EMA上市后变更
Classification of changes: questions and answers 变更分类问答
http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/q_and_a/q_and_a_detail_000172.jsp&mid=WC0b01ac0580a53f5e
2.1. Introduction of a new manufacturing site forthe finished product. What changes can I submit under a single type II scope?(Classification category B.II.b.1) 引入新的制剂生产场所。在单一II类变更范围内我能提交什么变更？（分类B.II.b.1）
The following complex related changes could be considered for submissionunder a single type II scope B.II.b.1 - Addition of a new finished product (FP)manufacturing site: changes to the manufacturing process, batch size andin-process controls to adapt to the new manufacturing site settings.
在单一II类B.II.b.1范围中，可以考虑提交以下较为复杂的变更申报---增加新的制剂（FP）生产场所：变更生产工艺、批量和中控以使用新的生产场所设置。
Complex related changes submitted under a single type II should always beclearly identified in the application form as following: a clear description ofall the related changes should be provided in the precise scope. All therelated changes should be listed in the present/proposed table.
在单一II类范围内提交的较为复杂的变更都需要在申报表中清楚写明以下内容：在准确范围内提交所有相关的变更的清楚描述。所有相关的变更均要列在呈报/所拟表格中。
Changes affecting the FP not directly related to the introduction of thenew manufacturing site such as changes in excipients, specification parameters/limits for the FP, container closure system including suppliers should besubmitted as additional variation scopes.
影响FP但不直接与引入新的生产场所相关的变更，例如，辅料、FP质量标准参数/限度、容器密闭系统包括供应商变更应作其它变更范围提交。
Any pre-submission queries of any intended submission of complex relatedchanges under one single type II scope should be addressed to the appointedProcedure Manager.
所有关于单一II类范围较复杂变更所拟申报资料提交之前的咨询应提交给指定的流程经理。
2.2. Introduction of a new manufacturing site foran active substance. What changes are covered by a single type II scope?(Classification categoryB.I.a.1) New June 2017 引入新的活性物质生产场所。单一II类范围覆盖哪些变更？（分类B.I.a.1）
The introduction of a new manufacturing site for an active substancesupported by an ASMF should be submitted under a single Type II scopeB.I.a.1.b. The introduction of a new manufacturer of the active substance notsupported by an ASMF that requires significant updates to 3.2.S should besubmitted under a single Type II scope B.I.a.1.g).
引入新的活性物质生产场所时，如果工厂有ASMF支持，则应在单一II类范围B.I.a.1.b项下提交变更。引入活性物质新生产商，但没有ASMF支持从而需要对3.2.S进行重大更新时，要在单一II类范围B.I.a.1.g项下提交变更。
It should be noted that in cases where the introduction of the new activesubstance manufacturer has an impact at the level of the finished productmanufacturer (e.g. changes to the active substance specifications or relatedanalytical methods) separate variations have to be submitted under thecorresponding B.I.b. categories and may be grouped together, if related to theintroduction of the new active substance manufacturer.
要注意的是，如果引入新的活性物质生产商对于制剂生产商会产生影响（例如，活性物质质量标准或相关分析方法变更），则必须在相应的B.I.b类中提交单独的变更，如果与引入新的活性物质生产商有关的话，也可以放在一起提交组合变更。
Any pre-submission queries related to upcoming submissions pertaining tosuch changes should be addressed to the appointed Procedure Manager.
所有与提交含有此类变更的申报资料之前相关的咨询请联系指定的程序经理。
2.3. How should a change to Module 3.2.S or theupdate of an ASMF, which is part of Module 3 (human) of a marketingauthorisation be submitted? (B.I.z) New June 2017 作为上市许可申报资料中模块3（人药）一部分的模块3.2.S.变更或ASMF更新的变更应如何提交？（B.I.z）
The update of Module 3.2.S can be submitted as a grouped variationapplication, if conditions 5 or 6 of Annex III of the Variation Regulation (EC)No 1234/2008 apply.
