近日，歐盟委員會發(fā)布了新版條例EC 1234/2008-2025《人用藥上市許可條款變更審查》。
此外，歐盟還發(fā)布了新版《變更指南》，2026年1月15日生效。
EMA也同步更新了《變更分類問答》和《變更穩(wěn)定性試驗指南》（2026年1月15日生效）。
文件翻譯如下：
02008R1234 — 20250101 — 004.001
concerning the examination of variations to the terms of marketing authorisations for medicinal products for human use
歐盟委員會條例（EC）第1234/2008號
人用藥上市許可條款變更審查2025版
CHAPTER I
第一章
GENERAL PROVISIONS
總則
Article 1
第一條
Subject matter and scope
適用范圍與目的
This Regulation lays down provisions concerning the examination of variations to the terms of marketing authorisations for medicinal products for human use granted in accordance with Regulation (EC) No 726/2004 or Directive 2001/83/EC.
本條例就依據(jù)歐盟委員會條例（EC）第 726/2004 號或歐盟理事會指令 2001/83/EC 獲批的人用藥品上市許可條款變更的審查事宜，制定相關(guān)規(guī)定。
This Regulation shall not apply to transfers of a marketing authorisation from one marketing authorisation holder (hereinafter holder) to another.
本條例不適用于上市許可從一名上市許可持有人（以下簡稱 “持有人”）向另一名持有人的轉(zhuǎn)讓事宜。
Chapter II shall apply only to variations to the terms of marketing authorisations granted in accordance with Chapter 4 of Directive 2001/83/EC.
第二章僅適用于依據(jù)歐盟理事會指令 2001/83/EC 第四章獲批的上市許可條款變更。
3a. Chapter IIa shall apply only to variations to the terms of purely national marketing authorisations.
3a. 第二章 a 節(jié)僅適用于純國別上市許可的條款變更。
Chapter III shall apply only to variations to the terms of marketing authorisations granted in accordance with Regulation (EC) No 726/2004 (hereinafter centralised marketing authorisations).
第三章僅適用于依據(jù)歐盟委員會條例（EC）第 726/2004 號獲批的上市許可（以下簡稱 “集中上市許可”）條款變更。
Article 2
第二條
Definitions
定義
For the purposes of this Regulation, the definitions in Article 1 of Directive 2001/83/EC shall apply.
就本條例而言，歐盟理事會指令 2001/83/EC 第一條給出的定義同樣適用。
The following definitions shall also apply:
下列定義同樣適用：
'Minor variation of type IA' means a variation which has only a minimal impact, or no impact at all, on the quality, safety or efficacy of the medicinal product concerned;
IA 類微小變更：指對相關(guān)藥品的質(zhì)量、安全性或有效性僅有極小影響，或無任何影響的變更。
'Major variation of type II' means a variation which is not an extension and which may have a significant impact on the quality, safety or efficacy of the medicinal product concerned;
II 類重大變更：指不屬于許可范圍拓展，且可能對相關(guān)藥品的質(zhì)量、安全性或有效性產(chǎn)生顯著影響的變更。
'Extension of a marketing authorisation' or 'extension' means a variation which is listed in Annex I and fulfils the conditions laid down therein;
上市許可范圍拓展（簡稱 “許可拓展”）：指列入本條例附件一且符合該附件所列條件的變更。
'Minor variation of type IB' means a variation which is neither a minor variation of type IA nor a major variation of type II nor an extension;
IB 類微小變更：指既不屬于 IA 類微小變更、也不屬于 II 類重大變更，同時也不屬于許可范圍拓展的變更。
'Member State concerned' means a Member State whose competent authority has granted a marketing authorisation for the medicinal product in question;
相關(guān)成員國：指其主管機關(guān)為相關(guān)藥品授予上市許可的歐盟成員國。
6a. 'Reference authority' means:
6a. 參考主管機關(guān)：指
(a) the Agency where at least one of the marketing authorisations concerned is a centralised marketing authorisation;
(a) 若相關(guān)上市許可中至少有一項為集中上市許可，則指歐洲藥品管理局；
(b) the competent authority of the Member State chosen by the holder and accepted by that competent authority, or chosen by the coordination group referred to in Article 27 of Directive 2001/83/EC if none of the competent authorities of the Member States agrees to act as the reference authority, in the other cases;
(b) 其他情況下，指由持有人選定且該主管機關(guān)同意擔(dān)任此角色的成員國主管機關(guān)；若成員國主管機關(guān)均不同意擔(dān)任，則指由歐盟理事會指令 2001/83/EC 第二十七條所述協(xié)調(diào)小組選定的主管機關(guān)。
'Relevant authority' means:
相關(guān)主管機關(guān)：指
(a) the competent authority of each Member State concerned;
(a) 各相關(guān)成員國的主管機關(guān)；
(b) in the case of centralised marketing authorisations, the Agency;
(b) 若為集中上市許可，則指歐洲藥品管理局。
'Urgent safety restriction' means an interim change in the terms of the marketing authorisation due to new information having a bearing on the safe use of the medicinal product;
緊急安全限制措施：指因出現(xiàn)與藥品安全使用相關(guān)的新信息，而對上市許可條款作出的臨時變更。
'Purely national marketing authorisation' means any marketing authorisation granted by a Member State in accordance with the acquis outside the mutual recognition or decentralised procedure and that has not been subject to a complete harmonisation following a referral procedure.
