Aurobindo warned for lax investigations, repeat GMP violations

The US Food and Drug Administration (FDA) hit Indian drugmaker Aurobindo with a warning letter for inadequately investigating batch failures related to its manufacturing of active pharmaceutical ingredients (APIs) and for failing to evaluate the potential effect of changes on its intermediates and APIs.

The firm was warned for “significant deviations from current good manufacturing practice (CGMP) for active pharmaceutical ingredients.”

The company’s Telanga, Hyderabad site was handed the warning letter following an August 2021 inspection. It was issued on 12 January 2022 and posted to FDA’s website on earlier this week.

The firm was targeted for failing to evaluate the effect of changes on the quality of drug intermediates and APIs. For example, the company increased acceptance limits for starting materials without evaluating the effect of this increase on the quality of drug intermediates and the APIs.

The warning letter said that the company “performed a lab scale study to justify an increase in the acceptable [redacted] limit.” Yet the firm did not consider the “generation of the other substituted potential impurities” before increasing the acceptable limit of the starting material.

The firm was also criticized for not “fully” investigating discrepancies in test results. The heavily redacted warning letter notes that “during method transfer for the gas chromatography-mass spectrometry (GC-MS) … you failed to pass the method transfer acceptance criteria for inter laboratory precision because of observed peak splitting.”

The agency said the failing result was invalidated “without a scientific rationale.” The firm attributed the failing result to a “dirty and/or degraded column” and replaced the column with a fresh sample and obtained a passing result.

In its response to FDA, Aurobindo “reconfirmed” that the column was the root cause for the failing results, and that the GC-MS method had been adequately transferred. The company affirmed the failing test was the result of an “isolated” incident from an interaction of the sample with the deteriorated column.

FDA was not satisfied with this response, stating “if the assigned root cause is an inherent instability between with the sample and a deteriorated GC-MS column, you failed to provide any equipment controls to prevent peak splitting in the future, not did you consider whether the analytical methods was appropriate for the intended [redacted] testing.”

FDA said similar cGMP violations were observed and discussed with the company during a 29 July 2019 meeting. The agency said that “repeated failures demonstrate that executive management oversight and control over the manufacture of drugs is inadequate.”

The agency warned it may “withhold approval of new applications or supplements listing your drug as a drug manufacturer until any deviations are completely addressed and we confirm your compliance with CGMP.”

The company has been cited for previous GMP violations in earlier inspections.

In June 2019, the firm was slapped with a warning letter related to nitrosamine impurities found in its angiotensin II receptor blockers (ARBs), prompting FDA to recall hundreds of lots of the drugs from multiple manufacturers. That letter went to the company’s site in Srikakulam District, Andhra Pradesh, India. (RELATED: FDA sends warning letters to Aurobindo, API repackers, Regulatory Focus 3 July 2019).

Four months later, in October 2019, Aurobindo’s site in in Polepally, India, received a Form 483 for deficient OOS investigations and product complaint investigations. (RELATED: FDA sends Form 483s to Lupin, Aurobindo and Cipla sites, Regulatory Focus 14 October 2019)

Warning Letter

Aurobindo warned for lax investigations, repeat GMP violations

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