如果符合EC第1234/2008号变更法规附录III的条件5和6，则可以将模块3.2.S更新作为组合变更申报来提交。
An update or change of a stand-alone ASMF is not foreseen and can only beaddressed in connection with a marketing authorisation. The type of thevariation(s) is dependent on the type of the single changes introduced in theupdated version. The update – including changes to the open and /or restrictedpart - can be submitted as a grouped application, if condition 5 of Annex IIIof the Variation Regulation (EC) No 1234/2008 applies.
独立ASMF的更新或变更是无法预知的，只能与上市许可资料一起变更。变更类型取决于更新后版本中引入单一变更的类型。如果符合EC第1234/2008号变更法规附录III的条件5和6，则对公开部分和/或保密部分的更新------包括变更----可以作为组合变更提交。
However, in case of substantial changes in the updated version of Module3.2.S or the ASMF it is recommended to submit a single type II variation undercategory B.I.z. However, it is a prerequisite for the validation of thesesingle variations that the “present/proposed” section of the application formis filled in correctly and completely.
但是，如果在模块3.2.S或ASMF的更新版本中有重大变更，则建议在B.I.z项下作为单一II类变更提交。但是，这些单一变更验证的前提条件是申报表的“呈交/拟定”部分填写正确且完整。
In all cases, updates of the ASMF must be submitted by the ASMF holder(open and closed part to EMA, open part to marketing authorisation holder)whilst the variation as such has to be submitted by the marketing authorisationholder. We encourage a close dialogue between MAH and ASMF holder to establishthe correct classification of all the changes introduced within a new versionof an ASMF to avoid validation issues.
在所有情形下，ASMF更新都必须由ASMF持有人提交（公开部分和保密部分给EMA，公开部分给上市许可持有人），而变更则必须由上市许可持有人提交。我们鼓励MAH和ASMF持有人之间进行密切对话，为在新版本ASMF中引入的所有变更订立正确的分类，从而避免验证问题。
Any pre-submission queries related to upcoming submissions pertaining tosuch changes should be addressed to the appointed Procedure Manager.
所有与提交含有此类变更的申报资料之前相关的咨询请联系指定的程序经理。
2.4. How should I submit an updated Certificateof Suitability (CEP)? (Classification category B.III.1) 我应该如何提交更新后的CEP？（B.III.1类）
In line with the Marketing Authorisation Holder’s (MAH) obligation to keepthe dossier up to date, a new or updated Certificate of Suitability (CEP) foran active substance (AS), excipient or starting material/reagent/intermediateused in the manufacturing process of the AS should be submitted as a variation.It is however understood that only the versions of the CEP (i.e. updatedcertificates) which were used in the manufacturing process of a batch offinished product (FP)/ AS need to be included in the dossier.
MAH应履行其义务保持注册文件更新，因此新的或更新后的活性物质（AS）、辅料或AS生产工艺所用起始物料/试剂/中间体的适应性证书（CEP）均应作为变更提交。不过只需要在注册文件中包括用于制剂（FP）/AS生产工艺中的CEP的版本号（即更新后的证书）就可以了。
CEP updates should be submitted under the appropriate variationclassification scope within subsection B.III.1. Each CEP update should besubmitted as a variation scope, i.e. an update covering more than one CEPversion should be submitted as a grouped variation.
CEP更新应在B.III.1子部分中适当的变更分类范围下提交。每个CEP更新均应作为一个变更范围，也就是说覆盖多于一个CEP版本的更新应作为组合变更提交。
When applying for an update of an approved CEP, the MAH should refer to thepreviously agreed version of the CEP within the ‘Present/Proposed’ section ofthe application form.
如果是已批准的CEP的更新，则MAH应在申请表格的“当前/所拟”部分填写之前已同意的CEP版本号。
If with the submission one or more revisions of the CEP are omitted, theMAH should confirm in the variation application form (section ‘Precise scopeand background for change’) that substance/material from the omitted CEPversion(s) was not used in the manufacture of the FP and/or AS during thevalidity of this certificate(s). Additionally it should be confirmed that anychanges introduced by the omitted CEP update(s), do not affect the quality ofthe AS and/or FP. In case such confirmation is missing, a negative Type IAnotification may be issued.
