FDA Warning Letter on Data Integrity Issues

On June 18, 2024, the FDA issued a Warning Letter to the Dominican company Laboratorio Magnachem International regarding CGMP violations. The Warning Letter is based on an FDA inspection in November 2023. The company's responses dated December 1, 2023 to the complaints listed in the Form 483 were insufficient in the FDA's view. FDA Warning Letters always reference 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))"

In general, comprehensive control of CGMP data is expected to ensure that all changes, deletions and additions of information to electronic records are authorized and documented.

Observations

• The laboratory equipment used to generate analytical data for the release of finished medicinal products has no access protection and no further controls.
• There are no adequate controls to prevent data deletion and record alteration
• There is no definition of unique user names and passwords
• Laboratory staff have administrator rights that allow uncontrolled access to delete or modify HPLC files
• There is no way to track individuals who have deleted or modified data generated by the IT system
• There are no adequate backup copies of the data generated by the laboratory equipment

Response from the company

The company's responses to this observation were inadequate. Why?

The company stated that it had found a supplier for the management of equipment data and that the HPLC management system was being assessed by this supplier. They had a process in place to address data integrity issues. The FDA was not satisfied with these statements. No interim measures were taken to protect patients and ensure drug quality, e.g.

• Notification of customers
• Recall of products
• Conducting additional tests
• Inclusion of batches in the stability program
• Increased monitoring of complaints

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

• A complete assessment of the documentation systems used throughout the manufacturing and laboratory operations to determine where documentation procedures are inadequate
• A detailed CAPA plan that comprehensively corrects the company's documentation practices to ensure that the company maintains assignable, legible, complete, original, accurate and timely records throughout the operation
• A comprehensive, independent assessment and CAPA plan for the security and integrity of the computer system
• Interim controls should also be described and details provided of when the procedures for the CAPAs will be implemented

Source: Warning Letter to Laboratorio Magnachem International from June 18th 2024