Enabling novel paradigms: a biological questions-based approach to human chemical hazard and drug safety assessment.
Enabling novel paradigms: a biological questions-based approach to human chemical hazard and drug safety assessment.
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实现新的范式：基于生物学问题的人类化学危害和药物安全评估方法。
DOI：
10.1093/toxsci/kfad124
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Shipkowski,KellyA
中科院分区：
文献类型：
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作者：
Berridge,BrianR;Bucher,JohnR;Sistare,Frank;Stevens,JamesL;Chappell,GraceA;Clemons,Meredith;Snow,Samantha;Wignall,Jessica;Shipkowski,KellyA
产量需求、时间和资源成本，以及对在危害和安全评估研究中使用动物的担忧，促使人们对采用新方法和方法用于产品开发和风险评估越来越感兴趣。然而，目前定义“下一代风险评估”的努力在商业和监管部门之间存在很大差异，并且普遍缺乏评估危害所需数据的生物学范围的优先定义。我们认为，在危害评估过程中缺乏可以回答的明确定义的问题是产生足够灵活的范例以用于不同产品开发和批准决策环境的主要障碍。在此，我们提出了一种基于生物学问题的危害和安全评估方法（BQBA），以促进适合目的的方法选择和更有效的循证决策。这种新方法的关键支柱是生物利用度、生物活性、逆境和易感性。该BQBA与目前的危害方法进行了比较，并应用于不同病理生物学理解和/或监管测试要求的情况。为了进一步确定能够更好地预测和描述人类健康危害的范例和关键问题，应在利益攸关方群体之间开展多学科合作。
Throughput needs, costs of time and resources, and concerns about the use of animals in hazard and safety assessment studies are fueling a growing interest in adopting new approach methodologies for use in product development and risk assessment. However, current efforts to define “next-generation risk assessment” vary considerably across commercial and regulatory sectors, and ana prioridefinition of the biological scope of data needed to assess hazards is generally lacking. We propose that the absence of clearly defined questions that can be answered during hazard assessment is the primary barrier to the generation of a paradigm flexible enough to be used across varying product development and approval decision contexts. Herein, we propose a biological questions-based approach (BQBA) for hazard and safety assessment to facilitate fit-for-purpose method selection and more efficient evidence-based decision-making. The key pillars of this novel approach are bioavailability, bioactivity, adversity, and susceptibility. This BQBA is compared with current hazard approaches and is applied in scenarios of varying pathobiological understanding and/or regulatory testing requirements. To further define the paradigm and key questions that allow better prediction and characterization of human health hazard, a multidisciplinary collaboration among stakeholder groups should be initiated.