Validation & regulatory acceptance
Validation is defined as the process by which the reliability and relevance of a particular approach, method, process or assessment, is established for a defined purpose (OECD, 2005). Since the validation process generates and/or assesses empirical information on reliability and relevance of a test method/approach under standardised and controlled conditions, it is generally accepted to facilitate and/or accelerate the international (regulatory) acceptance of alternative test methods/approaches.
In 1995, based upon experience from large-scale validation studies, and in consultation with various international experts, ECVAM published recommendations concerning the practical and logistical aspects of validating alternative test methods in prospective studies (Balls et al, 1995). These criteria were then taken up internationally and are described in the OECD Guidance Document 34 (OECD, 2005).
In 2004, ECVAM proposed a modular approach to the validation of alternative methods (Hartung et al., 2004), according to which the various information requirements for peer-review and as generated during the validation process are broken down into seven independent modules. According to this modular approach, the information requirements can be fulfilled by using data obtained from a prospective study, by a retrospective evaluation of already existing data/information, or by a combination of both.
Validation contributes strongly to the international acceptance of any proposed test method and encourages and supports worldwide Mutual Acceptance of Data (MAD). The regulatory acceptance of tests that have not been subjected to prevailing validation processes is discouraged (OECD, 2005).
Following adequate validation studies demonstrating the utility and the applicability of a test method/approach, it may be considered for adoption by regulatory agencies.
Regulatory acceptance of a test method is its formal acceptance by regulatory authorities indicating that the test method may be used to provide information to meet a specific regulatory requirement. This includes, but is not limited to, a formal adoption of a test method by EU and/or OECD as an EU test method and included in the EU Test Methods Regulation (EC, 2008) and/or as an OECD Test Guideline, respectively.
In this section, the validation and regulatory acceptance status of alternative methods is provided according to the field they cover:
- Acute toxicity
- Reproductive Toxicity (under construction)
- Repeated Dose Toxicity
Environmental Toxicity & Fate
Photo: Scientist in EURL ECVAM laboratory. Copyright EU 2011.
OECD. (2005). Guidance document on the validation and international acceptance of new or updated test methods for hazard assessment, Series on Testing and Assessment, No. 34. OECD, Paris.
Balls M, Blaauboer BJ, Fentem JH, Bruner L, Combes RD, Ekwall B, Fielder RJ, Guillouzo A, Lewis RW, Lovell DP, Reinhardt CA, Repetto G, Sladowski D, Spielmann H & Zucco F (1995) Practical Aspects of the Validation of Toxicity Test Procedures. The Report and Recommendations of ECVAM Workshop 5. ATLA 23: 129-147
Hartung T., Bremer S., Casati S., Coecke S., Corvi R., Fortaner S., Gribaldo L., Halder M., Hoffmann S., Roi A.J., Prieto P., Sabbioni E., Scott L., Worth A., Zuang V. (2004). A modular approach to the ECVAM principles on test validity. Altern. Lab. Anim. 32, 467-472.
European Commission (EC) (2008a) REGULATION (EC) No 440/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 30 May 2008 laying down test methods pursuant to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH). Official Journal of the European Union 638 L142, 1-739.