OECD Workshop on Harmonization of Validation and Acceptance Criteria for Alternative Toxicological Test MethodsSummary of OECD Working Group 2: Practical Approaches to ValidationBy Errol Zeiger, Ph.D., J.D. This group was chaired by Drs. Alan Goldberg (CAAT) and Michael Balls (ECVAM). Rapporteurs were Drs. Leon Bruner (Procter & Gamble) and Horst Spielmann (ZEBET). The validation process is designed to establish the reliability and relevance of a method for a specifically-defined purpose. The goal of this group was to discuss validation approaches, and to review validation procedures used and discuss their adequacy. We were also asked to consider the acceptability of adopting various approaches to validation, rather than just a single one-size-fits-all approach. Aspects such as study design, statistical considerations, candidate test selection, independent study review, study management, GLP's, data evaluation and practical matters were also to be considered. All of these topics were vigorously discussed. The report developed by the group presents and distinguishes the various components of the test development process and the validation process, and the ordering of these components. Generalized flow charts were prepared which group and order the various components in these processes. It was agreed that validation is not designed to develop or optimize protocols, but is a confirmation process that is designed to determine the operational parameters of the test, and to define its usefulness. Topics specifically addressed in the group's report are: test definition; test optimization; peer review; assessment of readiness (of the new method) for validation; the prediction model (what it is and how it is used); planning the validation study; conduct of testing; specific statistical recommendations; and reporting (of validation study results). It is important that a method be well-defined (in terms of having a clear description of its basis and intended purpose, the role it would play in a toxicological testing framework, a clear and comprehensive protocol, and information regarding its reproducibility and quality of results) before being subjected to a formal validation procedure. Many of these factors are addressed during the "test optimization" phase of development. This term was proposed as a synonym for "prevalidation" because it is more descriptive of the purpose of the process. The majority of discussions centered around the various phases in the validation process, and the need to have the process be flexible so as to accommodate all types of tests, and different proposed uses of the tests and the data. Emphasis was also placed on the need to have a biostatistician as an integral member of any management or validation planning and oversight team, with some discussions about the appropriate statistical approaches to use with continuous data. Among other points of emphasis was the need to have peer-review of the test development data, the test protocol and of the appropriateness of the prediction model used. Dr. Zeiger is senior toxicologist, Environmental Toxicology Program, National Institute of Environmental Health Sciences | 
