FDA 483 - Teva Pharmaceutical Works Private Limited Company - January 29, 2016

This FDA Form 483 document details eleven observations made during an inspection, indicating significant deficiencies in laboratory controls, quality systems, manufacturing processes, and facility maintenance.

**Observation 1** highlights incomplete laboratory records, specifically regarding microbial monitoring. Multiple instances are cited where initial colony counts were recorded, plates discarded, and then re-examined shortly after, revealing significantly different, higher counts. This includes personnel monitoring, surface contact samples, and volumetric air samples. Additionally, records for microbial monitoring samples failed to accurately identify and report colony counts, with examples of widespread growth reported as zero CFU or incomplete calculations.

**Observation 2** identifies a failure to thoroughly review unexplained discrepancies. Investigations into contaminated vials during media fills, where operator behavior was identified as the root cause (e.g., non-sterile tape, aseptic technique failures, cleaning procedure non-compliance), did not include review of video recordings from previously manufactured or subsequent commercial batches to assess similar behavior or verify corrections. A sterility test failure investigation for a drug product also lacked a thorough evaluation of potential manufacturing root causes.

**Observation 3** points to inadequate validation of sterilization processes and procedures designed to prevent microbiological contamination. Integral units were rejected during media fills without adequate justification, and media fills were invalidated without sufficient cause, even when significant numbers of integral vials had been filled. Not all personnel with cleanroom access participated in media fills. Smoke studies for filling lines failed to include evaluations of defined interventions or represent maximum filling tank activity. Validated