The recent recall of nearly two dozen drugs manufactured by Premier Pharmacy Labs reinforces the importance of the newly updated compounding regulations. But compounding experts worry it may stifle development in an already precarious supply chain.
Premier Pharmacy Labs, a sterile compounding pharmacy, issued a nationwide recall last week of injectable drugs such as the opioid overdose treatment naloxone, sodium bicarbonate, which is used in nearly every hospital, and the anesthetic lidocaine after the Food and Drug Administration couldn’t ensure their sterility.
The recall follows recent updates to compounding regulations over sterile preparations as well as nonsterile products, radiopharmaceuticals and hazardous drugs. It is, in part, a response to ongoing quality issues related to sterile drug preparation. Sixty-nine reported sterile IV compounding errors from 2001 to 2017 led to 1,418 adverse events and 114 deaths, according to the Pew Charitable Trusts.
“The varying levels of quality is staggering from one state to the next,” said Sean Brynjelsen, CEO of Deer Park, Ill.-based Eton Pharmaceuticals. “There are numerous instances of compounded products not being sterile, potency issues and shipping products with limited testing.”
Compounders bypass the FDA review process, he added.
Quality and production issues contribute to the short supply of sterile injectables. They are resource intensive, which has caused more manufacturers to leave the space. Sterile injectables also typically yield low margins. Compounders often step up when drug shortages arise, but experts worry that the new shorter mandated shelf life of compounded drugs could slow their response.
The new framework for compounded sterile drugs includes revising contamination risk levels from low, medium and high to Category 1 and Category 2, which are based on the probability for microbial growth and how quickly they must be used. Certain preparations that use compounding aseptic containment isolators will require a dedicated cleanroom space.
Under the new guidelines going into effect Dec. 1, Category 1 drugs have a shorter maximum beyond-use date while Category 2 pharmaceuticals have a longer date since they must be produced in a clean room. Compounded drugs would also have to perform monthly surface sampling, which was previously only required “periodically.”
Many “medium-risk” compounders, which include a vast majority of U.S. hospitals, must adapt to Category 2, meaning they must adhere to more stringent standards. About 40% of hospitals do compounding in-house and the rest contract with external organizations, Brynjelsen said.
The University of Rochester (N.Y.) Medical Center has moved a lot of its sterile compounding operations in-house. It can directly control quality and safety issues instead of relying on external compounding pharmacies, said David Webster, the associate director of pharmacy operations at the university.
The updates will make production safer by boosting standards on environmental monitoring, he said. But the shorter expiration dates may make the process more inefficient.
“I think it will drive some places to consider production outside of the hospital, as most don’t have room to expand clean-room operations. We are struggling with this too,” Webster said.
Large-batch sterile compounders needed more scrutiny, but it also implemented some overly burdensome requirements, Webster said, adding that they are cumbersome and costly.
The updates put compounders a step closer to what traditional drug manufacturers have to follow, said Brynjelsen, who supported alignment.
“Some are pushing against this because it affects their bottom line,” he said, adding that it will increase costs because they have to drive up quality standards. “This is a logical step forward; it needs to happen.”
Technically, compounding companies are supposed to test sterility for four weeks because the product could fail after three. But some manufacturers cut corners to get shipments out faster, Brynjelsen added.
PharMedium Services, a Lake Forest, Ill.-based IV bag and preloaded syringe manufacturer owned by distributor AmerisourceBergen, has been repeatedly called out for safety concerns, culminating in a recent consent decree that cut off some of its production after the FDA found contaminated products.