Shredding Key Documents and Leading Investigators to Incorrect Rooms - An unusual FDA Warning Letter

The U.S. Food and Drug Administration (FDA) has issued a warning letter dated March 10, 2020, to India-based pharmaceutical manufacturer Windlas Healthcare Private Limited, who was placed on Import Alert 66-40 on January 21, 2020.

During an inspection from August 26 to 30, 2019, the FDA investigators observed significant violations of current good manufacturing practice (cGMP) regulations for finished pharmaceuticals.

Samples were retested until passing results were achieved

According to the FDA, the firm "did not maintain complete and accurate data from all laboratory testing." Furthermore, the firm "failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications."

For example, the FDA lists the following observations:

• The inspector found unknown peaks in gas chromatography (GC) that were not reported or integrated as required per the firm's SOPs.
• The peak detection function was disabled multiple times during the GC residual solvent testing.
• Unknown peaks were observed, which were not identified or integrated as discussed.
• Unknown peaks were not reported or integrated during the method transfer of related compounds testing for API batches.
• Multiple investigations lacked adequate scientific rationale for root cause determination.
• A test was repeated four times, each time with a new test solution. The first three tests failed. The firm reported only the final, passing data.

The FDA expects, among other requirements, a retrospective, independent review of all invalidated laboratory incidents and out-of-specifications (OOS) results for U.S. products.

Unusual observations during the inspection

In the warning letter, the FDA describes in detail two very unusual observations.

First of all, it says: "When our investigators arrived at your firm just 30 minutes after announcing our inspection, they observed numerous employees in the process of moving off-site cartloads of trash bags containing shredded and tom documents and binders. Upon closer examination, the investigators discovered batch reconciliation forms, cleaning and dispensing logs, training assessments, and scale balance printouts."

The company argued that the employees violated the internal documentation procedure. As the root cause, the company identified an "inadequate awareness of data integrity principles, training and education, supervision, and problem-solving capabilities." For the FDA, this response was inadequate in that it did not fully evaluate the scope of this deficiency.

Later in the inspection, the FDA inspector noted that "live-feed cameras showed production staff expediently signing and passing documents to one another." When requesting to visit the production staff location, the inspector was routed to an incorrect area. According to the FDA, this incident delayed the investigator and "prevented contemporaneous verification of the activities being performed."

In response to the form FDA 483, Windlas Healthcare Private Limited argued that the firm's procedure for camera locations was incorrect. This was also found to be inadequate by the FDA, as the company did not "address why two QU personnel reviewed and approved an incorrect camera location procedure approximately one week before the start of this inspection."

Based upon the nature of the violations, the FDA strongly recommends engaging a consultant to assist Windlas Healthcare Private Limited in meeting cGMP requirements. The FDA also required the company to perform a detailed evaluation and to provide a response within 15 working days. The company should specify what was done since the inspection to correct the violations and to prevent their recurrence.

The original warning letter to Windlas Healthcare Private Limited is published on the FDA website.