On September 4, 2025, the U.S. Food and Drug Administration (FDA) issued a Warning Letter (320-25-106) to Somerset Therapeutics Private Limited following an inspection conducted from February 10–21, 2025 at its sterile drug manufacturing facility in Bengaluru, India. The inspection revealed multiple significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals under 21 CFR parts 210 and 211. As a result, the FDA considers the company’s drug products adulterated within the meaning of FD&C Act §501(a)(2)(B).
Additionally, the company failed to submit a Field Alert Report (FAR) within the required three working days for a sterility-related event, in violation of 21 CFR 314.81(b)(1)(ii).
Key Non-Conformances Identified
The inspection and subsequent FDA Warning Letter highlighted several critical lapses in Somerset’s operations, summarized below as key non-conformances:
Inadequate Investigations of Failures and Discrepancies
Regulatory Citation: 21 CFR 211.192
- Media Fill Failure: In September 2024, a contamination event occurred on the (b)(4) filling line. The investigation cited tubing breach and operator activities, but did not fully assess risks to similar equipment (ampoule line) or Bacillus cereus resistance to sterilization.
Related Article: Media Fill Tests In Sterile Manufacturing
- Out-of-Specification (OOS) Results: Unspecified impurity detected in validation and commercial batches was linked to one API lot, but OOS investigations lacked thorough root cause analysis and cross-batch risk evaluation.
- Environmental Monitoring (EM): At least 16 aborted air sampler events were recorded in classified areas during February 2025. Limited electronic retention (~115 entries) prevented a complete data review and hindered timely investigation.
Inadequate Maintenance of Aseptic Facilities and Equipment
Regulatory Citation: 21 CFR 211.42(c)(10)(vi)
- Inspectors observed detached tape securing components inside the ISO 5 (Grade A) area of the (b)(4) filling line. The tape, uncleanable and particulate-shedding, posed risks to airflow integrity and sterility.
- Post-hoc airflow studies and surface sampling were insufficient to justify aseptic suitability under these insanitary conditions.
Insufficient Procedures to Prevent Microbiological Contamination
Regulatory Citation: 21 CFR 211.113(b)
- Interventions: Operators used RABS (Restricted Access Barrier Systems) in ways equivalent to direct Grade A interventions, increasing contamination risks.
SEE ALSO: RABS vs Isolators
- Material Transfers: Barrier openings were held ajar for extended periods during stopper bag transfers.
- Airflow Visualization: Smoke studies and video recordings failed to adequately represent actual interventions, omitting critical activities and insufficiently visualizing hazards.
SEE ALSO: Smoke Studies in Cleanrooms
Failure to Submit Field Alert Report (FAR) Timely
Regulatory Citation: 21 CFR 314.81(b)(1)(ii)
- Following the September 2024 media fill failure, Somerset failed to submit a FAR within three working days. The FAR was only filed after the FDA inspection concluded, delaying regulatory awareness of a significant sterility event.
CAPA Plan Recommendations
Based on the FDA’s observations, the team at GMP Insiders recommends the following CAPA steps to restore compliance and strengthen long-term quality systems:
Non-Conformance 1: Inadequate Investigations
Root Cause Analysis (RCA): Weak investigation framework, lack of scope expansion rules, insufficient supplier oversight, and poor data retention for environmental monitoring.
Corrective and Preventive Actions (CAPA):
- Establish a tiered investigation system with predefined expansion criteria for related equipment, products, and utilities.
- Incorporate organism-specific challenge assessments (e.g., Bacillus cereus) into sterilization validation.
- Improve supplier lifecycle management for API impurities, including robust impurity profiling and incoming lot qualification.
- Upgrade Environmental Monitoring systems for data retention and audit-trail review, ensuring aborted samples are captured, investigated, and trended.
- Provide investigation training with a focus on evidence-based root cause analysis and CAPA effectiveness checks.
Non-Conformance 2: Aseptic Equipment and Facility Maintenance
RCA: Reliance on temporary fixes and inadequate preventive maintenance oversight.
CAPA:
- Immediately remove and prohibit the use of tape or other non-conforming materials in ISO 5/Grade A areas.
- Perform comprehensive equipment walkdowns and implement an engineering change program with validated cleanroom-compatible parts.
- Conduct re-qualification smoke studies demonstrating restored unidirectional airflow.
- Introduce daily visual inspection standards for aseptic environments and assign named engineering responsibility with oversight at management review.
Non-Conformance 3: Microbiological Contamination Prevention
RCA: Underestimation of contamination risks due to poor intervention design, extended barrier openings, and inadequate airflow visualization.
CAPA:
- Conduct a comprehensive contamination risk assessment covering interventions, ergonomics, airflow, personnel/material flow, and hold times.
- Redesign material transfer procedures and introduce time-bound controls for barrier openings with automated alarms and logging.
- Re-film airflow studies with third-party oversight, ensuring worst-case interventions are modeled and properly visualized.
- Revise media fill protocols to replicate real-world interventions in frequency and duration.
Non-Conformance 4: Field Alert Reporting (FAR)
RCA: Lack of clear triggers and delayed RA/QA decision-making.
CAPA:
- Develop a FAR trigger matrix including confirmed and unconfirmed sterility-related events.
- Establish daily RA/QA triage meetings to ensure same-day decision-making and documentation.
- Maintain a time-stamped FAR log and conduct periodic drills to ensure reporting readiness.
Timeline for Implementation
Immediate Actions (0–3 Months):
- Remove insanitary materials from aseptic areas; re-qualify equipment.
- Expand investigation into September 2024 media fill failure, including organism susceptibility.
- Upgrade EM data retention and initiate trend reporting.
- Implement FAR trigger matrix and start daily RA/QA reviews.
Short-Term Actions (3–6 Months):
- Complete contamination risk assessment; redesign transfer procedures and intervention controls.
- Re-shoot smoke studies with third-party oversight.
- Establish API impurity lifecycle management program with enhanced supplier oversight.
Long-Term Actions (6–12 Months):
- Institutionalize investigation playbook with scope-expansion rules.
- Embed CAPA effectiveness reviews at 90/180 days.
- Trend metrics for EM aborted events, FAR timeliness, and investigation closure rates in management review.
Conclusion
FDA’s Warning Letter to Somerset Therapeutics highlights systemic failures in investigations, facility maintenance, aseptic practices, and regulatory reporting. These issues underscore the need for stronger investigation systems, contamination control strategies that reflect real interventions, robust data governance, and timely communication with regulators. By adopting the recommended CAPA plan and adhering to the outlined timelines, Somerset can move toward restoring CGMP compliance, safeguarding product quality, and rebuilding regulatory trust.
