Foul API Batches and Data Integrity Issues Result in FDA Warning for Cadila

The FDA has cited Cadila Pharmaceuticals for poor data integrity practices and sloppy investigations into foul smelling batches of active pharmaceutical ingredients (APIs), violations that the agency threatened could result in an import alert.

The agency’s warning letter stems from an inspection of Cadila’s Guajarat, India, facility in March that found since 2011 the company had failed to properly investigate product complaints and make changes to prevent problems from recurring.

The FDA letter citied several data integrity problems at the plant, an area that has received heightened scrutiny from investigators.

For example, an audit trail that can show who accesses the gas chromatography unit has been available since 2009, but wasn’t used until October 2013. Instruments such as an ultraviolet spectrophotometer also were connected to stand-alone computers instead of to a network, and Cadila didn’t have back-up systems for the devices, according to the FDA’s Oct. 15 letter.

Investigators also discovered a backlog of samples that needed to be tested for stability, a repeat observation from a 2012 inspection.

In another violation, the FDA observed that Cadila had received a complaint in September 2011 of a foul smelling batch of APIs, which the company attributed to a control for an impurity, but didn’t provide specifics. The FDA found the firm’s investigation into the matter didn’t include data to support such a claim and offered no assurance that changes to the manufacturing process regarding the control were related to the odor issue.

Less than a year later, Cadila received the same complaint about another batch of foul APIs. In addition to the odor problem, the batch failed tests for maximum impurity levels, according to the FDA. Cadila once again blamed the unpleasant odor on a process impurity, but again failed to provide enough data to back that conclusion up, said the letter.

The FDA openly questioned whether Cadila has an effective quality system, and warned that failure to make a turnaround could result in holds on any new applications or supplements that list Cadila as an API supplier. The agency also could slap Cadila with an import alert, effectively preventing the manufacturer from shipping API to the U.S.

Cadila has already faced quality problems earlier this year, recalling more than 10,000 bottles of antihistamine due to a drug mix-up.

The drugmaker was not available for comment.

To read the warning letter, visit www.fdanews.com/11-11-14-CadilaWarning.pdf. — Robert King