FDA新药上市申请(NDA)和生物制品上市申请(BLA)审评过程概述

NDA/BLA审评过程概述及完成审评的主要步骤

本篇文章来源于FDA的桌面参考手册（Desk Reference Guide）“CDER 21st Century Review Process”，有兴趣的小伙伴们可以去FDA网站上找找原文。本文只提供了部分内容的中文翻译，纯属个人兴趣爱好，仅供参考，如有不当敬请原谅！！后续会陆续提供其它部分的翻译，小伙伴们拭目以待吧~~~~

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一、Overview of the NDA/BLA Review Process and Major Steps for Completing the Review图解NDA/BLA审评过程概述及完成审评的主要步骤二、Summary of the Major Process Steps主要审评步骤总结

CDER’s NDA and BLA Review Process involves a total of six major steps, two of which occur outside the actual review time frame-namely, Pre-Submission Activities and Post-Action Feedback to the Applicant. Monitoring the progress of the review occurs continuously throughout the review process. The timelines to take action for applicati** that are notin the PDUFA V “Program” are 6-months from receipt for a priority review and 10-months for a standard review. The timelines for NMEs and BLAs that fall under PDUFA V’s “Program” Review Model are 10-months for standard applicati** and 6-months for priority reviews from the 60-day filing date (or 12 months and 8 months respectively from the date of submission of the application). FDA may plan to conduct an expedited review for some “Program” applicati**. Expedited reviews are a subset of priority reviews (e.g., certainhigh priority applicati** that have received breakthrough therapy designation) where the review team plans to act at least one month prior to the PDUFA goal date. In such cases, expedited timelines will be communicated during the course of the review provided no significant unexpected review issues arise and the review team does not experience an unexpected shift in work priorities or team staffing. If unexpected issues arise during the course of the review, the review plan will default to normal priority review timelines.

CDER的NDA和BLA审评过程总共包括六个主要步骤，其中的两个步骤--递交前活动和事后行动反馈给申请人--不计算审评时间。在整个过程中不断地监控评审进展。对于不属于《处方药企业付费法案》（PDUFA）V“程序”的新药申请，优先审评时间为6个月，标准审评时间为10个月。对于属于《处方药企业付费法案》（PDUFA）V“程序”的NMEs（新化学实体）和BLA（生物制品许可申请）申请，从第60天的申请日算起，优先审评时间为6个月，标准审评时间为10个月（或者说从资料提交日算起，优先审评时间为8个月，标准审评时间为12个月）。FDA可能会对一些“程序”采用加速审批。加速审批属于优先审批的一种（例如，某些获得突破性治疗指征的高优先级申请），评审小组计划在PDUFA目标日之前至少一个月采取行动。对于这种情况，在审评过程中FDA会针对加速审批时间与申请人进行沟通，只要没有发生重大的意外评审问题，评审小组一般不会调整工作重点或小组人员配备。如果在审评过程中发生意外情况，审评计划会默认为正常的优先审评时间。

For expedited reviews, applicantsare expected to:

对于加速审批，FDA希望申请人可以：

- Be familiar with expedited review programs (e.g., Fast Track, Breakthrough Therapy) and begin discussi** with FDA about how those programs may enhance development and review of their proposed product.

熟悉加速审批程序（例如，快速通道、突破疗法），并就此程序如何加速拟申报产品的开发和审评进度与FDA进行讨论。

- Be prepared for timely and frequent interacti** with FDA regarding their planned submission.

准备好与FDA就他们的申报计划进行及时频繁地互动。

- Submit complete lists of clinical and manufacturing sites as early as possible, but no later than the time of submission.

尽早地（但不晚于提交时间）提交完整的临床和生产场地清单。

- Have facilities ready for inspection at the time of submission.

在提交申请时就做好了迎接现场核查的准备。

- Respond to information requests from FDA review team in a timely and complete manner.

及时完整地回复FDA审评小组提出的补充资料要求。

- Submit unsolicited amendments only in rare cases.

仅在少数情况下提交主动修正案。

- Engage in early communication of proposed labeling and PMRs/PMCs.

尽早地参与标签和上市后需求/上市后承诺的讨论。

1. Ensure Readiness for Application through Pre-Submission Activities The first step in the process is composed of activities that applicants can take advantage of to improve the quality and content of their NDA/BLA application prior to submitting it to FDA.

通过提交前活动确保申请已经准备好该过程的第一步是由一系列的活动组成的，包括：在提交申请之前，申请者可以充分利用资源来提高NDA/BLA文件的质量和内容。

2. Process Submission Applicati** are received and processed by document control room staff and then distributed tothe appropriate review division. The RPM conducts an initial assessment of the NDA/BLA to assure that certain regulatory requirements are met and that a user fee has either been paid, the fee waived, or the application exempted. Reviewer assignments are made at this time.

过程递交首先由文件控制室的员工来接收和处理申请，然后分发给合适的审评部门。RPM（法规项目经理）对NDA/BLA进行初步评估以确保该申请满足法规要求，并已支付用户费用、或免除费用或免除申请。分配审评员的动作是在这个时候进行的。

3. Plan Review of the Application The review team conducts an initial assessment of the NDA/BLA and associated labeling. Each discipline makes a recommendation on fileability of the application at the filing meeting that is held by day 45 of the review (day 30 for priority reviews). If the application is found fileable a planning meeting is held to further discuss timelines, high-level labeling revisi** and review activities.

计划审评评审小组对NDA/BLA和涉及的标签进行初步评估。在第45天召开的提交会议（优先审批第30天）上，各领域针对申请的提交可行性（fileability）进行讨论并给出一个建议。如果觉得该申请是可提交的（fileable），就会召开一个计划会议来进一步讨论时间表、标签修改和评审活动。

4. Conduct Scientific/Regulatory Review of the Application During the review phase, the primary reviewers analyze their assigned portion of the application, propose labeling revisi**, and write their reviews; team leaders interact with reviewers and provide guidance on a regular basis. For PDUFA V “Program” reviews, a late-cycle meeting is held between the review team and the applicant. An additional two months is available for PDUFA V “Program” applicati** to address complex review issues and attempt to remedy minor problems with the application.

进行科学/法规审评在审评阶段，由主审分析他们收到的审评任务，提出标签修订意见，并撰写审评报告；组长与审评员互动，并定期提供指导。对于PDUFAV“程序”的评审来说，申请人和审评员一起召开一个较晚的周期会议。对于该“程序”，会有额外的两个月时间以解决复杂的审评问题，并弥补审评过程中遇到的小问题。

5. Take Official Action on the Application Based on the signatory authority’s review of the Action Package and on discussi** with the review team, the signatory authority determines the action to be taken on the application. The final action decision is conveyed to all team members.

针对申请采取正式行动根据签署机构对行动方案的审查以及与审评小组的讨论，签署机构决定针对申请采取的行动。最后的行动决定传达给所有的审评员。

6. Provide Post-Action Feedback to the Applicant The focus of this activity is on learning from the review experience. This optional meeting can take place as either an End of Review Conference, typically held following an action other than an approval, and/or a post-approval feedback/less** learned meeting. These two meetings can be combined into a single meeting if appropriate.

事后行动反馈给申请人该活动的重点是学习并总结本次审评经验。该会议可以在评审会议结束时（通常是在批准以外的行动中召开）进行，也可以在批准后的反馈/经验教训会议上进行。如果合适的话，这两次会议可以合并为一次会议。

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