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Warning letters, 483s, Recalls, Import Alerts, Audit observations
Warning letters, 483s, Recalls, Import Alerts, Audit observations
The USFDA issued a Warning letter to Hikal’s API facility in Jigani, Bangalore, India. The Warning Letter follows an inspection by USFDA investigator Marcellinus D Dordunoo at the facility (FEI 3003560263) in February 2025. The letter highlights serious concerns regarding metallic/black particulate contamination in APIs, inadequate complaint investigations, and deficiencies in the supplier qualification program.
Metallic /Particulate contamination of APIs &Customer Complaints
The Warning letter cited multitude of customer complaints related to metallic contamination and black particles in APIs. Hikals investigations variously attributed these issues to:
However, the investigations lacked scientific rigor and failed to establish a definitive root cause. There was no evidence to support metallic particles present are inherent to the manufacturing process. Even the misapplied excipient guideline’s requirements for material evaluation and mitigation strategies were not fulfilled. Investigations indicated cleaning deficiency as a likely root cause, but also cited no exact root cause identified. Also the metal detector was not adequately qualified to detect particulates from equipment, considering material of construction and composition. Investigations into complaints of foreign material contamination of APIs were inadequate and CAPAs were ineffective, as additional complaints continued despite prior corrective actions. Risk Assessment performed with complaint investigation was also not scientifically sound which ranked the issue as an unlikely failure, despite repeated similar complaints.
Hikal’s response included a re-evaluation of the metal detector and engagement of a third-party consultant. However, the FDA deemed the response inadequate, noting:
FDA has asked for a comprehensive and independent review of Hikals procedures for investigation, complaint classification, full review of retain samples of all batches for particulate contamination, impact assessment and remediation plans and evaluation of suitability of all equipment.
Supplier Qualification Program deficiencies
The Warning letter also flagged gaps in the Supplier Qualification Program. There was no procedure for re-evaluation of a supplier when quality deficiencies are detected. This allowed Hikal to continue using supplies from a Drum and Lid supplier, though investigations identified it as most likely source of particulates in the API. FDA has asked for an independent, comprehensive review of the material system and supplier qualification program.
Key Takeaways
One key takeaway is that Investigations of deviations and failures should focus on defining the issue and identifying the root cause and appropriate CAPA. Confusing and conflicting narratives in an investigation, pulling in multiple aspects to justify or defend a stand do not help in identifying a root cause and CAPA. It also exposes the weakness of the systems and procedures for a comprehensive investigation.
Also Supplier Qualification Programs should have a periodic review. It will be a good practice to review qualified status of a supplier when recurring  quality issues are observed in incoming material.
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