On January 17, FDA issued its opening sally in the new compounding pharmacy enforcement regime by issuing a Warning Letter to Avella of Deer Valley in Phoenix, AZ. The letter is based on a nearly year-old inspection (February 2012) and cites the following violations with respect to unapproved new drug products, misbranded drug products, and adulterated drug products:
Manufacture and distribution of drug products without valid prescriptions for individually-identified patients are not the subject of approved applications;
Sterile drug products are prepared, packed, or held under insanitary conditions whereby they may have been contaminated with filth, or whereby they may have been rendered injurious to health;
Significant CGMP violations.
The DQSA added section 503B to the Federal Food, Drug & Cosmetic Act, which FDA interprets as creating a new voluntary category of "outsourcing facilities" who will register with FDA and follow GMP if they dispense sterile products outside of an individually-identified prescription. Once a facility dispenses such products, according to FDA, they are no longer compliant with section 503A, which permits state regulation by the Board of Pharmacy.
In its response to the Form 483, Avella had referenced its compliance with United States Pharmacopeia (USP)-National Formulary (NF) General Chapter <797>, "Pharmaceutical Compounding - Sterile Preparations." However, in the letter FDA explicitly stated that by filling prescriptions that were not for individually-identified patients, Avella was no longer exempted under 503A and must comply with full drug manufacturing regulations, including 21 CFR Parts 210 and 211. FDA did not offer registration as a 503B outsourcing facility as an option, seemingly forcing Avella's hand to participate in the "voluntary" 503B registration process.
FDA is calling out the dispensing of drug products without individually-identified patient scrips. This is a bold move, and is not endorsed by the language of the FDCA. Nor is it supported by Congress' interpretation of the DQSA: immediately following passage of the law. Several key lawmakers spotted precisely this potential problem and rose to clarify:
Because office-use compounding is not addressed by the compounding section of FDA law, the agency should not overstep states' authority in this area, said Sen. John Boozman (R-AR).
"The omission of office-use from section 503(a) of the Food, Drug and Cosmetic Act should not signal to the FDA that it has the authority to encroach upon state authority to regulate office-use," Boozman said, according to the congressional record.
"This is not the intent of the law, and I will closely monitor FDA implementation as this process moves forward. If the State of Minnesota wants to prohibit drug repackaging and compounding--that is its decision. But again, this law is by no means a green light for the FDA to usurp the rights of States. I want to make that crystal clear."
Several times in the Warning Letter FDA references "interstate commerce." This may be a nod to FDA's technical jurisdiction solely over interstate and not intra-state prescriptions. 503A has traditionally used a 5% interstate threshold. It will be interesting to see how FDA treats those pharmacies that operate fully intra-state and those with less than 5% interstate business.
FDA inspections, 483s and Warning Letters to other pharmacies who use <797> compliance, compound sterile, and sell interstate are sure to follow. Please contact the author for more information. Polsinelli would be pleased to support you, along with our other compounding pharmacy clients currently dealing with this new FDA enforcement regime.