A Modular Approach to the ECVAM Principles on Test Validity

Abstract

The European Centre for the Validation of Alternative Methods (ECVAM) proposes to make the validation process more flexible, while maintaining its high standards. The various aspects of validation are broken down into independent modules, and the information necessary to complete each module is defined. The data required to assess test validity in an independent peer review, not the process, are thus emphasised. Once the information to satisfy all the modules is complete, the test can enter the peer-review process. In this way, the between-laboratory variability and predictive capacity of a test can be assessed independently. Thinking in terms of validity principles will broaden the applicability of the validation process to a variety of tests and procedures, including the generation of new tests, new technologies (for example, genomics, proteomics), computer-based models (for example, quantitative structure–activity relationship models), and expert systems. This proposal also aims to take into account existing information, defining this as retrospective validation, in contrast to a prospective validation study, which has been the predominant approach to date. This will permit the assessment of test validity by completing the missing information via the relevant validation procedure: prospective validation, retrospective validation, catch-up validation, or a combination of these procedures.

Preclinical safety and efficacy models for pulmonary drug delivery of antimicrobials with focus on in vitro models

“…The currently existing models can be seen as prototypes, still suffering from limitations and proper validation according to criteria and approaches as proposed by international regulatory bodies, such as the European Centre for the Validation of Alternative Methods (ECVAM) [179,180]. Better models, but also more standardized protocols are required including defined readouts.…”

Availability, Standardization and Safety of Human Cells and Tissues for Drug Screening and Testing

“…If a cell line-based assay for the tests to be undertaken is already available, then it is important to assess the level of validation that has been achieved in line with international requirements [6]. If proceeding with the selected method it is important that the cell line should be obtained from the original or otherwise qualifi ed source of cells, as a cell line transferred through different laboratories may undergo signifi cant changes [7].…”

“…This should also involve routes of communication between the researcher and the surgeon, via the tissue bank that originally supplied the tissue in question, when appropriate. 6. Users of human tissue should undergo a process of accreditation, to en sure that a minimum set of criteria are fulfi lled.…”

Alternativmethoden zum Tierversuch

“…Die Ursachen liegen nicht nur darin, dass die Entwicklung solcher Verfahren viel Zeit in Anspruch nimmt. Auch ihre Validierung sowie behördliche und internationale Anerkennung erfordern erfahrungsgemäß einen Zeitraum von mehreren Jahren [4,5,6]. Die Beratungskommission der GT steht mit ihrer vorsichtigen Haltung gegenüber dem Fortschritt bei und den Entwicklungsmöglichkeiten von Alternativmethoden nicht allein.…”

“…Die weltweite Zusammenarbeit der Industrienationen auf diesem Gebiet, hier besonders der EU, USA und Japan, wird durch die OECD koordiniert. Neu entwickelte Alternativmethoden werden in mehreren Schritten validiert (Über-sichten in [2,3,4]), was nach bisherigen Erfahrungen in Europa zumeist 5-6 Jahre benötigt. Bei Eignung der Methode für einen genau umrissenen Anwendungsbereich folgt ihre wissenschaftliche Anerkennung 2 und schließlich die "regulatorische" Anerkennung durch die zustän-digen Behörden der Mitgliedsstaaten bzw.…”