WARNING LETTER KVK-Tech, Inc MARCS-CMS 592387 — FEBRUARY 11, 2020
1. Your firm failed to establish and document the accuracy, sensitivity, specificity, and reproducibility of its test methods (21 CFR 211.165(e)).
Your firm failed to properly integrate co-eluting peaks during impurity testing of phentermine HCL capsules, which resulted in your analysis failing to detect out-of-specification (OOS) results for at least one lot of drug product.
You self-identified this problem in 2016. In a deviation report, you wrote that analysts were using “(b)(4) methods” and the “reported impurity levels may not reflect the true concentrations found in the drug.” Your firm conducted training on May 24, 2016, reportedly to teach analysts to properly integrate and measure closely co-eluting peaks during impurity analysis of your drugs. Despite this training, in December 2016 your analyst performed (b)(4) integration to calculate the area of the peaks for a stability impurity test for Lot 12456A of phentermine HCL capsules. If the appropriate (b)(4) integration had been performed, the test result for the drug product lot would have exceeded the impurity specification limits. This lot remained on the market until it failed (b)(4) stability impurity testing on June 20, 2017. Your secondary quality review of the December assay also failed to detect the error. Multiple examples of your firm’s failure to properly integrate closely co-eluting peaks were observed during our inspection...
3. Your firm failed to exercise appropriate controls over computer or related systems to assure that only authorized personnel institute changes in master production and control records, or other records (21 CFR 211.68(b)).
Data generated from your laboratory testing systems is not adequately protected from deletion or alteration. For example, (b)(4) of your quality assurance employees had administrator access privileges in (b)(4) chromatographic testing software, which is used for HPLC assay and impurity analysis of finished drug products.
Additionally, data files could be modified or overwritten without being captured on audit trails on your stand-alone laboratory equipment, including your (b)(4) spectrophotometer, and Fourier transform infrared spectrophotometer...
