可沥滤物研究怎么设计

结论：可提取物回答「最多能出来什么」，可沥滤物回答「实际会出来多少」

这两个概念常被混用，但它们回答的问题不同：

可提取物研究在加严条件下进行——更强的溶剂、更高的温度、更长的时间。目的是找出材料中「可能」释放的物质谱，作为筛查。

可沥滤物研究在模拟实际使用的条件下进行。目的是测出在真实使用中「实际」释放的量，作为风险评估的直接输入。

两者的关系是：先做可提取物找出物质清单，再做可沥滤物测实际量。 如果可提取物的结果已经表明即使按最大量也无风险，可沥滤物研究可以简化甚至省略。

什么时候需要做

不是所有产品都需要可沥滤物研究。需要做的典型情形：

可提取物研究发现了风险物质，且按加严条件的量评估风险不可接受；产品与人体长期接触或接触量大；产品接触的是敏感部位（血液、体内植入、黏膜）；以及监管方明确要求。

反过来，如果可提取物的结果已经能支撑安全结论，就没有必要再做。 这个判断能省下不少工作，值得在设计阶段认真做。

条件设定的依据

可沥滤物研究的条件要模拟实际使用，需要确定：

条件设定要有依据，且依据要写下来。 比如温度取体温，因为产品在体内使用；时间取某个时长，因为说明书规定单次使用不超过这个时长。

保守性要适度。 条件设得比实际更严，结果偏保守，如果这样都能通过，结论更稳。但条件严过头会导致本来安全的产品显示出风险，反而增加不必要的工作。

分析方法的要求

可沥滤物的浓度通常低于可提取物，所以对方法的要求更高：

灵敏度要足够。 检出限必须低于评估所需的判断限值。这一点在可沥滤物研究中尤其关键，因为浓度本来就低。

方法要经过验证。 在实际的基质中验证，而不只是在纯溶剂中。模拟体液的基质可能干扰测定。

目标物明确。 可沥滤物研究通常是针对可提取物研究识别出的特定物质做定量，属于目标物分析，与可提取物的筛查性质不同。

回收率要测。 在实际基质中加标回收，说明方法的可靠性。

样品与对照

样品状态。 最终成品，经过全部加工、包装、灭菌。

样品数量。 要能反映批间差异，建议至少覆盖多个批次。

空白对照。 同样的介质、同样的容器、同样的处理，不放样品。用于扣除背景。

容器的影响。 容器材料本身可能吸附目标物或释放干扰物。这个影响要通过对照评估。

「容器吸附」是容易被忽略的误差来源。 某些物质容易吸附在容器壁上，导致测得的浓度偏低。做加标回收可以发现这个问题。

结果的使用

得到可沥滤物数据后：

换算成人体暴露量。 按实际的接触方式和时间换算。这一步的假设要明确。

与毒理学限值比较。 得出各物质的风险判断。

考虑累积。 重复使用或长期使用的产品，要考虑累积暴露。

考虑特殊人群。 如果使用者包括儿童或其他敏感人群，限值可能需要调整。

给出整体结论。 综合各物质的判断得出结论。

「特殊人群」这一项在康复辅具类产品上有实际意义，因为使用者常常是老年人或有基础疾病的人群，与一般成人的假设可能不同。

与其他工作的衔接

可沥滤物研究不是孤立的，它与几项工作相关：

与材料清单。 目标物的确定来自材料信息和可提取物结果。

与生物学试验。 两者互补——化学数据说明有什么物质，生物学试验说明产品的整体生物学反应。

与变更管理。 材料或工艺变更后，可能需要重新做或至少评估影响。

与稳定性。 储存期间材料可能降解，产生新的可沥滤物。长货架期的产品建议在货架期末做验证。

最后一项容易被漏掉。 只测新产品的可沥滤物，不能代表接近有效期时的状态。

与稳定性研究的结合

对于有货架期的产品，可沥滤物与储存时间相关。建议的做法是：

在货架期初和货架期末分别取样测定。 看可沥滤物谱和量是否发生变化。

关注降解产物。 储存期间材料可能降解，产生新的物质，而这些物质在新品中检测不到。

考虑包装的影响。 包装材料的物质可能迁移到产品上，再随使用进入人体。

加速老化的适用性要论证。 用加速条件代替实时储存时，要说明加速条件的合理性。

把这项与稳定性研究合并安排，可以共用样品和取样点，减少重复工作。

方案的评审

这类研究成本不低，方案定稿前建议做一次评审，核对几点：

目标物清单是否完整、依据是否充分；条件设定是否有依据、是否过于保守；方法的检出限是否低于评估限值；样品是否最终状态、批次是否足够；对照和质控是否齐备；以及数据出来之后怎么用、能不能支撑结论。

