FDA Warns API Manufacturer about Quality and Data Integrity Issues

In a warning letter dated March 2, 2017, FDA cited Badrivishal Chemicals & Pharmaceuticals with current good manufacturing practice (CGMP) violations found at the company’s Maharashtra, India facility. The violations, which include quality and data integrity deficiencies, were observed during an FDA inspection conducted Aug. 16–19, 2016.

The various quality CGMP violations found by inspectors included an inadequately monitored and controlled water purification system. Source water from a nearby river that passes through farmland was not tested and was kept in a storage tank with a hole open to the environment.  These violations caused the potential for water contamination and, therefore, product contamination. Procedures for sanitizing the water system were not followed, nor had the company completed a performance qualification of the water system. “Your firm has used this unqualified system routinely since its installation in 2014, despite having no scientific evidence that the system is capable of producing water of adequate quality,” the agency stated in the letter.

FDA stated in the letter that the company was aware of that their water system had an excessive amount of total aerobic microbial counts (TAMC) yet had failed to investigate the deviations. The company’s response to the investigators’ findings were inadequate, according to the agency. The warning letter stated that the company must provide a plan to address the open source water storage tank; an update on performance qualification of the water source; corrective actions and preventive actions (CAPA) for source water test results that exceed limits; and a scientific rationale for setting microbial limits.

A number of data integrity and documentation violations were also found by investigators. Original laboratory and production records were found in trash bags behind the facility. Data on the trashed documents did not match official records, and the quality unit did not investigate the discrepancies. Investigators later found that the trash bags containing the documents had been removed. “Removal of the trash bags containing additional torn documents prevented our investigators from examining these documents. It also prevented your firm from performing a global reconciliation of all torn documents with their official versions,” the agency stated.

The company also failed to ensure that contract testing laboratories were qualified, and when asked to provide method verifications, the company provided draft protocols and did not specify which contract testing laboratory performed the verification experiments.

The agency recommended the company obtain a CGMP consultant, revise quality agreements, and perform data integrity remediation. FDA placed the company on Import Alert 66-40 on Dec. 19, 2016. “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 … Failure to correct these deviations may also result in FDA continuing to refuse admission of articles manufactured at Badrivishal Chemicals and Pharmaceuticals located at Gat No. 29, Village Jambwade (Induri) and Plot No. 13, Revenue Colony, Talegaon Dabhade, into the United States…,” the agency stated in the letter.

Source: FDA