January 1, 1970 (Vol. , No. )

Michael S. Koeris

The quick answer here up front for all those fans of instant gratification: not very! That hasn’t stopped industry players like Astra-Zeneca, the Anglo-Swedish pharmaceuticals group, from looking at developing lower-cost versions of its rivals’ expensive biological medicines as soon as they go off patent.

They aren’t alone as Pfizer, Merck, and others have recently ramped up in-house biosimilar efforts as well. The action signals increasing concern that there may not be sufficient innovative new drugs in companies’ pipelines to offset existing products coming off patent over the next few years and a desire to generate alternative sources of income.

Why is it that for something that on the face of it seems remarkably similar to the widely accepted small molecule generics, biosimilars are faced with fresh questions, doubt, and in the end uncertain, different, as well as changing regulation?

To figure that out we must look back in time a little (not too long though) and also recall what makes biosimilars similar (pardon the pun) to generic small molecule drugs and what makes them different. Biosimilars are generic versions of biotechnology products —great so they are the same! Hold on, not so fast. They are made in living organisms, and manufacturing processes are kept a trade secret, so the argument du jour is that generic versions of biologics cannot be identical to their reference products. Ah hah, we see now that therefore, they cannot be true generics and need to be treated differently from generics of small molecule drugs, again the argument from the lobby opposing the biosimilars.

But then again isn’t all manufacturing for biologicals inherently nonreplicable, even between manufacturing places? It’s the old argument for replicability in manufacturing that is terribly important. So the argument really boils down to the manufacturing process for these biologicals that have to be cultured in live cells, extracted, processed, purified, and so on.

I for one can see it both ways, which of course explains why this is complicated. So simply put, an abbreviated, expedited approval process for biosimilars is, in my opinion, desirable.

Now (as promised) for the legal stuff: In 2004 the European Commission adopted a new directive laying out the legal ground for the approval of biosimilars. With more than five biosimilars approved to date, Europe is clearly leading the way in biosimilars.

In the U.S., political issues and the tug of war between innovators and generic companies have delayed the formulation of legislation regarding approval of biosimilars, and the FDA has been reluctant to issue any guidance. However, increasing expenditure on biologics (both by Medicare and private insurers) has spurred lawmakers into action.

In the first half of 2007, three different bills have been proposed for the approval of biosimilars of biologics approved under the Biologic License Application (BLA). Two that have caused little stir are The Access to Life-Saving Medicine Act (introduced into Congress by Representative Waxman and into the Senate by Senator Schumer) and the Patent Protection and Innovative Biologic Medicine Act (Rep. Inslee).

These bills have not gone very far unfortunately because the two cancel each other out. The Waxman-Schumer bill is heavily pro-biosimilar, and the Inslee bill is heavily weighted toward innovators; i.e., patent protection.

There is a compromise that has been reached by both parties, but the proposed bill has been heavily criticized, and strong lobbying efforts are under way since June 2007 by both the pro-patent as well as the pro-biosimilar lobbies. One can hope that a reasonable solution will be worked out.

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