Last week’s news saw an outbreak of stories concerning meningitis-contaminated steroid injections. According to reports, the outbreak has been traced to New England Compounding Center, a “compounding laboratory.” (More on that designation in a moment.) NECC prepared steroid injections–typically used for pain treatment–for direct-to-physician use. The injections, however, were contaminated with fungal meningitis. As of this blog post, twelve people have died and over 100 people have been hospitalized across ten states. (Florida, Indiana, Maryland, Michigan, Minnesota, New Jersey, North Carolina, Ohio, Tennessee, and Virginia.) At the core of the NECC controversy is whether the FDA had (and properly exercised its) oversight over the laboratory. Interestingly, several news outlets have reported that because NECC was a “compounding laboratory,” it fell into a “legal no man’s land, between the federal government and the states. . . . putting them under a patchwork of state rules.” (Denise Grady, Scant Oversight, N.Y. Times, Oct. 6, 2012.) The New York Times also reports that the FDA attempted to regulate compounding laboratories, but the regulations were struck down by the Supreme Court in 2002. What makes the NECC outbreak particularly interesting is the issue it raises concerning federal versus state regulatory authority.
Before we analyze these issues, it’s important to understand what the difference is between “drug manufacturers” and “compounding laboratories.” To begin with, when we speak of “drugs” or “pharmaceuticals,” what we’re really talking about is a combination of two things: “active ingredients” and “inactive ingredients.” Active ingredients are the actual drug; in its simplest terms, the thing that makes a patient feel better. Inactive ingredients are generally everything else. A typical pill of Tylenol, for example, has one active ingredient: acetaminophen. It also has thirteen inactive ingredients, such as carnauba wax, castor oil, and red dye. These inactive ingredients are added so that the drug, Tylenol, can form a pill and be safely digested.
Although they’re called inactive ingredients, they’re still important. Different inactive ingredients will have different properties that may affect how the body processes the active drug. These, in turn, may make an important difference in whether the active ingredient works in the complex system that is the human body. Pills, gels, aerosols, injectables–these are all simply different “formulations” of inactive ingredients. At its heart, “pharmaceutics” is the study of formulations.
In the FDA context, “drug manufacturers” are companies that develop or manufacture active ingredients. “Compounding laboratories,” however, do not manufacture active ingredients. Rather, they “compound”–that is, make a formulation of–commercially available active and inactive ingredients. Historically, the regulation of drug manufacturers active has been left to the FDA, while the regulation of compounding laboratories has been left to the states. For many years, the FDA nonetheless regulated some aspects of compounding laboratories’ safety practices. In 2002, however, the Supreme Court overturned a small provision of the statute concerning compounding labs’ marketing practices. Because the Court also affirmed the lower court’s opinion that the marketing provision was not “severable” from the rest of the statute, the entire law was thrown out. That case, Thompson v. Western States Medical Center, 535 U.S. 357 (2002), provides a good, brief synopsis of these distinctions.
Much of the news commentary has focused on blame: That the FDA didn’t do enough or that Congress was derelict in its duties by not reauthorizing the remaining part of the FDCA that the Supreme Court didn’t explicitly throw out in Thompson. While both of these are salient criticisms on the national level, there’s been little discussion of what could have been done under the “patchwork of state rules” that typically regulate pharmacies.
Because NECC operated in Massachusetts, the Massachusetts Board of Registration in Pharmacy had jurisdiction to approve or reject NECC’s license. (Mass. Gen. Law ch. 112, § 39.) While Massachusetts law allows for the Board to revoke compounding labs’ licenses for safety reasons, the statute curiously has no inspection provision. That is, Massachusetts seems to require compounding labs to operate safely but does not permit or require the Board to conduct safety inspections of compounding laboratories. The Division of Health Professions Licensure is, however, permitted to inspect schools for medical and x-ray technicians, physicians, “wholesale druggists” (historical, chemical supply companies), nursing schools, funeral homes, and manicurists and beauticians. (Mass. Gen. Law ch. 112.) There is another provision of Massachusetts law that allows for the inspection of “food and drugs,” but it’s a bit antiquated: it’s concern is with the misbranding of “patent medicine,” (including those containing long-since banned substances, like cannabis), not with the typical safety concerns at issue in the NECC controversy. (Mass. Gen Law ch. 94.) While I’m no expert on Massachusetts law, and it’s certainly possible that there is an inspection provision I couldn’t find, the Board of Registration in Pharmacy’s reminder letter” is telling: while it reminds compounding pharmacies to comply with the law, and hints at license revocation, it mentions nothing about the Board having any inspection power.
While the federal regulatory issues in the NECC are deeply troubling, the state regulatory issues are equally so.