FDA Issues Warning Letter to Torrent Pharmaceuticals Over Impurities in Sartan APIs
The US Food and Drug Administration (FDA) has posted a Warning Letter to Torrent Pharmaceuticals in Ahmedabad, Gujarat, India for several manufacturing violations at its facility in Taluka-Kadi, Indrad, Gujarat, India. Torrent manufactures losartan potassium tablets and has been one subject of an ongoing global investigation into nitrosamine impurities in angiotensin II receptor blockers, such as valsartan, losartan and irbesartan.
The Warning Letter follows the FDA’s inspection of the facility from April 8 to 16, 2019 and outlines several manufacturing violations, including failure to follow written procedures for production and process control and failure to adequately investigate batch discrepancies.
Specifically, the FDA cited the company for not appropriately following its written and approved process validation (PV) protocol that required quality attributes to be met for three consecutive batches to qualify an alternate active pharmaceutical ingredient (API). The agency said that several PV batches using a new alternate API were manufactured for losartan potassium tablets USP 50 mg and USP 100 mg without appropriately following the company’s protocol.
The agency also said in its Warning Letter that the company’s investigations into out-of-specification (OOS) testing results were inadequate. The agency said that multiple OOS investigations were closed without assignable root cause or lacked adequate scientific justification for root cause and that the company disregarded initial failing OOS results and released batches based on retested results.
The FDA is requiring the company to take several actions. With respect to process validation, the agency is requiring the company to provide: (1) a detailed summary of its validation program for ensuring a state of control throughout the product lifecycle, along with associated procedures; (2) a timeline for performing appropriate process performance qualification for each of its marketed drug products; and (3) a review of all data that supports its process validation for commercially distributed drug products.
With respect its OOS investigations, the FDA is requiring the company to provide a retrospective, third-party review of all invalidated OOS (including in-process and release/stability testing) results for products currently in the US market and within expiry as of the date of the Warning Letter and a report summarizing the findings of the analysis, including specific details for each OOS.
In its Warning Letter, the FDA acknowledged that the company has hired a consultant to address these issues.