FDA Inspections Find Issues at Compounding Pharmacies

By Kim Smiley

Unsafe practices at compounding pharmacies were found during recent Federal Drug Agency (FDA) inspections.  The FDA visited about 30 pharmacies in 18 different states, focusing on the production of sterile drugs which was determined to be the highest risk to patient safety.   The inspection findings include a number of potential contamination issues such as inadequate ventilation, unidentified particles in vials of supposedly sterile medications, cleanliness issues in clean rooms such as rust and mold, and insufficient microbiological testing. Interest in compounding pharmacies was increased after the fall 2012 outbreak of fungal meningitis that killed 50 and sickened hundreds was traced back to compounded injectable steroid medication that had been shipped across the country.

A root cause analysis of the issues at compounding pharmacies can be done by building a Cause Map.  A Cause Map visually lays out the different causes that contribute to an issue and is a way to intuitively illustrate the problem.  Compounding medications are an issue because they can pose both indirect and direct risks to patient safety and patients are using them.   The indirect risk is that patients may inadvertently use an ineffective medication.  Compounded medications are not regulated by the FDA and have not gone through a formal approval process that requires extensive testing.  Medications that are compounded can also be a direct risk to patient safety if they are contaminated or sub- or super-potent.  As the fatal fungal meningitis outbreak unfortunately demonstrated, contamination of supposedly sterile drugs can have deadly consequences. Compounded drugs are receiving more attention than traditionally manufactured drugs because some of the facilities may have less oversight and the recent investigations found more issues with the work processes at the compounding pharmacies than is typically discovered at drug manufacturing facilities.

Many are asking questions about how compounding pharmacies are regulated and overseen.  Compared to drug manufacturers, the FDA’s regulatory authority over compounding pharmacies is limited.  Compounding pharmacies are not generally even required to inform the FDA what drugs they are making or register with the FDA.  State boards of pharmacy regulate the compounding pharmacies and the FDA typically becomes involved only to do for-cause inspections upon receiving reports or complaints or when states have requested assistance.

It’s worth noting that compounding pharmacies do serve an important need.  Some individuals cannot be treated with standard manufactured medication.  An example of this is when somebody is allergic to an inactive ingredient, such as a dye, in an approved medication.  The real concern is that the creation and  use of compounded medications seems to be changing from its traditional function.  According to Ilisa Bernstein, acting director of Center for Drug Evaluation and Research’s Office of Compliance, “Some aspects of these firms’ operations appear more consistent with those of drug manufacturers than with those of traditional pharmacies. Some firms make large amounts of drugs that appear to be copies of FDA-approved, commercially available drugs when it does not appear that there is a medical need for an individual patient to receive a compounded version of the drug.”

There have been a number of voluntarily recalls as a result of the recent inspections.  The FDA and state regulatory boards are working together to address the issues that were uncovered.  Additionally, the FDA is pushing for new legislative authority over the highest-risk compounding pharmacies, but there isn’t agreement on whether changes are necessary and it’s not clear what the outcome will be.

For more information about compounded medications, please visit the FDA website.