Preclinical Safety, Alcon Research, LTD, Fort Worth, TX, 76134, USA.
Preclinical Safety, Alcon Research, LTD, Fort Worth, TX, 76134, USA.
Regul Toxicol Pharmacol. 2018 Aug;97:24-32. doi: 10.1016/j.yrtph.2018.06.003. Epub 2018 Jun 6.
Medical device biocompatibility testing is used to evaluate the risk of adverse effects on tissues from exposure to leachates/extracts. A battery of tests is typically recommended in accordance with regulatory standards to determine if the device is biocompatible. In vitro cytotoxicity, a key element of the standards, is a required endpoint for all types of medical devices. Each validated cytotoxicity method has different methodology and acceptance criteria that could influence the selection of a specific test. In addition, some guidances are more specific than others as to the recommended test methods. For example, the International Organization for Standardization (ISO) cites preference for quantitative methods (e.g., tetrazolium (MTT/XTT), neutral red (NR), or colony formation assays (CFA)) over qualitative methods (e.g., elution, agar overlay/diffusion, or direct), while a recent ISO standard for contact lens/lens care solutions specifically requires a qualitative direct test. Qualitative methods are described in United States Pharmacopeia (USP) while quantitative CFAs are listed in Japan guidance. The aim of this review is to compare the methodologies such as test article preparation, test conditions, and criteria for six cytotoxicity methods recommended in regulatory standards in order to inform decisions on which method(s) to select during the medical device safety evaluation.
医疗器械生物相容性测试用于评估浸提物/提取物暴露于组织时产生不良反应的风险。根据监管标准，通常建议采用一系列测试来确定器械是否具有生物相容性。体外细胞毒性是标准的一个关键要素，是所有类型医疗器械的必需终点。每种经过验证的细胞毒性方法都有不同的方法和验收标准，这可能会影响特定测试的选择。此外，一些指南比其他指南更具体地推荐了测试方法。例如，国际标准化组织（ISO）引用了对定量方法（例如四唑盐（MTT/XTT）、中性红（NR）或集落形成测定（CFA））的偏好，而不是定性方法（例如浸提、琼脂覆盖/扩散或直接），而最近的 ISO 标准接触镜/镜片护理液专门要求进行定性直接测试。定性方法在美国药典（USP）中有描述，而定量 CFA 则在日本指南中列出。本综述的目的是比较监管标准中推荐的六种细胞毒性方法的方法学，如测试品制备、测试条件和标准，以便为医疗器械安全性评估过程中选择哪种方法提供信息。
