E.g. for a general limit of 100 ppm: MACO = 0.01% of the minimum batch size (MBS), and for a general limit of 10 ppm: MACO = 0.001% of the minimum batch size (MBS).
例如，对于通用限度为100ppm：MACO = 最小批量（MBS）的0.01%，对于通用限度为10ppm：MACO = 最小批量（MBS）的0.001%。
Remarks: The ICH impurity document (Q 3) indicates that up to 0.1% of an individual unknown or 0.5% total unknowns may be present in the product being tested.
注：ICH杂质文件（Q3）指出，在被测试的产品中，单个未知杂质可以达0.1%，总未知杂质可以达到0.5%。
A general upper limit for the maximum concentration of a contaminating substance in a subsequent batch (MAXCONC) is often set to 5-500 ppm (100 ppm in APIs is very frequent) of the previous product into the next product depending on the nature of products produced from the individual company (e.g. toxicity, pharmacological activity …).
根据各公司所生产产品的属性不同（例如，毒性、药物活性等），从上一产品带入下一产品中的污染物质最大浓度通用上限通常设定为5-500ppm（原料药中100ppm是很常见的）。
The Threshold of Toxicological Concern (TTC) concept could be applied to intermediates or API’s with no clinical (e.g. early development) or toxicological data. This concept includes three categories of products with limited or no data: 毒性关注阈值（TTC）概念可以应用于没有临床（例如早期研发阶段）或毒性数据的中间体或原料药。这个概念将数据有限或没有数据的产品分为3个类别
??Products that are likely to be carcinogenic; ??可能致癌的产品
??Products that are likely to be potent or highly toxic;
??可能具有效价或高毒性的产品
??Products that are not likely to be carcinogenic, potent or highly toxic. ??可能致癌、具有效价或高毒性的产品
The corresponding ADE’s recommended for these three categories are 1, 10, 100 μg/day, respectively.
对应此三类所推荐的ADE值分别为1、10和100μg/天。
Another possibility to calculate your ADE for intermediates or API’s, with no clinical or toxicological data (e.g. early development), is based upon the exposure duration of your next product. The values of the CHMP guideline on the Limits of Genotoxic Impurities (ref. EMEA/CHMP/SWP/431994/2007) can be used for your ADE. 在没有临床或毒性数据（例如研发早期）时，计算中间体或API的ADE还有另一个办法，就是基于下一产品的暴露时长。可以将CHMP指南“基因毒性杂质”（参见EMEA/CHMP/SWP/431994/2007）限度值可以用于ADE计算。 Note - If you decide to employ the concept of levels of cleaning (ref. section 5), then different safety factors (ppm limits) may be used for different levels. Especially if the product cleaned out is within the same synthetic chain and covered by the specification of the API, much higher (qualified) levels are acceptable.
注：如果你决定采用清洁水平概念（参见第5部分），则对于不同水平可以采用不同的安全系数（ppm限度）。特别是如果被清洁的产品是在同一条合成链中，且其限度包括在原料药的质量标准中，则残留水平较高（确认过的）时也是可以接受的。
4.2.5 Swab Limits 擦拭限度
If homogeneous distribution is assumed on all surfaces, a recommended value can be set for the content in a swab. The maximum allowable carry over from one batch to another can be established based on e.g. ADE, NOEL or TDD (see above). If the total direct contact surface is known, the target value for contamination per square meter
can be calculated according equation 4.2.5-I. This can be used as basic information for preparation of a method of analysis and detection limit.
如果假定所有表面上残留的分布是均匀的，可以给擦拭样品设定一个推荐值。可以根据例如ADE值、NOEL或TDD（见上）设定一批到另一批的最大允许残留值。如果知道直接接触产品的总面积，则可以根据4.2.5-I公式计算单位面积上的污染目标值，该值可以在制订方法验证方案和检测限值时参考。
MACO[μg] Equation 4.2.5-I Target value [μg/dm2] = Total surface [dm2]
MACO[μg] 公式 4.2.5-I 目标值 [μg/dm2] = 总表面积 [dm2]
Also other methods with different swab limits for different surfaces in a piece of equipment and/or equipment train can be used. If the equipment can be divided in several parts, different swab limits may be taken for the different parts building up the equipment train. If the result of one part is exceeding the target value, the whole equipment train may still be within the MACO limit. The Carry Over is then calculated according equation 4.2.5-II (see below).
也可以对同一设备和/或设备链不同的表面使用不同的擦拭限度。如果设备被分为几个部分，对可以针对设备链不同部分采用不同的擦拭限度。如果一个部件的结果超出了目标值，整个设备链的残留值仍可能是在MACO的限度以内。这时，可以按公式4.2.5-II（见下）计算残留量。
During equipment qualification and cleaning validation hard to clean parts can be determined. Rather than declaring the hard to clean part as the worst case swab limit
for the whole equipment train, it could be separated and dealt with as mentioned above. It should be noted that different types of surfaces (e.g. stainless steel, glass lined, Teflon) may show different recoveries during swabbing. In those cases it may be beneficial to divide the equipment train in several parts, and combine the results in a table or matrix. The total calculated amount should be below the MACO, and the individual swab results should not exceed the maximum expected residues established during cleaning validation / equipment qualification. Recovery studies and method validation are necessary when applying swabbing as a method to determine residues. 在设备确认和清洁验证中，可以确定哪个部件是难以清洁的。其实可以采用上述的方法来将难以清洁的部件分开来，而不需要采用最难清洁的部件作为最差擦拭情况的限度用于整个设备链。要注意不同材质表面（例如，不锈钢、搪玻璃、聚四氟乙烯）可能有不同的擦拭回收率。在这种情况下，如果把设备链划分为几个部分，将结果在一份表或类别中合并可能会比较好。合计数量应低于MACO值，单个擦拭结果不应超过在清洁验证/设备确认中所设立的最大高期望值。在使用擦拭方法测定残留量时，要进行回收率研究和方法验证。 Equation 公式 4.2.5-II
CO [μg] = Σ(Ai[dm2] × mi[μg/dm2]) CO True (measured) total quantity of substance (possible carryover) on the cleaned surface in contact with the product, calculated from results of swab tests. Ai Area for the tested piece of equipment # i. 所测试的 i 设备的面积 采用擦拭检测结果计算出的与产品直接接触的已清洁表面实际总残留量 mi Quantity in μg/dm2, for each swab per area of swabbed surface (normally 1 dm2) 单位擦拭面积的残留数量 APIC 201405原料药厂清洁验证指南：4.0可接受标准（下）（中英文）
2014-07-17 julia翻译 蒲公英
4.2.5.1. Setting Acceptance Criteria for Swab Limits 对擦拭限度设定可接受标准
For each item tested, the following acceptance criteria (AC) apply. 以下可接受标准适用于各测试项目：
AC1. The cleaning result of an individual part should not exceed the maximum expected residue.
单个设备清洁结果应不超过最大可接受残留量。
AC2. For the total equipment train the MACO must not be exceeded. 总设备链的MACO不得超过。
In determining acceptance limits, all possible cases of following products in the relevant equipment shall be taken into account. It is proposed that a matrix be set up in which the limits for all cases are calculated. Either acceptance criteria for each product in the equipment can be prepared or the worst case of all product combinations may be selected.
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