FDA Warns Italian API Maker for Deleting Quality Data

September 17, 2014

The FDA has slapped a warning on an Italian active pharmaceutical ingredient manufacturer for deleting quality data, the latest indication the agency is serious about clamping down on poor manufacturing data integrity.

Trifarma S.p.A. received the warning letter for violations stemming from a January inspection of its Rozzano, Italy, plant.

Agency investigators chastised Trifarma for deleting all electronic raw data surrounding its high performance liquid chromatography (HPLC) testing of API products. “In addition, your firm failed to retain basic chromatographic information such as injection sequence, instrument method or integration method for tests,” said the July 7 letter.

Trifarma had said in response to a Form 483 issued after the inspection that it would have a backup system online by this fall, however the system doesn’t address the backup of the injection sequence, instrument method or audit trail, the FDA said.

In addition, the FDA cited the company for granting all laboratory personnel full privileges to delete or alter raw data on the laboratory systems. At the time of the inspection, the company’s HPLC and gas chromatograph software had no audit trails to show when raw data was changed and who changed it.

The systems now have audit trails and the company has started retaining raw data on a local hard drive, the FDA acknowledged. But the measures lack “proper safeguards to ensure they cannot be deleted prematurely,” it added.

Trifarma also failed to document any training of operators in the synthesis plant, the letter said. Plant management was unaware of standard operating procedures for issuing certificates of analysis on API batches. “Without documented training, there is a lack of assurance that your employees can reliably execute their API responsibilities,” the letter said.

A November 2013 review of Trifarma’s Ceriano Laghetto plant uncovered similar violations.

Trifarma needs to hire a qualified consultant to improve its quality systems, and create an action plan to investigate the extent of the training problems. If the company doesn’t address the violations, the FDA could withhold approval of new applications or supplements that list Trifarma as an API supplier, the letter said.

Aldo Rucano, chair of Trifarma’s European office, told DGR that the drugmaker will inform the agency of its plans to install a protected and validated electronic management system.

Trifarma is the 13th international drugmaker to be warned since the FDA’s fiscal year began in October over data integrity failures, up from eight the year before. Agency officials recently signaled that data integrity is a priority for inspections (see related story).

To read the warning letter, visit www.fdanews.com/ext/resources/files/07/07-16-14-TrifarmaWarning.pdf. — Robert King