FDA Warning Letter: 1,500 OOS Results with Numerous Inadequate Investigations

The U.S. Food and Drug Administration has issued a Warning Letter dated 13 November 2025 following an inspection of an API manufacturing site in Bangalore (India) conducted in April 2025.

The authority identified systemic failures in the handling of Out-of-Specification (OOS) results, laboratory investigations, and the overall CAPA system.

1,500 Laboratory Incidents Involving OOS Results

The FDA states that since 2023, approximately 1,500 laboratory incidents (including OOS results and major analytical events) were recorded. The FDA found that:

• OOS investigations were frequently scientifically inadequate,
• root cause analyses were missing or superficial,
• CAPAs were ineffective or inconsistent, and
• manufacturing investigations were often not initiated, despite inconclusive laboratory root causes.

Critical Example Cited by FDA

As only one example out of numerous inadequate investigations observed during the inspection, the authority describes the following case: Repeated OOS results due to an “unknown peak” in stability samples were invalidated after a later passing re-test using freshly prepared solutions. The FDA criticized that:

• the contaminant was never identified,
• the origin and cause remained unclear,
• no manufacturing investigation was conducted, and
• the implemented CAPA (“refresher training”) was not scientifically justified.

In this context, the FDA mentions that the "corrective action of providing 'refresher training for personnel on good laboratory practice' contradicted the investigation’s own initial finding that the analyst was trained and qualified to perform the HPLC test according to your procedure."

Regulatory Expectation Emphasized by FDA

The FDA points out that a suspected laboratory error alone is insufficient to close an OOS investigation. If no conclusive laboratory root cause is demonstrated, a full manufacturing investigation is mandatory.

The FDA requests, among other things:

• independent system-wide reassessment of the OOS and deviation investigation system,
• retrospective review of all OOS cases over the last four years, including already released U.S. batches.

Additional Laboratory-Related Deficiency

The FDA also identified major shortcomings in method validation and verification. Several in-house analytical methods were inadequately validated, with deficiencies in precision, robustness, and system suitability testing.

For further information, please see the complete Warning Letter to Cdymax India Pharma Private Limited on the FDA's website.