Integrated Approaches to Testing and Assessment

Abstract

The concept of Integrated Approaches to Testing and Assessment (IATA) has been advanced by the Organisation for Economic Cooperation and Development (OECD) member countries to enable a progressive shift from traditional chemical assessments largely based on the observation of the adverse effect in animal models, using individual methods or predefined batteries of standard toxicity tests, to assessment strategies integrating diverse lines of evidence. The flexible nature of IATA allows the inclusion of mechanistic data generated with non-animal methods and with new technologies (e.g. high-throughput and high content methods). The assessment process within IATA is typically conducted through weight-of-evidence which inevitably includes the elements of subjective expert judgement. For these reasons, IATA cannot be fully harmonized across sectors and countries. Nevertheless, some of the IATA components, such as defined approaches, which consist of a fixed data interpretation procedure (DIP) applied to data generated with a defined set of information sources, can be harmonized. The focus of this MiniReview is to provide an illustration of the differences between the IATA developed so far in the areas of regulatory toxicology, and ongoing activities related to the international harmonization of defined approaches that rely on multiple non-animal information sources.

Requirements for Animal Experiments: Problems and Challenges

“…The IATA concept has been proposed by the Organization for Economic Cooperation and Development (OECD) member countries, in order to progressively shift from traditional drug assessment using animal models. [76] IATA uses new approaches like high-content screening and high-throughput screening methods, together with different computational methods used for data generation, interpretation, and integration. [77,78] The use of adverse outcome pathways (AOP) in developing IATA can be useful to organize and understand the key events within biological pathways that lead to adverse outcomes induced by chemicals.…”

“…The general framework on how AOP can be used for this purpose is the following: 1) formulation and identification of the problem (e.g., regulatory question, end point of interest, and decision context); 2) gathering and evaluating the existing information available for the chemical of interest; 3) assessing the weight of evidence of the gathered information and evaluate whether this information is adequate for decision-making regarding a potential risk; 4) if additional information is needed, the AOP can help to develop a testing strategy to generate supplementary information; and 5) when the information is adequate, make a regulatory decision or final conclusion. [76,79] Several computation methodologies have been used in IATA, including quantitative structure-activity relationship (QSAR) models, physiologically based kinetic (PBK) models, in vitro tests, and integrating existing sources of data on chemical analogs (read-across). [78,80] QSAR modeling represents one of the most popular computer-aided tools utilized for drug discovery and leads optimization, being particularly powerful when no 3D structures of specific drug targets are available.…”

Is it possible to overcome issues of external validity in preclinical animal research? Why most animal models are bound to fail

“…The US is making significant investments in organ-on-chip technologies [ 7 ] and the Netherlands is aiming to phase out animal use in the regulatory safety testing of medicines and chemicals by 2025 [ 65 ] regarding new technologies as able to increase research relevance and deliver more reliable risk assessments whilst maintaining existing safety levels [ 66 ]. Systematic reviews are being used to review legacy data on drug safety [ 67 ] and this evidence, alongside low-risk approaches such as microdosing in clinical trials [ 68 ], could provide a valuable safeguard during a transition to new technologies [ 69 ]. Systematic reviews will also have a role in synthesising emerging evidence about the efficacy of new technologies.…”

Toxicology Meets Pharmacodynamics and Pharmacokinetics – New Concepts, Models and In Vitro Approaches and Tools

“…Integrated Approaches to Testing and Assessment (IATA) is a novel procedure outlining science‐based approaches for toxicological decision‐making based on the integration of multiple information sources from in vivo , in vitro and in silico . The IATA concept is a tool to promote risk assessment by non‐animal testing methods, and it is already used for some end‐points such as skin corrosion/irritation and skin sensitization, where validated in vitro tests are available and in conjunction with other relevant information . The assessment process within IATA is typically conducted through weight‐of‐evidence which inevitably includes elements of subjective expert judgement .…”

“…The IATA concept is a tool to promote risk assessment by non‐animal testing methods, and it is already used for some end‐points such as skin corrosion/irritation and skin sensitization, where validated in vitro tests are available and in conjunction with other relevant information . The assessment process within IATA is typically conducted through weight‐of‐evidence which inevitably includes elements of subjective expert judgement . The application of IATA depends, at least partially, on the use context, available evidence and data gaps.…”