WARNING LETTER Windlas Healthcare Private Limited MARCS-CMS 595494 — MARCH 10, 2020
1. Your firm failed to ensure that laboratory records included complete data derived from all tests necessary to ensure compliance with established specifications and standards (21 CFR 211.194(a)).
Your firm did not maintain complete and accurate data from all laboratory testing. Without reliable laboratory data, you cannot assure appropriate decisions regarding batch release, product stability, and other drug aspects of quality. For example:
a. On May 19, 2018, the peak detection function was disabled multiple times during the gas chromatography (GC) residual solvent testing of your incoming active pharmaceutical ingredient (API), (b)(4) batch (b)(4). After reviewing the chromatograms, our investigators noted unknown peaks that were not reported or integrated as required per your procedure.
Our investigators requested your firm to reprocess the sample set sequence, which subsequently showed > (b)(4)% total unknown impurity peaks. You used this batch of API to manufacture multiple batches of (b)(4) tablets which were released to the U.S. market.
This was not an isolated incident. Our investigators also noted unknown peaks which were not reported or integrated during the method transfer of related compounds testing for (b)(4) USP API batch (b)(4). Your firm did this study to support the (b)(4) for (b)(4) tablets....
b. On April 16, 2019, you cancelled a test sequence during 18-month related substances testing that included (b)(4) mg tablets batch (b)(4). Your investigation stated the cancellation was due to "oven leak error." The chromatogram for this initial run showed impurities that would yield an out-of-specifications (OOS) result. The initial run was invalidated, and you prepared and tested a new sample solution on April 17, 2019. The retest failed percent relative standard deviation (RSD) and you invalidated this second run too. On April 22, 2019, you prepared a third sample solution and repeated the test. The third sample solution also failed percent RSD and again you invalidated the run. On April 29, 2019, you prepared a fourth sample solution. This test yielded passing data. You reported the final, passing data after multiple testing failures. You did not adequately investigate the failing results as required by your laboratory incidents (LI) procedure. Your firm also did not identify clear root causes for the repeated analytical problems that caused you to invalidate the first three analyses.
2. Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).
Your investigations into laboratory incidents (LI) testing results are inadequate. Multiple LI investigations lacked adequate scientific rationale for root cause determination. Without adequate scientific rationale, your firm invalidated the failing OOS results that were included in these LI. You subsequently reported the passing retest results.
For example, during your analytical method verification for residual solvent for (b)(4) API, your firm initiated numerous LI concerning failures of the test's accuracy, method precision, or intermediate precision parameters. The probable root causes of these LI were attributed to contamination and analyst error. We note your retesting plans did not specify retesting by an analyst other than the one who performed the original test. In addition, samples were retested until passing results were achieved. Your CAPA for these LI stated "training on standard operating procedure (SOP) of 'Good laboratory practices of QC laboratory' shall be imparted to concern person [sic]." Your method verification report was approved on May 3, 2018. We note that on May 19, 2018, unknown peaks were observed using this test method which were not identified or integrated as discussed in Charge 1 of this letter.
