| Question问 | Answer答 |
| Is an assessment of blend uniformity via the acceptance value (AV) according to USP 905 generally still tolerated? In particular with regard to the batch release? | USP 905 exclusively refers to the Uniformity of Dosage Units. The Stratified Sampling scheme from the DRAFT Guidance dated 2003 was based on the former, non-harmonised USP Content Uniformity (CU) monograph. Strictly speaking, the use of the harmonised CU monograph in conjunction with the scheme for routine production had never been formally accepted. Moreover, the FDA clearly positioned itself in 2013: a batch release only on the basis of <905> is rejected by the Agency, testing in accordance with ASTME2810 is rather expected.The AV doesn't play any role in the framework of the revised ISPE's BU/CU Guideline. |
| 根据USP 905，通过接受值(AV)对混合均匀性的评估是否仍然可以接受?特别是关于批次放行? | USP905专门针对制剂的均匀性。2003年指南草案的分层取样方案是基于以前的、USP含量均匀性(CU)专论。严格地说，使用该含量均匀性专论配合常规生产计划的做法从未得到正式接受。此外，FDA在2013年明确定位:仅以<905>为基础的批次放行被FDA拒绝，而按照ASTME2810进行测试则更为期待。AV在修订后的ISPE BU/CU指南中没有任何作用。 |
| In our process of validation, the tolerated standard deviation is derived as acceptance criterion depending on the sample size and mean in accordance with the label claim from the ASTM. Is this procedure acceptable? | As long as you refer to the tables laid down in ASTME2810, this procedure is - as far as I am concerned - correct, however only insofar as you consider a pure random sample. Stratified Samples require other statistics. |
| 在我们的验证过程中，根据ASTM的标签声明，根据样本量和平均值，可接受的标准偏差被认为验收标准。这个方法可以接受吗? | 只要你参考ASTME2810中列出的表格，该方法——就我而言——是正确的，但是只在你认为是纯粹的随机样本的情况下。分层样本需要其他统计数据。 |
| Does the assessment include reviews for normal distribution and trend test? | Testing the normal distribution is not performed. The submission of a normal distribution is - to my knowledge - accepted. |
| 评估是否包括正态分布和趋势测试的评估? | 未执行正态分布测试。服从正态分布，据我所知是可以接受的。 |
| Does the approach of validation of mixing remain the same for more than one API? | Usually yes, unless one of the drug substances would be present in very high concentration so that one could argue that a determination of the mixing homogeneity shouldn't be required. |
| 对于多个API，混合验证的方法是否保持不变? | 通常是这样的，除非其中一种药物的浓度非常高，这样就可以认为不需要确定混合均匀性。 |
| Is it acceptable for revalidating established processes to validate according to USP <905> or is there a risk of getting a finding in case of an inspection? | Basically, the FDA has adopted a clear position and rejects the use of USP 905 for batch release. According to me, this also excludes the use of USP 905 for revalidation. Insofar, there is some risk that a US inspector would criticise the procedure you described. |
| 根据USP <905>对已建立的工艺进行再验证是否可以接受，或者在检查时是否存在发现的风险? | 基本上，FDA已经采取了明确的立场，拒绝使用USP 905进行批次放行。根据我的说法，这也排除了使用USP 905进行再验证。到目前为止，美国检查员可能对你描述的规程吹毛求疵。 |
| Do you apply sampling already in the routine? How will you ensure in practice that samples are taken at 30 sampling locations? Will the samples be combined and should I take more in case that a pill falls off? | Yes, sampling at 20 or 40 sampling locations has to be exactly planned. We usually set the sampling times on the basis of significant events and then distribute the remaining samples according to the period between e.g. the beginning of the batch, change of template and batch end. It is quite not unusual to take more than e.g. 3 samples per locations so that for example a pill that fell off can be replaced. We usually take reserve samples. |
| 你是否已经在日常工作中应用取样?在实际生产中，你如何确保在30个取样位置进行取样?样本是否会合并，我是否应该多取一些以防止某药片失效? | 是的，在20或40个取样点的取样必须精确计划。我们通常会根据重要的事件来设定采样时间，然后根据批次开始、更改模具和批量结束之间的时间来分配剩余的样品。在每个地点取多于3个样品是很正常的，例如，一个药品失败可以被替换。我们通常采取备用样品。 |
| Will the ISPE recommendation be soon implemented in a guideline? | To my knowledge, the implementation in a guideline is not being planned. Through the publication of the ISPE recommendation, a method aligned with the state of the art is now available so that there is no actually need for a FDA Guideline. |
| ISPE的建议会很快在指南中实施吗? | 据我所知，一个指南的实施没有计划。通过ISPE建议的发布，一种符合当前技术水平的方法现在可以使用了，因此实际上不需要FDA指南。 |
| Is the ISPE table provided validated? If yes, can the validation documents be made available? | The table as such is - to my knowledge - not validated. This should be caught up for in operation. |
| ISPE表格是否经过验证?如果有，是否可以提供验证文件? | 就我所知，这个表格本身并没有得到验证。这在实际操作中应该加以注意。 |
| Should the acceptance value be taken into consideration for BU and CU? | The acceptance value only applies to the CU testing in accordance with USP 905. Within the scope of ISPE's testing it is not applicable. |
| BU和CU的可接受值是否需要考虑? | 可接受数值仅适用于符合USP 905的CU测试。在ISPE的测试范围内是不适用的。 |
| Why is the USP provision far less strict than the expectations of the FDA & Co? | In my opinion, many tests traditionally used in the pharmaceutical industry are not particularly demanding. Especially considerations about the risks for consumers are often excluded from the test criteria. Especially in the USA, the scientific debate is moving to more demanding tests. |
| 为什么USP的规定远没有FDA的期望严格? | 在我看来，许多传统上用于制药行业的测试并不是特别苛刻。对于消费者风险的考虑通常被排除在测试标准之外。特别是在美国，科学辩论正转向要求更高的测试。 |
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