純國別上市許可：指成員國依據(jù)歐盟既有法律，通過非相互認(rèn)可程序、非分散審評程序授予，且未經(jīng)過相關(guān)協(xié)調(diào)程序?qū)崿F(xiàn)完全協(xié)調(diào)統(tǒng)一的上市許可。
Article 3
第三條
Classification of variations
變更的分類
In relation to any variation which is not an extension the classification laid down in Annex II shall apply.
對于所有不屬于許可范圍拓展的變更，其分類適用本條例附件二的規(guī)定。
A variation which is not an extension and whose classification is undetermined after application of the rules provided for in this Regulation, taking into account the guidelines referred to in Article 4(1) and, where relevant, any recommendations delivered pursuant to Article 5, shall by default be considered a minor variation of type IB.
對于不屬于許可范圍拓展的變更，在適用本條例規(guī)定、參考第四條第 1 款所述指南且酌情參考第五條所述建議后，若其分類仍無法確定，則默認(rèn)歸為 IB 類微小變更。
By way of derogation from paragraph 2, a variation which is not an extension and whose classification is undetermined after application of the rules provided for in this Regulation shall be considered a major variation of type II in the following cases:
有悖于第 2 款規(guī)定，對于不屬于許可范圍拓展的變更，在適用本條例規(guī)定后分類仍無法確定的，在下列情形下應(yīng)歸為 II 類重大變更：
(a) upon request from the holder when submitting the variation;
(a) 持有人在提交變更申請時，主動要求按 II 類重大變更申報的；
(b) where the competent authority of the reference Member State referred to in Article 28 of Directive 2001/83/EC ('the reference Member State'), in consultation with the other Member States concerned, or the Agency in the case of a centralised marketing authorisation, or the competent authority in the case of a purely national marketing authorisation, concludes, following the assessment of validity of a notification in accordance with Article 9 (1), Article 13b (1), or Article 15 (1) of this Regulation and taking into account the recommendations delivered pursuant to Article 5, that the variation may have a significant impact on the quality, safety or efficacy of the medicinal product concerned.
(b) 歐盟理事會指令 2001/83/EC 第二十八條所述參考成員國的主管機關(guān)（以下簡稱 “參考成員國主管機關(guān)”）經(jīng)與其他相關(guān)成員國主管機關(guān)協(xié)商后，或集中上市許可對應(yīng)的歐洲藥品管理局，或純國別上市許可對應(yīng)的主管機關(guān)，在依據(jù)本條例第九條第 1 款、第十三條 b 第 1 款或第十五條第 1 款對變更申報的有效性進(jìn)行評估，并參考第五條所述建議后，認(rèn)定該變更可能對相關(guān)藥品的質(zhì)量、安全性或有效性產(chǎn)生顯著影響的。
Article 4
第四條
Guidelines
指南
The Commission shall, after consulting the Member States and the Agency, draw up guidelines on the details of the various categories of variations, on the operation of the procedures laid down in Chapters II, IIa, III and IV of this Regulation, and on the documentation to be submitted pursuant to those procedures.