如果是在申报资料中跳断一个或多个CEP版本号，则MAH应在变更申请表格中确认（“变更准确范围和背景”部分）所跳断的CEP版本的物质/物料在此证书的有效期间没有用于FP和/或AS的生产。此外，还要确认由于所跳断的CEP更新而引入的所有变更并不影响AS和/或FP的质量。如果没有此类确认，则可能会收到被拒IA类通知。
The MAH should also clearly indicate in the ‘Present/Proposed’ section allchanges introduced in the CEP between the latest approved version and the new revision,including all revisions that were not notified. Any changes e.g. tomanufacturing sites, additional residual solvents introduced in the CEP bysubsequent updates should be declared.
MAH还应在“当前/所拟”部分清楚写明在CEP最后批准版本与新修订中引入的所有变更，包括所有未通知的修订。要写明随后更新中CEP所引入的所有例如生产场所、增加残留溶剂的变更。
Example: 举例
Submission of an updated CEP version for an already approved manufacturer:R0-CEP-xxxx-xx-rev.02 when the current certificate in the dossier is:R0-CEP-xxxx-xx-rev.00.
当前注册文件中引用的证书编号为R0-CEP-xxxx-xx-rev.00，生产商已批准，现在要提交一份该CEP更新，已批准的版本号为R0-CEP-xxxx-xx-rev.02。
If during the validity of R0-CEP-xxxx-xx-rev.01, material of the CEP wasused in the manufacture of the FP and/or the AS, then the MAH should submit agrouping of two IA variations to include both certificates (rev. 01 and rev.02) in the Module 3. The foreseen conditions for each of the respectivevariations should be met.
如果在R0-CEP-xxxx-xx-rev.01有效期间，CEP物料被用在了FP和/或AS的生产，则MAH应提交一份2个IA变更的组合变更，在模块3中包括2个证书（版本01和02），每个变更所需要的条件均应分别满足。
If during the validity of R0-CEP-xxxx-xx-rev.01, material of the CEP wasnot used in the manufacture of the FP and/or AS, the MAH should only submit asingle Type IA variation to include the updated certificateR0-CEP-xxxx-xx-rev.02 in Module 3. The foreseen conditions for the variationshould be met.
如果在R0-CEP-xxxx-xx-rev.01的有效期间，CEP物料没有被用在FP和/或AS的生产中，则MAH只需要提交单一IA类变更，在模块3中包括更新后的证书R0-CEP-xxxx-xx-rev.02，需要满足变更所设定的条件。
The MAH should also confirm in the variation application form thatmaterial/substance from R0-CEP-xxxx-xx-rev.01 was not used in the manufactureof the FP and/or AS during the validity of this certificate and that changesintroduced by the revision R0-CEP-xxxx-xx-rev.01 do not affect the quality ofthe AS and/or the FP. MAH should also clearly list within the‘Present/Proposed’ section of the application form all changes introduced tothe CEP with revisions 01 and 02.
MAH还应在变更申请表中确认R0-CEP-xxxx-xx-rev.01物料/物质在此证书有效期间并没有被用在FP和/或AS生产中，并且R0-CEP-xxxx-xx-rev.01所引入的变更并不影响AS和/或FP的质量。MAH还应在申报表格的“当前/所拟”部分清楚列出CEP修订01和02所引入的所有变更。
2.5. What is considered to be a non-significantin-process control or specification parameter? (Classification categoryB.I.a.4.c, B.I.b.1.d, B.I.c.2.c, B.II.b.5.c, B.II.c.1.c, B.II.d.1.d, B.II.e.2.cand B.IV.2.f) 什么样的中控和质量标准参数可以认为是不重要的？（分类B.I.a.4.c, B.I.b.1.d, B.I.c.2.c,B.II.b.5.c, B.II.c.1.c, B.II.d.1.d, B.II.e.2.c 和 B.IV.2.f）
Variation scopes B.I.a.4.c, B.I.b.1.d, B.I.c.2.c, B.II.b.5.c, B.II.c.1.c,B.II.d.1.d, B.II.e.2.c and B.IV.2.f of the 'Variations Guidelines’ 2013/C 223/01, deal with thedeletion of a non-significant in-process control (IPC) test or specificationparameter. Provided all relevant conditions and documentation requirements aremet, all these variations fall under the Type IA category (do-and-tell).
