On July 1, the Food and Drug Administration (FDA) issued interim guidance describing the Agency’s expectations for compliance with current Good Manufacturing Practice (cGMP) requirements for compounding outsourcing facilities under Section 503B of the federal Food, Drug, and Cosmetic Act (FDCA).

Under section 503B of the FDCA, as added by the Drug Quality and Security Act (DQSA) on November 27, 2013, a compounding pharmacy can register as an outsourcing facility with FDA. Unlike traditional compounding pharmacies, outsourcing facilities may compound sterile drugs without individual prescriptions. The DQSA requires that outsourcing facilities comply with cGMP requirements. Because outsourcing facilities generally compound smaller quantities of drugs than conventional drug manufacturers, however, certain cGMP requirements under 21 CFR Part 211(the regulations defining cGMP for finished pharmaceutical products) are not practical for outsourcing facilities. This interim guidance reflects FDA’s intent to adapt cGMP requirements to the specific compounding operations of outsourcing facilities in light of the differences between outsourcing facilities and conventional drug manufacturers. The primary focus of the guidance is on aspects of Part 211 that relate to sterility assurance of sterile drug products and to compounded drug safety with respect to strength and labeling designed to prevent drug product mix-ups.

The draft guidance details specific cGMP standards for: facility design; control systems and procedures for maintaining suitable facilities; environmental and personnel monitoring; equipment, containers, and closures; component testing; production and process controls; release testing; laboratory controls; stability/expiration dating; packaging and labels; and quality assurance activities, including complaint handling.. In each category the guidance stresses the requirements that are considered critical for compounded drugs. In some categories the guidance identifies certain requirements for conventional manufacturers – such as laboratory testing on each batch of drug product – that it does not intend to enforce against outsourcing facilities if certain conditions are met. 

FDA also seeks comments on two alternative approaches that would utilize the Drug Master File (DMF) process to reduce the need for duplicative testing by multiple outsourcing facilities. First, if a component supplier were to submit a DMF to FDA that satisfies certain requirements and receives a no-comment letter from FDA, FDA would exercise enforcement discretion to allow outsourcing facilities to use that supplier’s components without performing periodic laboratory testing to confirm the information in the supplier’s certificates of analysis (COAs). Second, if a testing laboratory were to submit a DMF and receives a no-comment letter from FDA, outsourcing facilities may be allowed to rely on third-party final release testing from that laboratory in lieu of performing their own in-house laboratory final release testing.

The policies of this guidance and the proposed alternatives affect current and potential outsourcing facilities, laboratory testing laboratories, hospitals, and other parties relying on outsourcing facilities for compounding. If FDA ultimately adopts these proposed alternative approaches for outsourcing facilities to satisfy cGMP requirements, that decision will beg the question of why pharmaceutical companies may not use similar approaches, at least in certain circumstances.

Interested parties are encouraged to submit comments within sixty days.

Kelsey Moran