Towards an animal-free human health assessment: starting from the current regulatory needs

Bos, Peter; Geraets, Liesbeth; Wit-Bos, Lianne de; Heringa, Minne B.; Engelen, Jacqueline van

doi:10.14573/altex.1912041

Cited by 7 publications

(8 citation statements)

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“…Enquiries among Dutch researchers learned that there are several biobanks, which can provide frozen human tissues but hardly any fresh tissues (Fentener van Vlissingen et al, 2017). Furthermore, there is an abundant potential supply of vi-tory safety assessment can benefit significantly from regular interactions between all stakeholders involved (see also Bos et al, 2020). In this respect, workshops attended by developers, toxicologists and regulators, where information is exchanged on how OCs can be used for regulatory purposes, have proven to be a useful format for such interaction.…”

Section: Availability Of Cellsmentioning

confidence: 99%

The value of organs-on-chip for regulatory safety assessment

Heringa

2019

ALTEX

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complete replacement of animal tests is not yet possible. Especially in case of the more complex systemic endpoints (e.g., carcinogenicity and reproductive toxicity), adequate animal-free methods are not yet available. Similarly, sufficiently predictive animal-free models to obtain information on toxicokinetics (absorption, metabolism and excretion), which is indispensable to calculate safe exposure limits for humans from in vitro assays, are still lacking. In short, from a regulatory point of view, the transition to a more predictive safety assessment of chemical and pharmaceutical substances requires the development of novel models and methods that reflect complex human physiology and biology in vitro.In this respect, one of the fastest-growing, most promising innovative technologies is the organ-on-chip (OC) technology (Marx et al., 2016). However, its value for regulatory safety assessment of chemical substances and pharmaceuticals is still unclear. Its role is in part dependent on the future development of regulatory safety assessment, which is widely recognized to be in need of a transition to accommodate the increased level of toxicological knowledge and animal welfare considerations (Piersma et al., 2018b).

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Section: Availability Of Cellsmentioning

confidence: 99%

The value of organs-on-chip for regulatory safety assessment

Heringa

2019

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“…In most cases, they do not give direct information on pathological outcomes, and the NAMs data are difficult to relate to external doses and to various exposure situations. Two fundamental strategies have been developed which work together to bridge the gap between the types of data provided by NAMs and the type of data used for regulation: the adverse outcome pathway (AOP) concept and in vitro to in vivo extrapolation (IVIVE) (Terron et al 2018 ; Punt et al 2020 ; Bos et al 2020 ; Kisitu et al 2020 ).…”

Section: Components Of Tiered Approaches For Hazard and Exposurementioning

confidence: 99%

A framework for chemical safety assessment incorporating new approach methodologies within REACH

Ball¹,

Bars

Botham

et al. 2022

Arch Toxicol

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The long-term investment in new approach methodologies (NAMs) within the EU and other parts of the world is beginning to result in an emerging consensus of how to use information from in silico, in vitro and targeted in vivo sources to assess the safety of chemicals. However, this methodology is being adopted very slowly for regulatory purposes. Here, we have developed a framework incorporating in silico, in vitro and in vivo methods designed to meet the requirements of REACH in which both hazard and exposure can be assessed using a tiered approach. The outputs from each tier are classification categories, safe doses, and risk assessments, and progress through the tiers depends on the output from previous tiers. We have exemplified the use of the framework with three examples. The outputs were the same or more conservative than parallel assessments based on conventional studies. The framework allows a transparent and phased introduction of NAMs in chemical safety assessment and enables science-based safety decisions which provide the same level of public health protection using fewer animals, taking less time, and using less financial and expert resource. Furthermore, it would also allow new methods to be incorporated as they develop through continuous selective evolution rather than periodic revolution.

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“…With the aim to improve toxicological safety and risk assessment and preclinical safety predictions in pharmacology, regulatory scientists should keep pace with advances in basic and applied science and technology. At the same time, regulatory scientists should critically appraise new technologies for their fitness-for-purpose and use, in line with the regulatory needs for information relevant to human health (Fitzpatrick and Sprando 2019;Bos et al 2020). Using OoC to generate information for demonstrating safety, discussions are needed on how to gain confidence in the performance of the technology.…”

Section: Toward Coordinated Development and Implementation Of Organ-on-chipsmentioning

confidence: 99%

Applicability of organ-on-chip systems in toxicology and pharmacology

Schneider

Oelgeschlaeger

Burgdorf

et al. 2021

Critical Reviews in Toxicology

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Organ-on-chip (OoC) systems are microfabricated cell culture devices designed to model functional units of human organs by harboring an in vitro generated organ surrogate. In the present study, we reviewed issues and opportunities related to the application of OoC in the safety and efficacy assessment of chemicals and pharmaceuticals, as well as the steps needed to achieve this goal. The relative complexity of OoC over simple in vitro assays provides advantages and disadvantages in the context of compound testing. The broader biological domain of OoC potentially enhances their predictive value, whereas their complexity present issues with throughput, standardization and transferability. Using OoCs for regulatory purposes requires detailed and standardized protocols, providing reproducible results in an interlaboratory setting. The extent to which interlaboratory standardization of OoC is feasible and necessary for regulatory application is a matter of debate. The focus of applying OoCs in safety assessment is currently directed to characterization (the biology represented in the test) and qualification (the performance of the test). To this aim, OoCs are evaluated on a limited scale, especially in the pharmaceutical industry, with restricted sets of reference substances. Given the low throughput of OoC, it is questionable whether formal validation, in which many reference substances are extensively tested in different laboratories, is feasible for OoCs. Rather, initiatives such as open technology platforms, and collaboration between OoC developers and risk assessors may prove an expedient strategy to build confidence in OoCs for application in safety and efficacy assessment.

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Towards an animal-free human health assessment: starting from the current regulatory needs

Cited by 7 publications

References 0 publications

The value of organs-on-chip for regulatory safety assessment

The value of organs-on-chip for regulatory safety assessment

A framework for chemical safety assessment incorporating new approach methodologies within REACH

Applicability of organ-on-chip systems in toxicology and pharmacology

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