FDA’s Insanitary Conditions Revised Draft Guidance: Required Reading for Compounding Facilities

Late last month, FDA published revised draft guidance, titled “Insanitary Conditions at Compounding Facilities: Guidance for Industry.”  The revised guidance comes two years after FDA released its August 2016 draft guidance addressing what it considers “insanitary conditions” during inspections of both Section 503A pharmacies and Section 503B outsourcing facilities (collectively, “compounding facilities”).  What has changed from that initial draft (see our previous post here)? The revised  guidance contains far more detail about “insanitary” conditions FDA has actually observed over the past two or three years at compounding facilities, and which are violative of FDCA section 501(2)(A).  Interestingly, during the evolution (and increase) of FDA’s inspections of compounding facilities since the New England Compounding Center tragedy, FDA has focused  on both the specific statutory requirements in Section 503A (e.g., must compound for individually identified patients, and not essentially copies, etc.),  and 503B (e.g., must compound from ingredients on Bulks List 1, and not essentially copies, etc.).  It also seems to be placing heightened emphasis on entities that compound under more vaguely defined “insanitary conditions,” and thus may violate of section 501(2)(A)).  A compounder that compounds in violation of Section 501(2)(A), or the specific provisions of sections 503A and 503B, loses certain important statutory exemptions for compounders (such as new drug, adequate directions for use, and exemptions from cGMP regulations if a Section 503A compounder).   For physician compounders, however,  the guidance contains an important “footnote 2.”  FDA states that it “generally does not intend to take action under Section 501(a)(2)(A) against a physician who is compounding or repackaging a drug product, or who is mixing, diluting or repackaging a biological product, provided that such activities occur in the physician’s office where the products are administered to dispensed to his own patients.”  Revised Guidance at 1, n 2.

Thus, the revised guidance serves as a much needed, detailed guideline of what FDA expects from a compounding facility that produces either sterile or non-sterile drug products.  Compounders should study the document so that they have a thorough understanding of what FDA has observed at other facilities, and thus FDA’s thinking about what it considers “insanitary conditions.”  For most of the conditions listed in the revised guidance, compounders probably will say “of course those conditions should not be present….”  Notwithstanding that sentiment, FDA has observed all of these conditions to date (and likely more…).  In sum, the guidance is a well-crafted reminder of what compounders should look for, and correct, at their own facilities to stay out of the Agency’s crosshairs.

A few “observations” of particular interest:

• Concerning sterile and non-sterile drugs, FDA lists several conditions that could cause patient harm when present in both non-sterile and sterile drug production. Some of these conditions include (but are not limited to) vermin, visible microbial contamination, standing water, or construction in the production area. FDA also specifically addresses the handling of hazardous, sensitizing or highly potent drugs. FDA notes it has observed inadequate segregation, control, and cleaning concerning such drug products. Finally, FDA states that it has observed use of both active and inactive ingredients with higher levels of impurities than pharmaceutical grade or compendial equivalents.
• Concerning the production of sterile drug products, FDA walks through a detailed litany of considerations for gowning and aseptic practices, equipment and facilities, sterilization, and other general insanitary conditions.
• Corrective actions for insanitary conditions. Although all insanitary conditions identified should be evaluated and corrected immediately, FDA provides a list of conditions that it has observed and considers “particularly serious.” FDA states that if any one of these conditions exists, then the Agency “strongly recommends” that the facility immediately initiate a recall and cease sterile operations until the condition has been corrected. These conditions are listed at pages 9-10 of the revised guidance.

The comment period closes on November 26, 2018.