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In vitro test systems offer the potential for high consistency and resulting high predictive capacity. This promise comes from the ability to control many of the independent variables that can lead to the variability of responses in vivo. Furthermore, most of the in vitro tests currently employed, have undergone some level of formal validation or at least multi-center evaluation to establish formal or informal standards of performance. Those standards generally include methods for test system qualification, data acceptance criteria based on positive and negative control responses, and routine use of benchmark materials. These efforts have allowed many companies to use certain assays as full replacements for in vivo studies in their product development/safety programs. A goal of many developers and users of in vitro assays has been the formal acceptance of these tests by the regulatory community. The regulatory community needs to be able to evaluate data, from a wide range of laboratories, against common standards so that reviewers can make equitable decisions. In some cases, the regulatory agencies have established performance standards that are designed to link the validated test methods with the specific assay used for regulatory submission. This presentation will focus on the tools that allow this to be accomplished: test system qualification, selection and use of benchmark materials, and the importance of concurrent controls and associated assay acceptance criteria.