Biocon Biologics Limited – FDA 483, Apr 7, 2017

This FDA Form 483 details observations from an inspection of Biocon Ltd., highlighting significant discrepancies and deficiencies in their manufacturing and quality control processes for drug substances and drug products.

**Key Observations:**

1. **Documentation Discrepancies:** Inconsistencies exist between submitted information (b)(4) and actual manufacturing processes. Examples include differing in-process specifications, unlisted hold times for formulated bulk, and varying definitions for acceptance criteria versus action limits in batch manufacturing records (BMRs).

2. **Inadequate Quality Assurance:** The Quality Assurance unit approved and implemented documents that do not ensure appropriate production, testing, deviation review, and release of commercial material. * **Batch Release Issues:** Procedures allow release of drug substance batches with open deviations or Out-of-Specification (OOS) results, and drug product made from such drug substance, without proper conditional quarantine status. * **Insufficient Data Review:** Procedures permit the analyst performing testing to also review data and release it to QA or make raw material usage decisions, lacking independent verification.

3. **Inadequate In-Process Sample Handling:** * Unprocessed bulk bioburden samples are settled for up to (b)(4) prior to testing, not mixed, and tested with (b)(4) above settled cells. * No time limits exist between sampling in manufacturing and transfer to QC laboratories.

4. **Lack of Quality Oversight