新WHO指南：多源药品变更

julia朱玉姣

GMP News
03/08/2016

NewWHO guidance on variations to multisource pharmaceutical products

新WHO指南：多源药品变更

The World Health Organizaton recentlypublished a new Annex 10: WHO general guidance on variations to multisourcepharmaceutical products.

WHO最近公布了一份新的附录10：WHO对多源药品变更的通用指南。

The document is "intended to serve as a guide forestablishing national requirements for the regulation of post-approval changes."Proposed categories and reporting procedures are provided. Modifications may bejustified in light of risk-benefit and legal considerations specific to eachnational medicines regulatory authority (NMRA).

该文件“意在作为一份指南建立国家要求来规范批准后变更”。文件中给出了提议的分类和报告程序。根据利弊平衡和各国药监机构（NMRA）的具体考虑可以进行修订。

The guideline can be used with respect to changes to thequality sections of product dossiers and should be read in context with the Guidelines on submission ofdocumentation for a multisource (generic) finished product: quality partas well as other related WHO guidelines or applicable national guidelines.

指南可用于与药品申报文档质量部分相关的变更，应与“多源（仿制）药品质量部分文件申报指南”及其它相关WHO指南和适用的国家指南一起解读。

The guideline emphasizes that "even well-resourcedagencies find it difficult to evaluate all the pharmaceutical changes that aremade to all products." Therefore, "a shift towards increasedself-assessment of changes by the marketing authorization (MA) holder" hasbeen observed. In this context "it is necessary, to define thosechanges that can be made without the NMRA´s prior approval(self-assessable changes) and those that require prior approval based on anunderstanding of the risk and how best to manage the risk."

指南强调了“即使资源丰富的药监机构也发现要评估对所有的药品所做的所有变更是很困难的”，因此“逐渐转向由MA持有人对变更进行自我评估”成为趋势。在此情况下，“有必要根据对风险的了解来定义哪些变更可以不需要NMRA的提前批准即可实施（可以自我评估的变更），哪些需要提前批准，并且如何能最好地管理这些风险”。

Description of the reporting categories are discussed insection 5 of the Annex:

报告分级的描述在附录的第5部分进行了讨论：

• Notifications: They can be made for     changes to the product that may have no potential or minimal potential to     have a negative impact on the quality, safety and efficacy (QSE) of a     finished pharmaceutical product (FPP). Implementation of such variations     may be possible without prior approval by the NMRA (e.g. submission of     these variations as annual notifications).
• 通知：对制剂（FPP）的质量、安全性和有效性（QSE）没有或很小潜在不良影响的变更。实施此类变更可能不需要NMRA提前批准（例如，作为年度通知提交这些变更）。
• Minor variations: Changes with moderate     or negative impact on the QSE. Such changes must be submitted to the NMRA     with all required documentation prior to implementation. The MA     holder may implement the change if no objection has been issued within a     specific time period by the NMRA.
• 轻微变更：对QSE有中等或负面影响的变更。此类变更必须在实施之前与所需的文件一起提交给NMRA。如果NMRA在指定的时限内没有提出反对意见，则MA持有人可以实施变更。
• Major variations: They have a     significant potential to have a negative impact on the QSE. A major     variation should be reviewed and approved by the NMRA prior to     implementation of the change. To increase the efficiency NMRAs may accept     grouping of variations under specific circumstances (see also FDA´s     new policy regarding grouping of CMC changes).     
• 重要变更：对QSE有重大的负面影响。一个重要变更应在实施之前经过NMRA的审核和批准。为了提高效率，NMRA可能会在特定情形下接受变更组合（参见FDA的CMC变更组合新政）。
• Editorial changes: They typically need     not to be submitted and can be included as a notification together with a     subsequent variation concerning that part of the dossier.
• 编辑性变更：一般不需要提交，可以包括在通知里与该部分文档相关的变更一起提交。
  

Certain changes can be so fundemental that they require asubmission of a new dossier. Examples of such changes are:

