CAAT Newsletter: Vol. 13, No. 3, Summer 1996

OECD Workshop on Harmonization of Validation and Acceptance Criteria for Alternative Toxicological Test Methods

Summary of OECD Working Group 1: Discussions, Principles and Criteria for the Validation and Acceptance of New or Modified Toxicological Tests

By William S. Stokes, D.V.M.

This working group was co-chaired by Drs. Eric Walum of Sweden and Hiroshi Ono from Japan. Drs. Robin Fielder of the United Kingdom and Christoph Reinhardt from Switzerland served as rapporteurs. The objective of this group was to reach consensus on harmonized principles and criteria for the validation and acceptance of any new or revised test method, including both animal and non-animal methods. The participants were provided with an extensive set of reference documents, including recent publications from OECD, CAAT, the European Center for the Validation of Alternative Methods (ECVAM) and the report from the recent workshop sponsored by the National Toxicology Program (NTP) and the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM). The criteria that were developed were largely derived from concepts in these documents.

The group developed consensus criteria for validation, which included: a clearly stated scientific rationale and regulatory purpose; a description of the relationship of the test endpoint to the in vivo biological effect or toxicity of interest; formal detailed protocols; a description of the limitations of the method; evaluation of intra and interlaboratory variation; evaluation of test method performance in relation to existing relevant toxicity data and information from the relevant target species; independent scientific peer review; availablity of all data supporting the validity of a method; and ideally, the collection of data in accordance with GLPs.

Criteria for regulatory acceptance included: the method provides data that adequately predict the endpoint of interest; the method generates data useful for risk assessment and its use provides for a comparable or improved level of protection; there are adequate data for chemicals/products applicable to the regulatory program involved; and there has been adequate consideration of the Three Rs. The group agreed that a prerequisite for regulatory acceptance is validation according to the criteria listed above.

The group emphasized that acceptance of a new method would be greatly facilitated by the early and continued involvement of regulatory agencies throughout the validation process. It also emphasized the need to consider both the validation and regulatory acceptance criteria during the planning and design stages of any validation study. Other recommendations addressed: the need for flexibility and application of validation criteria on a case by case basis; the validation of individual test methods used in a battery approach; validation of adjunct tests; the encouragement of parallel submissions of data from existing and new methods. The group also recommended that OECD develop a policy that would allow for the acceptance of patented test methods, which are currently not permitted in OECD Test Guidelines.

I was impressed with the cooperative and enthusiastic spirit of all the participants. Their efforts demonstrated the commitment of the international community to work together to facilitate the validation and acceptance of new test methods that will benefit human health, the environment and animal welfare.

Dr Stokes is Associate Director for Animal and Alternative Resources, National Institute of Environmental Health Sciences.