QbR-translation

Question-based Review (QbR) for Sterility Assurance of Terminally

Sterilized Products: Frequently Asked Questions

关于最终灭菌产品无菌保证的问卷式评审：常见问题

Disclaimer: These are general answers and may not be applicable to every product. Each application is reviewed individually. Each application may have unique product-specific or process-specific review issues. This document represents the Office of Generic Drugs’ (OGD’s) current thinking on these topics.

免责声明：这些都是一般性的回答且可能并不适用每种产品。每个申请被单独地评审。每个申请可能有独一无二的特定产品或者特定工艺评审的问题。本文件代表了FDA仿制药办公室的对这些主题现行的想法。

Submission and Format: 呈交和格式：

Q: How can the Question-based Review approach be applied to a Quality Overall Summary for an

application that contains sterility assurance information?

问题：问卷式评审途径如何应用到关于涵盖无菌保证信息申请的质量综述（QOS）中？

A: The Chemistry Question-based Review (QbR) approach was designed with the expectation that applications

would be organized according to the Common Technical Document (CTD) format, a submission format adopted by multiple regulatory bodies including the FDA. Firms are strongly encouraged to submit their applications in the CTD format (either eCTD or paper).

答：设计化学问卷式评审途径是期望这些申请能基于一般性技术文件(CTD)格式即被多法规机构包括FDA

接受的提交格式组织起来。强烈鼓励厂商提交CTD格式的申请（无论电子CTD还是纸质版）。 Like the Chemistry QbR-QOS, we believe the QbR approach can be used to address sterility assurance aspects of an application, and that a summary of the sterility assurance information from Module 3 may be provided in a Sterility Assurance Quality Overall Summary (SA-QOS). By answering QbR questions according to a SA-QOS outline (in Module 2, Section 2.3), firms are more likely to provide a complete summary of the sterility assurance information and facilitate a more efficient review process.

就像化学QbR-QOS，我们相信QbR途径可以用来提出申请中无菌保证的各个方面，并且来自模块3中无菌保证信息的总结可能提供在无菌保证质量综述（SA-QOS）中。按照SA-QOS大纲（模块2,第2.3章）回答QbR中的问题，厂商更喜欢提供一个完整的无菌保证信息的总结和促成一种更有效的评审过程。

Q: Is a SA-QOS necessary for sterile product applications? 问题：对于无菌产品申请，SA-QOS是否是必须的？

A: No, the SA-QOS is not a requirement for sterile product applications. 答：不，SA-QOS并不是无菌产品申请的需求。

Q: Should separate chemistry and sterility assurance QOS documents be submitted? 问题：单独的化学和无菌保证QOS文件是否应该被提交？

A: Yes, separate QOS pdf and Word files should be submitted for both chemistry and sterility assurance

sections.

答，是，对于化学和无菌保证章节，单独的QOS pdf 和 Word 文档应该被提交。 Q: What should be included in the SA-QOS? 问题：SA-QOS 应该包含哪些内容？

A: The SA-QOS in Module 2 (Section 2.3) is a summary of the sterility assurance information provided in

Module 3. Supporting information such as validation data reports, SOPs, protocols, and batch records should not be included in Module 2.

答：SA-QOS的模块2（第2.3章节）是对在模块3中无菌保证信息的总结。支持信息如验证数据报告，SOP，

方案，和批记录不应该包括在模块2中。

Q: Should the SA-QOS be submitted electronically? 问题：SA-QOS是否应该提交电子版？

A: Yes, all QBR applications, both eCTD and paper submissions, should include an electronic SA-QOS. Do

not provide separate files for each section or question. For paper submissions, it is recommended that both the electronic SA-QOS and a paper SA-QOS be included.

答：是的，所有的QBR应用，无论电子CTD还是纸质提交版，应该包括一份电子的SA-QOS。不要对每

个章节或问题提供单独的文件。对于纸质的提交版，建议要包含电子版的SA-QOS和纸质版的SA-QOS。

Q: What file format should be used for the SA-QOS? 问题：SA-QOS应该用什么文件格式？

A: For OGD QbR submissions, the electronic SA-QOS should be provided as both a pdf and a Microsoft Word file.

答：对于仿制药QbR提交文件，电子版的SA-QOS应该以pdf格式和微软word格式提交。 Q: What fonts should be used in the SA-QOS? 问题：SA-QOS中应该使用什么样的字体？

A: Because of FDA’s internal data management systems, please only use these True Type fonts: Times

New Roman, Arial, Courier New. Times New Roman is recommended as the main text font.

