FDA 483 - Zhejiang Huahai Pharmaceutical - November 20, 2024

During an FDA inspection from November 12-20, 2024, Zhejiang Huahai Pharmaceutical Co., Ltd., an Active Pharmaceutical Ingredient (API) manufacturer, received an FDA Form 483 citing numerous significant cGMP violations. The primary issues centered on severe data integrity failures and inadequate quality control.

Observations included a lack of complete raw test data for cleaning samples, specifically regarding solution preparation and calculations, leading to unreliable results and potential cross-contamination. The company failed to follow its own analytical procedures, such as not preparing reference standards for system suitability and using incorrect calculation methods. Laboratory investigations into Out-of-Specification (OOS) results were deficient, lacking scientific justification and failing to identify root causes, with equipment continuing to be used despite failures.

Further concerns arose from a lack of investigation into approximately 101 discovered facility and equipment deviations (e.g., rusted equipment, uncontrolled paper records), coupled with inconsistencies in contemporaneous data recording in batch records. Quality Unit oversight was found lacking, as testing continued despite known data reliability issues, and no control existed over the destruction of GMP documents.

Batch production records were inadequate, missing critical details like specific processing speed ranges and scientifically established drying times, leading to potential batch-to-batch variability. Equipment was not maintained in a good state of repair, posing contamination risks. Lastly, cleaning sample collection procedures were deficient, with operators physically entering equipment without proper protocols, risking further contamination.

These observations highlight a systemic breakdown in adherence to quality systems, data integrity, and process control. Zhejiang Huahai Pharmaceutical is required to provide a robust response detailing corrective and preventative actions to address these serious deficiencies and ensure the safety, quality, and purity of APIs for the U.S. market.