The U.S. Food and Drug Administration (FDA) inspected Catalent Indiana, LLC’s sterile drug manufacturing facility in Bloomington, Indiana (now acquired by Novo Nordisk), from June 23 to July 14, 2025. The inspection resulted in the issuance of Warning Letter 320-26-20 on November 20, 2025, citing significant violations of Current Good Manufacturing Practice (CGMP) regulations under 21 CFR Parts 210 and 211.
FDA concluded that Catalent Indiana’s drug products were adulterated under Section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act due to failures in investigation practices, aseptic process control, supplier qualification, and quality oversight.
Although Novo Nordisk acquired the facility during the period in which contamination events occurred, the FDA emphasized that the release of potentially contaminated drug products continued after the acquisition, indicating unresolved systemic weaknesses.
The firm’s responses to FDA Form 483 observations were repeatedly deemed inadequate, lacking supporting data, documented procedures, and evidence of effective corrective and preventive actions (CAPAs).
Key Non-Conformances Identified
FDA cited two core CGMP violations, both of which are tightly linked. Weak investigations allowed contamination risks to persist, while inadequate aseptic controls ensured they continued to recur.
Non-Conformance 1: Failure to Adequately Investigate Deviations and Batch Failures
Regulatory Citation: 21 CFR 211.192
FDA identified a systemic breakdown in the firm’s investigation process, particularly where contamination events intersected with batch disposition decisions.
Key Findings
- More than 20 deviations since August 2023 involving mammalian hair contamination in or around vial stopper regions.
- Hair was observed:
- In stopper areas
- In proximity to the product
- In some cases, in direct contact with a sterile drug product
- Affected:
- Multiple drug products
- Multiple customers
- Both before and after Novo Nordisk acquisition
- Investigations:
- Were not initiated in a timely manner
- Lacked supporting data for assigned root causes
- Were not expanded to include potentially impacted batches or products
- Failed to assess CAPA effectiveness
- Trending:
- Ineffective due to restricted search terms and limited timeframes defined in procedures
- Batch disposition:
- Contaminated units were culled
- Remaining units were released
- Customers later reported the same contamination in the received product
- At least (b)(4) batches associated with mammalian hair were released post-acquisition
Media Fill Failures
- More than five media fill batches have been terminated since November 2023.
- At least two terminations:
- Related to stoppering issues and extrinsic particles
- Were not captured as deviations at the time of occurrence
- Media fills were re-executed and accepted:
- Without documented root cause analysis
- Without documented CAPA implementation
- Without evaluation of aseptic control failure modes
SEE ALSO: Media Fill Tests: Aseptic Process Simulation (APS) in Sterile Manufacturing
FDA’s Core Concern
- The firm repeatedly relied on passing sterility, endotoxin, and environmental monitoring results to justify the conclusion that no product impact existed.
- FDA made it clear that this approach misunderstands sterility assurance, which is process-based and not test-based.
Non-Conformance 2: Failure to Establish and Follow Adequate Aseptic and Contamination Control Procedures
Regulatory Citation: 21 CFR 211.113(b)
The investigation failures described above are inseparable from weaknesses in Catalent’s contamination control strategy. FDA’s findings show that contamination hazards were identified but not effectively controlled.
Visual Inspection Program Deficiencies
- Defects were trended only at a high-level criticality grouping (critical, major, minor).
- No routine trending of:
- Individual defect types (e.g., hair, glass, atypical particulate)
- This approach limited:
- Early detection of contamination signals
- Data-driven escalation and intervention
Aseptic Process and Environmental Monitoring Weaknesses
- Environmental monitoring failures linked to:
- Occluded equipment surfaces
- Surfaces not reliably exposed to (b)(4) decontamination
- High-risk interventions:
- Involved stopper handling and equipment manipulation
- Occurred within ISO 5 environments
- Were already identified as risky in internal assessments, yet remained permitted
- Sampling methodology:
- Use of contact plates with sweeping motion
- Inability to attribute contamination to specific surfaces
- Reduced sensitivity compared to swab sampling for irregular or critical surfaces
SEE ALSO: Types of Sampling Methods in Environmental Monitoring
Stopper Control as a Contamination Risk
- Reliance on pre-shipment (tailgate) samples supplied by stopper vendors.
