Regulating compounding pharmacies after NECC.

n engl j med 367;21 nejm.org november 22, 2012 1969 requiring drugs to be safe and properly labeled. In 1962, a requirement was introduced for proof of drug efficacy through “adequate and well-controlled investigations,” partly in response to the thalidomide tragedy. Rules protecting humanresearch subjects owe a debt to Tuskegee and Nuremberg. Sometimes it takes a disaster to spur the adoption of appropriate regulation. Today, compounding pharmacies are at the center of a controversy after a rare outbreak of fungal meningitis that was traced to several lots of the injectable glucocorticoid methylprednisolone acetate compounded by the New England Compounding Center (NECC). Congress is already discussing new federal regulations. Since 1938, the FDA has had clear authority to regulate drug manufacturing, but compounding falls into a gray area between state and federal oversight. The FDA’s authority here is generally limited to reacting to problems identified by others. Traditional compounding pharmacies are not registered with the FDA as drug manufacturers, the agency doesn’t approve their prescriptions before marketing, and related adverse events need not be reported to the FDA. State law generally controls recordkeeping, certifications, and licensing for compounding pharmacies (see timeline). Such a regulatory structure is not unusual: many U.S. health care laws embrace federalism principles, preserving substantial realms for state control. States have primary authority over the practice of both medicine and pharmacy. But over time, compounding has evolved into a business far removed from the mortar and pestle. Once it becomes an industrial-scale national business, the arguments for federal regulation become stronger. For more than two decades, the FDA has struggled to regulate industrial-scale compounding. In 1992, it issued a Compliance Policy Guide, attempting to police the line between traditional compounding and drug manufacturing. This guide attracted enough criticism that Congress created a safe-harbor compounding statute in 1997, amending the FDCA with a new section, 503A. But 2 days before this law was to take effect, seven compounding pharmacies sued to block it. Section 503A(c) banned the advertising and promotion of compounded drugs; the theory was that since traditional compounding occurred in response to individual prescriptions, advertising was unnecessary. The advertising ban was the law’s Achilles’ heel. In 2002, in a 5-to-4 decision in Thompson v. Western States Medical Center (an early example of the Regulating Compounding Pharmacies after NECC