Template for the description of cell-based toxicological test methods to allow evaluation and regulatory use of the data_suppl

Abstract

Only few cell-based test methods are described by Organisation for Economic Co-operation and Development (OECD) test guidelines or other regulatory references (e.g., the European Pharmacopoeia). The majority of toxicity tests still falls into the category of non-guideline methods. Data from these tests may nevertheless be used to support regulatory decisions or to guide strategies to assess compounds (e.g., drugs, agrochemicals) during research and development if they fulfill basic requirements concerning their relevance, reproducibility and predictivity. Only a method description of sufficient clarity and detail allows interpretation and use of the data. To guide regulators faced with increasing amounts of data from non-guideline studies, the OECD formulated Guidance Document 211 (GD211) on method documentation

Taking the leap toward human-specific nonanimal methodologies: The need for harmonizing global policies for microphysiological systems

“…A general annotated toxicity test method template (ToxTemp) has been developed to fulfill the requirements listed in the OECD Guidance Document 211 (GD211), which describes method documentation for the purpose of safety assessment, as well as to guide end users on the types of answers and information required, the definition of acceptance criteria, and the level of cell model characterization. Such templates can assist both method developers to keep note of the required deliverables while designing the system and regulators in terms of what information would be required to make a regulatory decision ( Krebs et al., 2019 ).…”

New approach methods to assess developmental and adult neurotoxicity for regulatory use: a PARC work package 5 project

“…This approach ensures the use of data with a significant level of confidence. In the case of the DNT-IVB v1.0, elevated standards of readiness and robustness have already been demonstrated ( Bal-Price et al, 2018 ; Krebs et al, 2019 ; Blum et al, 2022 ). To assess DNT-IVBv1.0 performance, a set of 45 reference (i.e., performance) compounds, consisting of 28 substances that were considered DNT positive and 17 substances that were considered DNT negative by the assay developers were used.…”

Acceptance criteria for new approach methods in toxicology and human health-relevant life science research – part I

“…Imagine the following little scenario: you develop a new scientific method (e.g., an in vitro or in silico toxicity assay), you describe the method well (according to OECD guidance document 211, e.g., using the ToxTemp form (Krebs et al, 2019)), you develop and establish a definite, logical or systematic plan for executing the test method, detailing all the steps to be taken in a logical order (e.g., a standard operating procedure, SOP), and you deposit it in a curated methods database (see details in the GIVIMP guidance (OECD, 2018) or explanations, e.g., in Krebs et al, 2020). Then, you initiate some form of validation (e.g., a method readiness assessment; Bal-Price et al, 2018;Patterson et al, 2021;Schmeisser et al, 2023).…”

“…Some terms are used differently depending on the field of study, the regulatory area, or the professional background. This issue applies in particular to "test methods", i.e., a general description of the methodological basis of new approach methods (NAM; Leist and Hengstler, 2018;Leist et al, 2012b;OECD, 2018;Schmidt et al, 2017;Krebs et al, 2019Krebs et al, , 2020Pamies et al, 2022). The terms "test", "assay", "method", or "test method" are often used interchangeably.…”