FDA Issues Warning Letter to Contract Testing Laboratory for Inadequate OOS Investigations

The U.S. Food and Drug Administration (FDA) has issued a Warning Letter to an Indian contract testing laboratory located in Bangalore, India, following an inspection conducted from 20 to 24 January 2025. The inspection revealed significant violations of Current Good Manufacturing Practice (CGMP) regulations, which rendered drug products tested by the laboratory adulterated under U.S. law.

Inadequate Investigations of OOS Results

The firm failed to thoroughly investigate out-of-specification (OOS) results. Investigations lacked scientific rigor and did not consistently explore potential root causes. New results were used to invalidate prior OOS outcomes without sufficient justification. Furthermore, recurring laboratory errors were not adequately addressed through corrective and preventive actions (CAPA).

According to the FDA, in its response to the findings, the company did not adequately address how it will ensure in future that "laboratory OOS results are adequately investigated using scientifically sound and appropriate procedures for retesting, hypothesis testing, re-sampling, and root cause analyses."

Data Integrity Concerns

FDA investigators found torn and discarded original CGMP documents, including weighing and pH meter printouts. The Warning Letter states: "The discarded balance printouts were observed containing test weights that were different from those weights documented in testing of raw materials and finished products (including those intended for the U.S. market)." Additionally, electronic data audit trails revealed hundreds of unauthorized actions such as “Add/Modify/Delete peaks,” suggesting poor control over data modifications.

The FDA concludes that the firm’s quality systems are inadequate and writes: "It is important to maintain strict control over electronic data to ensure that any additions, deletions, or modifications of information in [the] electronic records are authorized and appropriately documented."

Required Actions

The agency requests a retrospective review of all OOS and laboratory incident investigations over the past three years, including an assessment of impacted products intended for the U.S. market. In addition, the FDA expects an independent evaluation of the firm’s documentation practices, analyst competencies, and QU oversight. Revised SOPs and CAPA measures must be implemented to restore compliance.

Given the serious nature of the violations, the FDA recommends the engagement of an external CGMP consultant in accordance with 21 CFR 211.34. However, the responsibility for compliance remains within the company.

The full Warning Letter to Shiva Analyticals Private Limited is available on the FDA website.