FDA 483 - Lupin Limited - February 08, 2019

This FDA Form 483 document details observations from an inspection, citing two key violations.

**Observation 1** addresses a failure to thoroughly review unexplained discrepancies and out-of-specification (OOS) results, specifically regarding procedure CQA-004-17 "Handling of out of Specification test results." The procedure lacks statistical justification for releasing batches based on retest data. An OOS investigation (OOS/C/18/GA/FP/042) for (b)(4) and (b)(4) tablets USP (b)(4) mg / (b)(4) mg, Batch Nos. (b)(4) and (b)(4), showed initial assay failures. Retesting involved reinjection, re-vialing, and re-dilution without establishing system precision. Although a dilution error was identified as the root cause, tabulated results did not substantiate area responses, and the impact of standard response on assay was not evaluated. A third-party consultant initially found the root cause unsatisfactory but later concurred. These batches were released to the US market based on confirmatory tests.

**Observation 2** highlights the absence of written procedures for production and process controls to assure drug product identity, strength, quality, and purity. Specifically, the (b)(4) procedure, as per approved batch records, requires continuous (b)(4) without discharge. However, during manufacturing, the (b)(4) is discharged into