FDA 483 - Bioiberica, SAU - February 04, 2022

The FDA Form 483 details observations from an inspection concerning the manufacture of drug substances.

**Facility and Operations:** The firm engages in campaign manufacturing of drug substances, utilizing equipment for successive batches.

**Violations and Observations:**

1. **Cleaning Procedures:** Cleaning procedures for manufacturing equipment are not validated. Current methods involve water for manufacturing equipment and dry cloths/spraying for cleanroom equipment. This is insufficient to prevent build-up and carry-over of contaminants (degradants, microorganisms) between campaigns. Evidence includes five OOS investigations and non-conformities for microbial contamination leading to batch reprocessing, a non-conformity for content due to particle build-up from a previous batch, and multiple customer complaints of "dark particles" in finished drug substance drums traced to process equipment.

2. **Process Control and Validation:** * Control procedures are not established to monitor and validate manufacturing processes causing variability. * Critical process parameters for USP drug substance are not controlled or monitored during process validation studies. * "Reprocessing" of OOS batches (due to microbiological contamination or high content) is performed using an industrial method not part of the original validated manufacturing process. This reprocessing uses an industrial method for up to twice the validated time, lacks real-time monitoring, and has no studies on its effect on microbiological and degradant control. * At least 23 batches from 2020-2