变更指南2013/EC 223/01的变更范围B.I.a.4.c, B.I.b.1.d, B.I.c.2.c, B.II.b.5.c, B.II.c.1.c,B.II.d.1.d, B.II.e.2.c 和B.IV.2.f，是关于不重要的中控（IPC）检测和质量标准参数删除的。如果满足所有相关条件和文件要求，则所有这些变更都属于IIA类（先实施后告知）。
For the categories listed above and other variations related tospecifications of active ingredients, excipients, finished product, packagingmaterial or measuring or administration device, the deletion of an obsoleteparameter is given as an example. For finished products, this is furtherexemplified by mentioning of odour and taste. Although it is not possible togive similar examples for all of the categories mentioned above, these examplesserve as an indication of the types of changes considered to fall under thisvariation category, regardless if this is related to in-process controls orspecifications. This is therefore intended to be used for truly obsolete teststhat are no longer part of normal specifications for newer products, but haveremained for historical reasons in older products.
对于上列类别，以及其它与活性成分、辅料、制剂、包材和测量和管理装置有关的变更，将删除无用的参数作为例子。对于制剂，进一步以气味和味道监测作为例子说明。尽管不可能给对所有上述类别都给出相似的例子，但这些例子可以说明哪些是可以列为此类变更的变更指标，而不管它是否与中控或质量标准有关。因此，这些是要用作真的非常过时的检测，不再是更新的药品的常规标准，但还是因为历史原因保留在老产品中。
This variation category is not intended to include changes in relation torevisions of the control strategy with an intention to minimise redundanttesting of parameters and attributes (critical or non-critical) that are testedat different stages during the production, or cases where process/ productcharacterisation performed after authorisation has shown that the attribute/parameter is non-critical. Such changes require regulatory assessment and areto be handled as Type IB or II variations as appropriate.
此变更类别不包括为了减少多余的参数和属性（关键或非关键）检测，而修订控制策略的变更。这些参数在不同生产阶段进行检测，或者是在批准之后所实施的工艺/产品定性情况中检测，发现这些属性/参数并不关键。此类变更要进行注册评估，适当时应作为IB类或II类变更处理。
2.6. When applying for a new pack size, what isconsidered to be within /outside range? (Classification category B.II.e.5) 在申请新包装规格时，哪些认为是范围内哪些是范围外的（分类B.II.e.5）？ New Jun2017
The introduction of a new pack size (i.e. in addition to currently approvedpack sizes) should be submitted as a variation under scope B.II.e.5.a).
引入新的包装规格（即，除了当前已批准的包装规格以外）应按B.II.e.5.a提交变更。
A range is defined from the smallest to the largest approved pack size(i.e. not from ‘0’) for the same pharmaceutical form and strength. The packsize equals to the number of units of the pharmaceutical form (e.g. tablets,sachets, ampoules, etc.) contained in the outer packaging. Pack sizes notincluded within this range are considered to be outside of the range.
相同药品形式和剂量其范围界定是从最小到最大已批准规格（即并不是从“0”开始）。包装规格等于外包装中所包含的药品形式（例如，片剂、小袋、安瓿等）单位数量。不在此范围内的包装规格则认为是超范围的。
For the addition of a new pack size where the number of units of the packis within the range of the currently approved pack sizes for the strength andpharmaceutical form, applicants should submit a IAIN variationB.II.e.5.a.1.
如果是针对已批准的剂量和药品形式的包装规格范围内增加包装单位数量，则申报人应提交IA通知类B.II.e.5.a.1变更。
For the addition of a new pack size where the number of units of the packis outside the range of the currently approved pack sizes for the strength andpharmaceutical form, applicants should submit a IB variation B.II.e.5.a.2.
如果是针对已批准的剂量和药品形式的包装规格范围外增加包装单位数量，则申报人应提交IB类B.II.e.5.a.2变更。
In support of a timely introduction of new pack sizes to the market, EMAaccepts the following approach for the introduction of various pack sizesfalling outside the range within a single grouped submission. The biggest or thesmallest pack size per strength outside the range should be classified as IBvariation B.II.e.5.a.2. This presentation defines the new limits of the rangeso that any intermediate pack size for the strength and pharmaceutical form canbe classified as IAIN variation B.II.e.5.a.1.