有些变更可能非常重要，需要提交一份新的申报文档才可以。此类变更例子有：

• Change of the API to a different API,
• 原料药品种变更
• Inclusion of an additional API in a     multicomponent product,
• 在复方药品中增加一种原料药
• Removal of one API from a multicomponent     product,
• 从复方药品中拿掉一种原料药
• Change in the dose and/ or strength of     one or more APIs,
• 一种或多种原料药剂量变更
• Change from an immediate-release product     to an extended- or delayed-release dosage form or vice versa,
• 从即释药品改为缓释或延释剂型，或相反的变更
• Change from a liquid to a powder for     reconstitution or vice versa,
• 从液体制剂变更为粉末组成，或相反的变更
• Changes in the route of administration.
• 摄入途径的变更
  

For any change in the SmPC, patient information leaflet(PIL)  and/or labels the NMRAS should be notified and submission of therevised product information and/or labelling is expected as percountry-specific requirements.

对于SMPC、患者信息说明书（PIL）和/或标签的任何变更，应通知NMRA，并根据国家具体要求提交修订后的产品信息和/或标签。

Proposed recommendations on the regulatory procedures forthe reporting of changes to the NMRA are discussed in section 8 of the Annex:

在法规程序中所提议的向NMRA报告变更的建议在附录的第8部分中进行了讨论：

• General: It is essential that different     branches of the NMRA interact and exchange information effectively. They     should, for example, discuss whether a change may require a GMP inspection     or may be reviewed during the next routine inspection.
• 概述：NMRA不同分支之间的进行有效沟通和交流是很必要的。他们应该，例如，讨论一个变更是否需要GMP检查，或者在下一个常规检查中进行审核。
• Presubmission meetings: Procedures     should be established to allow MA holders the opportunity to obtain advice     prior to submitting variations.
• 申报前会议：应该建立程序来允许MA持有人有机会在提交变更之前获得建议
• Proposed documentation for minor     variations: Basic information like
• 建议轻微变更所提交的变更文件：基本信息如：
       -     covering letter, 封面函
       - application form, 申报表
       - a list of subsections of the current dossier affected by the change(s), 受变更影响的现行文件子部分清单
       -     a list and description of each change, reason for change(s) and the date     each change was implemented, 所有变更描述、变更理由和各变更实施日期的清单
       - relevant summary of data from studies and tests performed, 来自所实施的研究和测试的数据的相关汇总摘要
       - copies of the updated subsections of the original dossier, 原始文件更新后的部分
       should be included as part of the immediate or annual notification, where     prior approval is not required. 如果不需要预批准的话，应包括作为立即报告或年度报告的一部分。
• Proposed documentation for variations     requiring prior approval: Additionally to the documents mentioned under     "minor variations":
• 需要在实施前被批准的变更所需提交文件建议：除了轻微变更所提到的文件外，还要
       - replacement of the relevant subsections of the dossier     in accordance with the acceptable dossier format for the NMRAs concerned,     with the proposed changes clearly annotated,
       根据各NMRA可接受的文档格式，提交文件的替代相关子部分，在其中清楚标明所提议的变更
       - copies of the SmPC, PIL and labels, if relevant,
       SMPC、PIL和标签的复本，如果需要的话
       - registration status and date of the proposed change(s)     in other countries and/or agencies that have already approved the     variation(s), especially the country of origin and the reference agencies.
       所提议的变更在其它国家和/或药监局的注册状态和日期，已经批准，尤其是所引用当局的国家
• Review procedures: NMRA should adopt a     risk-based review strategy for assessment, concentratiing most effort on     those changes considered to carry the greatest risk. NMRA may consider     whether it will rely on decisions and/or assessment reports made by other     national authorities or prepare its own full assessment report or use a     combination of those approaches.
• 审核程序：NMRA应采纳一个基于风险的审核策略用于评审，将时间精力订中用于被认为带有最大风险的那些变更。NMRA可以考虑是否要依赖于另一国家药监的决定和/或评估报告，还是起草制订其自己的全面评估报告，或是与其它方法联合应用。
  

For more Information please see the new Annex10 - WHO general guidance on variations to multisource pharmaceutical products.

更多信息参见官方指南。

scslk0045

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globle002

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zzhpxke

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volador

TRS 981, Annex 3  WHO guidelines on variations to a prequalified product
预认证产品变更指南

有翻译过吗？