FDA again warns Sun Pharma over Dadra facility

Generic drugmaker Sun Pharmaceuticals was reprimanded by the US Food and Drug Administration (FDA) for several violations of good manufacturing practices (GMPs) at one of its facilities in India.

The warning letter cites the company for inadequately investigating batch failures and for cleaning lapses and follows other recent warning letters and a consent decree related to similar GMP issues.

In an 18 June warning letter posted on Tuesday, FDA cited the company for GMP problems found at its Dadra site in Dadra and Nagar Haveli and Daman and Diu during an inspection in mid-December 2023. On its website, the company claims to be the fourth largest specialty generic pharmaceutical company in the world.

Investigators noted that the firm “failed to adequately clean and maintain your equipment used for drug product manufacturing.” Investigators noted that 450mL of an unspecified “stagnant liquid” within a non-dedicated piece of equipment that was used to make multiple drug products.

A chemical analysis of the unknown liquid using liquid chromatography mass spectrometry (LC/MS) found “numerous peaks” in the liquid and a microbiological analysis identified “too numerous to count” (TNTC) results for yeast and mold.

The company attributed the liquid accumulation to a valve on the equipment which failed to close when it was disassembled in June 2023. The company said that drug products and APIs were identified in each liquid. The firm also identified microorganisms Sphingomonas paucimobilis, Bordetella bronchiseptica, and Pseudomonas stutzeri in the liquid.

The firm recalled batches that were affected between June 2023 and December 2023. Yet this did not allay FDA’s concerns on Sun’s handling of this cross-contamination situation. “You failed to provide a full characterization of each unknown peak from your chemical analysis. It remains imperative that your investigations are comprehensive to prevent recurrence of inadequate equipment maintenance. We also understand from your recent correspondence that a third-party consultant identified numerous gaps in your equipment maintenance program, but you conclude no critical or major findings were noted.”

The firm also conducted out of specification (OOS) investigations which “lacked scientific rationale for root cause determinations.” For example, the firm was conducting an OOS investigation for an unknown impurity detected in a sampling of tablets placed on a 12-month stability sample. The result exceeded specifications and the firm attributed the problem to “dirty glassware.” After reopening the investigation, the company noted the root cause stemmed from contamination from another product.

The agency said that the company “did not explain why root cause determinations in the OOS investigation were accepted by your firm multiple times, although insufficiently justified.”

Repeat observations

The warning letter repeats earlier observations made in previous warning letters to Sun citing the same facility in March 2019, for problems related to inadequate equipment cleaning, and in April 2017, for lax investigation into batch failures.

Other sites in Sun’s manufacturing network have been cited for other GMP violations; a 15 December 2022 warning letter chastised its site in Halol for poor aseptic processes, inadequate cleanroom design and environmental monitoring and failure to keep manufacturing equipment clean. The warning letter was later amended on 16 October 2023. (RELATED: FDA cites Sun Pharma with litany of GMP violations, including poor aseptic practices, Regulatory Focus 11 January 2023).

In May 2023, Sun was the subject of a consent decree after FDA’s inspections found backdating of records at its Mohali plant.

FDA said that “significant findings in this letter demonstrate that your firm does not operate an effective quality system in accord with CGMP. In addition to the lack of effective management oversight of your production and laboratory operations, we found your QU is not enabled to exercise proper authority and/or has insufficiently implemented its responsibilities. Executive management should immediately and comprehensively assess your company’s global manufacturing operations to ensure that your systems, processes, and products conform to FDA requirements.”

FDA recommended the firm hire a GMP consultant and gave it 15 days to respond to the warning letter. The agency told the firm to correct these violations promptly or it may withhold approval of new applications or supplements.

Warning letter

FDA again warns Sun Pharma over Dadra facility

Related topics

Recommended content

Welcome to the new RAPS Digital Experience