FDA Issues Cadila Warning Over Complaint, Data Integrity Issues

The FDA warned Cadila Pharmaceuticals for cGMP violations that include quality controls, complaint handling and data integrity at its Gujarat, India, active pharmaceutical ingredients manufacturing plant.

Cadila’s APIs failed to meet specifications for quality and purity and the firm released an API batch with an unknown peak in the residual solvents chromatogram that neither the analyst nor supervisor noticed or evaluated during reviews, the agency says.

The complaints were laid out in a Feb. 25 warning letter that brings to four the number of warning letters issued to Indian manufacturers since the first of the year.

The warning letter detailed one instance in which a customer complained about a batch, the firm found contamination occurred during the manufacturing process, but didn’t implement any controls to prevent contamination from recurring.

Cadila also repeatedly failed to investigate complaints and extend investigations to other batches of API that may have been affected.

Another complaint investigation from 2011 concluded that a particular impurity might be the cause of an odor, but no data were provided to support the conclusion and officials closed the inquiry before implementing corrective actions. Yet another complaint of batch odor received in August 2012 wasn’t investigated until March 2014, and data to support it were not retained, the warning letter says.

FDA investigators also rapped Cadila for failing to prevent unauthorized access to data or changes or omissions of data. An audit trail feature of the company’s gas chromatography instruments was not used until October 2013, even though a 2009 software validation included an evaluation of the capability. There are also no assurances that the firm maintains complete raw data for the gas chromatography instruments, and the company doesn’t test stability samples at required intervals, the letter says.

This is not the first time Cadila has been warned on data integrity and impurity issues. In November, the company was warned for sloppy investigations into foul-smelling batches and failing to use the audit trail for the gas chromatography unit at the same Gujarat plant.

The FDA urged Cadila to conduct a comprehensive evaluation of all of its global manufacturing operations to ensure compliance with cGMPs. The agency also told the firm to notify CDER’s Drug Shortages Program if any corrective measures it takes could reduce the number of APIs it produces.

The warning letter followed a March 24-28, 2014, inspection. Read it at www.fdanews.com/03-17-15-CadilaWarning.pdf. — Kellen Owings