- The Food and Drug Administration has disclosed new details on why it rejected an AstraZeneca medication for high blood potassium levels.
- The agency released an 11-page Form 483 on Wednesday identifying six instances where a production facility in Coppell, Texas, slated to produce the drug in question, called ZS-9, didn't meet the agency's manufacturing standards.
- Form 483s are issued when a facility violates provisions set out by the Food Drug and Cosmetic Act. In the case of the Coppell plant, the agency issued its warning after an inspection that took place between Jan. 18 and Jan. 30.
While much of the Form 483 had been blacked out before its public release, it's clear that manufacturing problems continue to stall ZS-9's move to market.
The FDA cited issues with a range of protocols, from equipment maintenance to data quality control. For example, inspectors noted one of the facility's reactors had a history of interior gaskets that weren't up to code. The reactor's interior gasket had a crack in its head and was missing pieces as of October. Though the gasket was replaced, the new one was in a "similar condition" by the time of the January inspection.
The agency also questioned the reliability of electronic data. Initial testing of one analytical tool yielded "anomalous results," and the FDA criticized the facility for not thoroughly investigating the root cause for those results. There was also insufficient audit documents for another instrument.
"Your firm failed to conduct any sort of analysis into the implications of this instru ment lacking appropriate controls," the agency said of the instrument. "This equipment is used to assess the compliance of all batches to specification."
The form reinforces the notion AstraZeneca hasn't gotten ZS Pharma manufacturing facilities, which includes the Coppell plant, into compliance since acquiring the company for $2.7 billion. Other drugmakers have had similar issues when pursuing M&A. Pfizer picked up a heap of manufacturing sites that weren't up to code when it bought Hospira in 2015, and has been busy shutting them down and responding to warning letters since.