发布时间 : 星期五 文章APIC 201405原料药厂清洁验证指南：4.0可接受标准更新完毕开始阅读
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.
在制订可接受限度时，要考虑在相关设备中可能生产的所有后续产品。建议画出矩阵图，在其中对所有情况下的限度进行计算，然后针对在该设备中生产的每个产品分别制订可接受标准，也可以对所产品选择最差情况下的可接受标准。 4.2.5.2. Evaluation of results 结果评估
When all surfaces have been sampled and the samples have been analyzed, the results are compared to the acceptance criteria. Companies may find it easier to evaluate against the MACO. However, it is advisable to have a policy for swab limit as well. Especially because analytical methods are validated within a certain range for swab results. Another reason is that some pieces could be very contaminated, and it is not good practice to clean certain pieces very thoroughly in order to let others be dirty. Thus, limits for both MACO and swabs should be set.
在对所有表面取样后，对样品进行分析，将结果与可接受标准进行比较。公司可以发现采用MACO来评估会比较容易。但是，还是建议对于擦拭限制订一个原则，主要是因为擦拭样品分析方法的验证是在一定的浓度范围内进行的。另一个原因是有一些部件的污染可能会比较严重，没有理由让一些部件清洁的非常彻底而让另一些部件很脏。因此，应同时设定MACO限度和擦拭限度。 4.2.6. Rinse Limit 淋洗限度
The residue amount in equipment after cleaning can also be determined by taking rinse samples. During equipment qualification it should be established that all direct content parts of the equipment is wetted / reached by the rinsing solvent. After the last cleaning cycle (last rinse), the equipment should be assessed as ‘clean’. In some cases it may be advisable to dry the equipment in order to do a proper assessment. Thereafter, the rinse cycle can be executed, and a sample taken (sampling rinse). The procedure for the rinse cycle and sampling should be well established and described to assure repeatability and comparability