FDA 483 - Biocon Limited - January 24, 2020

The FDA Form 483 details multiple deficiencies observed during an inspection.

**Cleaning Validation:** Protocols for assessing product-to-product carryover in non-dedicated equipment are inadequate. Specifically, SOP No. QA/SOP/016 requires total carryover calculation based on swab results, but documentation (Equipment Cleaning Checklist, Technical Information Sheet for Equipment Cleaning Sample) fails to record diluent used, diluent volume, or total area swabbed during swab sample collection, as required by protocols and the SOP.

**Non-conformance Investigations:** Investigations into Out-of-Specification (OOS) impurity test results are insufficient. For instance, potential impact of critical process parameter settings was not documented in production batch records before a change control (Ref No. BPCF-PC1/9/040) was implemented. Per SOP No. QA/SOP/057, Phase II investigations should be initiated when laboratory error is unclear or assignable cause is not identified in Phase I. Of 21 impurity-related OOS initiated for US-distributed products from January 2015 to January 2020, only 3 escalated to Phase II. Deficiencies were not considered contributing factors until an Out-of-Trend (OOT) impurity result for batch BPI/007/19/01 was reported, with Technical Report PEL/TR/BL.14.0625/19/