by Michael R. Cohen, R.Ph.
The deadly, multistate meningitis outbreak our country is currently dealing with brings much needed scrutiny to the compounding pharmacy business. The scale of the outbreak makes it the worst among a series of fatal or harmful infections and overdoses linked to compounding pharmacies in the U.S., rivaling other key drug safety issues in the more distant past that have led to substantial drug safety legislation. For example, in 1937, more than 100 patients died after the S. E. Massengill Co. compounded an elixir of sulfanilamide using diethylene glycol (antifreeze), which the company did not recognize as poisonous because safety testing had not been conducted. The tragedy was the driving force behind the 1938 Federal Food, Drug, and Cosmetic (FD&C) Act, which for the first time required drug safety testing.
Exactly 50 years ago this past week (October 10, 1962), in response to severe birth defects associated with thalidomide, Congress passed the Kefauver-Harris Amendment to the FD&C Act, requiring drug manufacturers to provide proof of safety and effectiveness. Up until now, there have been 200 adverse events involving 71 compounded products in the past 2 decades, many with devastating outcomes. Each case has prompted calls for federal oversight of compounding pharmacies, which are not subject to the same controls as drug manufacturers but whose regulation falls between the state board of pharmacy, the state department of health, and the FDA. While the present outbreak cannot be considered an outlier event, it should certainly be the very last event before enacting federal legislation to protect the public from preventable compounding errors and contamination. The magnitude of the current tragedy must serve as a wake-up call for Congressional action, just as it was in the above tragedies.
In April, 2011, I blogged about the need for federal and state oversight after 9 patients died in Alabama due to contamination of nutritional solutions made by a compounding pharmacy. Compounding pharmacies should be testing and monitoring the environment in which products are compounded, training and closely supervising staff, adhering to the recognized standards for compounding safety that were formulated by the United States Pharmacopeia (in Chapter <797> of the USP) and detecting process deviations before they cause harm. Yet, an analysis of recent cases of contamination of products from compounding pharmacies that have led to adverse health outcomes revealed that breaches of standards, unsafe staff behaviors, untrained and unskilled personnel, improper use of equipment, extended beyond use dating outside of manufacturer labeling without sufficient testing, and/or a general lack of good compounding skills had been involved in almost all cases. Since 2004, FDA has issued 49 warning letters to compounding pharmacies around the country for significant safety violations; 19 previous deaths may be associated with these pharmacies. Without federal oversight and/or greatly improved state oversight of compounding pharmacies, patients will continue to be harmed.
As we move forward and learn from the most recent outbreak, Congress must act quickly to address the need for laws on the federal level to fill in current regulatory gaps. Regulations must be equal to what is required of pharmaceutical companies when compounding pharmacies dispense in mass quantities without individual patient prescriptions, or manufacture sterile products from non-sterile active ingredients. These pharmacies must be registered with FDA and subject to periodic inspections. FDA must clearly articulate requirements for IV compounders to register, regulate them and subject them to periodic inspections. For pharmacies that dispense sterile products only on receipt of an individual patient's prescription, FDA must also support the state boards of pharmacy, and expectations regarding the state boards' role in helping to ensure compounding pharmacy safety.
Healthcare providers must use commercially available, ready-to-use products from pharmaceutical manufacturers when available since they are approved by FDA under industry quality standards. When products are not commercially available, providers, including physicians who use these products, must carefully assess and select the compounding pharmacy it will use. All pharmacy staff have a moral and legal obligation to compound preparations using the least risky processes while adhering to the highest standards possible. Even the slightest misstep could result in a disaster such as the tragedy before us.
Selected Pharmacy Sterile Compounding Misadventures