FDA 483 - Granulation Technology, Inc. - March 02, 2023

Granulation Technology, Inc. received an FDA Form 483 following an inspection conducted from February 13 to March 2, 2023. The inspection revealed significant deviations from current Good Manufacturing Practices (cGMP) for drug products, with several observations being repeats from a November 2017 inspection. Key violations in quality systems included a pervasive failure to thoroughly investigate out-of-specification microbial results in the water system and finished products, lacking scientific justification for root causes and failing to assess product impact. The company also did not establish alert limits or address out-of-trend results. The Quality Control Unit failed to implement a control system for changes impacting drug product quality, omitting change controls for equipment installations and water system modifications. Deficiencies extended to complaint handling, where investigations lacked critical details like reviewed lot numbers and definitive root causes. In production, the firm failed to adequately validate manufacturing processes, including capsule banding, metal detection, and the water purification system, which consistently produced microbially contaminated water. Facility and equipment issues were noted, such as inadequate cleaning and maintenance of a blender and capsule filling machine, showing residual product despite being marked clean. The warehouse lacked orderly placement, with released, quarantined, and R&D materials co-mingled without proper segregation. Additionally, routine calibration checks were insufficient, exemplified by a fluctuating and unleveled weigh scale used for in-process checks. Finally, packaging and labeling operations exhibited poor control, with product labels not being reconciled accurately after use, rejected labels improperly documented, and unprinted labels left unsecured on the packaging line overnight. Granulation Technology, Inc. is required to provide a comprehensive response to the FDA addressing these observations with a plan for corrective and preventive actions to ensure compliance.