Data Integrity and Validation Issues identified during GMP Inspection

Recommendation

5/6 June 2024

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Following FDA´s August 2019 inspection of a Canadian manufacturer of over-the-counter (OTC) drug products, the Agency now issued a Warning Letter due to non-compliance with cGMP.

Data Integrity issues

The FDA inspectors found discrepancies between HMI (human machine interface) data and batch records and practices of operators not following batch instructions. Therefore the agency requires to provide 

• a comprehensive investigation into the extent of the inaccuracies in data records and reporting;
• results of the data review for drugs distributed together with a detailed description of the scope and root causes of the data integrity lapses.

Validation issues

The agency observed a lack of process validation and, in addition, a lengthy bulk hold time prior to filling drug products without assuring that this practice does not impact the chemical and microbiological quality.
The agency therefore requests 

• a detailed summary of the validation program for ensuring a state of control throughout the product lifecycle,
• associated procedures including process performance protocol(s), and written procedures (and a program) for qualification of equipment and facilities;
• a detailed program for designing, validating, maintaining, controlling and monitoring of manufacturing processes that includes monitoring of intra-batch and inter-batch variation to ensure an ongoing state of control.

Particles and OOS Results

According to FDA, the company failed to adequately investigate and document the presence of particles in a product. The manufacturer concluded that the particles were from a broken belt on the filling line, and the corrective action (CA) was to reject a number of units of this lot. However, this CA did not expand to cover batches that were previously filled at the same line or a preventative maintenance plan to prevent recurrence of similar incidents. In addition, the company failed to conduct an adequate investigation into an OOS test result for content. The FDA therefore requests to provide

• a comprehensive, independent assessment of the overall system for investigating deviations, discrepancies, complaints, OOS results, and failures,
• an independent assessment and remediation plan for the CAPA program,
• a comprehensive assessment and remediation plan to ensure that the QU (Quality Unit) is given the authority and resources to effectively function.