歐盟委員會經(jīng)與各成員國及歐洲藥品管理局協(xié)商后，應(yīng)制定指南，明確各類變更的詳細(xì)劃分標(biāo)準(zhǔn)、本條例第二章、第二章 a 節(jié)、第三章及第四章規(guī)定程序的運行細(xì)則，以及依據(jù)這些程序申報時需提交的文件要求。
The guidelines referred to in paragraph 1 shall be regularly updated.
第 1 款所述指南應(yīng)定期更新。
The Agency, in cooperation with the competent authorities of the Member States, shall report annually to the Commission on recommendations on unforeseen variations referred to in Article 5 that result in new classification of variations and provide information on necessary updates to be included in the guidelines referred to in paragraph 1.
歐洲藥品管理局應(yīng)與各成員國主管機關(guān)合作，就第五條所述的、導(dǎo)致新增變更分類的突發(fā)變更相關(guān)建議，每年向歐盟委員會提交報告，并提供需納入第 1 款所述指南的必要更新信息。
The Commission shall without undue delay consider the report and integrate new classification of variations and necessary updates to the guidelines.
歐盟委員會應(yīng)盡快審議上述報告，并將新增的變更分類及必要的更新內(nèi)容納入指南。
The Commission may publish the electronic version of the guidelines on its website. This electronic version may include new classification of variations and necessary updates to the guidelines before the regular update pursuant to paragraph 2.
歐盟委員會可在其官方網(wǎng)站發(fā)布指南的電子版。該電子版可在依據(jù)第 2 款進(jìn)行定期更新前，先行納入新增的變更分類及必要的指南更新內(nèi)容。
Article 5
第五條
Recommendation on unforeseen variations
突發(fā)變更的分類建議
Prior to the submission of a variation whose classification is not provided for in this Regulation, a holder may request a recommendation on the classification of the variation as follows:
對于本條例未明確分類的變更，持有人可在提交申請前，按以下途徑申請變更分類建議：
(a) from the Agency, where the variation refers to a marketing authorisation granted under Regulation (EC) No 726/2004;
(a) 若變更針對依據(jù)歐盟委員會條例（EC）第 726/2004 號獲批的上市許可，可向歐洲藥品管理局申請；
(b) from the competent authority of the Member State concerned, where the variation refers to a purely national marketing authorisation;
(b) 若變更針對純國別上市許可，可向相關(guān)成員國主管機關(guān)申請；
(c) from the competent authority of the reference Member State, in the other cases.
(c) 其他情況下，可向參考成員國主管機關(guān)申請。
Where a recommendation is requested from the Agency as set out in the first subparagraph, point (a), it shall consult the coordination group if the recommendation is expected to result in a new classification of variation.
若按前款 (a) 項規(guī)定向歐洲藥品管理局申請建議，且該建議可能產(chǎn)生新的變更分類，則歐洲藥品管理局應(yīng)征求協(xié)調(diào)小組的意見。
Where a recommendation is requested from the competent authority of the Member State concerned or of the reference Member State as set out in the first subparagraph, points (b) and (c), the relevant authority shall consult the coordination group and the Agency, if the recommendation is expected to result in a new classification of variation.
若按前款 (b) 項和 (c) 項規(guī)定向相關(guān)成員國主管機關(guān)或參考成員國主管機關(guān)申請建議，且該建議可能產(chǎn)生新的變更分類，則相關(guān)主管機關(guān)應(yīng)征求協(xié)調(diào)小組及歐洲藥品管理局的意見。
The recommendations shall be consistent with the guidelines referred to in Article 4 (1). It shall be delivered within 60 days following receipt of the request and sent to the holder, the Agency, and the coordination group.
分類建議應(yīng)與第四條第 1 款所述指南保持一致，且需在收到申請后 60 日內(nèi)作出，并送達(dá)持有人、歐洲藥品管理局及協(xié)調(diào)小組。
1a. Prior to the examination of a variation whose classification is not provided for in this Regulation, a competent authority of a Member State may request a recommendation on the classification of the variation to the coordination group.
1a. 對于本條例未明確分類的變更，成員國主管機關(guān)可在開展審查前，向協(xié)調(diào)小組申請變更分類建議。
The recommendation referred to in the first subparagraph shall be consistent with the guidelines referred to in Article 4 (1). It shall be delivered within 60 days following receipt of the request and sent to the holder, the Agency, and the competent authorities of all Member States.
