FDA指南：ANDA：原料药和制剂稳定性试验问答（中英文4/5）-未完待续

巴西木

FDA指南：ANDA：原料药和制剂稳定性试验问答（中英文4/5）----翻译人：Julia

15: Do the small scale batches need to be manufactured in accordance with all CGMP regulations, or is it acceptable to manufacture the small scale batches in a research setting?

小批是否需要根据所有CGMP法规要求进行生产，还是可以在小规模的研发设施中进行？

A15: All ANDA submission batches should be made under CGMP.

所有ANDA申报批应在CGMP条件下生产。

Q16: Do the small scale batches need to meet the same finished product specification as the pilot scale batches?

小批是否需要符合中试批次的药品质量标准？

A16: Yes. The specification should be the same for all three ANDA submission batches.

是的。质量标准应与所有三批ANDA申报批次相同。

Q17: For sterile products, is it acceptable to manufacture the small scale batches in a nonsterile facility and allow variance from sterility and particulate criteria?

对于无菌产品，是否可以在非无菌设施中生产小批量，允许无菌质量与特定的标准有一些差异？

A17: No. Batches should not be manufactured in a nonsterile facility. Sterility is a critical quality attribute (CQA) for sterile products.

不可以。所有批次不可以在非无菌设施中生产。无菌性无菌产品的关键质量属性。

Q18: Do small scale batches need to be produced at the proposed commercial site?

小批是否需要在申报的商业生产场所进行生产？

A18: Yes. The primary batch information submitted in the application is used to support the proposed commercial product manufacture. Product batches produced at a different site than the proposed commercial site would not be considered as primary batches.

是的。包括在申报中的基本批次信息是用于支持目标产品生产的。在不同于目标生产场所生产的产品批次将不会被作为基本批次。

Q19: In cases where an intermediate bulk material is identical between the various strengths (dose proportional blends, bulk solutions, etc.), is it sufficient to perform stability on one lot of each strength, when each strength is produced from a separate intermediate bulk?

如果中间体散装物料不同剂量（按剂量成比例混合、散装溶液等）中用量相同，每个剂量由一个独立的中间体散装批号生产得到，是否仅对每个剂量取一批进行稳定性试验就可以了？

A19: No. For ANDAs that contain multiple strengths (that are dose proportional), three separate intermediate bulk granulations (or blends) should be manufactured. One batch of bulk granulation (or blend) should be used to manufacture all the strengths proposed. The other two bulk granulations (or blends) can be used to manufacture only the lowest and the highest strengths, in addition to the strength used in BE studies. Stability testing should still use all three batches of drug product.

不可以。如果ANDA包括多剂量（按剂量成比例），应生产3个单独的中间体散装颗粒（或混合）批号。一批颗粒（或混合）应用于生产所有申报剂量的生产。其它2批颗粒（或混合）可用于生产最低和最高剂量，用于生物等效性研究的剂量除外。稳定性研究应使用所有3个制剂批号。

Q20: What are the exception criteria from meeting the minimum size for pilot scale recommendations for ANDA submission batches? What justification would be needed if we wanted to deviate from the guidance recommendations?

ANDA申报批次所规定的最小批量是否可以有例外？如果我们想采用的批量不符合指南推荐的批量，需要有哪些论述？

A20: The submission ANDA batches can have a smaller size than the established pilot scale, according to the ICH definition, when any one of the following circumstances prevails:

              根据ICH定义，在以下情况下，ANDA申报批次的批量可以小于中试批量。

The reference listed drug product has an orphan drug designation.

药品为相关清单所列的孤儿药

Use of a controlled drug substance is based on a Drug Enforcement Administration allocation.

对受控药品的使用受到药品实施管理要求的限制。

The test batch size is the same as the commercial batch size with the commitment that a prior approval supplement (PAS) will be provided when there is a scale-up.

测试批量与商业批量相同，同时提交“如果放大批量则会递交一个预批准补充申报（PAS）”的承诺。

Q21: Are scale-up and postapproval changes (SUPAC) level one and two variations and changes permitted among the three ANDA submission batches for components and composition?

3个ANDA申报批次中，是否允许对成分和组成进行批量放大和批准后变更（SUPAC）第1级和第2级变更？

A21: No. The three ANDA submission batches should maintain the chosen formula based on product development studies for components and composition.

不允许。3个ANDA申报批次中的成份和组成应保持研发时所选择的配方。

Q22: Can some specific examples of cases where statistical analysis is required and type of analysis needed be provided?

有些特殊例子时，是否需要进行统计分析，是否需要提供分析的类型？

A22: The stability guidance recommends analysis of data in accordance with ICH Q1E, Appendix A. The flowchart in that guidance provides clear situations where analysis is normally recommended or unnecessary. In addition, ICH Q1E B.7 figures provide example diagrams for assay and degradation products that illustrate how plots should be generated for the three batches using regression lines and upper and lower confidence limits.

稳定性指南推荐根据ICH Q1E附件A的要求进行数据分析。该指南中的流程图对不同情况作了明确说明是否需要进行统计分析。另外，ICH Q1E B.7图提供了含量和降解产物的样例，说明了如何从3批数据中产生线性回归和上下限置信区间限度的图表。

【大结局】 FDA指南：ANDA：原料药和制剂稳定性试验问答（中英文5/5）
https://www.ouryao.com/forum.php?mod=viewthread&tid=228784&fromuid=4683


201308 FDA指南：ANDA：原料药和制剂稳定性试验问答（中英文3/5）----未完待续
https://www.ouryao.com/forum.php? ... 18&fromuid=4683

201308 FDA指南：ANDA：原料药和制剂稳定性试验问答（中英文2/5）-未完待续
https://www.ouryao.com/forum.php? ... 81&fromuid=4683

201308 FDA指南：ANDA：原料药和制剂稳定性试验问答（中英文1/5）-未完待续
https://www.ouryao.com/forum.php? ... 03&fromuid=4683

一沙一叶

学习一下，谢谢。

hwmm

学习一下，谢谢

beiwei5du

Q19(i) : In cases where an intermediate bulk material is identical be t ween the various strengths (dose proportional blends, bulk solutions , etc.) , is it sufficient to perform stability on one lot  of each strength, when each strength is produced from a separate intermediate bulk?  
  
A19(i) :   No.   For ANDAs that contain multiple strengths  (that are dose proportional) , three separate intermediate bulk  granulation s  (o r blend s ) should be manufactured.  One batch of bulk granulation (or blend) should be used to manufacture all the strengths proposed .   The  other two bulk granulation s  (or blends )  can be used  to  manufacture only  the lowest and the highest strengths, in addi tion to the strength used  in  BE studies (i.e., the strength(s) tested in the BE studies should have three batches).  Stability testing should still use  all three batches of drug product.  

Q19(ii): Are differences in the capsule shell (i.e., imprint, color,  size, etc.), allowed i n cases where  a  multi-strength capsule product is dose-proportional across all strengths (based on common bead blend)?

A19(i i) :    Yes differences in the capsule shell are allowed in the described case .  

这两个问题如何理解呢？？？求指教！

dhh

谢谢分享谢谢分享谢谢分享