医疗器械的生物相容性试验

根据美国食品和药物管理局(FDA), biocompatibility is “the ability of a device material to perform with an appropriate host response in a specific situation.简单地说, the compatibility of medical devices within a biological system is assessed with biocompatibility testing.

Biocompatibility tests evaluate the interactions that occur between medical devices and the living tissues and cells which are exposed to devices as they come into contact with one another. 一般, testing is performed on small animal species with the intent of replicating potential responses that would be observed within the human body.

生物风险评估是获得监管部门批准的强制性要求, 生物相容性测试是生物风险评估的重要组成部分. FDA批准的每个器械都必须提交这个过程, 甚至是最具创新性的, best-designed products have the potential to yield unintended complications if patients experience an adverse reaction to materials used. Even well-known materials used frequently within the industry can produce unexpected reactions if they are incorporated into a device in such a manner that results in contamination, 退化, 或者有毒物质的潜在浸出. 因此, 所有医疗器械必须经过生物风险评估, 其中包括生物相容性测试, 保护病人免受任何有毒物质的侵害, 生理, 免疫原性, 或者是诱变效应.

如表1所示, ISO 10993 provides a Materials Biocompatibility Matrix outlining biological test methods including cytotoxicity testing, 敏感分析, 急性全身毒性试验, 过敏测试, 亚慢性毒性试验, 基因毒性测试, 植入测试, 血液相容性测试. 除了这些方法, multiple sections of the ISO 10993 guidance focus on chemical characterization or extractable and leachables testing. 有了新的设备和更先进的分析方法, regulatory agencies are continuing to focus more on these supplementary analyses as a complement to in vivo biocompatibility testing. 例如, the most recent 欧洲an Medical Device Regulation (MDR) requirements outline more robust data requirements regarding material and chemical characterizations. 结合毒理学风险评估, 化学测试提供保护患者安全所需的关键数据, 包括特定分析物的有害暴露水平.

表1. ISO 10993材料生物相容性矩阵

定义生物相容性及其在医疗器械监管提交中的作用

根据FDA, biocompatibility is “the ability of a medical device or material to perform within an appropriate host response in a specific application.“其核心是, biocompatibility describes the ability of a medical device to function according to its intended purpose, 当医疗设备在人体内引起不良反应时, 这些反应被限制在允许和容忍的范围内.

因为医疗设备经常被触摸, 无论是直接还是间接受到患者的影响, 不希望和/或不合理的副作用是不能容忍的. To ensure these undesirable side effects are mitigated and any negative long-term effects patients may experience are limited, medical devices and materials are tested for biocompatibility to evaluate and quantify risks at defined endpoints. 当考虑长期植入与短期植入装置, the likelihood of leaching potentially harmful substances increases with the use of long-term implantable devices, 如表2所示.

表2. 生物相容性建议和替代方案

证明医疗器械监管提交的生物相容性

Demonstrating biocompatibility begins with characterizing materials and chemical to identify the exact composition of the device, as well as an evaluation of potential similarities between the new device and other competitive devices. 这确保了专利不被侵犯, 或者如果市场上有类似的设备(称为“谓词设备”), 所述谓语装置可用于与新医疗装置进行比较. 此外, chemical characterization studies determine what additional chemicals may leach out during typical use or what worst-case extractables need to be considered.

im体育APP offers multiple services for biocompatibility to help medical device developers and manufacturers meet the requirements of the ISO 10993-18, 5.2标准. Our team of consultative scientists assist clients with material selection for medical devices, 以及他们对监管要求的深刻理解, 能否提供有关材料成分测试要求的指导.

im体育APP can also determine whether a client’s materials or device are chemically equivalent or superior to an approved, 现有的设备. 对FDA来说，材料等效性的证明通常是足够的. 如果一个等效的设备可以被识别和证明, 化学特性被认为是被批准的, 然后这些要求就被认为满足了. Material equivalence can be established with material composition or extractable profile data compared to existing material, 前提是使用经过验证的方法来生成数据.

此外，还可以建立最坏情况下的化学物质释放曲线. 举个例子，考虑一个长期植入式装置. 在这个最坏的测试场景中, 科学家们将在模拟体液和实际体液中对该设备进行比较, 非极性有机溶剂. 一旦最坏的情况出现, 然后可以对这两种提取物进行分析，以确定是否有杂质. Below are representative methods that im体育APP’s team of expert scientists use to determine biocompatibility. 虽然不是每种技术都适用于每个项目, 我们根据需要采用适用的方法, 如表3所示.

表3. 医疗器械可萃取物和可浸出物的试验方法

在分析使用最坏情况下从设备中提取的内容时, a team of scientists will then perform a leachant study to assess how the medical device will perform under normal conditions of use. im体育APP offers two different scenarios: accelerated aging design and real-time usage design for device 退化 study per ISO 10993-13. Accelerated and real-time 退化 study designs both use testing intervals extrapolated from the device usage period with various exposure temperatures and solvents applied for simulation.

Correlations are made of the leachants found in the extractable studies previously performed on the device components. Leachant compounds are identified and compared to the established thresholds of toxicological concern (TTC). Analytical Evaluation Thresholds (AET) for all leachants from a device are derived from the threshold of toxicological concern (TTC), 哪一个是120微克/天. 如果渗滤液高于TTC, im体育APP can work with leading toxicologists for a thorough review and understanding of the safety threshold of specific leachants that have been identified. 通常是在毒性水平较高的情况下, 它可能是一种无害的渗滤液, 结果是, 不需要修改建筑材料. 然而, 有时需要改变器件或材料以确保化合物低于TTC, 说明医疗器械在设计阶段生物相容性测试的重要性.

为医疗器械的生物相容性测试选择合适的合作实验室

im体育APPim体育平台app下载领先的咨询团队, knowledgeable scientists can provide extensive regulatory and analytical support to help support the approval of medical devices. 我们结合了无与伦比的监管和科学专业知识, 先进的设备, and an unmatched client-centric experience to ensure timely compliance to regulatory standards. 元件符合cGMP要求, FDA注册, 和DEA许可的合同开发和制造组织(CDMO), 根据您的具体需求和设备提供定制的项目计划, 在紧迫的时间内交货, 并具有解决分析和配方难题的经验.