Heriot-Watt University, Edinburgh, UK.
University Ca' Foscari of Venice, Venice, Italy.
Nanotoxicology. 2022 May;16(4):484-499. doi: 10.1080/17435390.2022.2103470. Epub 2022 Aug 1.
Due to the unique characteristics of nanomaterials (NM) there has been an increase in their use in nanomedicines and innovative medical devices (MD). Although large numbers of NMs have now been developed, comprehensive safety investigations are still lacking. Current gaps in understanding the potential mechanisms of NM-induced toxicity can make it challenging to determine the safety testing necessary to support inclusion of NMs in MD applications. This article provides guidance for implementation of pre-clinical tailored safety assessment strategies with the aim to increase the translation of NMs from bench development to clinical use. Integrated Approaches to Testing and Assessment (IATAs) are a key tool in developing these strategies. IATAs follow an iterative approach to answer a defined question in a specific regulatory context to guide the gathering of relevant information for safety assessment, including existing experimental data, integrated with model predictions where available and appropriate, and/or experimental procedures and protocols for generating new data to fill gaps. This allows NM developers to work toward current guidelines and regulations, while taking NM specific considerations into account. Here, an example IATA for NMs with potential for direct blood contact was developed for the assessment of haemocompatibility. This example IATA brings together the current guidelines for NM safety assessment within a framework that can be used to guide information and data gathering for the safety assessment of intravenously injected NMs. Additionally, the decision framework underpinning this IATA has the potential to be adapted to other testing needs and regulatory contexts.
由于纳米材料（NM）具有独特的特性，因此在纳米医学和创新医疗器械（MD）中的应用有所增加。尽管现在已经开发出了大量的 NM，但仍缺乏全面的安全性研究。目前，对于 NM 诱导毒性的潜在机制的理解存在差距，这使得确定支持 NM 纳入 MD 应用所需的安全性测试变得具有挑战性。本文为实施临床前定制安全性评估策略提供了指导，旨在增加 NM 从实验室开发到临床应用的转化。综合测试和评估方法（IATAs）是开发这些策略的关键工具。IATAs 采用迭代方法在特定监管背景下回答一个明确的问题，以指导安全性评估相关信息的收集，包括现有实验数据，以及在适用和/或适当的情况下整合模型预测，并生成新数据以填补空白。这使得 NM 开发者能够遵循当前的指南和法规，同时考虑 NM 的具体情况。这里，开发了一种具有直接血液接触潜力的 NM 的 IATA 示例，用于评估血液相容性。该示例 IATA 将 NM 安全性评估的当前指南汇集在一个框架内，可用于指导静脉内注射 NM 的安全性评估的信息和数据收集。此外，该 IATA 所基于的决策框架有可能适应其他测试需求和监管环境。
