FDA 483 - Lupin Limited (Unit II) - December 04, 2018

During a U.S. Food and Drug Administration (FDA) inspection of Lupin Limited (Unit II), an Active Pharmaceutical Ingredient (API) manufacturer in Mandideep, India, from November 26 to December 4, 2018, several significant Good Manufacturing Practice (GMP) deficiencies were observed. The primary issues included inadequate cleaning validation for manufacturing equipment and utensils, specifically regarding reduced swab sampling without scientific justification and insufficient evaluation of continuous manufacturing's impact on impurity carryover. Additionally, critical water treatment systems lacked complete performance qualification monitoring studies before final approval. The Quality Unit's oversight was found to be deficient, as failed equipment cleaning results were not properly investigated with root cause analysis or corrective actions, and there was a lack of independent verification for equipment cleaning. Lastly, user access controls for computerized SCADA systems were not clearly defined or aligned with standard operating procedures. As a result, Lupin Limited is required to submit a comprehensive response outlining corrective and preventive actions to address each observation and ensure compliance with regulatory requirements for pharmaceutical manufacturing.