Insufficient handling of data integrity and validation of analytical methods lead to FDA warning letter

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

This FDA warning letter issued on 9 May, 2018 to Indian API manufacturer Reine Lifescience is based on an FDA inspection which took place in October/November 2017.

It became clear during the inspection that the company could not provide data to validate and verify their analytical methods. The FDA inspector found data which differed significantly from the recorded results.

Moreover, there were no adequate controls of the computer systems in order to prevent unauthorised data access. During the FDA inspection, it was revealed that the HPLC System's Audit Trail had been deactivated.

In the company's response to the FDA, Reine Lifescience had previously committed to validating all their computerised systems, including the implementation of Audit Trails, access control and the restriction of data.

This response wasn't sufficient since it did not include any interim control measures for the control and verification of analytical data.

In the warning letter, Reine Lifescience has now been prompted to compile the following information for the FDA:

• a summary of all interim measures to prevent the deletion and alteration of data;
• determination of the roles and responsibilities of the personnel with access to analytical instruments and data;
• access authorisation details for each analytical system;
• detailed summary of the updated procedure and the related training;
• detailed summary of how Audit Trails are to be reviewed in the future;
• a global CAPA plan on the management's strategy for preventing these deviations in the future;
• a risk assessment analysing the risk patients have been exposed to due to the release of medicinal products despite lacking data integrity.

Because of the large number of serious deviations, the FDA has issued an Import Alert..

For more information please also see the complete FDA warning letter to Reine Lifescience.