Therapeutic Dose: Enemies Within

Nov. 29, 2012
FDA’s hard pressed to inspect offshore facilities; now it also faces compounders and other domestic challenges.

Remember that old Chinese curse, “May you live interesting times?” Well, we’re living in them.

Every day, with memories of heparin and melamine contamination, we discuss the safety of a supply chain that includes China, India and other developing countries. Recently, an Indian regulator reminded us that it was “caveat emptor” for Western companies when they purchase from APIs or products from India. Indian manufacturers are under no obligation to follow GMPs, he said. Instead, it’s up to us to inspect every place from which we purchase materials. We are negotiating with these countries for the FDA to make site inspections (China used to have to “invite” the FDA to come).

These are all positive developments. We are getting a world of cooperation from EMA and even China’s SFDA. Our inspectors are getting schooled in international rules and potential hurdles. There’s just one problem. To put it simply, we have enemies here at home, or as they said in one classic musical, “The Music Man,” (those of you under 40, check it out) “We have troubles right here in River City.”

First, there is the new inspection frontier of nutritional supplements and nutraceuticals manufacturers here in the United States. Even though FDA has hired and trained more inspectors (and CDER and OGD are recruiting again), these products are now included in GMPs. (Makes me wonder how many of these manufacturers even know what GMPs are, much less, what the “actives” are in their particular products.) 

Now, the outbreak of meningitis caused by contamination at U.S. compounding facilities has resulted in another domestic problem for the U.S. public and FDA. Recent news has focused on the compounder, NCCE of Massachusetts. But if you see one cockroach, how many more are hiding? There are thousands of compounding pharmacies in the United States. Originally, every institution that made drugs in the U.S. was a compounding pharmacy; that’s why the USP came into existence back in the 18th century. However, as more and more of our drug products were made in larger and larger lots, there was an official divide (firewall?) built between commercial and compounding companies.

In a simple explanation, “commercial” pharmaceutical companies (the ones we normally address in our publication) make large numbers of bottles of capsules or tablets and sell to numerous (dispensing) pharmacies and distribution centers. They are under strict supervision of the FDA, subject to inspections, and need to adhere to cGMPs. Most are subject to yearly inspections by trained FDA inspectors and are open to any number of legal consequences to errors.

The compounding pharmacies can make as little as one bottle of capsules (as a local one used to do for my last dog) to hundreds of, say, pre-filled syringes for select customers. They are not subject to the FDA, but, rather, are regulated by state pharmacy boards. In the case of NCEE, they were not only selling large amounts of product to distributors (not legal), but their sanitary conditions were (are) terrible. The states, in almost every case, cannot oversee these sites. Clearly, the FDA needs to be in charge here, also.

Then we have the GMP compliance problems at larger generics and name brand manufacturing companies. Consider pharma’s poster child for recent recalls, J&J. It has been around for decades; it had even hired an ex-FDA inspector a few decades ago to head the Quality department; and, it is the “baby company” that would never fail its littlest customers. As a consequence, perhaps there were assumptions that it was good and would stay that way.

The response to the number of “oops’” they had with smells and mislabeling was to address each as if it were an isolated incident. After a few dozen “isolated incidents,” it was seen that there may have been a problem with the overall quality program. In any case, it was a large distraction... but, there were no fatalities. The same cannot be said about the unfolding meningitis tragedy.

Just like the Chinese when barbarians infiltrated the Great Wall, we find our defenses against offshore threats weakened by inadequate quality management systems at home.

Do we need many, many more FDA inspectors? Or, should we increase the penalties for lawbreakers? Interesting times, indeed.

About the Author

Emil Ciurczak | Contributing Editor