最后一条是评审的关键。 如果按这个方案做出数据仍不能得出结论，方案就要调整。做完才发现数据不够用，代价是重做。

我们的做法

设计这类研究时，我们会先确认三件事：是否真的需要做（可提取物结果是否已足够）、目标物是哪些、以及实际使用条件是什么。 这三点定下来，方案就清楚了。

方法方面，我们会在实际基质中做方法验证并测加标回收，把检出限与评估限值放在一起核对。检出限达不到要求的方法，做出来的数据用不了。

如果你在准备这类研究，不确定要不要做、怎么设计，可以把可提取物结果和产品使用方式发过来一起讨论，或者直接联系：132 4819 8029。能力范围见服务介绍，送检要求见送检要求，其他问题见常见问题。

English version

Conclusion. The two concepts are often conflated but answer different questions. Extractables studies run under exaggerated conditions, with stronger solvents, higher temperature and longer duration, to establish the spectrum of substances a material could release, serving as a screen. Leachables studies run under conditions simulating actual use, to measure how much is actually released in real use, serving as direct input to risk assessment. The relationship is sequential: extractables establish the substance list, leachables measure the real quantity. Where extractables results already show that even the maximum quantity presents no risk, the leachables study can be simplified or omitted.

When it is needed. Not every product needs one. Typical cases are where extractables have identified a substance of concern whose risk is unacceptable even at the exaggerated quantity; where the product contacts the body for long periods or over a large area; where contact is with a sensitive site such as blood, implantation or mucosa; and where the regulator requires it. Conversely, where extractables results already support a safety conclusion, there is no need to proceed. Making that judgement carefully at the design stage saves considerable work.

Basis for setting conditions. Conditions must simulate actual use, and several parameters need fixing. The medium should represent the body fluid or working liquid contacted. Temperature should reflect actual use. Duration should reflect single and cumulative contact. Contact area should reflect what actually contacts. Flow rate applies to fluid path products. And the number of uses applies to reusable products. Each setting needs a stated basis: temperature at body temperature because the product is used internally, duration at a given period because the instructions limit single use to that period. Conservatism should be moderate. Conditions stricter than reality bias the result conservatively, and passing under them makes the conclusion robust. Conditions far too strict, though, make a genuinely safe product appear risky and generate unnecessary work.

Analytical requirements. Leachable concentrations are usually lower than extractable ones, so methods must be more demanding. Sensitivity must suffice, with detection limits below the threshold the assessment needs; this is especially critical here because concentrations are inherently low. Methods must be validated in the actual matrix rather than in pure solvent, since simulated body fluid matrices can interfere. Target analytes must be defined, since a leachables study normally quantifies specific substances identified by the extractables work, making it targeted analysis rather than screening. And recovery must be measured by spiking in the actual matrix to demonstrate reliability.

Samples and controls. Samples must be final product, fully processed, packaged and sterilised. Sample numbers should reflect batch-to-batch variation, covering several batches. Blanks must use the same medium, containers and handling without sample, to subtract background. And container effects must be assessed, since container materials can adsorb target analytes or release interferents. Container adsorption is an easily overlooked source of error: some substances adhere to container walls and measured concentrations come out low. Spike recovery reveals the problem.

Using the results. Convert to human exposure according to actual contact mode and duration, with the assumptions stated explicitly. Compare against toxicological limits to judge each substance. Consider accumulation for repeatedly or chronically used products. Consider special populations, adjusting limits where users include children or other sensitive groups. And give an overall conclusion drawing the individual judgements together. Special populations matter genuinely for rehabilitation products, where users are frequently elderly or have underlying conditions and the assumptions appropriate to a general adult may not apply.

Connections to other work. Leachables work does not stand alone. It connects to the material list, since target analytes derive from material information and extractables results. It complements biological testing, with chemical data showing what substances are present and biological testing showing the product's overall biological response. It connects to change management, since material or process changes may require repeating the study or at least assessing the effect. And it connects to stability, since materials may degrade during storage and generate new leachables, so products with long shelf lives should be verified at end of shelf life. The last is easily missed: measuring leachables on new product does not represent the state near expiry.

How we handle it. In designing these studies we establish three things first: whether the study is genuinely needed given the extractables results, which substances are the targets, and what the actual conditions of use are. With those settled the protocol follows. On methods we validate in the actual matrix, measure spike recovery, and check detection limits against assessment thresholds side by side, because a method whose detection limit falls short produces data that cannot be used.

Send us the extractables results and how the product is used and we will design the study. Phone or WeChat: +86 132 4819 8029.