Statistical bases for defining level of assurance

Assurance of a low risk that material produced in cell culture harbours adventitious agents is provided through carefully conducted clearance studies, as well as quality control testing. Clearance studies are a form of quality assurance, and are used to demonstrate the ability of the manufacturing process to minimize or neutralize unwanted contaminants. Quality control testing is confirmation of a low risk that manufactured lots are contaminated with an adventitious agent. Neither of these can guarantee, however, that product released to the customer will be completely free of contaminants. Clearance studies provide information on log reduction of a contaminant, but by their nature cannot demonstrate complete elimination. In quality control testing, the ability to support the claim that there is minimal risk of a lot containing an adventitious agent depends on the quantity of material being tested and on the sensitivity of the detection assay. Statistical methods can be used both to design clearance studies, as well as control tests, to achieve a desirable level of assurance that the contaminant is below a defined threshold in the product. Basic data analysis methods, such as confidence intervals, improve the quality of information, by showing the range of adventitious agent reduction or level.