With the COVID-19 pandemic still raging, the FDA has yet to resume on-site inspections at manufacturing facilities abroad. Without boots on the ground, some market watchers are concerned about the quality of drugs flowing across U.S. borders, and now a university system's pharmacy is taking matters into its own hands.
Researchers at the University of Kentucky (UK) filed a petition with the FDA to recall one lot each of Mylan and Hikma's versions of injectable diuretic acetazolamide after finding high impurity levels in tested lots, the university said last week.
After testing performed in August, the researchers found that samples of Mylan's version of acetazolamide contained only between 80% and 87% of the listed active pharmaceutical ingredient (API). The rest was composed of unknown impurities that UKHealthCare Chief Pharmacist Philip Almeter called "obscure chemicals that could result from breakdown of product or from reagents used in the manufacturing process."
In some cases, the impurity levels in Mylan's version were more than seven times higher than the FDA's accepted amount, Almeter said in an email. Those findings were later confirmed by AMRI, a contract manufacturer and independent testing lab, the university said.
"There is little to no data on what danger these (impurities) pose because they have not been studied," Almeter said. "Given the unknowns we felt it was important to file the petition with the FDA as soon as possible."
Mylan's version of the injectable was manufactured in India, researchers said, and Hikma's version was made in Portugal. Representatives for the drugmakers could not be reached for comment by press time.
Mylan and Hikma are two of just three manufacturers on the U.S. market for injectable acetazolamide, which Almeter called "concerning" for patients on the drug.
So far, researchers have not received side effect reports from patients, but the university's healthcare system has pulled supply of those drugs off shelves. The UKHealthCare Pharmacy is believed to be just one of two pharmacies quality testing their supplies of medicines, the university said.
UK touted its role as an independent testing lab as the FDA has severely curtailed international inspections amid the COVID-19 pandemic.
In July, FDA Commissioner Stephen Hahn, M.D., said the administration would resume "prioritized" domestic manufacturing inspections after a four-month moratorium on most on-site walk-throughs. Meanwhile, inspections abroad have been held on a "mission critical" basis, with overseas manufacturers even calling for the FDA to resume inspections to keep the supply chain running.
The UK researchers pointed to that overseas ban in their petition, noting that an extended delay on inspections could leave blind spots in drug quality.
"We value the work the FDA is doing to ensure quality in our drug supply chain; however, we know this task can be difficult to accomplish given that manufacturing is a globalized business and the FDA has a much more difficult task at hand today than they did 20 years ago," Almeter said.