The US Food and Drug Administration’s (FDA) Center for Drug Evaluation and Research (CDER) on Tuesday released four warning letters sent to prescription drug, active pharmaceutical ingredient (API) and over-the-counter (OTC) drug manufacturers in China, India and Canada.
Outlined below are the violations and FDA’s comments, with links to the warning letters in the sub-headings.
Apotex Research Private Limited
Just a day after receiving the first expedited generic drug approval, Apotex received a warning letter on 9 August at its Bangalore, India-based drug manufacturing site for failing to thoroughly investigate any unexplained discrepancy or failure of a batch and for failing to establish valid in-process specifications.
“Your investigations into out-of-specification (OOS) laboratory results and manufacturing deviations are insufficient and do not include scientifically-supported conclusions,” FDA said, offering four examples.
FDA also said the firm’s inspectional history indicates that the quality unit “does not fully exercise authority, such as ensuring that appropriate investigations are performed with sound conclusions, identifying root causes, and supporting scientific justification. Your firm must provide your quality unit with appropriate authority, sufficient resources, and staff to carry out its responsibilities and consistently ensure drug quality.”
Yicheng Goto Pharmaceuticals Co., Ltd.
The Xiangyang, China-based API manufacturer was cited for four violations, including failures to adequately validate the process for cleaning and maintaining equipment, to ensure that all test procedures are scientifically sound and appropriate, and to design a documented stability program to monitor the stability characteristics of API.
“FDA cited similar CGMP observations during inspections we conducted from September 12 to 15, 2011; and September 1 to 4, 2014. You proposed specific remediation for these observations in your responses. These repeated failures demonstrate that your management’s oversight and control over the manufacture of intermediates and API is inadequate,” the warning letter says.
JT Cosmetics & Chemicals Pvt. Ltd.
The Gujarat, India-based OTC drug manufacturer was cited by FDA for releasing products without testing for the identity and strength of active ingredients. The firm was cited for inadequate master and batch production records and for failing to test incoming raw materials, including active ingredients, for their identity, purity, strength or other quality attributes.
“Your personnel also informed our investigators during the inspection that microbiological test results recorded on your certificates of analysis (COA) in support of your decision to distribute drugs were falsified, and the testing had not been performed,” the warning letter says.
Bill Beauty and Health Products Ltd.
The Ontario, Canada-based OTC drugmaker was found to have released products to the US without testing the identity and strength of each API.
“Your firm failed to perform identity tests on incoming API. Your firm also failed to test incoming API and other components to determine their conformance to purity, strength, and other appropriate specifications,” FDA said.
“Your firm has not validated the processes used to manufacture your drug products. You failed to perform process qualification studies, and lacked an ongoing program for monitoring process control to ensure stable operations and consistent drug quality.”