Validation Study and Quality Assurance of Pharmaceutical Water, Waterborne Microorganisms and Endotoxins

Abstract

　Water for injection (WFI) and purified water are the most widely used and stringently regulated raw material in pharmaceutical manufacturing. WFI is utilized for a parenteral drug product. Water system is monitored at frequent and routine frequency for demonstrating the overall system control and stability of performance. The critical ports demonstrating systemic control should be monitored more frequently. For reducing the overall risk of microbial contamination or microbial build-up, it is important to develop appropriate alert and action levels. The assignment of alert and action levels should be performance-based, derived from the historic data and well below water specifications. These levels and overall excursion rates should be assessed annually. An action level should not be established at a level equivalent to the specification. Consecutive or multiple alert level excursions and each action level excursion should be comprehensively investigated with appropriate corrective and preventive action. It is important to analyze the efficacy of the corrective and preventive action to reduce the overall excursion rates.