Determination of Cleaning Limits Considering Toxicological Risk Evaluation to Minimize the Risk of Cross Contamination.

Abstract

The historical approaches that have been used to establish cleaning validation acceptance limits should be updated to recent approaches to prevent cross contamination. In the present investigation, a cleaning method was validated using high performance liquid chromatography. Method modification critical parameters including spiking, swab sampling from PVC, Stainless Steel, and Polyethylene, extraction technique from swab, solubility, potency, toxicity (LD50), and improvement of limit of detection (LOD) of the method through analytical method validation were studied. In addition, roughness, mechanical and electro-polishing, consideration of dosage form as a quantitative factor, acceptable daily exposure (ADE), and permitted daily exposure (PDE) in the worst-case determination were considered in the study. The method was validated based on USP and ICH guidelines for specificity, limit of detection, limit of quantitation, precision, accuracy, linearity, and range. Linear regression analysis of data for the calibration plot in the range of 7.43, 10.89, 21.78, 43.56, 87.12 µg/mL, and relative standard deviation (R.S.D.) found to be 0.5, 0.4, 0.2, and 0.2, respectively with correlation coefficient of R2 = 0.999997. The LOD and the limit of quantitation (LOQ) were 2.23 and 7.43 µg/mL, respectively. Good recoveries in the range of 73.65-81.20%, and precision with relative standard deviation values lower than 15% have been obtained. The proposed method developed for cleaning validation is specific, precise, and useful for determination of cleaning acceptance limits using health-based limit and Quality Risk Management to develop an appropriate cleaning program for engineering design, safety of patients, and worker protection.