The folks in biotech have a saying, "The process is the product." In their world, drugs are so complex and difficult to characterize
that you can't just run a set of simple chemical tests to ensure that what comes out of the bioreactor today is the same thing
that came out a month ago. Instead, you have to develop a rigorous process and stick to it absolutely. There are chemical
checks you can make, and they're getting better all the time, but in the end, the way you assure that you've got the right
product is to stick to the process. They're thinking of process in the narrow sense—maintaining cell lines, monitoring temperatures,
carrying out purification processes, things like that. But as the past few weeks have reminded us, process can mean a whole
range of things—who you buy supplies from, who they buy their supplies from, how your raw ingredients are treated, and, of
course, what you do to ensure that no one ekes out your active ingredient by loading it up with counterfeit APIs and contaminants.
That, of course, is what happened to Baxter. Somewhere along the chain of actions that leads from hog guts to heparin—an old
and valuable anticoagulant—someone apparently mixed in a cheap chemical based on chondroitin sulfate, a commonly used dietary
supplement made from animal cartilage. As we went to press with this issue, FDA and Chinese officials were still investigating,
but it was impossible to doubt that the contamination was deliberate, the result either of an attempt to cut costs or of an
unscrupulous vendor sneaking the chemical into the supply chain.
The heparin case is the subject of a story in this month's Pharm Exec, written by Senior Editor Walter Armstrong (see page 66). Walter makes the case that if the heparin contamination is in fact
counterfeiting, as it seems to be, it represents counterfeiting on a whole new level. This is not a matter of substituting
deadly but cheap ethylene glycol for glycerine (as one Chinese manufacturer did not so long ago). In this case, some clever
chemist identified a cheap product that could be made to resemble heparin, then chemically modified it so the resulting product
could pass all the standard tests of purity. It's fraud on a molecular level—an appalling waste of human skill, talent, and
ingenuity in the service of greed and destruction.
It's essential for pharma to protect itself against this sort of crime—not least because FDA and others are making ominous
rumblings about criminal prosecutions for executives whose products go bad, whether the defect was deliberate or not, and
whether the executive knew about it or not.
But how? It's really not reasonable to expect that chemical testing will be adequate to thwart deliberate deception—in the
heparin case, FDA and Baxter had to use state-of-the-art technologies to simply locate a contaminant it knew was there. Biologics
are intrinsically complex and resistant to definitive analysis.
In the long run, the answer is probably going to be the classic biotech answer: If you want your product to be pure, control
the process. But as Walter's story demonstrates, that won't be easy. In the heparin case, the Chinese government argued that
it had no responsibility for supervising exports. And suppliers on the upstream side said they couldn't or wouldn't inspect
their vendors. To get the Wild East under control will be the work of decades. But it has to happen. If you lose the process,
you've lost the product.