FDA cites Sun Pharma with litany of GMP violations, including poor aseptic practices

Regulatory NewsRegulatory News | 11 January 2023 |  By 

The US Food and Drug Administration (FDA) admonished Sun Pharmaceutical Industries in a recent warning letter for a several good manufacturing practice (GMP) violations, including poor aseptic practices, inadequate cleanroom design and environmental monitoring and failure to keep manufacturing equipment clean.
 
These violations prompted FDA to place the firm on import alert on 7 December.
 
FDA inspected the firm’s Gujarat India facility from 26 April to 9 May 2022. The agency told the firm that “because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drug products are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B).”
 
FDA said the firm failed to have adequate safeguards for preventing microbiological contamination, including running media fills which failed to “accurately simulate” commercial operations for medroxyprogesterone acetate injectable suspension USP, 150 mg/mL prefilled syringes and vials.
 
Personnel simulated the manual addition of sterile active pharmaceutical ingredients (API) material to the compounding tank, yet this process was not consistent with routine commercial manufacturing, where a different amount of sterile API was added to the canisters.
 
“If a media fill program fails to incorporate contamination risk factors and closely simulate actual drug product exposure, the state of process control and sterility assurance cannot be accurately assessed,” said FDA.
 
In a related area, FDA lambasted the firm’s poor aseptic practices, such as having an operator sticking his gloved hand into a sterile canister, and operator movements in critical filling areas that were not slow and deliberate.
 
The company also failed to perform a timely risk assessment of distributed medroxyprogesterone acetate injectable suspension pre-filled syringes that were affected by a “significant” media fill failure in November 2021. The company waited more than five months to recall the affected batches, and its failure to resolve these issues in a timely way put patients at risk, according to FDA.
 
FDA investigators also charged that ISO 5 cleanroom areas were “poorly designed” and “lacked adequate protections.” For example, the cleanroom areas lacked physical barriers to prevent potential contamination of sterile API during “manually intensive” dispensing and compounding operations where operators’ bodies and hands were in immediate proximity to the sterile API during dispensing, compounding and syringe-loading in the filling station.
 
Sun also lacked a robust environmental monitoring program, the warning letter states, and “failed to perform viable (surface and air) environmental monitoring in close proximity to aseptic dispensing operations.”
 
Lastly, equipment was not suitable designed for filling of viscous parenteral drug product. “Inappropriately designed vial filling equipment led to substantial extraneous matter contamination in testosterone cypionate injection 200 mg/mL, 1 ml vials. Further, your production department failed to establish adequate personnel practices and supervisory oversight to prevent the use of damaged equipment.”
 
The firm also failed to adequately investigate “substantial” water leaks on the service floor, and attributed leaks to an “old, punctured” piece of equipment.
 
“Although you sealed gaps in the ceiling, you did not sufficiently inspect the service floor… for mold growth and water damage after the repairs were made.”
 
Lastly, FDA said the firm failed to adequately clean and maintain equipment used for drug product manufacturing. Investigators observed visible residue on equipment after it was identified as clean. Also, colored particles and pellets containing the API were observed inside equipment crevices.
 
FDA told the firm that “significant findings in this letter demonstrate that your firm does not operate an effective quality system in accordance with CGMP. In addition to the lack of effective oversight of production operations to ensure reliable facilities and equipment, we found your QU is insufficiently resourced or enabled with authority to carry out its responsibilities.”
 
FDA gave the company 15 days to respond to the warning letter.
 
Warning letter
 
 

 

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