Inadequate follow-up after the discovery of particle contamination and poor aseptic technique on the production line highlight GMP violations in Warning Letter NWE-10-18W. The letter's recipient, Thomas D'Ambra, is CEO at Albany Molecular Research; the facility is that of Hyaluron, a Massachusetts CMO that it purchased in June.
Hyaluron specializes in aseptic fill services for liquid and lyophilized products. Its Bubble Free technology for parenterals, involving online vacuum filling and stoppering, is among the capabilities that attracted AMRI, affording it access to the prefilled syringe business.
The warning cites three instances of inadequate investigation of contamination, which involved particles as large as 8 mm in syringes and 5 mm in vials. One instance involved particles "short, dark, and fiber-like." The FDA says the company neglected to re-inspect the remainder of the sub-lots. Nor did Hyaluron conduct a risk assessment to discern the effect on product quality.
The FDA inspection took place in March. The company's April response "lacks sufficient corrective actions," the letter says. "Your response states that the products were manufactured in compliance with CGMP because all release specifications were met and all non-conforming units were rejected," according to the letter. But the FDA then asks the company to review rejected-lot batch records for trends and to determine the severity of the rejects. "Inform both the appropriate client and FDA of your findings and all follow-up corrective and preventative actions you intend to take."
Concerning aseptic technique, the FDA notes in the letter that inspectors saw manufacturing technicians "stabbing at stoppers with the blade end of a scalpel to move them," in addition to such gowning violations as wiping sterile gowning pant legs on the floor. The regulator says it agrees with the company's response action of discontinuing poor practices, revising procedures and providing additional employee training. But it also says the company should review all SOPs and cleanroom practices to identify elements that jeopardize product quality. "In your response, please provide a time frame for completing this review."