答：因为FDA的内部数据管理系统，请仅使用这些正确类型的字体：Times New Roman, Arial, Courier

New。正文字体推荐使用Times New Roman。

Q: Can color be used in the SA-QOS? 问题：SA-QOS中能使用颜色？

A: Yes, but applicants should ensure that the SA-QOS is legible when printed in black and white. 答，是的，但是申请者要确保当SA-QOS以黑白打印的时候，它是清晰的。

Q: Should the applicable QbR question be presented for each section of the QOS, followed by the applicant's

answer?

问题：随着申请者的答案，对QOS每个章节适用的QbR问题是否应该提出？

A: Yes, include all the QbR questions without deletion in the SA-QOS. If a question is not applicable, answer as

not applicable, with a brief justification. This also applies to multi-part questions.

答：是的，包括所有在SA-QOS中未删减的QbR问题。如果问题不适用，答案也就不适用了，要带个简单

的辩解。这也适用于多部分的问题。

Q: For amendments to applications, should the documentation consist of a revision of the SA-QOS? 问题：对于申请的修正，是否文件可由SA-QOS的修订版组成？

A: The SA-QOS does not have to be updated after submission of the original application. However, if substantial

changes are made to Module 3, then a revised SA-QOS is recommended with the changes indicated. 答：SA-QOS并不需要在最初申请提交后更新。但是，如果模块3中大量的内容改变，那么推荐带有指示改

变SA-QOS修正版。

Q: Can the SA-QOS be submitted for both ANDAs and NDAs? 问题：对于ANDA和NDA，SA-QOS能否提交？

A: Yes, the SA-QOS outline is appropriate for both NDAs and ANDAs. 答：是的，SA-QOS大纲对于NDA和ANDA是合适的。

Q: May the SA-QOS information presented in Module 2 be submitted in lieu of the traditional Module 3

information?

问题：在模块2中的SA-QOS信息能否代替在传统模块3信息被提交？

A: No, the Module 2, Section 2.3 SA-QOS information may be considered an overview of the detailed data, study reports, protocols, SOPs, batch records, etc. typically submitted in Module 3.

答：不，模块2，第2.3章节的SA-QOS信息是对模块3中代表性提交的详细数据，研究报告，方案，SOP，

批记录等经过深思熟虑后的概述。

Q: Can the SA-QOS FAQ information be used for supplemental applications? 问题：SA-QOS FAQ信息能否对补充性的申请使用？

A: Yes, the relevant QBR and FAQ information can be used for supplements. 答：是的，相关的QBR和FAQ信息能对补充部分使用。

Q: Can a DMF submission be organized according to the SA-QOS outline? 问题：DMF提交文件能否按照SA-QOS大纲组织起来？

A: Yes, the relevant section headings and details as described in this SA-QOS can be used for organizing

sterility assurance information in DMF submissions. CTD formats for DMFs are recommended. 答：是的，描述在SA-QOS中的相关章节的标题和详细信息能够用于DMF提交文件中无菌保证信息的

组织。推荐DMF使用CTD格式。 Content: 内容：

Q: How is “design space” defined in terms of production and validation for a terminally sterilized drug

product?

问题：“设计空间”是如何按照最终灭菌药品生产和验证定义的？

A: ―Design space‖ as defined by ICH Q8(R1) Pharmaceutical Development is ―the multidimensional

combination and interaction of input variables (e.g., material attributes) and process parameters that have been demonstrated to provide assurance of quality. Working within the design space is not considered a change. Movement out of the design space is considered to be a change and would normally initiate a regulatory post-approval change process. Design space is proposed by the applicant and is subject to regulatory assessment and approval.‖

答：“设计空间”就如ICH Q8（R1）药物开发中定义到的“输入变量（如：物料属性）和工艺参数的多

维的组合和相互作用已经证明可以提供质量的保证。在设计空间里面工作并不认为是一种变更。在设计空间外活动认为是一种变更并且将正常发起一种监管批准后变更程序。设计空间是申请者提议的，并且受制于监管评估和批准。”

For example, in terms of container/closure systems, the design space may include materials (container and closure type and composition), dimensions and tolerances, production assembly process parameters, and production sterilization/depyrogenation conditions (parameters and limits).

例如：在容器密封系统方面，设计空间可能包括物料（瓶子和封盖类型和组成），规模和容差，生产装配工艺参数，和生产灭菌/去热源条件（参数和限值）。

For example, in terms of sterilization and depyrogenation processes, the design space may include process