FDA 483 - Rentschler Biopharma SE - March 07, 2023

This FDA Form 483 details several observations regarding a firm's manufacturing processes and quality systems.

**Facility and Operations:** The firm operates GMP suites for upstream and downstream processing of drug substance intermediates and product samples, including a Point of Use (POU) for batching and product manufacturing. They also handle cell banks and utilize a REDACTED system for purification.

**Violations and Observations:** 1. **Inadequate Microbial Contamination Prevention:** The firm continuously recovered endospore formers, objectionable microorganisms, and human isolates in GMP suites and product samples. Numerous deviations (e.g., DEV-2021-0027, 2022-0313, 2023-003) were raised between 2021-2023 for Bacillus spp., Paenibacillus glucanolyticus, Enterococcus spp., and human isolates. This led to batch REDACTED being rejected as "Not for Human Use" due to Bacillus spp. contamination (OOS-OOT-2021-0077, 2021-0080, 2021-0161, 0131). 2. **Infrequent Endotoxin Monitoring:** The REDACTED POU (REDACTED) used for batching and product manufacturing is infrequently monitored for endotoxins. RL-SOP