Nitto Avecia Pharma Services, Inc. – FDA EIR, May 24, 2019

This FDA Pre-Approval Inspection of Nitto Avecia Pharma Services, Inc. took place from May 20-24, 2019, targeting the company's sterile human drug manufacturing operations under specific New Drug Application programs. The inspection was conducted according to regulatory frameworks for Pre-Approval Inspections and Sterile Drug Process Inspections. Investigators identified several critical deficiencies, documented in a nine-item Form FDA 483. Main issues included that the manufacturing process used for registration batches did not align with the proposed commercial process, particularly after recent enhancements to address filling line issues. The firm failed to conduct performance qualification for its filling line before producing registration batches. Furthermore, sterilization processes for registration batches were not validated, and sterility testing methods were inconsistently applied. The visual inspection program for finished products was deemed deficient, with inadequate training for personnel inspecting suspension drug products. Other significant violations noted a lack of complete in-process sampling information and missing procedures for critical in-process tests (e.g., density measurement, bioburden testing) in production batch records. Environmental monitoring procedures were not adequately supported by media growth promotion testing. Integrity monitoring and scheduled replacement were absent for gloves on the aseptic capping machine. Additionally, the company conducted an inadequate investigation into the use of an expired raw material and failed to verify the absence of other expired materials in drug product batches. Lastly, reserve samples for registration batches were either not collected or improperly identified. Management committed to providing a written response to the FDA within fifteen business days to address these observations.