A MODEL OF ANALYSIS IN ANALYTICAL METHODOLOGY FOR BIOPHARMACEUTICAL QUALITY CONTROL

Abstract

One key quality control parameter for biopharmaceutical products is the analysis of residual cellular DNA (rcDNA). To determine small amounts of DNA (around 100pg) that may be in a biologically-derived drug substance, an analytical method should be sensitive, robust, reliable and accurate. In principle, three techniques have the ability to measure rcDNA: radioactive dot-blot a type of Hybridization; Threshold and quantitative Polymerase Chain Reaction (qPCR). Quality Risk Management (QRM) is a systematic process for evaluating, controlling and reporting of risks which may affects method capabilities and supports a scientific and practical approach to decision making. This paper evaluates by QRM, an alternative approach to assessing the performance risks associated with quality control methods used with biopharmaceuticals, using the tool Hazard Analysis and Critical Control Points (HACCP). HACCP provides the possibility to find the steps in an analytical procedure with higher impact on method performance. By applying these principles to DNA analysis methods, we concluded that the radioactive dot-blot assay has the largest number of critical control points (CCP), followed by qPCR and Threshold. From the analysis of hazards (i.e. points of method failure) and the associated method procedure CCP, we concluded that the analytical methodology with the lowest risk for performance failure for rcDNA testing is the qPCR.