Acceptance
The inventors view
The validation process is the most important way to get the methods accepted. This process needs to be speeded up. The acceptance would probably increase by considering the mechanistic relevance of the methods under development as well as an early involvement of regulators.
The view of the end users
Most frequently, it was indicated that a single end point (like cytotoxicity) is used. Although it is recognised that cytotoxicity is a weak endpoint, it is considered as sufficient for the expectations assigned to the assay. Nevertheless, the results obtained with in vitro metods have a limited impact on the corporate final decision mainly due to the lack of clear and unambigious guidelines. An additional important point is that the users are waiting for specific guideline(s) on how to implement their battery of assays.
The manufacturers view
The lack of regulatory and scientific aceptance for alternative toxicity tests, as well as the inherent conservatism of regulatory processes is a draw back for commercialising alternative methods. Proper guidelines for validation, which includes the need of policies and standards to validate assays, definition of materials for validation studies, capacities for e.g. statistical support, and quicker procedures, for example.
Increased efforts to compare and validate in vitro data with in vivo data would increase the acceptance for alternative toxicity tests.
Comments from the Expert meeting
There is a climate of change concerning application of in vitro test methods. Europe is keen to speed up the process of acceptance. To accept a new test model on the European level you need a majority but within OECD you require consensus. US authorities are more flexible in bringing in new “alternatives” in the meaning to exchange an animal method against an in vitro method. There is an international cooperation for harmonization. Common criteria would be helpful for the acceptance of in vitro methods.
Legal acceptance would probably increase if the stakeholders - the legal authorities, industry, CROs and academia - cooperate from an early stage during the development of a new test method. There should be a continuous communication about new methods with regulators. In vitro methods can give more information on what mechanisms are involved in the toxicological response compared to the established animal tests. The demands of quality of in vitro methods today are much higher than when the existing in vivo methods were established. It is important that those who develop a method are clear in their communication of how a new method works. Science comes closer to regulatory regulations every year.
In order to facilitate scientific acceptance (as well as making it more attractive for scientists to spend time in developing new methods), new and improved alternative methods should be published in peer review journals. The journal ”Toxicology in Vitro” has a section for new methods and some other journals also publish articles about methods. Considering the issue of publishing versus patenting there is no problem to publish the results the day after submitting a patent application.