Glenmark Pharmaceuticals Ltd – FDA 483, May 24, 2018

The FDA Form 483 details multiple deficiencies at a pharmaceutical manufacturing facility.

**Key Violations and Observations:**

1. **Unvalidated Test Methods:** The QC laboratory has not validated analytical methods for determining active residue from equipment used to process various products, including Capsules USP mg & mg, Tablets USP mg, mg, & mg, Tablets, Tablets, Capsules USP mg, and Tablets USP mg & mg. The firm's justification of using an Assay by HPLC method validation in place of a UPLC cleaning method was deemed insufficient due to fundamental differences in sample preparation and concentration. This creates a potential for cross-contamination due to unverified cleaning effectiveness of non-dedicated manufacturing equipment.

2. **Deficient Sampling Plans:** SOP CM/QA034 "Sampling Methodology" for Tablets USP mg & mg, and Tablets USP mg is deficient. Specifically, section 5.5.2 lacks clear instructions on the amount of sample to be collected during unloading from various locations, and there is no weighting tape to indicate collected sample weight. Process validation and batch production records also lack specific instructions regarding glass bottle size for samples.

3. **Inadequate Discrepancy Review:** The QC unit failed to thoroughly investigate issues, including an API peak in blank injections during method validation for related substances by HPLC, and unintegrated system suitability standard peaks (10 ppm) which, upon reintegration, changed standard areas by over 30%.

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