FDA Warns of the Potential of Contamination at API Facility

FDA sent a warning letter, dated March 9, 2018, to Malladi Drugs & Pharmaceuticals Limited after an inspection of the company’s Tamil Nadu, India facility found deviations in current good manufacturing practices (CGMPs). Inspectors found inappropriately designed and cleaned equipment and vermin near equipment used for manufacturing. The FDA inspection was conducted from Sept. 4–8, 2017.

According to the warning letter, portions of the company’s facility are open to the outdoors, and inspectors observed birds and insects near open equipment that is used for drug manufacturing. FDA stated that the company failed to take adequate precautions to prevent contamination of product and must “provide a risk assessment for all drugs within their re-test date manufactured and distributed in the United States.”

The company also failed to use equipment suitable for production, and equipment was improperly cleaned. Vessels were partially filled with standing water, which may increase the risk of contamination, according to FDA. The agency stated the company should replace its equipment with equipment suitable for its intended use.

Proper process validation was also lacking at the facility. Processes lacked adequate control and out-of-specification test results were found in 24 batches over two years for an unspecified impurity. “Prior to the manufacture of process qualification batches, a manufacturer should identify all significant sources of variability and develop robust controls throughout the operation. Your process validation program failed to sufficiently address process parameters and other variables in the commercial manufacturing operation to support process reproducibility. It is essential that your process validation program provide substantial information and data to determine if the process can consistently produce acceptable quality products under commercial manufacturing conditions,” the agency stated.

FDA requested the company provide a data-driven and scientifically sound process validation plan, results from a stability study of validation batches, an evaluation of the company’s change management and correction action and prevention action systems, and an assessment of drug quality risk and toxicity of the impurity.

The agency placed the facility on Import Alert 66-40 on December 13, 2017 and stated, “Until you correct all deviations completely and we confirm your compliance with CGMP, FDA may withhold approval of any new applications or supplements listing your firm as a drug manufacturer.”

Source: FDA