Why validation of methods and approaches is important?
In 1981, the OECD and its member countries established the Mutual Acceptance of Data (MAD) system. This OECD Council Decision was the result of a political will to create a level playing field for chemical safety data that would be exchangeable and accepted across all countries using OECD Test Guidelines (TGs) and Good Laboratory Practices (GLP). OECD TGs are the scientific standard to generate toxicity data on chemical properties and hazards of regulatory interest (e.g. reproductive toxicity, genotoxicity, etc.), while GLP are a quality assurance system that testing facilities can adhere to. The MAD system enables to reduce duplicative testing and saves costs and animal lives used in testing.
Making regulatory decision on the basis of data generated using agreed standards at the global level also saves time. Data generated using validated methods are less prone to rebuttal and dispute, give greater legal certainty, and help maintain that level playing field across countries. For that purpose, validation and validated methods are potent instruments to ensure the availability of standardised methods in the long term.
Roadmaps and target dates for phasing out animal testing have been announced in the last years until recently. To make that transition a realistic goal, the initiative needs to be supported by the possibility to use trustable alternatives methods and approaches that have been demonstrated to be relevant and reliable. There are currently too few methods and approaches that have passed the stage of validation and reached regulatory acceptance for phasing out of animal testing: only topical hazards such as skin and eye irritation, skin sensitisation can be evaluated without animal tests. Method developers struggle to attract sufficient funding to carry out a validation study with partner laboratories. Academic researchers are mostly not interested in engaging in validation because repeating the same experiment multiple times and replicating it in other laboratories is not attractive for journal publications and does not help career advancement. This work relates more to translational research for applications in chemical safety. Small innovative businesses run by method developers will also need investors’ money to validate their methods in view of commercial use.
In 2023, the OECD published a call for urgent mobilisation of national and regional resources for the demonstration of reproducibility and reliability of methods developed in single laboratories. It is of critical importance that dedicated public money is invested in new approach methods validation (mostly non-animal), to balance the offer, maintain confidence, ensure transparency, facilitate acceptance, and guarantee sustainability of methods.
Large research programmes of the past two decades have delivered potential solutions that are amenable to standardised methods and approaches. They have stimulated research and the emergence of promising methods during the life of individual projects, but the last mile to transform the most promising candidate methods into validated tools often remains to be accomplished.
Whilst validation can take a couple of years or more for various reasons including difficulties in identifying targeted funding, efforts are underway to facilitate validation, to reduce the time/resources involved. It is key to do this without compromising on the quality of the work, the scientific credibility, and the reliability of the end product. It is important to recognise that validation remains a serious endeavour that facilitates acceptance. If Member countries, regions, stakeholders and public seriously consider phasing out animal testing for chemical safety purposes, it is high time to invest in solutions that will pass regulatory acceptance.
An OECD workshop on organisational and financial aspects of validation was organised on 14-15 December 2023. It was preceded by a survey where costs of validation were collected from practitioners. A rough estimation shows that depending on the complexity of the method between 200-500 kEUR are necessary to cover expenses of the lab costs (excluding manpower) to validate a method. For more details on costs, the workshop report should be consulted.
RESOURCES AVAILABLE FROM THE OECD
| Case example | Presenter |
| OECD TG 125: Nanomaterial Particle Size and Size Distribution of Nanomaterials | Kerstin Kämpf |
| OECD TG 249: Fish cell line acute toxicity – The RTGILL-W1 cell line assay | Kristin Schirmer |
| Gregory Lemkine | |
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OECD TG 439 - Skin irritation validation studies (presentation includes several case studies) |
Helena Kandarova |
| OECD TG 442E on skin sensitisation: Validation of GARDSkin | Henrik Johansson |
|
Anne Milcamps Ingrid Langezaal |
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| Experience gained at PEPPER | Philippe Hubert |
| The human thyroid microtissue assay | Helena Hogberg |
| In vitro Skin sensitisation test: EpiSensA (for inclusion in TG 442D) | Takao Ashikaga |
Other resources available
Validation bodies/Validation centres:
Institutes actively promoting non-animal methods and providing training or other services:
Reference chemicals selection:
Database of non-animal methods:
Funding opportunities for validation/standardisation/confidence building:
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