FDA Issues Warning Letter to Indian Manufacturing Company

January 6, 2016
BioPharm International Editors

FDA issues a Warning Letter to Cadila Healthcare Limited for cGMP violations.

On Dec. 23, 2015, FDA issued a Warning Letter to Cadila Healthcare Limited as a result of a 2014 inspection of two of the company’s pharmaceutical facilities located in Ahmedabad, India. The company was cited for violations of cGMP regulations for finished products (Title 21, Code of Federal Regulations, Parts 210 and 211) and deviations from cGMP for API manufacture.

FDA states in the Warning Letter that Cadila failed to investigate batch failures and out-of-specification (OOS) laboratory test results of warfarin sodium tablets at its Ahmedabad City facility, which the agency discovered during an FDA inspection from Aug. 28–Sept. 5, 2014. Cadila responded to FDA’s findings by suspending manufacture of the products affected until completion of a corrective actions and preventive actions (CAPA) investigation and implementation. The company resumed production after the CAPA investigation; however, FDA was informed in June 2015 that additional lots of the affected product had failed after production resumed. According to FDA, this quality problem previously occurred in 2013, which included a recall of one lot of the product.    

“The current inspection continued to find inadequate investigations into warfarin tablet failures. The recurrence of product quality failures following the completion of your investigation indicates that your CAPA was ineffective. The recurrence of these failures is apparently due to inadequate identification of root causes and lack of action to resolve this manufacturing problem …. These persistent failures indicate that your manufacturing process is not in a state of control. Nevertheless, at this time, drugs from this facility are being released to the market,” FDA states in the letter.

FDA also cited the Sarkhej-Bavla Road facility with failing to properly respond to and address consumer complaints and is asking the company to “conduct and provide the details of your risk assessment to determine the adequacy of your firm’s investigations into product complaints and effectiveness of the CAPAs you have taken in response to those complaints. Provide details of the specific changes you have made to ensure prompt identification, correction, and follow-up for all problems associated with your drug products. Significant problems must also be reported to FDA in accord with FDA field alert requirements. Include your revised SOP to remediate your systems for problem identification and trending, including but not limited to complaint handling.”

Batch failures and inadequate CAPA were also cited at the company’s Zyfine facility. The Zyfine facility was also cited for failure to control computerized systems to prevent unauthorized access and failing to ensure that quality-related activities are recorded at the time they are performed.

FDA states, “In your response to the observation, you explained that this failure occurred during qualification of your water system, which was still in progress at the time of your response. Your response was deficient; the fact that your investigation into the presence of Pseudomonas sp. in your water system transpired during the qualification of that system is irrelevant. You must document all cGMP activities at the time you perform them, including equipment qualification and any deviations observed during such activities … These examples … of our findings at your Zyfine facility raise serious concerns about the effectiveness of your manufacturing controls, the integrity of your computerized records, and the accuracy of your cGMP records.”

Source: FDA