FDA Cites Italian API Supplier Trifarma for Data-Integrity Issues

Trifarma S.p.A., a manufacturer and supplier of active pharmaceutical ingredients (APIs) headquartered in Milan, Italy, has received a Warning Letter from the US Food and Drug Administration (FDA) for cGMP deviations for API manufacturing at the company’s manufacturing facility in Rozzano, Italy. The FDA inspected the facility from January 27 to January 29, 2014, and cited the firm for data-integrity issues.

Specifically, the FDA cited the firm for failure to maintain complete data derived from all testing and ensuring compliance with established specifications and standards pertaining to data retention and management. In its letter, FDA said that the firm 
did not retain complete raw data from testing performed to ensure the quality of its APIs. The FDA said that the firm deleted all electronic raw data supporting its high-performance liquid chromatography (HPLC) testing of all API products released to the US market. In addition, the FDA said that the firm failed to retain basic chromatographic information, such as injection sequence, instrument method, or integration method for the tests. In addition, the FDA said that the company’s laboratory management was unaware of, and therefore did not follow, the written procedure detailing the review of analytical data and that its management confirmed that the review of analytical data did not include evaluating the system suitability parameters to ensure proper column performance

In its response to the FDA, Trifarma said that the firm has been researching backup systems since July 2013 and will have a backup system on line by the third quarter of 2014 and the company has begun  provisionally storing backup data on each computer, including the integration method as part of that data. The FDA, however, noted that the company did not address the backup of the injection sequence, the instrument method, audit trails, or how to ensure that electronic files are not deleted prematurely from local computers. 

The FDA also said that the firm failed to prevent unauthorized access or changes to data and to provide adequate controls to prevent omission of data. The FDA also noted that the firm lacked electronic raw data supporting cleaning, method, and process validations. The FDA also cited the firm for failing to ensure that employees receive appropriate and documented training on the particular operations that the employee performs, specifically citing a lack of documentation for the training of production employees. The company noted that it had updated its training in standard operating procedures in July 2013 to include on-the-job training and cGMP training, but the FDA said it did not follow this procedure.

In its letter, the FDA concluded: “Our review of the significance of current findings indicates that your quality unit is not able to fully exercise its responsibilities. It is essential that you provide the quality unit with the appropriate authority and staff to carry out its responsibilities. We also recommend that you hire a qualified consultant to provide your firm's staff with guidance and training on cGMP and laboratory data integrity.” The FDA said that the cGMP violations at the company’s Rozzano facility included similar deficiencies to those cited in the Form FDA-483 from the November 2013 inspection of the company’s Ceriano Laghetto, Italy plant. 

Source: FDA  

Leave a Reply

Your email address will not be published. Required fields are marked *