FDA 483 to Catalent Indiana Flags Inadequate Investigation of Contaminants, Equipment Failure

Novo Nordisk owned Catalent Indiana sterile products formulation facility was inspected by USFDA in June – July 2025. The inspection, conducted by USFDA investigators  Joohi Castelvetere, Robert J.Ham, Martin M.Kimani and Shannon L.Maisano resulted in a USFDA Form 483 with six observations. These span inadequate failure investigations, microbial contamination control lapses, deficiencies in environmental monitoring and aseptic practices, and shortcomings in visual inspection procedures. The 483 also highlighted deficient electronic data control procedures over legacy equipment and failure of Catalent to verify components for DEG and EG contaminants.

Incomplete investigations: Many batch failures and component discrepancies lacked conclusions or follow-up:

• Investigations into particulate contamination and hair strands in sterile drug products were inadequate, despite an ongoing trend of hair-related stopper issues. No commercial lots were rejected due to hair. Not all deviations were investigated; impact analysis was limited to a one-year span and failed to assess complaints. Although components were identified as a potential root cause, no CAPAs were taken.
• Investigation into the observation of Staphylococcus hominis during surface monitoring did not consider the impact on previous batches or other syringe configurations. Though operator error and method were identified as potential root causes, no documented actions were taken.
• Investigation into a pest incident identified material syringes as a probable root cause, but no follow-up actions were taken with the material supplier.
• Investigation into an action-level result in microbial monitoring of water did not consider a reported incident involving hose attachment to the sampling port and residual water in the hose as possible root causes.
• Delays were observed in logging incidents related to visual inspection failures and particle appearance. Investigations and CAPAs were inadequate, and CAPA effectiveness checks were lacking.
• The root cause for a batch stability failure was identified as “man,” without scientific support, and no CAPA was implemented.
• Deviations were not triggered for all critical equipment failures and leaks.
• Timely and thorough investigations were not initiated for unexplained batch terminations.

Microbial contamination control procedures are not adequate:

• The media fill program does not include all high-risk or critical interventions. It does not track previous atypical interventions for inclusion in the media fill programme. Excursions in high-risk interventions compared to media fill studies do not trigger deviation logging or investigation.
• Multiple instances of first air violations by operators during set up, inconsistent operator practices during stopper chute installation were noted.

Deficiencies in environmental monitoring in aseptic processing areas

• Direct surface monitoring of all filling heads is not performed. No scientifically justified microbial recovery study supports filling head sampling activities. Surface contact sampling of aseptic connections is not performed.

Process control procedures are lacking:

• For 100% visual inspection, limits are not established for individual defect types—but only for overall defect criticality categories (e.g., critical, major, minor). The Automated Visual Inspection (AVI) system categorizes defects only as cosmetic or particulate and does not identify specific defect types (e.g., hair, glass, fiber), failing to provide visibility into critical defects such as hair in finished products.

Lapses in QC systems and procedures:

• Sterility sample counts are not documeted when taken during interventions
• The legacy UV-Vis spectrophotometer lacks login, data backup, audit trail features, and data review procedures. Audit trails are not reviewed. The Data Integrity (DI) Assessment and Remediation Plan does not identify all equipment with critical DI gaps.

Test Reports from suppliers are accepted without establishing reliability of supplier’s analyses

• High risk components like Polysorbate 20 and Polysorbate 80 are not tested by the Firm for diethylene glycol (DEG) and ethylene glycol (EG).