FDA Warning Letter: No Stability Studies for Reworked Batches

In June 2022, the U.S. FDA issued a Warning Letter (WL) to the Spanish company "Bioiberica, SAU" after having inspected its site in January and February 2022.

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

• "Failure to establish written procedures to monitor the progress and control the performance of processing steps that may cause variability in the quality characteristics of your intermediates and API."
•  "Failure to ensure that reworked batches have been subjected to appropriate evaluation and stability testing to show that the reworked material is of equivalent quality to that produced by the original process."

According to the U.S. FDA Warning Letter, the firm failed to do stability tests for 23 reworked API batches in 2020 and 2021.
Additionally, it is mentioned that there were no process controls established for the rework steps, which is mandatory to show equivalence of the batches which were produced by reworking compared to the batches of API which were produced by the original validated manufacturing process. The "ICH Q7 Good manufacturing practice for active pharmaceutical ingredients" guideline clearly states in chapter 14.3 "Reworking" that "Batches that have been reworked should be subjected to appropriate evaluation, testing, stability testing if warranted, and documentation to show that the reworked product is of equivalent quality to that produced by the original process."

The observed findings 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 listing the company as drug manufacturer until the site has addressed 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 Bioiberica, SAU.