THE BIOGENERICS DEBATE

With $10 billion worth of branded biologics set to go off patent in 2006, many generics manufacturers are gearing up to produce generic biologicals. And looking at the broader pharmaceutical market, 42 blockbuster drugs will loose their patent in 2007, accounting for an astonishing $82 billion in sales. However, debate rages as to whether true equivalents of biological drugs can be produced. The situation is mainly two-sided – generics manufacturers versus drug originators – with the exception of Biogen, one of biotech’s leaders, which refutes the argument that different cell lines cannot produce equivalent drugs. This is because Biogen’s drug, Avonex®, was approved by FDA despite the fact that clinical trials were conducted with product produced from a different cell line than the one used to produce the current marketed product.

In the biotech camp, industry representatives agree that protein analysis techniques are not advanced enough yet to allow for a safe generic biological. Their argument is that manufacturing methods vary. Proteins may be produced by mammalian cells, yeast, E. coli, or even genetically-engineered plants. All of these organisms have a unique biological signature in the form of post-translational modifications. In particular, regulators are concerned that changes in surface carbohydrates could impact efficacy or cause immunogenicity. At the same time, there is no clear regulatory pathway for the approval of generic biologicals at this time.

On the other side of the fence, generics manufacturers use Biogen as an example to demonstrate that bioequivalence can be achieved using different cell lines to produce the same drug. Generics manufacturers also argue that if a change occurs in a protein, there is no reason why they couldn’t go back and find out why.

The truth probably lies somewhere in between these two schools of thought. Analytical techniques need to advance, but the right expertise and process can go a long way toward mitigating the risks of generic biologicals.
It is also important to consider that costs to produce generic biologicals will probably not be too much different than the original therapeutic, especially since generics manufacturers will likely have to conduct some clinical trials.
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