FDA highlights procedural lapses at Cipla’s MP facility

The U.S. drug regulator has flagged quality and procedural lapses at Cipla Ltd.’s manufacturing facility in Pithampur, Madhya Pradesh.

The United States Food and Drug Administration conducted a current good manufacturing practises inspection at the sterile and non-sterile drug manufacturing facility in Pithampur from Feb. 6 through Feb. 17, the company said in an exchange filing on Feb. 18. “On conclusion of the inspection, the company has received eight inspectional observations in Form 483.”

Form 483 is issued when investigators have observed any condition that, in their judgment, may constitute a violation of the Federal Food, Drug, and Cosmetic Act and related acts.

“The company will work closely with the U.S. FDA and is committed to addressing these comprehensively within the stipulated time,” the company had said.

BQ Prime has obtained a copy of the observations.

Key highlights:

• Failure to review any unexplained discrepancy or failure of a batch or any components to meet specifications. A questionable media fill batch with turbidity was approved without identifying the root cause, and commercial batches were released.
• Procedures, especially manufacturing process simulation procedures designed to prevent microbiological contamination of drug products purporting to be sterile, are deficient to ensure safety and effectiveness. During manufacturing, various instances of breakdown and power failure were noted, and cleaning, which is considered the worst intervention that occurs rarely, was performed during media fill studies.
• Aseptic processing areas are deficient regarding the system for monitoring environmental conditions. The reports did not evaluate airflow patterns that showed turbulence or where certain surfaces were exposed to ensure no microbial contamination. The environmental monitoring of aseptic filling areas did not ensure that microbial contaminants that could impact critical areas were identified and investigated for products exported to the US. Surface swab samples were not collected during filling, and commercial lots of drug products were distributed in the US.
• Appropriate controls are not exercised over computers and related systems used in the manufacturing of commercial drugs to assure that original electronic data pertaining to critical process parameters and alarms is backed up, archived, and retained. Two separate instances were noted.
• Procedures related to the handling or investigation of oral and written complaints are inadequately written or followed. Some complaints were left open for extended periods, the quality unit failed to implement corrective actions to reduce the number of complaints received related to product performance, and repetitive complaints were received.
• Failure to submit a field alert report for complaints received, as required under the standard operating procedures, in the case of receipt of information concerning a failure of distributed drug batches to meet specifications. Potentially defective batches were used for manufacturing. Similar complaints were received associated with drug performance later.
• The quality unit failed to retain numerous original records of good manufacturing practices. Procedures requiring hard copies of documents to be retained until product expiry were not followed. There was a failure to take market action as per the product recall procedure.
• Laboratory records do not include complete data derived from tests, examinations, and assays necessary to assure compliance with established specifications and standards.

Cipla is yet to respond to BQ Prime’s emailed queries on the implications of the observations, steps being taken to address these issues, expected timelines for resolution, and whether there are any pending approvals from the facility that would be impacted.The company has a key launch—gAdvair for lung medication—from the facility that could be affected.

Vishal Manchanda, pharma analyst at Systematix, told BQ Prime, “The observations are grave, and we expect it to translate into an ‘official action indicated,’ which should delay the much-awaited gAdvair approval.”

An OAI classification would indicate a finding of objectionable conditions and recommend regulatory action by the U.S. regulatory authority.

Shares of Cipla were trading 3.84% lower as of 2.19 p.m. in comparison to a 0.7% decline in the Sensex. Bloomberg