Pharmacy Compounding: Federal Law in Brief

by Jonathan J. Darrow

Until recently, most ordinary people had never heard of “pharmacy compounding.”  Then, a number of deaths and illnesses caused by a drug that was compounded in a Framingham, Massachusetts pharmacy propelled drug compounding to the national spotlight (see, e.g., Denise Grady et al., Scant Oversight of Drug Maker in Fatal Meningitis Outbreak, N.Y. Times, Oct. 6, 2012).

Compounding is the practice of preparing a drug for an individual patient’s needs, and is used when those needs cannot be met by a mass-produced drug.  See Thompson v. Western States Medical Center, 535 U.S. 357, 360 (2002).  For example, if a patient is allergic to a particular excipient (inactive ingredient) in an FDA-approved medicine, a doctor may order a special compounding pharmacy to prepare the medicine without that excipient. Because of the very small scale of compounding, Congress in 1997 attempted to exempt (via 21 U.S.C. § 353a) the industry from a number of provisions of the Food Drug and Cosmetic Act, including the requirement to submit a new drug application prior to interstate sale (21 U.S.C. § 355), the requirement that the drug labeling bear “adequate directions for use” (21 U.S.C. § 352(f)(1)), and the need to strictly follow good manufacturing practices, or GMP (see 21 U.S.C. § 351(a)(2)(B)).  A number of controls on compounding were included, however, such as the requirement that there be a valid prescription from a licensed practitioner (21 U.S.C. § 353a(a)(1)), that the drug be compounded by a licensed pharmacist (or physician) (21 U.S.C. § 353a(a)(1)), and that the drug be compounded from ingredients that meet certain quality standards (21 U.S.C. § 353a(b)(1)(A)–(B)).

However, § 353a—and with it, all of the provisions and exemptions just mentioned—was held unconstitutional in its entirety in Western States Medical Center v. Shalala, 238 F.3d 1090 (9th Cir. 2001), aff’d 535 U.S. 357 (2002), on the basis of certain restrictions on free speech that were also contained within the statute and which, according to the Ninth Circuit, could not be severed from the remaining provisions because “Congress intended to exempt compounding from the FDCA’s requirements only in return for a prohibition on promotion of specific compounded drugs.” See 535 U.S. at 366. Thereafter, the FDA promulgated a policy by which it would primarily “defer to state authorities regarding less significant violations” but would enforce a number of provisions relating to ingredient standards, unapproved substances, commercial scale production, adulteration, and promotion.  The FDA made clear that its enforcement activities “need not be limited to” these or any particular areas, however, thus negating any expectations that Congress’ now-invalidated exemptions might nevertheless provide a safe harbor through the weight of influence, if not law. Since then, the FDA has in fact exercised oversight of compounding pharmacies, as is evident from the handfuls of warning letters that it sends to non-compliant facilities each year.  These letters have addressed, for example, promotion that made unsubstantiated efficacy claims, contamination, and the large-scale manufacture of what were essentially copies of FDA-approved drugs.

Despite some oversight by the FDA, state law and state health authorities remain the primary checks against transgressions by compounding pharmacies.  This may soon change.  If history is any guide, high-profile tragedies have repeatedly paved the way for intensified regulation of drugs at the federal level: the 1962 Drug Amendments followed on the heels of the thalidomide disaster; the 1938 Federal Food Drug and Cosmetic Act followed the deaths of more than 100 people in 15 states from a new form of Elixir Sulfanilamide; and the 1902 Biologics Act was prompted by a tetanus outbreak linked to a tainted diphtheria vaccine.  Similarly, the Framingham tragedy—which has so far killed 25 people in 19 states—may be the trigger that finally spurs Congress to fill the vacuum created after § 353a was held unconstitutional.

Those interested in learning more may wish to consult the consumer-friendly video of pharmacy compounding produced by the FDA, which provides a general overview of the practice.  Those seeking more formal guidance should consult the FDA’s Compliance Policy Guide § 460.200 [“Pharmacy Compounding”] as well as the relevant sections of the Code of Federal Regulations (e.g., 21 C.F.R. § 216.24).

This entry was posted in Bioethics, Doctor-Patient Relationship, FDA, Health Care Reform, Health Law Policy, History, Human Subjects Research, Jonathan Darrow, Market Design, Medical Quality, Medical Safety by jdarrow. Bookmark the permalink.

About jdarrow

Dr. Jonathan J. Darrow is a research fellow at Harvard Medical School and a post-doctoral fellow in the Program on Regulation, Therapeutics and Law at Brigham & Women’s Hospital. He holds a BS in biological sciences from Cornell, a JD from University, an MBA from Boston College, and an SJD (a dissertation-based doctorate and the law discipline’s highest degree) from Harvard, where he also completed the LLM program in 2009. After admission to the bar, Dr. Darrow practiced law in the Silicon Valley offices of Cooley Godward and later worked on patent litigation matters at Wiley Rein & Fielding in Washington, DC. He is admitted to practice before the USPTO and has served on the business law faculties of Boston College, Plymouth State University, and Bentley University (current). His legal scholarship on technology, intellectual property, and health has appeared in numerous publications including the New England Journal of Medicine, the Journal of Law, Medicine & Ethics, the Stanford Technology Law Review, the NYU Journal of Legislation & Public Policy, the Northwestern Journal of Technology & Intellectual Property, and the Harvard Journal of Law & Technology, among many others. He is a co-author of two major law textbooks: Cyberlaw: Text and Cases and The Legal and Ethical Environment of Business. Dr. Darrow previously explored the impact of intellectual property on global health during stints at both the World Trade Organization and World Health Organization in Geneva, Switzerland.