FDA 483 - AstraZeneca Pharmaceuticals LP - June 07, 2024

This FDA Form 483 details observations from an inspection concerning drug substance manufacturing.

**Observation 1** highlights unmitigated risks in upstream manufacturing systems, citing eleven contamination events in one building from April 27, 2022, to February 29, 2024, and twelve contamination events in another building from January 27, 2020, to November 9, 2023. These events affected drug substance and other products. The facility failed to timely identify and address system deficiencies, a repeat observation from a March 2-19, 2021 inspection.

**Observation 2** notes deficient procedures for manufacturing and QC testing. Specifically, a cleaning validation for a product on March 26, 2012, failed to include cleaning verification for equipment used for another product (Batch on April 16, 2022) before completion of a successful cleaning validation or deviation investigation. There is no procedure governing equipment cleaning validation failures and subsequent manufacturing.

**Observation 3** identifies a failure to thoroughly document product quality impact of quality events. Deviation investigation reports QE-090861 and QE-084599 described excursions of drug substance manufacturing process controls (critical and non-key process parameters). While concluding no product impact, the reports lacked thorough and clear evaluation, failing to provide clear documentation of data supporting the no-impact determination