Falling paint chips, dirt and rust--in addition to storage of rejected API in proximity to accepted material--have gotten American Pacific Corp Fine Chemicals in hot water with the FDA. A warning letter sent to the Rancho Cordova, CA, drugmaker in June follows a February visit during which FDA inspectors found the manufacturing deviations.
AMPAC had responded to the FDA regarding its completed and intended actions relating to the missteps, but the company apparently provided too little detail to assuage the regulator's concerns.
The name of the game is confidence when it comes to FDA warning letter replies. To get out of a GMP-violation mess as quickly as possible, drugmakers must make the FDA confident that they understand both the operations problems and their importance. And drugmakers must exude confidence concerning their ability to make the fixes.
AMPAC has fallen short, based on the FDA's comebacks to the company's response. For example, inspectors found dirt, blistering paint, rust and oil droplets near manufacturing equipment. Operators too had reported finding paint chips while manufacturing the API temozolomide, and eventually rejected the batch. The variance report filed following the incident explained that "the paint chips could have fallen into the reactor during solid charging (e.g., during preparation of the crude or during the purification of the material)," according to the warning letter.
The company responded by saying it attempted to fix the problem. But the fixes following the investigation were not effective. Not nearly a good enough response, the regulator says: "You provided no information concerning subsequent corrective actions implemented to reduce the risk of contamination."
Likewise, inspectors found a drum of returned temozolomide API stored in the same area as drums of the substance labeled as accepted and ready for release. The returned drum carried no indication of its status. AMPAC replied that it had developed new procedures regarding rejected batches. "Your response is inadequate because you have not addressed how you will manage returned APIs," the letter says.
- here's the warning letter