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

巴西木

----翻译人：Julia

B. Drug Master File 药物主文件

Q1: Please clarify the effect of the stability guidance on Drug Master File (DMF) holders.
请说明稳定性试验指南对DMF持有人的影响

Q1(i): Are stability data from three current good manufacturing practice (CGMP) batches required to be filed in the DMF to support the API retest date?
为了支持原料药的复验期，包括在DMF里的三批稳定性数据是否需要在GMP状态下生产？

A1(i): ICH Q1A(R2) recommends three primary batches[1] (at least of the pilot scale[2] size) for the drug substance filed in the DMF. These batches should be made under Current Good Manufacturing Practices (CGMP). The stability guidance recommends a minimum of 6 months of accelerated and 6 months of long-term data for the pilot scale batches to be submitted initially. Additional long-term data for all three batches, as the data becomes available through the proposed retest period, should be submitted as an amendment.

     ICH Q1A (R2) 建议三个基本批次（至少为中试批量）用于原料药DMF申报。这些批次应在CGMP的条件下生产。稳定性试验指南推荐在初始申报中包括中试批至少6个月加速试验和6个月长期稳定性试验数据。除了3批长期稳定性数据外，由于在提出的复试期内，能获得更多数据，这些后续数据应在增补中提交。

Q1(ii): How many months of long-term and accelerated data are required when a “Completeness Assessment” is performed on the DMF? Also, what should the DMF stability section contain for the same?

在对DMF进行“完整性评估”时，需要多少个月的长期和加速稳定性试验数据？DMF稳定性部分应包括哪些内容？

A1(ii): To pass the Completeness Assessment (see the draft guidance for industry on Initial Completeness Assessments for Type II API DMFs under GDUFA), DMFs should have the stability protocol, commitments, and data demonstrating that stability studies have started. The initial and one additional time point for the accelerated studies and long-term studies are sufficient. The DMF holder should amend the DMF with updated stability data to prepare for the full scientific review, if the DMF does not meet the recommendations under A1(i) above at the time of the Completeness Assessment.

要通过完整性评估（见行业指南草案：对二类原料药DMF根据GDUFA法案进行的初始完整性评估），DMF应包括稳定性试验方案、承诺、数据证明稳定性研究已开始。初始检验数据和一个时间点的加速和长期稳定性研究应足够了。如果DMF在完整性评估时不符合A1(i)中的要求，DMF持有人应提交更新的稳定性数据作为补充，为全面的科学性审阅作好准备。

Q2: Will submissions to DMFs be accepted based on stability data from production scale batches?

基于生产批量的批次的稳定性数据的DMF申报能被接受吗？

A2: Yes. Per ICH Q1A(R2), section II, A, 8, Stability Commitment (2.1.8), the submission is appropriate if satisfactory stability data from three production batches made under CGMP are filed in the DMF with 6 months of accelerated data and long-term data covering the proposed retest period.

是的。根据ICH Q1A(R2)，第II部分，A，8，稳定性承诺（2.1.8），申报文件中如果是在GMP条件下三个大生产批次，具有6个月加速和长期稳定性试验数据，覆盖建议的复验期，是可以接受的。

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[1] Defined in ICH Q1A(R2) Glossary.

[2] Ibid.

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? ... 228003&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?mod=viewthread&tid=228218&fromuid=4683

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
https://www.ouryao.com/forum.php?mod=viewthread&tid=228465&fromuid=4683
【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

清风化雨

谢谢分享....

youngzhou

下载学习了，谢谢老木

beiwei5du

这个没有拿进去呢!
Q3:     Should executed batch records for the three batches be included in the DMF submission?

A3:   One representative executed batch record will be sufficient.     

dhh

谢谢分享谢谢分享谢谢分享