The observations cited in the Form 483 range from improper validation to out-of-specification test results. Specifically the agency took issue with the fact that equipment used to manufacture drugs at the plant is not appropriately validated. One encapsulator for Rytary – the company’s potential idiopathic Parkinson's disease treatment -- has not been shown to deliver consistent amounts of component populations.
Rytary was rejected by the FDA in January 2013 due to cGMP issues at another Impax manufacturing site in Hayward, California. In May 2013 the company hired specialists to help it sort out its manufacturing issues.
In addition, the FDA says in its Form 483 for the Taiwanese facility that drug products “failing to meet established specifications are not rejected.” The company also fails to establish procedures “designed to prevent objectionable microorganisms in drug products not required to be sterile.”
Furthermore, the company failed to use enough testing material in its microbial limit tests for Rytary, its anti-diabetic drug Acarbose, and raw materials, such as Povidone. The FDA also cited the company for failing to initiate a timely corrective and preventive action plan for deviations in raw materials after metal was found in Fenofibrate 200 mg capsules.
Fred Wilkinson, president and CEO of Impax Laboratories, said in a statement: "We are already working diligently to address the observations raised by the FDA and will respond to these observations within the required 15 business day period from the receipt of the Form 483. We remain committed to our overarching goal of implementing a world class continuous quality improvement program and maintaining the highest quality standards across our facilities."
The Taiwan facility was approved for product manufacturing by the FDA in September 2009 and by the Taiwan FDA in July 2010. The facility currently manufactures 12 products for distribution in the US.
The company also said that the FDA did not provide any status or classification to these observations and, as is normal practice, the agency will wait until they have received and reviewed the company's response to provide this information. The company has also not been informed by the FDA of the impact this Form 483 may have on Rytary's October 9, 2014 review date under the Prescription Drug User Fee Act (PDUFA).