前款所述分類建議應(yīng)與第四條第 1 款所述指南保持一致，且需在收到申請后 60 日內(nèi)作出，并送達(dá)持有人、歐洲藥品管理局及所有成員國主管機關(guān)。
The Agency and the two coordination groups referred to in paragraph 1 shall cooperate to ensure the coherence of the recommendations delivered in accordance with that paragraph and publish those recommendations after deletion of all information of commercial confidential nature.
歐洲藥品管理局及第 1 款所述的兩個協(xié)調(diào)小組應(yīng)開展合作，確保依據(jù)該款作出的分類建議具有一致性，并在刪除所有商業(yè)保密信息后公布這些建議。
The recommendation referred to in paragraph 1 that results in a new classification of variation shall be regularly integrated in the guidelines referred to in Article 4(1) in accordance with Article 4(2), third subparagraph.
依據(jù)第 1 款作出且產(chǎn)生新變更分類的建議，應(yīng)按照第四條第 2 款第三項的規(guī)定，定期納入第四條第 1 款所述指南。
Article 6
第六條
Variations leading to the revision of product information
涉及藥品信息修訂的變更
Where a variation leads to the revision of the summary of product characteristics, labelling or package leaflet, this revision shall be considered as part of that variation.
若某一變更導(dǎo)致藥品特性概要、標(biāo)簽或說明書需要修訂，則該修訂應(yīng)視為該變更的組成部分。
Article 6a
第六條 a
Additional regulatory tools
補充監(jiān)管工具
For certain changes to the chemical, pharmaceutical and biological information for a medicinal product a holder may rely on a range of process parameters, quality attributes, protocols or summary documents, upon agreement of the relevant authority and subject to the conditions referred to in the Annexes and the guidelines referred to in Article 4 (1) with regard to the specific regulatory tool.
針對藥品化學(xué)、藥學(xué)及生物學(xué)信息的特定變更，上市許可持有人可依據(jù)一系列工藝參數(shù)、質(zhì)量屬性、試驗方案或匯總文件實施變更，但需獲得相關(guān)主管機關(guān)同意，且需符合本條例附件及第四條第 1 款所述指南中關(guān)于該特定監(jiān)管工具的相關(guān)條件。
Article 7
第七條
Grouping of variations
變更的合并申報
Where several variations are notified or applied for, a separate notification or application in accordance with Chapters II, III, or Article 19 as appropriate shall be submitted in respect of each variation sought.
若同時申報多項變更，應(yīng)根據(jù)實際情況分別依據(jù)本條例第二章、第三章或第十九條的規(guī)定，就每項擬申報的變更單獨提交申報材料。
By way of derogation from paragraph 1, the following shall apply:
有悖于第 1 款規(guī)定，下列情形適用合并申報規(guī)則：
(a) where minor variations of type IA to the terms of the same marketing authorisation are notified at the same time, a single notification as referred to in Article 8 or 14 may cover all such variations;
(a) 若針對同一上市許可同時申報多項 IA 類微小變更，可依據(jù)第八條或第十四條的規(guī)定，提交一份申報材料涵蓋所有此類變更；
(b) where several variations to the terms of the same marketing authorisation are submitted at the same time, a single submission may cover all such variations provided that the variations concerned fall within one of the cases listed in Annex III;
(b) 若針對同一上市許可同時申報多項變更，且相關(guān)變更均屬于本條例附件三所列情形之一，則可提交一份申報材料涵蓋所有此類變更；
(c) where several variations to the terms of the same marketing authorisation are submitted at the same time and the variations do not fall within one of the cases listed in Annex III, a single submission may cover all such variations provided that the competent authority of the reference Member State in consultation with the competent authorities of the Member States concerned or, in the case of a centralised marketing authorisation, the Agency agrees to such single submission.