- Sampling was not representative of received lots.
- Enhanced sampling:
- Implemented late
- Initially limited to one supplier
- Not justified with defined protocols, sample size rationale, or tightened acceptance criteria
- Re-inspection of finished product:
- Proposed but not supported by documented procedures or defined AQL controls
FDA treated these issues collectively as a failure to prevent microbiological and particulate contamination, not as isolated supplier or inspection gaps.
CAPA Plan Expectations and Regulatory Recommendations
Based on the cited violations, the FDA requires Catalent to implement comprehensive remediation supported by an independent assessment, with a clear distinction between immediate causal factors and underlying root causes. Corrective actions must address both execution failures and systemic weaknesses within the quality system.
Non-Conformance 1: Failure to Adequately Investigate Deviations and Batch Failures
Regulatory Citation: 21 CFR 211.192
Root Causes
- Absence of a structured, consistently applied investigation lifecycle
- Quality Unit oversight focused on batch disposition rather than process control
- Inadequate definition of the investigation scope, escalation criteria, and trend evaluation
- Lack of a formal process to assess CAPA effectiveness
- Insufficient management review of investigation quality and outcomes
Expected Corrective and Preventive Actions (CAPA)
- Perform an independent assessment of:
- Deviation management
- Complaint handling
- OOS/OOT investigations
- CAPA governance
- Revise investigation procedures to clearly define:
- When investigations must be initiated
- How scope and impact assessments are performed
- Documentation and data requirements
- Establish mandatory CAPA effectiveness checks tied to recurrence prevention
- Implement retrospective review of:
- Customer complaints
- Rejected units
- Media fill terminations
- Strengthen Quality Unit authority and management oversight over investigations and batch release decisions
Non-Conformance 2: Failure to Establish and Follow Adequate Aseptic and Contamination Control Procedures
Regulatory Citation: 21 CFR 211.113(b)
Root Causes
- Incomplete contamination control strategy across aseptic operations
- Insufficient evaluation of equipment design, accessibility, and decontamination coverage
- Lack of a comprehensive contamination hazards risk assessment
- Inadequate integration of supplier component risks into the aseptic control framework
- Absence of defined escalation and response criteria for recurring particulate contamination
Expected Corrective and Preventive Actions (CAPA)
- Conduct a comprehensive, CCS-aligned contamination hazards risk assessment covering:
- Aseptic processes
- Equipment design and occluded surfaces
- Routine and non-routine interventions
- Material and component flows, including stoppers
- Revise aseptic procedures to:
- Eliminate or redesign high-risk interventions
- Improve decontamination effectiveness and coverage
- Replace contact plate sampling with swab sampling where appropriate
- Establish defect-specific trending and quality limits for visual inspection findings
- Implement representative, on-site incoming inspection protocols for all stopper suppliers
- Define and document re-inspection procedures for the finished product when extrinsic matter is detected
Timeline for Implementation (FDA Expectations)
Immediate Actions (0–3 Months)
- Engage independent CGMP experts to assess investigation systems and aseptic controls
- Discontinue use of pre-shipment samples for component quality decisions
- Implement interim containment measures for contamination risk reduction
Short-Term Actions (3–6 Months)
- Complete retrospective reviews of:
- Complaints
- Media fill failures
- Contamination-related deviations
- Finalize and implement revised SOPs for:
- Investigations
- CAPA management
- Aseptic interventions
- Component inspection
- Generate data demonstrating CAPA effectiveness
Long-Term Actions (6–12 Months)
- Implement design or procedural changes to reduce contamination risk
- Strengthen management review and Quality Unit oversight mechanisms
- Establish routine, data-driven trending and escalation processes
Conclusion
This warning letter does not describe isolated execution errors. It documents a systemic failure to recognize contamination as a process signal, rather than a unit-level defect. Investigations were used to support batch release decisions rather than to challenge whether the process remained under control.
FDA’s message is clear: Passing test results cannot compensate for weak investigation logic, incomplete contamination control, or delayed quality escalation. Without demonstrable changes in how risks are identified, investigated, and governed, the same failures will continue to surface, regardless of ownership or investment.
