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Warning letters, 483s, Recalls, Import Alerts, Audit observations
Warning letters, 483s, Recalls, Import Alerts, Audit observations
Indian API manufacturer Global Calcium Pvt Ltd was issued a Warning letter by USFDA in January 2025. This was along expected lines, after serious data integrity issues and CGMP violations observed by FDA investigators Justin A. Boyd and Teresa I. Navas during an inspection at the facility in August 2024. The facility was also placed under an import alert by the FDA in December 2024.
During the inspection, FDA investigators had observed production records showing two different APIs manufactured simultaneously using the same equipment. Additionally, planned Excel files for cleaning validation samples, production details, and reports were present on a computer but were deleted overnight, preventing FDA auditors from following up the same. The responses from the firm were unconvincing to the FDA and were bizarre. Global Calcium claimed that the production head had directed the creation of falsified records to misrepresent API production in order to claim incentives. The Excel files were reportedly deleted to avoid unwanted conversations with investigators, and the computers were for personal use to record day to day activities.
The FDA also noted poor maintenance and facility upkeep, with liquid observed in a floor cavity and dripping onto a reactor from the floor above. Global Calcium claimed that the production area where these deficiencies were observed was under partial shutdown for upgrades with no production activities. However, the FDA rebutted these claims, noting that there was no information about a change control for the partial shutdown or upgrades during inspection. Global Calcium had also failed to evaluate the impact of manufacturing batches during maintenance activities or assess the state of repairs throughout the facility.
Furthermore, Global Calcium did not establish comprehensive impurity profiles for its APIs and simply listed impurities mentioned in the USP. Impurities were not monitored during stability studies. The company claimed that customers tested the batches for impurities and that there were no returned APIs due to quality issues. However, the FDA observed instances of returned products due to poor quality and complaints.
The warning letter highlighted the inadequacies in Global Calcium’s responses to the FDA’s observations and critical cGMP deviations, particularly the lack of thorough investigation and root cause analysis for each critical deviation. The company also failed to investigate the extent of similar CGMP deviations across the facility, how wide spread the practice of record fabrication is, potential contamination and / or failure of previously manufactured lots, and to implement comprehensive remedial actions to address the root causes and impacted batches.
The FDA has asked Global Calcium for taking comprehensive remediation measures, including assessment of quality systems with engagement of qualified CGMP consultant, reconciliation of all batches, an assessment of the impact of poor-quality batches, confirmation of the removal of employees involved in record fabrication, and external audits by a qualified consultant.
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