(c) 若針對同一上市許可同時申報多項變更，且相關(guān)變更不屬于本條例附件三所列情形，經(jīng)參考成員國主管機關(guān)與其他相關(guān)成員國主管機關(guān)協(xié)商同意，或?qū)τ诩猩鲜性S可經(jīng)歐洲藥品管理局同意，可提交一份申報材料涵蓋所有此類變更。
The submission referred to in subparagraphs (b) and (c) shall be made simultaneously to all relevant authorities by means of the following:
前述 (b) 項和 (c) 項所述的合并申報材料，應(yīng)通過以下方式同時提交至所有相關(guān)主管機關(guān)：
(i) a single notification in accordance with Article 9 or 15 where at least one of the variations is a minor variation of type IB and the remaining variations are minor variations;
(i) 若變更中至少包含一項 IB 類微小變更，其余均為微小變更，依據(jù)第九條或第十五條提交一份申報材料；
(ii) a single application in accordance with Article 10 or 16 where at least one of the variations is a major variation of type II and none of the variations is an extension;
(ii) 若變更中至少包含一項 II 類重大變更，且無任何變更屬于許可范圍拓展，依據(jù)第十條或第十六條提交一份申報材料；
(iii) a single application in accordance with Article 19 where at least one of the variations is an extension.
(iii) 若變更中至少包含一項許可范圍拓展，依據(jù)第十九條提交一份申報材料。
Article 7a
第七條 a
Super-grouping of variations
變更的超合并申報
By way of derogation from Articles 7 and 13d, the holder may submit a single notification of variations to the terms of more than one marketing authorisation referred to in Chapters II, IIa and III owned by the same holder where the same or several minor variations of type IA referred to in Article 8, Article 13a or Article 14 are notified at the same time and fall within one of the cases of super-grouping of variations listed in the guidelines referred to in Article 4(1) (‘super-grouping’).
有悖于第七條和第十三條 d 的規(guī)定，若上市許可持有人針對其持有的、屬于本條例第二章、第二章 a 節(jié)及第三章管轄范圍內(nèi)的多項上市許可，同時申報一項或多項符合第八條、第十三條 a 或第十四條規(guī)定的 IA 類微小變更，且相關(guān)變更屬于第四條第 1 款所述指南所列的超合并申報情形之一，則可提交一份申報材料涵蓋所有相關(guān)變更（下稱 “超合并申報”）。
A single notification as referred to in paragraph 1 shall be made simultaneously to the reference authority and all relevant authorities.
第 1 款所述的超合并申報材料，應(yīng)同時提交至參考主管機關(guān)及所有相關(guān)主管機關(guān)。
CHAPTER II
第二章
VARIATIONS TO MARKETING AUTHORISATIONS GRANTED IN ACCORDANCE WITH CHAPTER 4 OF DIRECTIVE 2001/83/EC
依據(jù) 2001/83/EC 號指令第四章獲批的上市許可之變更
Article 8
第八條
Notification procedure for minor variations of type IA
IA 類微小變更的申報程序
Where a minor variation of type IA is made, the holder shall submit simultaneously to all relevant authorities a notification containing the elements listed in Annex IV. That notification shall be submitted within 12 months following the implementation of the variation as an annual update for all minor variations of type IA or be submitted as part of grouping of variations in accordance with Article 7(2), first subparagraph, points (b) and (c), or as part of super-grouping of variations in accordance with Article 7a.
實施 IA 類微小變更的，上市許可持有人應(yīng)向所有相關(guān)主管機關(guān)同時提交申報材料，材料內(nèi)容需包含本條例附件四所列要素。該申報材料可作為所有 IA 類微小變更的年度更新文件，在變更實施后 12 個月內(nèi)提交；或依據(jù)第七條第 2 款第 1 項 (b) 目和 (c) 目規(guī)定，作為合并申報的組成部分提交；或依據(jù)第七條 a 規(guī)定，作為超合并申報的組成部分提交。
The notification shall be submitted immediately after the implementation of the variation in the case of minor variations requiring immediate notification for the continuous supervision of the medicinal product concerned.
對于為實現(xiàn)藥品持續(xù)監(jiān)管而需即時申報的微小變更，應(yīng)在變更實施后立即提交申報材料。
By way of derogation from the first subparagraph, in justified cases, the competent authority of the reference Member State may accept the immediate submission of the notification after the implementation of the variation.
有悖于本條第 1 款的規(guī)定，在具備正當(dāng)理由的情形下，參考成員國主管機關(guān)可同意持有人在變更實施后立即提交申報材料。
Within 30 days following receipt of the notification, the measures provided for in Article 11 shall be taken.
