Late last month, the Alabama Department of Public Health (ADPH) and the federal Centers for Disease Control and Prevention (CDC) reported infection outbreaks at 6 Alabama hospitals that left 9 people dead and 10 others injured. This tragedy should have major implications for FDA and state pharmacy boards throughout the country.
Health officials confirmed this past week that the outbreak was caused by nutritional IV solutions (known as parenteral nutrition or PN) provided by a single compounding pharmacy and contaminated with bacteria known as Serratia marcescens. Samples of the organism matched the bacteria found in the 19 infected patients. Officials found that bacteria on a faucet used to rinse a mixing container and stirrer and in the amino acid powder used to make PN somehow passed through a sterilization filter and got into the PN solutions.
Any type of sterile compounding activities must be undertaken with great care and in compliance with relevant standards. In this case the prevailing standard is found in United States Pharmacopeia (USP) Chapter <797>, Pharmaceutical Compounding: Sterile Preparations. The chapter describes a network of systems and processes “to prevent patient harm and fatality from microbial contamination (nonsterility), excessive bacterial endotoxins, large content errors in the strength of correct ingredients, and incorrect ingredients in compounded sterile preparations.”
In the past, most sterile compounding was completed in-house in hospital pharmacies. However, this trend has shifted over the years as many pharmacies have found it too difficult or too costly to meet all the requirements of the USP standard, which was most recently revised in 2008. A recent survey conducted by Pharmacy Purchasing & Products showed that 66% of pharmacies now outsource at least some portion of their sterile compounding.
Reliance on compounding pharmacies has continued to rise due to an unprecedented escalation in shortages of critically important drugs, including recent shortages of vitamins, electrolytes, and other pharmaceutical components of PN. When hospitals cannot get these from commercial manufacturers, they must rely instead on compounding pharmacies to take up the slack.
I think the real issue to be learned from the tragedy is that better oversight and licensing and/or registration requirements for compounding pharmacies are required. Individual state boards of pharmacy vary in their positions on <797>. Only 14 states have even adopted the chapter in its entirety. Most have chosen to incorporate only portions into laws, regulations, or board policies and procedures. Pennsylvania is among the states that do not mention it at all in their regulations. Nor does our state have specific language requiring compliance with sterile compounding or injection preparation regulations as does New Jersey and Delaware. In addition, most state boards have insufficient funding to send experienced and trained surveyors to actually inspect pharmacy operations to ensure compliance. While the Alabama Board of Pharmacy does have a regulation that required pharmacies to adhere to <797>, there’s more to be learned about the board inspection process, pharmacy compliance, and the cause of the filtration breakdown.
As we move forward and learn from the most recent outbreak, we can only hope that all state boards of pharmacy expect compounding pharmacies to comply with all aspects of the USP standard, and to survey these pharmacies regularly to enforce compliance. To do this, state pharmacy boards must be provided with additional resources to adequately train and deploy surveyors to assess compliance. Today, many pharmacy boards are ill equipped to take on this responsibility; without additional resources, the assignment of responsibility will not result in improved oversight. FDA needs to work collaboratively with the state boards of pharmacy to provide them with the necessary support and training to survey compounding pharmacies for compliance.
Compounding pharmacies that distribute sizeable quantities (to be defined by FDA) of sterile preparations, and those operating interstate, should be registered with FDA and subject to periodic inspections. Currently, there is no such requirement. FDA does have plans to publish guidance on Good Pharmacy Compounding Practices for Sterile Drug Products, and Outsourcer Pharmacy Operations Compliance Policy Guide, to clearly articulate requirements for registration with FDA, periodic inspections, support available to the state boards of pharmacy, and expectations regarding the state boards’ role in regulating compounding pharmacies.
This cannot come too soon. FDA has been aware of multiple problems with compounded preparations that have resulted in recalls, patient injuries, and deaths. However, when we communicated with the FDA recently to discuss this event, no one could clearly articulate how the agency regulates compounding pharmacies.
Finally, last week we also communicated with all US hospitals asking that all pharmacies, pharmacists and pharmacy technicians who compound sterile preparations, regardless of where they work and regardless of size, know and comply with USP <797> to the fullest extent possible. All pharmacy staff has a moral and legal obligation to compound preparations using the least risky processes while adhering to the highest standards possible. So preparing items from raw powders should be avoided if at all possible. Also we recommend establishing an internal quality surveillance and review team to regularly monitor compounded preparations, the environment, compounding equipment, and personnel for compliance with key aspects of <797>, much like an internal peer-review process.
Unfortunately, there are too many in health care who feel that, if it hasn’t happened to them, the adverse experiences of others do not apply, which is why regulation and oversight is necessary. If the continuing investigation into this event uncovers heretofore unrecognized aspects of compounding that have so far been overlooked in either the <797> standard or in staff practices, then we need to learn from it, incorporate necessary changes, and provide leadership and oversight to assure that patients are kept safe.
For more on ISMP's consumer website, go www.consumermedsafety.org.