Compounded Drug Policies Released by the FDA

The FDA has released several document intended to clarify the FDA’s expectations for products coming out of the compounded drug industry. The documents include a draft guidance describing current good manufacturing practice (CGMP) requirements for facilities that compound human drugs, a proposed rule to revise the FDA’s list of drugs that may not be compounded, and a final guidance generally addressing the compounding of drugs by pharmacies. The release reflects the FDA’s hope that the documents will assist members in the compounding industry with compliance and the protection of patients.

CGMP Guidance

The draft guidance discusses appropriate manufacturing practices for facilities that compound human drugs and are registered outsourcing facilities under section 503B of the federal Food, Drug, and Cosmetic Act (FDC Act). Specifically, the draft guidance serves to explain the FDA’s interpretation of what the current CGMP requirements are in 21 CFR parts 210 and 211 until the FDA can release additional regulations that are specifically focused on outsourcing facilities. The draft guidance sets out specific standards for cleanliness including air quality requirements. The guidance also recommends specific control systems and monitoring procedures that manufacturers should use to prevent contaminations in sterile processes. The guidance discusses regulations in 21 CFR 211.42(c)(10)(iv) that pertain to personnel and environmental monitoring and suggests how manufacturers that compound drugs can address those requirements. The FDA also addresses labeling and packaging requirements for compound drugs.

Component Controls

The draft guidance places some specific focus on controls used to monitor the source and quality of components used in the products that compound drug manufacturer’s produce. It sets out standards for when a component may be used or should be rejected. The FDA also put out a specific call for public comments within the guidance to ask for alternative methods that manufacturers could employ, as alternatives to periodic laboratory testing, in order to determine the safety and quality of incoming components.

Release Controls

The CGMP guidance also focuses on other product controls, and details the requirements for release testing that a manufacturer must go through to be sure a product meets required final product specifications. The FDA put out an additional call for comments and recommendations as to how manufacturers can satisfy release testing requirements without requiring outsourcing facilities to establish an in-house laboratory to perform the testing.

Proposed Drug List

The newly released Proposed rule addresses the requirements in section 503A of the FDC Act that govern compounding of human drugs. Specifically, the Proposed rule addresses the requirement that a licensed pharmacist or licensed physician not compound a drug product that appears on a list found at 21 CFR 216.24. The requirement specifically applies to outsourcing facilities, which are entities that are registered as such with the FDA pursuant to section 503B of the FDC Act. Outsourcing facilities that satisfy the requirement of not using prohibited drugs in compounds are exempted from certain regulatory requirements. Satisfaction of the 503A requirements leads to exemption from certain manufacturing, labeling, and approval regulations found in section 501(a)(2)(B), 502(f)(1), and 505 of the FDC Act.

In other words, when a drug found on the list is included in a compound drug, the drugs will not qualify for the regulatory exemptions. The drugs that appear on the list include drugs or drug products that have been removed from the market because they were found to be unsafe or not effective. The FDA indicates in the Proposed rule that it invites public comments as to how the list can be updated going forward. The Proposed rule adds 25 drugs to the list of prohibited drugs for compounding, lists each of the 25, and discusses the reason each is on the list.

Pharmacy Compounding Guidance

The FDA also released a final guidance related to its regulatory power over compounding pharmacies as granted by section 503A of the FDC Act. The FDA indicates that the guidance does not apply to outsourcing facilities under 503B of the FDC Act. Generally, section 503A governs the conditions that are necessary for drug products compounded by a licensed pharmacist to qualify for the same manufacturing, labeling, and approval exemptions discussed above that are found in sections 501(a)(2)(B), 502(f)(1), and 505 of the FDC Act.

The final guidance sets out the specifics of how section 503A is satisfied. The FDA addresses the necessary steps that a pharmacy must take to ensure that each of the 503A requirements is met. The guidance indicates that the FDA will take action against violators of the FDC act in the form of warning letter, seizure of product, injunction, and/or criminal prosecution. The FDA offers examples of violations that include drug products that contain “filthy, putrid, or decomposed substance” or were composed in unsanitary conditions. Other violations include the making of compounds with components that don’t meet quality or purity standards, drugs that don’t meet labeling and packaging requirements, and drugs that have false or misleading advertisements.