Data Integrity: New Inspection Focus of the FDA

Recommendation

12-14 December 2023

Stability by Design - Live Online Training
- Stability Testing in Product Design and Method Development- Focus mainly on small-molecule APIs and drug products

In recent years, the number of complaints in FDA Warning Letters with regard to data falsification and fraud - especially in analytical GMP laboratories regarding the use of chromatography data systems (CDS) - has been increasing. Triggered by the cases of fraud at Able Laboratories in 2007, the requirements for audits of data integrity during FDA Pre-Approval inspections have been set in the Compliance Programme Guide (CPG) 7346.832. Moreover, FDA's inspectors have been explicitly trained on computer systems and the data they contain.

In 2014, three new contributions were added to FDA's Q&A webpage on Current Good Manufacturing Practices which reflect those current developments:

Question 5: Why is FDA concerned with the use of shared login accounts for computer systems?

Question 6: Can electronic signatures be used instead of handwritten signatures for master production and control records?

Question 7:  In warning letters to firms, why has FDA objected to the practice of using actual samples to perform system suitability testing (sometimes also referred to as "trial," "test," or "prep" runs)?

Previously - already in 2010 - clarification had been provided through question 3 about the fact that the FDA always expects the electronic raw data for HPLC chromatograms. Keeping the printed chromatogram only is no longer sufficient to meet the CGMP expectations, since too many significant pieces of information would get lost.

This background explains the increased number of complaints about data integrity observed during FDA inspections. At present, this can be seen in many Warning Letters, especially in January 2015. Currently, typical findings are so-called "trial sample injection practices" through which companies try to disguise unfavourable OOS results. For example, please see the Apotex Warning Letter from 30 January 2015 and the Warning Letter for Micro Labs Limited from 9 January 2015.

Further, please also access FDA's Q&A webpage on Current Good Manufacturing Practices.

Source: FDA, USA