FDA Warning Letter on missing Audit Trails and Raw Data Review

On 24 February 2025, the FDA issued a warning letter to a south african company with regard to CGMP violations. The warning letter is based on an FDA inspection in September 2024. The company's responses dated 8 October 2024 to the complaints listed in the Form 483 were insufficient in the FDA's view. FDA warning letters always refer to the GMP requirements set out in 21 CFR Part 211, in this case for data integrity complaints: 

Your firm failed to exercise appropriate controls over computer or related systems to assure that only authorized personnel institute changes in master production and control records, or other records (21 CFR 211.68(a))

Observations

To ensure data integrity, Production and the Quality Unit should have reviewed electronic raw data and the audit trails. This was not the case. In the example described, operators did not record and print negative filter integrity tests. Only passed filter integrity tests were obtained and printed. The inspector observed this behavior on several days.

Response from the company

The company fully acknowledged the deficiency and commit to perform a full audit trail review on their production equipment. 

But the response was inadequate. Why?

• The company did not provide details of the investigation outcome
• The company made no statements on the implementation of effective CAPA measures
• The scope and time period of the retrospective reviews with regard to affected batches was also missing

What does the FDA expect when responding to this Warning Letter?

A comprehensive investigation into the extent of the inaccuracies in the data records and reports, including a detailed description of the scope and root causes of the data integrity deficiencies:

• A current risk assessment of the potential effects of the observed failures on the quality of the drugs
• A management strategy for the firm that includes the details of the global CAPA plan

A comprehensive assessment and remediation plan to ensure the QU has the authority and resources to work effectively. The assessment should also include, but not be limited to.:

• A determination of whether procedures used by the firm are robust and appropriate
• Provisions for QU oversight throughout their operations to evaluate adherence to appropriate practices
• A complete and final review of each batch and its related information before the QU disposition decision
• Ensurance that appropriate procedures are in place regarding the review of all critical electronic data (e.g., filter integrity testing).

Source: Waning Letter to Aspen Pharmacare Holdings Limited from February 24, 2025