4.1 This guide is not intended to specify the exact method of conducting a test for any particular material or final, finished device but only to present some of the criteria that should be considered in method design and possible problems that could lead to misleading results. In the development of the actual test protocol, it is recommended that alternatives to animal testing be considered as appropriate. If tumor bioassays are considered necessary, experimental design should include valid methods3 and an adequate number of animals should be included for meaningful statistical evaluation of the data.

4.2 The recommendations given in this guide may not be appropriate for all applications, types of implant materials, or all medical devices. These recommendations should be utilized by experienced testing personnel in conjunction with other pertinent information and the requirements of the specific application.

1.1 This guide is intended to assist the testing laboratory in the conduct and evaluation of tumorigenicity tests to evaluate the potential for materials to evoke a neoplastic response.

1.2 Carcinogenicity, which includes tumorigenic potential, is one of several biological effects that should be considered when evaluating the biological response to a material or a final, finished medical device as recommended in Practice F748. It is assumed that the evaluator has already determined that this type of testing is necessary for a particular material or medical device before consulting this guide. The recommendations of Practice F748 should be considered before a study is commenced.

1.3 Whenever possible, it is recommended that a battery of genotoxicity tests be proposed and initiated as an alternative to an in vivo tumorigenicity bioassay. Chemical information and data from the literature regarding non-genotoxic carcinogens, if present, may also be considered when evaluating the carcinogenic potential. Genotoxicity assays may also be considered as initial screening procedures due to the sensitivity of the assays, the significant reduction in time to gain valuable data, and the desire to reduce the use of animals for testing. Genotoxicity assays that may be considered are outlined in Guide E1262 and in OECD 471, OECD 487, and OECD 490. The investigator is advised to carefully consider the appropriateness of a particular method for application after a review of the published literature.

1.4 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety, health, and environmental practices and determine the applicability of regulatory limitations prior to use.

1.5 This international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for the Development of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee.