FDA WARNING_LETTER - Nephron Sc Inc - April 20, 2022

The FDA inspected Nephron SC Inc. from March 28 to April 20, 2022, identifying significant CGMP violations for finished pharmaceuticals, rendering drug products adulterated. The firm also failed to submit an NDA Field Alert Report (FAR) within three working days.

Violations include inadequate and untimely investigations into cross-contamination and microbial contamination. Cross-contamination of Bupivacaine was found in at least three drug product lots, attributed to shared equipment (BFS machines, sterilizers) between 503B compounding and conventional manufacturing, and permeable container closure systems (CCS). The investigation was deemed inadequate for failing to identify the root cause, scope, and impact on sterility/potency, and for inappropriate interpretation of ICH Q3B. A voluntary recall of Ketorolac Tromethamine Injection, USP, 60 mg/2 mL, and four outsourcing products occurred on August 10, 2022, following FDA contact.

Microbial contamination, specifically *Pseudomonas aeruginosa*, was detected in BFS mandrel cooling water during media fills and environmental monitoring. The firm's investigation and CAPA were insufficient, including a single repeat media fill for requalification and invalidating results without clear evidence.

The firm failed to establish appropriate written procedures to prevent microbiological contamination, including inadequate environmental monitoring (EM) action levels for ISO 5 critical areas and deficient sampling methods for BFS machines. The firm inappropriately applied USP <797