为了支持及时将新包装规格引入市场，EMA接受按单一组合申报按以下方式引入范围外的不同包装规格。每个剂量的最大或最小包装规格超出范围，应作为IB类变更B.II.e.5.a.2。此方法定义了新的范围限度，因此所有该剂量和药品形式的中间包装规格均可以作为IA立即通知类B.II.e.5.a.1变更提交。
Example 1 举例
The “Medicinal Product A” has currently two approved pack sizes of 30 and60 tablets for the pharmaceutical form“film coated tablets” and the strength“20mg” and the MAH intends to apply for two new pack size(s) of 90 and 120tablets at the same time.
“药品A”的“薄膜包衣片”形式“20mg”剂量目前有2种已批准的包装规格30片和60片，MAH想要同时申请2种新的包装规格90片和120片。
The introduction of a new pack size of 120 tablets for the “20mg” strengthis considered outside the range of packs and should be classified as variationB.II.e.5.a.2 (IB). This pack size defines a new limit for the range (30-120),so that the introduction of a pack size of 90 tablets as a grouped (or alatter) submisison can be classified as a variation B.II.e.5.a.1 (IAIN).
为“20mg”的剂量引入新的包装规格120片是超出包装范围的，应作为B.II.e.5.a.2 (IB)变更提交。此包装规格定义了一个新的范围限度（30-120），因此引入90片包装规格就可以作为一个组合（或后者）申报以B.II.e.5.a.1 （IA立即通知）提交。
The MAH should therefore apply for a grouped variation of 1 x Type IB -B.II.e.5.a.2 variation and 1x type IA B.II.e.5.a 1 variation.
因此，MAH应申请一个IB 类B.II.e.5.a.2组合变更，一个IA 类B.II.e.5.a 1变更。
Example 2 例2
The “Medicinal Product B” has currently two approved pack sizes of 2 and 10pre-filled syringes for the pharmaceutical form “solution for injection” forboth strengths of “20mg” and “40mg”.The MAH is applying for four new packsizes:5 prefilled syringes for the “20 mg” strength; 30 pre-filled syringes forthe “20 mg” strength; 5 prefilled syringes for the “40 mg” strength; 30pre-filled syringes for the “40 mg” strength.
“药品B”的“注射液”药品形式2种剂量“20mg”和“40mg”目前各自有2个批准的包装规格2支和10支预装注射针。MAH正在申报4个新包装规格：“20mg”剂量5支预装注射针、“20mg”剂量30支预装注射针、“40mg”剂量5支预装注射针、“40mg”剂量30支预装注射针。
For the “20mg” strength, the introduction of a new pack size of 5pre-filled syringes strength is considered within the range of approved packs(2-10) and should be classified as variation B.II.e.5.a.1 (IA) and theintroduction of a new pack size of 30 pre-filled syringes is considered outsidethe range of approved packs (2-10) and should be classified as variationB.II.e.5.a.2 (IB).
对于“20mg”剂量，引入5支装新的包装规格是在批准的包装规格内（2-10），应作为B.II.e.5.a.1(IA)变更提交。引入新的包装规格30支装则是在批准范围外（2-10），应作为B.II.e.5.a.2 (IB)变更提交。
For the “40mg” strength, the introduction of a new pack size of 5pre-filled syringes strength is considered within the range of approved packs(2-10) and should be classified as variation B.II.e.5.a.1 (IA) and theintroduction of a new pack size of 30 pre-filled syringes is considered outsidethe range of approved packs (2-10) and should be classified as variationB.II.e.5.a.2 (IB).
对于“40mg”剂量，引入5支装新的包装规格是在批准的包装规格内（2-10），应作为B.II.e.5.a.1(IA)变更提交。引入新的包装规格30支装则是在批准范围外（2-10），应作为B.II.e.5.a.2 (IB)变更提交。
The MAH should therefore apply for a grouped variation application underthe scopes referred above.
