FDA EIR - AstraZeneca Pharmaceuticals LP - March 19, 2021

The FDA conducted a pre-license inspection of AstraZeneca Pharmaceuticals LP Frederick Manufacturing Center from March 02-19, 2021. The inspection, guided by regulatory frameworks such as CP 7356.002M, CP 7346.832, and ICH Q7, focused on the manufacture of two specific drug substances, (b)(4) and (b)(4), under the Food, Drug and Cosmetics Act.

During the inspection, a Form FDA 483 detailing observations was issued, alongside several verbal discussion items concerning objectionable conditions. Primary issues identified centered on deficiencies in quality systems and manufacturing controls. These included numerous microbial ingress and bioburden deviations, with over 30 instances across various products and processes, involving diverse microorganisms. Notably, nine bacterial growth events in bioreactors resulted in the termination or rejection of eight drug substance batches, and five (b)(4) showed repeated microbial contamination. One commercial batch was released despite exceeding microbial limits, only to be subsequently refused by the license holder.

Further observations highlighted inadequate investigations and ineffective corrective actions for these microbial events and other recurring process deviations, such as frequent leaks during manufacturing. The facility also lacked a standardized system for tracking repeated deviations. Additional concerns included insufficient disinfectant efficacy, gaps in environmental monitoring, and procedural weaknesses related to employee training, change control processes, and data integrity within laboratory systems.

AstraZeneca management committed to providing a formal response to the inspectional observations within 15 days, indicating an intent to improve microbial control processes and overall responses to adverse events.