies, EMEA stated in
a November 2004 policy document that because of the complexity of
biological products, “the generic approach is scientifically not
appropriate.”
Generics makers argue that no one-size-fits-all testing approach is
appropriate because biopharmaceuticals have a broad range of
complexity. Protein products with a long history of patient use and
multiple manufacturers should be able to gain market approval on the
basis of product characterization plus pharmacodynamic studies that
document bioequivalence. Additional clinical studies should be required
only when there is still uncertainty about product comparability
remains even after analytical and bioequivalence studies, and some kind
of abbreviated regulatory pathway should be possible even for
more-complex products. (continued)