因此，MAH应按上述变更范围申请一个组合变更。
It should be highlighted, that for variations introducing additional presentationsor pack sizes for centrally approved products, each additional presentation orpack size attracts separate fees (x additional presentations = x separatefees). Each presentation and pack size should therefore be declared as aseparate variation on the variation application form under the section‘variations included in this application’.
要强调的是，如果是集中审评程序批准的药品，引入更多的形式或包装规格的变更中，每个增加的形式或包装规格要单独计费（增加X个形式= X倍单独费用）。因此，在变更申报表格中“本申请中包括的变更个数”部分要为每个形式和包装规格单独计数。
Changes to strength, pharmaceutical form and route of administration are tobe submitted as an Extension of a marketing authorisation.
剂量、药品形式变更和给药途径变更要作为上市许可延伸提交。
For additional guidance on changes to existing presentation that cantrigger new EU number(s) please see the EMA post-authorisation guidance for Type IA, Type IB and Type II variations.
可能会激活新EU编号的现有形式变更更多指南参见上述网址。
2.7. How should I submit a new working cell bank(WCB)? (Classification category B.I.a.2 a) New June2017 我应该如何提交新的工作细胞库（WCB）？（分类B.I.a.2.a）
If a new WCB is introduced using the limits/conditions as detailed in anapproved qualification protocol, the new WCB is covered by the existing qualityassurance system and there is no need to submit a variation.
如果是采用已批准的确认方案中详细写明的限度/条件引入新的WCB，则新的WCB是覆盖在现有质量保证体系内的，不需要提交变更。
If the documentation of the WCB in the dossier does not include an approvedqualification protocol for introducing new WCBs, the MAH should file avariation B.I.a.2 a type IB (as condition 5 is not met).
如果注册资料中WCB文件没有已批准的引入新WCB的确认方案，则MAH应提交IB类B.I.a.2.a变更（因为不符合条件5）。
To introduce a qualification protocol for preparation of a new WCB, the MAHshould file a variation type II B.I.a.2.c. The addition of the new WCB can becovered as part of this single variation type II.
如果引入新WCB制备确认方案，则MAH应提交II类 B.I.a.2.c变更。增加新的WCB可以作为此单独的II类变更的一部分。
Changes to an approved standard procedure (protocol) should be filed usinga variation type IB B.I.a.2.a, or a variation type II B.I.a.2.c, as relevantdepending on the complexity of the change. The addition of a new WCB can becovered as part of this single variation.
对已批准标准程序（方案）的变更应采用IB类变更B.I.a.2.a或II类变更B.I.a.2.c，依据变更的复杂性具体决定。增加新WCB可以作为此单一变更的一部分。
2.8. How should I submit a newreference standard for a biological medicinal product? 我应该如何提交一份新的生物药品对照品？New June 2017
If a new reference standard is introduced using the limits/conditions asdetailed in an approved qualification protocol, the new reference standard iscovered by the existing quality assurance system and there is no need to file avariation.
如果是采用已批准的确认方案中详细写明的限度/条件引入新的对照品，则新的对照品是覆盖在现有质量保证体系内的，不需要提交变更。
If no qualification protocol has been approved and the old material isstill available and the MAH is able to provide comparability test results usingboth reference standards, the MAH should file a type IB variation either underB.I.b.2.e for Active Substance or under B.II.d.2.d for Finished Product.
如果没有批准过的确认方案，还有旧的物料，而MAH可以提交新旧对照品的对比测试结果，则MAH应提交一份IB类变更，原料药为B.I.b.2.e，制剂为B.II.d.2.d。
If no qualification protocol has been approved and the old material is not availableanymore and therefore no direct comparison new/old material is possible the MAHshould file a type II variation either under B.I.b.2.d for Active Substance orunder B.II.d.2.c for Finished Product.
如果没有批准过的确认方案，旧的物料已经没有了，因此无法直接对比新旧物料，则MAH应提交一份II类变更，原料药为B.I.b.2.d，制剂为B.II.d.2.c。
To introduce a qualification protocol for the preparation of a newreference standard, the MAH should file a variation type II either underB.I.b.2.d for Active Substance or under B.II.d.2.c for Finished Product. Uponapproval of the variation, the introduction of a new reference standardaccording to the protocol will be covered by the existing quality assurancesystem.
