Zydus Lifesciences Limited – FDA 483, Mar 27, 2024

This FDA Form 483 details significant deficiencies at a facility manufacturing and distributing human drug products intended to be sterile.

**Violations and Observations:**

* **Environmental Monitoring Deficiencies:** From May to December 2023, the firm operated with an out-of-control environmental monitoring program, documenting 337 action level excursions for bacteria and fungi in Grades A and B aseptic processing areas. Responses to these excursions were inadequate; for example, moisture and microbial contamination of media plates from a supplier in July 2023 were documented, yet subsequent excursions were attributed to operator hands. A December 2023 retrospective evaluation of media, including a lot used for a US-marketed drug product, was inadequate, as a media lot with prior unacceptable results was deemed compliant. * **Inadequate Airflow Visualization Studies (Smoke Studies):** Smoke studies for the aseptic filling line were insufficient to demonstrate unidirectional airflow and revealed inadequate aseptic technique. Examples include insufficient smoke during sterile item transfer, no smoke over operator hands during critical operations, and inadequate smoke near critical aseptic connections. Operator sleeves were observed contacting fill tubing and assembly, violating procedure 0318-SOP-MFG-00028. The design for installing the was also noted as requiring operators to reach over the fill line, causing gowning contact. * **Deficient Procedures for Preventing Microbiological Contamination:** On March 21, 20