U.S. FDA issues warning letter to Intas Pharma over manufacturing lapses

The US-based food and drugs agency U.S. FDA (US Food and Drug Administration) has issued a warning letter to Ahmedabad-based pharma company Intas Pharmaceuticals for violations involving manufacturing lapses, including those related to current good manufacturing practice rules.

The warning letter pertains to the USFDA's inspection of the company's facility from May 1 to May 12, 2023. The letter flags significant violations of current good manufacturing practice (CGMP) rules for finished pharmaceuticals.

"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)," the US FDA letter, issued after receiving the company's response, reads.

The agency asks the company to correct these violations “promptly”. “FDA may withhold approval of new applications or supplements listing your firm as a drug manufacturer until any violations are completely addressed and we confirm your compliance with CGMP. We may re-inspect to verify that you have completed corrective actions to any violations," the U.S. FDA says in its warning letter.

During the inspection, the US agency found the company's quality control unit failed to ensure drug products manufactured meet specifications for "identity, strength, quality, and purity".

The violations include adequate oversight and ensuring the reliability of data related to the quality of finished drug products manufactured at the facility.

"Since 2021, visual inspectors manipulated particle and other defect counts on manual visual inspection records in many instances, in order to keep the finished product batches within rejection limits," the probe revealed.

More specifically, the probe found operators manipulated the defect quantities “to keep the category-wise rejections within limits to avoid a deviation and investigation.”

The agency also accused the company of “failing 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.

In addition to that, Intas also allegedly "failed to establish adequate written procedures for production and process controls". These are designed to give the drug products identity, strength, purity, and quality.

The company also failed to follow appropriate written procedures designed to prevent "microbiological contamination of drug products" purporting to be sterile, including validation of all aseptic and sterilisation processes. "Your procedures did not include a requirement for smoke studies to be performed in dynamic conditions in classified critical areas."

Notably, thorough smoke studies are essential to evaluate and qualify aseptic processing operations and ensure appropriate implementation of needed design remediations. The U.S. FDA concluded these violations are not intended to be "an all-inclusive list" of violations, but the company is responsible for investigating and determining these causes.