• Scott Gottlieb on compounding

    Yesterday, I wrote about how the conservative Boston Herald attacked Obama for allegedly loosening compounding drug rules. The claim failed the truth test. I praised the WSJ story yesterday, which was accurate.

    Today, Scott Gottlieb at the American Enterprise Institute questions the Obama FDA for tightening quality rules on the manufacture of sterile injectable drugs (the type of drugs at issue in the NECC compounding tragedy).

    Of the two, Gottlieb’s is by far better rooted in facts, but the essential argument is that when the FDA cracked down on quality problems at drug companies making sterile injectables, it helped to create drug shortages and shifted the demand to a less regulated supply, the interstate compounding pharmacies like NECC.

    Gottlieb is careful not to blame the FDA for NECC:

    While it’s highly unlikely that the decisions made by the Obama administration led to the recent tragedy, new policies create regulatory challenges that could make similar incidents more likely down the road.

    For good reason. A causal chain requires at least two steps to “blame Obama” for NECC. First, that improper FDA action caused a shortage in methylprednisolone acetate. Second, that such a shortage (if proven) shifted demand to NECC.

    The FDA maintains a comprehensive list of drug shortages, both current and resolved. Methylprednisolone acetate does not appear on either list. The ASHP reported a shortage of the generic versions of the drug on May 22, 2012, but did not specify a reason.  It is made by Teva and Sandoz. I could find no record of a shortage of the brand named version, produced by Pfizer (as Depo-Medrol). I also could not find the discontinuation date for Watson Labs and Akorn’s generic versions. It’s not clear that the Obama FDA created a shortage in this drug.

    In any event, who thinks the solution to the NECC problem is lower sterility standards at more drug plants? We may need a different way to pay for the manufacturing base for common low-cost drugs and vaccines, but no one is seriously arguing for lower quality standards right now.

    Prior TIE coverage here. h/t to Brad


    • I worked in Pharmaceutical Quality Control for much of my career. It is certainly true that the FDA has increased its expectations for how drugs are made. But this started decades ago, long before Obama. And similar increases in quality expectations have occurred outside the US, for example in Europe and Australia.

      There is much to criticize in how FDA develops and enforces manufacturing standards. Especially in things like sterility, which is inherently stochastic, there is an over-emphasis on paperwork and records (to make inspections easy) and an underemphasis on how the manufacturing process affects the actual quality of the product. In my experience, the current standards can be very annoying to the manufacturers, but in a practical sense they really do not add significantly to product costs.

      Large scale compounding has grown 100% as a way to avoid regulatory scrutiny and capital investment. Personally, I would never trust to the sterility of a drug made in one of these facilities. The kinds of processes that are adequate for making one dose at a time simply cannot be scaled up to the preparation of tens of thousands of doses.

      I read that the facilities using NECC materials were saving on the order of $10/dose compared to branded Depo-Medrol, used in a procedure that they bill at $300 or more. This surely is an example where trying to save health care dollars is a really bad idea.

    • It seems that the source of the NECC’s base ingredients would be under investigation as well. Any information on this?

    • Why not just replace the FDA minimal safety requirements with mandatory disclosure. Let anyone use any drug they want as long as they are fully informed of all known risks?

    • I should add that methyprednisolone acetate is particularly hard to manufacture. The drug is insoluble in water, so it is prepared as a suspension. It is also fairly unstable to heat. This means that the usual processes for sterilization (autoclaving, sterile filtering) cannot be used. A quite tricky process of combining pre-sterilized API with sterile vehicle is needed.

      I shudder at the thought of some pharmacy assistant trying to do this successfully in a laminar-flow hood.

    • Please note that NECC is regulated under a license from the State of Massachusetts that chooses not to use the standards maintained by the FDA for compounding pharmacies.