La qualité des enregistrements au cœur de cette mise en demeure...

Dans cette récente "Warning Letter", la FDA américaine mentionne plusieurs écarts importants dans la gestion des enregistrements réglementés :

1.    Failure to maintain complete data derived from all laboratory tests conducted to ensure compliance with established specifications and standards.

Your firm lacked accurate raw laboratory data records for API batches shipped by your firm. The inspection revealed that batch samples were retested until acceptable results were obtained. In addition, your quality control (QC) laboratory failed to include complete data on QC testing sheets.  Failing or otherwise atypical results were not included in the official laboratory control records, not reported, and not investigated...

2.    Failure to investigate and document out-of-specification results...
 
Your management failed to prevent the practices of product sample retesting without investigation, and rewriting and/or omission of original CGMP records persisted without implementation of controls to prevent data manipulation...

4.    Failure to record activities at the time they are performed.

Specifically, your staff used “finished product reports review data” worksheets to document critical laboratory information days after the actual testing was performed.  The worksheets reported observations from your firm’s secondary reviewer, and next to each of these listed observations the analyst marked them as corrected. A review of these worksheets revealed that your analysts did not always record data in the laboratory records in a contemporaneous manner as noted in the following examples...

Cette mise en demeure détaille également les missions à confier à un "data integrity" consultant chargé de la mise en conformité GMP :

Your data integrity consultant should:
 

1. Identify any historical period(s) during which inaccurate data reporting occurred at your facilities.
2. Identify and interview your current employees who were employed prior to, during, or immediately after the relevant period(s) to identify activities, systems, procedures, and management behaviors that may have resulted in or contributed to inaccurate data reporting.
3. Identify former employees who departed prior to, during, or after the relevant periods and make diligent efforts to interview them to determine whether they possess any relevant information regarding any inaccurate data reporting.
4. Determine whether other evidence supports the information gathered during the interviews, and determine whether additional facilities were involved in or affected by inaccurate data reporting.
5. Use organizational charts and SOPs to identify the specific managers in place when the inaccurate data reporting was occurring and determine the extent of top and middle management involvement in, or awareness of, data manipulation.
6. Determine whether any individual managers identified in item (5) above are still in a position to influence data integrity with respect to CGMP requirements or the submission of applications; and establish procedures to expand your internal review to any other facilities determined to be involved in, or affected by, the inaccurate data reporting.
7. As part of this comprehensive data integrity audit of your laboratory, your audit report also should include any discrepancies between data or information identified in approved applications (including Drug Master Files), and the actual results, methods, or testing conditions submitted to the Agency. Include an explanation of the impact of all discrepancies. Provide a corrective action operating plan describing the specific procedures, actions and controls that your firm will implement to ensure integrity of the data in each application currently submitted to the Agency and all future applications. This should not only cover methods validation, but any other testing (e.g., stability tests, release tests) or operations you have performed for customers that may have been used to support a drug application-related submission to the agency.

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