相關(guān)主管機關(guān)應(yīng)在收到申報材料后 30 日內(nèi)，采取第十一條規(guī)定的相關(guān)措施。
Article 9
第九條
Notification procedure for minor variations of type IB
IB 類微小變更的申報程序
The holder shall submit simultaneously to all relevant authorities a notification containing the elements listed in Annex IV.
上市許可持有人應(yīng)向所有相關(guān)主管機關(guān)同時提交申報材料，材料內(nèi)容需包含本條例附件四所列要素。
If the notification fulfils the requirement laid down in the first subparagraph, the competent authority of the reference Member State shall, after consulting the other Member States concerned, acknowledge receipt of a valid notification.
若申報材料符合前款規(guī)定的要求，參考成員國主管機關(guān)經(jīng)與其他相關(guān)成員國主管機關(guān)協(xié)商后，應(yīng)出具有效申報材料的接收回執(zhí)。
If within 30 days following the acknowledgement of receipt of a valid notification, the competent authority of the reference Member State has not sent the holder an unfavourable opinion, the notification shall be deemed accepted by all relevant authorities.
若參考成員國主管機關(guān)在出具有效申報材料接收回執(zhí)后 30 日內(nèi)，未向持有人發(fā)出負(fù)面意見，則該申報材料視為已獲所有相關(guān)主管機關(guān)認(rèn)可。
Where the notification is accepted by the competent authority of the reference Member State, the measures provided for in Article 11 shall be taken.
若申報材料獲參考成員國主管機關(guān)認(rèn)可，應(yīng)采取第十一條規(guī)定的相關(guān)措施。
Where the competent authority of the reference Member State is of the opinion that the notification cannot be accepted, it shall inform the holder and the other relevant authorities, stating the grounds on which its unfavourable opinion is based.
若參考成員國主管機關(guān)認(rèn)為申報材料不可接受，應(yīng)書面通知持有人及其他相關(guān)主管機關(guān)，并闡明作出負(fù)面意見的依據(jù)。
Within 30 days following the receipt of the unfavourable opinion, the holder may submit to all relevant authorities an amended notification in order to take due account of the grounds laid down in that opinion.
持有人可在收到負(fù)面意見后 30 日內(nèi)，針對意見中提出的問題修訂申報材料，并提交至所有相關(guān)主管機關(guān)。
If the holder does not amend the notification in accordance with the second subparagraph, the notification shall be deemed rejected by all relevant authorities and the measures provided for in Article 11 shall be taken.
若持有人未按前款規(guī)定修訂申報材料，則該申報材料視為已被所有相關(guān)主管機關(guān)駁回，并應(yīng)采取第十一條規(guī)定的相關(guān)措施。
Where an amended notification has been submitted, the competent authority of the reference Member State shall assess it within 30 days following its receipt and the measures provided for in Article 11 shall be taken.
若持有人提交了修訂后的申報材料，參考成員國主管機關(guān)應(yīng)在收到材料后 30 日內(nèi)完成評估，并采取第十一條規(guī)定的相關(guān)措施。
This Article shall not apply where a type IB variation request is submitted in a grouping that includes a variation type II and does not contain an extension. In such case, the prior approval procedure in Article 10 shall apply.
若 IB 類變更與 II 類變更合并申報，且申報內(nèi)容不包含許可范圍拓展，則不適用本條規(guī)定，應(yīng)遵循第十條規(guī)定的預(yù)先批準(zhǔn)程序。
This Article shall not apply where a type IB variation request is submitted in a grouping that includes an extension. In such case, the procedure in Article 19 shall apply.
若 IB 類變更與許可范圍拓展合并申報，則不適用本條規(guī)定，應(yīng)遵循第十九條規(guī)定的程序。
Article 10
第十條
'Prior Approval' procedure for major variations of type II
II 類重大變更的預(yù)先批準(zhǔn)程序
The holder shall submit simultaneously to all relevant authorities an application containing the elements listed in Annex IV.
上市許可持有人應(yīng)向所有相關(guān)主管機關(guān)同時提交申請材料，材料內(nèi)容需包含本條例附件四所列要素。
If the application fulfils the requirements laid down in the first subparagraph, the competent authority of the reference Member State shall acknowledge receipt of a valid application and inform the holder and the other relevant authorities that the procedure starts from the date of such acknowledgement.
