The US Food and Drug Administration (FDA) has slammed Sun Pharma, the country’s largest generic drug maker, for manufacturing violations such as failure to investigate discrepancies in batches of products, not cleaning equipment used in drug manufacturing and failing to prevent contamination at its Halol facility in Gujarat.
In a warning letter, the FDA has highlighted a series of lapses at Sun Pharma’s Gujarat plant, which has been put on an import alert list by the US drug regulator.
In the letter dated December 15, the FDA told Dilip Shanghvi, Managing Director, Sun Pharma, that it had observed significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals at the Halol facility. “Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drug products are adulterated,” the warning letter said.
Also read | FDA's warning letter points to cGMP violations at Halol facility: Sun Pharma
The FDA inspected Sun Pharma’s Halol plant from April 26 to May 9, 2022.
The company gave a detailed response to the US regulator on May 31 in response to Form 483. However, the FDA was not convinced and placed the Halol facility on import alert on December 7. In its letter, the US FDA pointed out that Sun Pharma failed to thoroughly investigate discrepancies in batches of products at the Halol facility.
‘Putting patients at risk’
The regulator said that in November 2021, despite experiencing significant media fill failure, resulting in serious flaws and risks, Sun Pharma failed to perform a timely risk assessment to evaluate if the quality and sterility of its distributed drug products were affected by these deficiencies.
“You waited over five months to initiate a recall of the affected batches. The failure to proactively identify deficiencies and implement timely and sustainable corrective actions and preventive actions (CAPA) is unacceptable because it puts patients at risk,” the warning letter said.
Also read | Sun Pharma clarifies on US FDA import alert on Halol plant
The FDA has further pointed out that Sun Pharma did not follow appropriate procedures to prevent contamination at the Halol facility. “Operators’ bodies and hands were in immediate proximity to the sterile active pharmaceutical ingredient (API) during dispensing, compounding, and syringe-loading in the filling station,” the letter said.
The warning letter also said that the pharma giant had failed to establish an adequate system to monitor environmental conditions. “Vigilant and responsive environmental and personnel monitoring programs should be designed to provide meaningful information on the state of control of your aseptic processing environment,” it said.
According to the warning letter, Sun Pharma had acknowledged the inadequacies of the environmental and personnel monitoring programme, stating that the drug products impacted by the observation are being recalled, and that the specific filling line involved in the observation was no longer in use. “You fail to adequately explain how your quality and operations management will ensure appropriate cleanroom design, control, aseptic practices, and cleanroom behaviour during production,” the letter said.
Failure to investigate discrepancies
The US FDA’s warning letter said that Sun Pharma had failed to use suitable equipment in manufacturing drug products.
“It is your responsibility to ensure that only appropriately designed and maintained equipment are used in the manufacture of your drug products,” the drug regulator said. It further stated: “Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed.”
Sun Pharma has been asked to provide a comprehensive, independent assessment of its overall system for investigation of discrepancies and to provide an action plan detailing how it will fix this system.
Drug contamination concerns
The warning letter from the US FDA also points out that Sun Pharma failed to sterilise equipment and utensils at appropriate intervals to prevent malfunctions or contamination that would alter the purity of a drug. The company has been asked to provide a comprehensive, independent retrospective assessment of cleaning effectiveness to evaluate the scope of cross-contamination hazards.
Also read | FDA's warning letter points to cGMP violations at Halol facility: Sun Pharma
Sun Pharma has been told that basis the findings at the Halol facility, the firm does not have an effective quality system in accordance with CGMP.
Company told to take corrective action immediately
The company has been asked to immediately carry out a comprehensive assessment of its global manufacturing operations to ensure that its systems, processes, and manufactured products conform to FDA requirements.
“Based upon the nature of the violations we identified at your firm, we strongly recommend engaging a consultant qualified to assist your firm in meeting CGMP requirements,” the FDA said.
The regulator, however, says that engaging a consultant does not relieve the firm of its obligation to comply with CGMP. “Your firm’s executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance,” the FDA said.
The FDA has given Sun Pharma 15 working days to respond to the warning letter, address violations and prevent their recurrence.