如果是引入一份新对照品制备确认方案，则MAH应提交II类变更，原料药为B.I.b.2.d，制剂为B.II.d.2.c。在变更批准之后，依据方案所引入的新对照品则覆盖在现有质量保证体系内。
2.9. What changes in manufacturing sites,buildings and rooms are covered by the company Quality Assurance System (GMP)? 生产场所、建筑和房间的哪些变更是覆盖在公司质量保证体系（GMP）内的？ NewJune 2017
Provided that module 3 is not impacted, with the exception of section3.2.A.1 (for biotech medicinal products), the changes listed below (not anexhaustive list) are covered under the company’s quality management system anddo not require a variation to the Marketing Authorisation:
如果模块3未受影响，（生物制品）3.2.A.1部分除外，下列变更（不是所有变更的清单）是覆盖在公司质量管理体系内的，不需要提交上市许可变更：
· Transfer of amanufacturing activity from one building to another in the same authorised site
· 在经过批准的相同场所内将生产活动从一幢建筑物转移至另一幢建筑物
· Transfer of amanufacturing activity from one room to another in the same authorised building
· 将生产活动从一个房间转移至已批准的相同建筑物内另一个房间
· Transfer of QCactivity from one building to another in the same authorised site
· 在经过批准的相同场所内将QC活动从一幢建筑转移至另一幢建筑中
· New filing lineidentical to an already approved one in an authorised room, building,manufacturing site
· 已批准的房间、建筑物、生产场所里增加与已批准的生产线相同的新生产线
· New isolator in anauthorised building
· 已批准的建筑中新的隔离器
· New media orbuffer preparation room in an authorised building
· 已批准的建筑中新的培养基或缓冲液制备间
· Changes in thelayout of an authorised manufacturing site
· 已批准的生产场所内平面布局变更
If as a result of any of the changes listed above, any amendments areintroduced to module 3 (with the exception of section 3.2.A.1 for biotechmedicinal products), such as changes to the manufacturing site address detail,changes to the manufacturing process, changes to the batch size, etc., the MAHshould file the appropriate variation(s).
如果上述变更会引起模块3的变更（生物药品3.2.A.1部分除外），例如生产场所详细信息变更、生产工艺变更、批量变更等，MAH都应提交相应的变更。
2.10. Changes in equipment used in themanufacturing process. What changes are covered by the company QualityAssurance System (GMP)? 对生产工艺所用设备进行变更，哪些类型的变更是覆盖在质量保证体系（GMP）中的？New June 2017
Provided that the new equipment is equivalent to the one currently used,and operates in the approved range of process parameters, the change is coveredby company’s quality assurance system.
如果新的设备等同于当前使用的设备，并且在已批准的工艺参数范围内运行，则该变更是覆盖在公司的质量保证体系内的。
If the introduction of new equipment has any impact on the processes anddetails registered in module 3 (with the exception of section 3.2.A.1 forbiotech medicinal products), the MAH should submit the appropriatevariation(s).
如果是引入了新的设备，对模块3中注册的工艺和详细内容产生影响（生物制品3.2.A.1部分除外），则MAH应提交适当的变更。
2.11. How should I update section 3.2.A.1 forBiotech medicinal products? 我应该如何更新生物药品的3.2.A.1部分呢？New June 2017
Notice to applicants for Medicinal products for human use (Eudralex –Volume 2B) establishes that information on facilities and equipment should beincluded in Appendix 3.2.A.1 for biotech medicinal products.
人药NTA（欧盟药事法第2B卷）中有生物药品附录3.2.A.1中应包括的设施和设备信息内容。
Any update of this section can be included as part of any upcomingvariation affecting Module 3. In case the MAH wants to update this section anddoes not foresee any upcoming variation affecting Module 3 in the short/mediumterm, the MAH may consider submitting a Type IB variation (B.II.z).
所有对此部分的更新都可以作为影响模块3的变更的一部分。如果MAH想要更新此部分但不知道在中短期内会有哪些影响模块3的变更，那么可以考虑以IB类变更提交（B.II.z）。
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