FDA 483 - Zydus Lifesciences Limited - August 28, 2018

The FDA Form 483 inspection document details several deficiencies at a facility manufacturing sterile small volume parenteral drug products.

**Observation 1** highlights a failure to follow procedures designed to prevent microbiological contamination during aseptic process simulation (media fill). Specifically, for a media fill batch performed between (b)(4) to demonstrate commercial readiness, there was no documentation identifying the reasons for the breach of container closure integrity of non-integral vials rejected prior to incubation, as required by SOP QA-00024, Version:4.0.

**Observation 2** indicates deficiencies in the environmental monitoring system for aseptic processing areas. Investigations for multiple Out of Limits (OOL) environmental monitoring results in Suite (b)(4), used for manufacturing (b)(4), were incomplete. These OOLs included active air sampling and personnel monitoring in Grade C and B areas, with results exceeding specified limits during cleaning activities.

**Observation 3** identifies issues with employee training and adherence to Standard Operating Procedures (SOPs). a) A qualified visual inspector failed to meet the acceptance criteria for visual inspection during a random test, as per SOP PK-002-00, Effective: 01/12/2017. b) The current SOP PK-004-00, Effective Date: 01/10/2017, classifies defects like (b)(4) and black particles as critical for small volume parenteral