Guide on Insanitary Conditions at Compounding Facilities

FDA has released a final guidance on “Insanitary Conditions at Compounding Facilities.” The document describes examples of insanitary conditions that FDA has observed during inspections. It specifically addresses drugs (including biological products) produced by pharmacies, federal facilities, and outsourcing facilities that compound or repackage drugs, or that mix, dilute, or repackage biological products.

CDER Office of Manufacturing Quality division director Ian F. Deveau says in an associated Web posting that the agency is still seeing too many pharmacies with insanitary conditions. After having conducted hundreds of compounding facility inspections over the past few years, many were found to have resulted in Warning Letters or recalls. “Many recalls were for drugs intended or expected to be sterile but recalled due to a lack of sterility assurance,” Deveau says. “We continue to receive reports of serious adverse events or drug quality issues, such as drugs contaminated with bacteria or fungi.”

FDA says that while product sterility is not a requirement for non-sterile drugs, it is possible for non-sterile drugs to become contaminated with microorganisms that can cause patient harm. It notes that non-sterile aqueous solutions are particularly susceptible to microbial growth if contaminated. “Contamination may also include non-viable filth and the presence of unintended drug components,” it says.  The following are FDA examples of insanitary conditions that have been observed and are applicable to both sterile and non-sterile drug production and applicable to the production of sterile drugs only: 

• Vermin (e.g., insects, rodents) or other animals (e.g., dogs) or evidence of their presence (e.g., urine, feces) in the production area6 or adjacent areas
• Visible microbial contamination (e.g., bacteria, mold) in the production area or adjacent areas
• Foreign matter in the production area (e.g., rust, glass shavings, hairs, paint chips)
• Producing drugs while construction is underway in a nearby area without adequate controls to prevent contamination of the production area and product
• Standing water or evidence of water leakage in the production area or adjacent areas
• Handling bulk drug substances or drug products that are hazardous, sensitizing, or highly potent (e.g., hormones) with inadequate controls to prevent cross-contamination.