若申請材料符合前款規(guī)定的要求，參考成員國主管機關(guān)應(yīng)出具有效申請材料的接收回執(zhí)，并通知持有人及其他相關(guān)主管機關(guān)，程序自回執(zhí)出具之日起正式啟動。
Within 60 days following the acknowledgement of receipt of a valid application, the competent authority of the reference Member State shall prepare an assessment report and a decision on the application, which shall be communicated to the other relevant authorities.
參考成員國主管機關(guān)應(yīng)在出具有效申請材料接收回執(zhí)后 60 日內(nèi)，編制評估報告并作出審批決定，同時將評估報告和決定通報其他相關(guān)主管機關(guān)。
The competent authority of the reference Member State may reduce the period referred to in the first subparagraph, having regard to the urgency of the matter, or may extend it to 90 days for variations listed in Annex V or for grouping of variations in accordance with Article 7 (2), first subparagraph, point (c).
針對本條例附件五所列變更，或依據(jù)第七條第 2 款第 1 項 (c) 目規(guī)定合并申報的變更，參考成員國主管機關(guān)可根據(jù)事項的緊急程度縮短前款所述期限，或延長至 90 日。
Within the period referred to in paragraph 2, the competent authority of the reference Member State may request the holder to provide supplementary information within a time limit set by that competent authority. In this case:
在第 2 款所述的期限內(nèi)，參考成員國主管機關(guān)可要求持有人在其指定的期限內(nèi)補充相關(guān)信息。出現(xiàn)該情形時：
(a) the competent authority of the reference Member State shall inform the other competent authorities concerned of its request for supplementary information;
(a) 參考成員國主管機關(guān)應(yīng)將補充信息的要求通報其他相關(guān)主管機關(guān)；
(b) the procedure shall be suspended until such supplementary information has been provided;
(b) 審批程序自提出補充信息要求之日起暫停，直至收到補充信息為止；
(c) the competent authority of the reference Member State may extend the period referred to in paragraph 2.
(c) 參考成員國主管機關(guān)可相應(yīng)延長第 2 款所述的審批期限。
Without prejudice to Article 13 and within 30 days following receipt of the decision and of the assessment report referred to in paragraph 2, the relevant authorities shall recognise the decision and inform the competent authority of the reference Member State accordingly.
在不影響第十三條規(guī)定的前提下，相關(guān)主管機關(guān)應(yīng)在收到第 2 款所述的審批決定和評估報告后 30 日內(nèi)，對該決定予以認(rèn)可，并將認(rèn)可情況通報參考成員國主管機關(guān)。
If, within the period referred to in the first subparagraph, a relevant authority has not expressed its disagreement in accordance with Article 13, the decision shall be deemed recognised by that relevant authority.
若相關(guān)主管機關(guān)未在前款所述期限內(nèi)依據(jù)第十三條規(guī)定提出異議，則視為該主管機關(guān)已認(rèn)可該審批決定。
Where the decision referred to in paragraph 2 has been recognised by all relevant authorities in accordance with paragraph 4, the measures provided for in Article 11 shall be taken.
若第 2 款所述的審批決定依據(jù)第 4 款規(guī)定獲得所有相關(guān)主管機關(guān)認(rèn)可，應(yīng)采取第十一條規(guī)定的相關(guān)措施。
This Article shall not apply where a type II variation request is submitted in a grouping that includes an extension. In such case, the procedure in Article 19 shall apply.
若 II 類變更與許可范圍拓展合并申報，則不適用本條規(guī)定，應(yīng)遵循第十九條規(guī)定的程序。
Article 11
第十一條
Measures to close the procedures of Articles 8 to 10
終止第八條至第十條相關(guān)程序的措施
Where reference is made to this Article, the competent authority of the reference Member State shall take the following measures:
凡援引本條規(guī)定時，參考成員國主管機關(guān)應(yīng)采取以下措施：
(a) it shall inform the holder and the other relevant authorities as to whether the variation is accepted or rejected;
(a) 通知上市許可持有人及其他相關(guān)主管機關(guān)該變更申請是否獲批；
(b) where the variation is rejected, it shall inform the holder and the other relevant authorities of the grounds for the rejection;
(b) 若變更申請被駁回，需向上市許可持有人及其他相關(guān)主管機關(guān)說明駁回理由；
(c) it shall inform the holder and the other relevant authorities as to whether the variation requires any amendment to the decision granting the marketing authorisation.
