United States: To Close Out 2018, FDA Published A Revised Draft Guidance On Human Drug Compounding For Outsourcing Facilities

In accordance with the United States Food & Drug Administration's ("FDA") 2018 Compounding Policy Priorities Plan, on December 11, 2018, FDA published its revised draft guidance regarding human drug compounding by outsourcing facilities entitled, "Current Good Manufacturing Practice—Guidance for Human Drug Compounding Outsourcing Facilities Under Section 503B of the FD&C Act Guidance for Industry," (the Revised Draft Guidance). FDA released this Revised Draft Guidance to describe FDA's current thinking on what FDA has described as a new flexible and risk-based approach to Current Good Manufacturing Practice ("cGMP") requirements for outsourcing facilities.

Outsourcing facilities must comply with cGMP requirements, and failure to do so risks that the compounded drug will be deemed adulterated under Section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act ("FDCA"). FDA has taken the position that it intends to promulgate more specific cGMP requirements for Section 503B outsourcing facilities in the future, but until FDA does so, outsourcing facilities are subject to the cGMP requirements established in 21 CFR parts 210 and 211. The Revised Draft Guidance illustrates FDA's current thinking on certain standards with examples of cGMP requirements where FDA would generally not take regulatory action as applied to outsourcing facilities.

Outsourcing facilities must comply with cGMP requirements, and failure to do so risks that the compounded drug will be deemed adulterated under Section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act ("FDCA"). FDA has taken the position that it intends to promulgate more specific cGMP requirements for Section 503B outsourcing facilities in the future, but until FDA does so, outsourcing facilities are subject to the cGMP requirements established in 21 CFR parts 210 and 211. The Revised Draft Guidance illustrates FDA's current thinking on certain standards with examples of cGMP requirements where FDA would generally not take regulatory action as applied to outsourcing facilities.

FDA's current thinking on cGMP requirements for outsourcing facilities

In the Revised Draft Guidance, FDA addresses stakeholder comments it received in response to its original 2014 draft guidance and sets forth standards it perceives as critical to producing high-quality drug products while maintaining the flexibility needed for compounding. The Revised Draft Guidance reflects FDA's intent to recognize the procedural differences between outsourcing facilities and traditional drug manufacturers and describes circumstances in which FDA does not intend to enforce certain cGMP requirements against outsourcing facilities (which are otherwise required for drug manufacturers). Unlike the initial draft guidance, in addition to including FDA's current thinking as to cGMP standards for sterile compounding, the Revised Draft Guidance now includes FDA's expectations for non-sterile compounding performed at outsourcing facilities.

For example, FDA outlines quality assurance activities to ensure microbiological quality for non-sterile drug products and certain facility design requirements to prevent objectionable microorganisms in non-sterile drug products. FDA also added an entirely new section to the Revised Draft Guidance regarding Beyond-Use-Dates (BUDs) for both non-sterile and sterile compounded drug products. This section offers guidance on default BUDs and BUDs based on limited stability testing information for non-sterile and sterile compounded drug products, which are further separated by aggregate batch size. For small batches (i.e., less than 5,000 units for non-sterile and less than 1,000 units for sterile), FDA generally does not intend to take regulatory action against the outsourcing facility if the relevant default BUDs are used for the expiration dates and certain other conditions in the Revised Draft Guidance are met.

The Revised Draft Guidance contains a much more extensive discussion of standards with examples of cGMP requirements that FDA has deemed would likely not warrant regulatory action if performed appropriately by an outsourcing facility. In general, FDA sets out standards in the Revised Draft Guidance that it believes will create processes and procedures at an outsourcing facility that should minimize contamination risks and ensure that quality drug products are produced.

What's next?

FDA is accepting comments and suggestions regarding the Revised Draft Guidance, which must be submitted by February 11, 2019. Although FDA's guidance documents do not establish legally enforceable responsibilities and are issued only to provide FDA's current thinking on a given topic, guidances like this one can help outsourcing facilities manage compliance and regulatory risk.

The issuance of this Revised Draft Guidance is another indication that FDA continues to actively oversee the regulation of drug compounding in its various enforcement initiatives. We therefore recommend that the Revised Draft Guidance be consulted by outsourcing facilities to both ensure compliance with all applicable standards and to be on notice as to what FDA investigators may be looking for during an inspection. Further, drug compounders, and especially those who have an outsourcing facility or are interested in acquiring or opening an outsourcing facility, should continue to closely monitor their compliance with all applicable state and federal regulations and guidance.

This article is presented for informational purposes only and is not intended to constitute legal advice.