sterileInsanitary conditions in compounding pharmacies can lead to tragedy. The 2012 outbreak of fungal meningitis, which killed more than 60 people and was caused by contaminated steroids, illustrates the seriousness of the problem. The FDA released guidance in August that represents the agency’s current thinking on insanitary conditions, which can be defined as “so dirty or ridden with germs as to be a danger to health.”

So what conditions are potential pitfalls for compounding pharmacies?

If a drug is produced in insanitary conditions, it is considered adulterated under the Food, Drug, and Cosmetic Act. The FDA has jurisdiction to inspect all compounding pharmacies for such conditions, and state regulatory agencies will contact the FDA if they observe poor practices during inspections.

The most serious insanitary conditions are:

  • Vermin (e.g., insects, rodents) in the ISO class 5 clean room or in adjacent areas;
  • Visible microbial contamination (e.g., bacteria, mold) in the ISO 5 area or in adjacent areas;
  • Non-microbial contamination in the ISO 5 areas (e.g., rust, glass shavings, hair);
  • Performing sterile manipulations outside of the ISO 5 area;
  • Exposing unprotected sterile product, including stock solutions, to lower than ISO 5 quality air (e.g., removing it from the ISO 5 area without a robust and intact container closure system);
  • Production of drugs while construction is underway in an adjacent area without adequate controls;
  • Consistent and frequent pressure reversals from areas of less clean air to areas of higher cleanliness;
  • The “sterilizing filter” is not adequate nor pharmaceutical grade;
  • Temperature and time conditions used for heat sterilization are not lethal to heat-resistant microorganisms; and,
  • Cleanroom areas with unsealed, loose ceiling tiles.

If any of these conditions exist, the FDA strongly recommends that the compounding facility immediately initiate a recall of drugs produced under unsanitary conditions and cease production until the conditions have been corrected. Compounding facilities should not rely on sterility tests because microbial contamination can be distributed within a sample. Passing a sterility test is not an excuse for insanitary conditions.

The FDA recommends that a compounding pharmacy that has discovered insanitary conditions should report the condition to its local FDA district and to the state regulatory bodies where its drugs are shipped.

Compounding pharmacies should attempt to prevent insanitary conditions by following the FDA’s detailed cleanroom regulations for sterile practices. The ISO 5 area should be certified every six months. As part of that certification, the airflow patterns should allow higher quality air to move to areas of lower air quality and not in the opposite direction. Even quickly moving near open containers or instruments can disrupt the airflow and cause contamination.

Daily environmental monitoring of the ISO 5 area is recommended. This includes testing for air particulates, personnel sampling such as fingertip sampling, and testing surfaces. Wood should not be used in a lab environment because it is difficult to clean and particle-generating.

Media fills, or process simulations in place of the drug solution, should be conducted to evaluate sterile drug production by placing microbiological growth mediums in conditions that provide a challenge to aseptic operations. The Hasson Law Group recommends that all compounding pharmacies have written protocols in place to ensure compliance with FDA regulations and guidance, and that pharmacies conduct periodic audits to measure compliance with those protocols. We further recommend that any pharmacy that discovers potentially unsanitary conditions seek immediate advice from qualified legal counsel.

If you have questions about compliance with federal and state laws and regulations that govern the practice of compounding pharmacies, contact Hasson Law Group.