Serious aseptic and sterility violations, including water damage and leaks in parenteral manufacturing areas, were documented by the US Food and Drug Administration (FDA) in the latest warning letter for Sun Pharmaceutical’s manufacturing plant in Halol, India.
Since the September 2014 inspection, FDA has withheld future product approvals from the Halol facility.
The company was cited in a separate warning letter in May 2014 for data integrity concerns (trash bags of good manufacturing practice records were found) at its manufacturing site in Gujarat, India, which is also included on FDA’s import alert list.
As far as this latest warning, Sun Pharma said it has already responded to the observations “with a robust remediation process that is still on-going, with significant investments in automation and training to enhance its Quality Systems.”
FDA documents numerous sterility concerns, particularly in the way that media fill records failed to include a specific description for why Sun rejected vials from certain batches.
“During the inspection, your deputy general manager and your Quality Assurance (QA) manager confirmed that the rejected vials were discarded during the media fill process without assignable causes recorded or documented,” FDA said.
In addition, the company failed to perform adequate airflow studies to determine how the movement of air and personnel during aseptic operations could pose sterility risks.
FDA calls on Sun to perform a risk assessment for its practice of rejecting media fill vials without a written justification and acceptance limits, as well as a revised standard operating procedure on media fills, specifically addressing the changes made on the rejection and investigation of these non-integral vials.
The company also failed to provide information on unknown impurities discovered in a six-month accelerated stability test (for products later distributed in the US), which was attributed to failures in product degradation from one of the company’s processes, but Sun failed to identify the specific impurities or their root causes.
In addition, Sun lacked audit trails or other controls to trace individuals who access the programmable logic controller levels or man-machine interface equipment.
One of FDA’s investigators also documented water leaks, stains and ceiling damage in the parenteral manufacturing area personnel corridor. Buckets with water collected from ceiling leaks in the manufacturing area were also found.
FDA calls on the company to address the “impact on environmental control from the start of the leakage and for the subsequent six months. Include all instances in which fungi or bacterial spore formers were identified, and also explain to what extent microbial identifications were done in these areas.”