FDA Warning Letter: Missing Qualification of Contract Labs for Release

Recommendation

23-25 April 2024
Barcelona, Spain

Global Registration and Life Cycle Management for APIs

In June 2022, the U.S. FDA issued a Warning Letter to the Dutch company "Fagron Group B.V." after having inspected their US American site "Fagron Inc." in November 2021.

The significant violations of cGMP regulations for active pharmaceutical ingredients (APIs), which are mentioned in the Warning Letter, are listed as follows:

• "Failure to perform repackaging of API under appropriate cGMP to avoid potential cross-contamination"
• "Failure to adequately investigate and document out-of-specification results and implement appropriate corrective actions"
• "Failure of your quality unit to exercise its responsibility to ensure the API manufactured at the facility are in compliance with cGMP"

The most important statement made in the U.S. FDA Warning Letter, is that the firm failed to ensure that its APIs comply with the cGMP requirements. This is linked to the finding which refers to the Quality Unit (QC and QA responsibilities), who missed to qualify its contract laboratories used to support the release. This was already observed during an inspection in 2017 and was now repeatedly detected. According to the U.S. FDA Warning letter, the firm's explanation that this observation occurred due to a lack of resources and will be fixed by additional QU personnel was acknowledged by the FDA.

In addition, a lack of data integrity was observed during the inspection, which is mentioned in the Warning Letter as follows:

"For example, investigators observed computers connected to CGMP-related laboratory equipment that allowed changes to or deletion of data generated to support the release of drugs without restriction."

This observation and also the remaining findings mentioned-above resulted in a long list of remediation activities and CAPA measurements requested.

Coming to the final conclusion mentioned in the Warning Letter, the U.S. FDA strongly recommends engaging a cGMP consultant to support the company in aligning their systems with cGMP requirements. Additionally, the U.S. FDA may refuse new applications until the US American manufacturer has addressed and corrected all observations and fully complies with cGMP requirements, which might be checked by a further inspection.

To view the complete list of violations and the conclusion given by the U.S. FDA, please see the Warning Letter Fagron Group B.V.