FDA 483 - AstraZeneca Pharmaceuticals LP - June 07, 2024

An FDA inspection conducted from May 30 to June 7, 2024, at AstraZeneca Pharmaceuticals LP Frederick Manufacturing Center, a drug substance manufacturer, identified four significant observations detailed in a Form FDA 483. The inspection highlighted critical deficiencies in quality and manufacturing controls. A primary concern was unmitigated risks in upstream manufacturing systems, evidenced by 23 contamination events across two buildings between 2020 and 2024. This was noted as a repeat observation, indicating a persistent failure to address system deficiencies. Further issues included deficient manufacturing and quality control laboratory procedures. These encompassed a lack of governance for cleaning validation failures, leading to subsequent production on inadequately validated equipment. Inspectors also found residual material in a "clean" raw material dispense area, dislodged HEPA screens, unsealed wall interfaces, deteriorated sealants, and uncleaned cabinet surfaces, all indicating poor facility control and deficient cleaning procedures. Additionally, numerous Quality Control lab temperature units were found in alarm conditions without a routine inspection procedure. The inspection also noted a failure to thoroughly document the product quality impact of quality events, with deviation reports lacking clear evaluation for "no product impact" conclusions. Lastly, analytical instruments used for manufacturing in-process controls, despite having audit trails, were not routinely reviewed, posing a data integrity risk. AstraZeneca is required to address these observations by implementing comprehensive corrective and preventive actions to ensure compliance with manufacturing standards.