David and Matt have mentioned the possibility of price controls on patent-expired biologics. But that brings up a big issue which is being hashed out right now: what a generic biologic would look like, and how it can be approved.

As a small-molecule guy myself, I find the industrial production of large proteins rather intimidating. Quality control, which can be a backwater in some companies, is a cutting-edge challenge in this area. Just making sure that the same substance is being produced every time is enough to keep a lot of people busy. And that’s the issue when these things go off patent: how do you show equivalence for the generic form?

For traditional small molecule drugs, the question is fairly straightforward. There are plenty of well-established methods (NMR, liquid chromatography/mass spectrometry) to assess the identity and purity of such compounds, and similar techniques to make sure that the formulation is identical. I’ve spent all my career working at large research-driven drug companies, but I have no doubts about generic equivalence for our drugs once their patents have expired. The generic folks can copy us just fine.

Proteins, though, are another question entirely. NMR is quite a difficult technique for these things, and requires a lot of computational horsepower to interpret. LC/MS-based technologies are getting better and better, and are a key way to establish purity. But there are still important things that could be missed, and the only way to really be sure that two protein drugs are equivalent is in human trials.

That’s going to be a much higher entry barrier than the standard ANDA process for small-molecule generics, which isn’t going to help bring down costs. There are a number of tricky regulatory issues as well, and in the end we’re probably going to have to settle for “biosimilar” instead of “bioequivalent”. For more details, I can recommend this recent post at PatentBaristas.