FDA Warning Letter to Contract Testing Laboratory in Uruguay due to Data Integrity Violations

The U.S. Food and Drug Administration (FDA) has issued a Warning Letter dated 30 April 2024 to a contract testing laboratory in Montevideo, Uruguay, following an inspection conducted from 20 to 22 November 2023.

The inspection revealed significant violations of Current Good Manufacturing Practice (CGMP) regulations, specifically related to the laboratory data integrity and documentation practices. Key issues included incomplete laboratory records, unreviewed out-of-specification (OOS) results, and lack of controls over electronic data and manual integrations.

The FDA found the company’s response to the Form FDA 483 that preceded the Warning Letter inadequate, because the firm "failed to provide supportive documentation for evaluation or adequate evidence of corrective actions taken to bring [the] operations into compliance with CGMP."

Key Findings

During the inspection, the FDA investigator observed specific violations in the following areas:

• Laboratory records: The firm failed to ensure that laboratory records included complete data from all tests necessary to comply with established specifications and standards. Specifically, the quality unit (QU) reviewed only printed analytical results, missing unprocessed and unreported HPLC sample injections that were out-of-specification (OOS) for a critical ingredient. These OOS results were not included in the final analytical reports reviewed by the QU. Furthermore, manual integration of sample assay peaks was performed, which the printed data reviewed by the QU did not indicate.
• Laboratory control: The procedures for data collection, review, and integration through electronic systems were insufficient. This included a lack of evaluation of reprocessed sample integrations, aborted runs, single injection data, and electronic audit trails.
• Inappropriate controls over computer systems: There were inadequate controls over analytical equipment and software, allowing analysts to delete electronic data generated by HPLC systems. Additionally, audit trails on some HPLC systems were not enabled.

Actions

As the quality system does not adequately ensure the accuracy and integrity of data, the FDA asked for several actions, including:

• Performing a comprehensive investigation and retrospective evaluation into the extent of the inaccuracies in data records and reporting.
• Developing a management strategy, including a detailed corrective action plan.
• Engaging a qualified consultant to conduct extensive annual audits, for at least two years, to assist in evaluating CAPA effectiveness.

Conclusion

The FDA concludes that the "failure to comply with CGMP may affect the quality, safety, and efficacy of the drugs" that were tested in the contract testing laboratory. Grupo Quimico SRL was given 15 working days to respond with a detailed plan to correct the identified deficiencies.

For further information, please see the complete Warning Letter on the FDA homepage.