“There is no quality control unit”: Emerging FDA Concerns in India

This week, the US Food and Drug Administration (FDA) posted its observations at Alembic Pharmaceuticals and Alkem Laboratories. The serious observations at both the companies come as yet another setback for the Indian pharmaceutical industry.

After eight days of inspecting Alkem’s finished formulation facility in March 2018, the FDA investigators concluded — “there is no quality control unit”.

Alkem’s head of quality control (QC) and quality assurance (QA) confirmed out-of-specification (OOS) results for the assay for a batch of tablets. However, the company did not recall the product, which was distributed in the US market.

Less than three weeks before the inspection, the “firm’s QC department deleted two-thousand one hundred one (2,101) files” on its computer network.

The investigators also found that the organization had a widespread practice of destroying logbooks.

Alkem’s Quality Unit also failed to conduct an investigation when unknown peaks on its chromatography systems were observed as they had activated the ‘inhibit integration’ function.

The practice of adjusting the settings of the chromatography systems to achieve favorable results has become a recurring observation ever since audit trails have been enabled.

The FDA found that the firm used electronic records. However, “they do not meet requirements to ensure that they are trustworthy, reliable and generally equivalent to paper records”. The Form 483 mentions “this is a repeat observation” and also found QC analysts entering data electronically into an excel spreadsheet in the absence of raw data.

There were also observations of walls being “spotted, dirty” and with “fungal growth”. The quality control area had “flying insects, including, but not limited to, mosquitos and gnats” which were too numerous to count, the FDA observed.

Alembic invalidates over 90 percent of its OOS results

In the seven days that the FDA investigator — Jessica L Pressley — spent at Alembic’s oral solid dosage manufacturing facility in Tajpura, Gujarat, she uncovered that the firm invalidated 131 of the 140 OOS results (an invalidation rate of 94 percent) for products marketed in the US. The firm attributed the invalidation to analyst errors. In 2017, the invalidation rate was 91 percent.

The Form 483 shares a concern that the “OOS results that were invalidated by the firm’s QC unit were without rationale and supporting documentation.”

The investigator found an analyst conducting analysis for multiple US marketed drug products for which “she was not properly trained on the test methods”.

“In addition, your firm failed to take appropriate corrective and preventive actions to re-qualify the analyst in a timely manner and instead allowed her to conduct analyses,” Pressley added.

At Alembic, there was also a concern over Hold Time Studies (studies that establish the time limit for holding the materials at different stages of production) that were conducted for drug products marketed in the US as the batch sizes used to establish hold times did not represent the commercial batch size of the drug products.

Our view

The latest 483s posted by the FDA demonstrate an emerging trend of compliance concerns at key players of the Indian pharmaceutical industry.

The concerns at Alembic regarding Hold Time Studies and the invalidation of OOS results resemble the observations at Lupin, which received a warning letter for its formulation manufacturing facilities in Goa and Indore. Lupin had failed to “thoroughly review any unexplained discrepancy”.

Lupin invalidated approximately 96 percent of all OOS results obtained at Pithampur and over 75 percent of them in Goa.

In the beginning of the year, PharmaCompass had shared how “Dr Reddy’s GMP problems provide a guide for upcoming FDA inspections” and companies should be prepared for in-depth, real-time scrutiny of production and analytical operations and procedures. We also highlighted how “employee retraining is not an effective corrective or preventive action for recurring problems.”

The concerns at Alkem and Alembic only reinforce the issues highlighted by us.

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Image Credit : gotta match ? by LASZLO ILYES is licensed under CC BY 2.0 // Modification: “There is no quality control unit” EMERGING FDA CONCERNS IN INDIA was added to the original image

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Alembic invalidates over 90 percent of its OOS results

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