(c) 通知上市許可持有人及其他相關(guān)主管機關(guān)，該變更是否需要對上市許可的批準(zhǔn)決定作出相應(yīng)修訂。
Where reference is made to this Article, each relevant authority shall, where necessary and within the time limit laid down in paragraph 1 of Article 23, amend the decision granting the marketing authorisation in accordance with the accepted variation.
凡援引本條規(guī)定時，各相關(guān)主管機關(guān)應(yīng)在必要情況下，于第二十三條第 1 款規(guī)定的期限內(nèi)，根據(jù)獲批的變更內(nèi)容修訂上市許可的批準(zhǔn)決定。
Article 12
第十二條
Human influenza vaccines
人用流感疫苗
By way of derogation from Article 10, the procedure laid down in paragraphs 2 to 5 shall apply to the examination of variations concerning changes to the active substance for the purposes of the annual update of a human influenza vaccine.
有悖于第十條的規(guī)定，針對人用流感疫苗年度更新所需的活性成分變更審查，適用本條第 2 款至第 5 款規(guī)定的程序。
The holder shall submit simultaneously to all relevant authorities an application containing the elements listed in Annex IV.
上市許可持有人應(yīng)向所有相關(guān)主管機關(guān)同時提交申請材料，材料內(nèi)容需包含本條例附件四所列要素。
If the application fulfils the requirements laid down in the first subparagraph, the competent authority of the reference Member State shall acknowledge receipt of a valid application and inform the holder and the other relevant authorities that the procedure starts from the date of such acknowledgement.
若申請材料符合前款規(guī)定的要求，參考成員國主管機關(guān)應(yīng)出具有效申請材料的接收回執(zhí)，并通知持有人及其他相關(guān)主管機關(guān)，程序自回執(zhí)出具之日起正式啟動。
The competent authority of the reference Member State shall assess the application submitted. Where deemed necessary, the competent authority of the reference Member State may request additional data to the holder in order to complete its assessment.
參考成員國主管機關(guān)應(yīng)對提交的申請材料進(jìn)行評估。如認(rèn)為有必要，可要求持有人補充相關(guān)數(shù)據(jù)，以完成評估工作。
The competent authority shall prepare a decision and an assessment report within 45 days from the receipt of a valid application.
參考成員國主管機關(guān)應(yīng)在收到有效申請材料后 45 日內(nèi)，作出審批決定并編制評估報告。
The 45-day period referred to in the first subparagraph shall be suspended from the moment when the additional data referred to in paragraph 3 is requested until the data is submitted.
前款所述的 45 日期限，自提出第 3 款所述的補充數(shù)據(jù)要求之日起暫停計算，直至收到補充數(shù)據(jù)為止。
Within 12 days from the receipt of the decision and the assessment report of the competent authority of the reference Member State, the relevant authorities shall adopt a decision accordingly and inform the competent authority of the reference Member State and the holder thereof.
相關(guān)主管機關(guān)應(yīng)在收到參考成員國主管機關(guān)的審批決定及評估報告后 12 日內(nèi)，作出相應(yīng)決定，并將該決定通報參考成員國主管機關(guān)及上市許可持有人。
Article 13
第十三條
Coordination group and arbitration
協(xié)調(diào)小組與仲裁
Where recognition of a decision in accordance with Article 10(4) or approval of an opinion in accordance with Article 20(8), point (b), is not possible on grounds of a potential serious risk to public health, a relevant authority shall request that the matter of disagreement be forthwith referred to the coordination group.
若因存在潛在的重大公共健康風(fēng)險，相關(guān)主管機關(guān)無法依據(jù)第十條第 4 款認(rèn)可某項決定，或無法依據(jù)第二十條第 8 款 (b) 項批準(zhǔn)某項意見，則應(yīng)要求立即將爭議事項提交協(xié)調(diào)小組處理。
The party in disagreement shall give a detailed statement of the reasons for its position to all Member States concerned and to the holder.
提出異議的主管機關(guān)應(yīng)向所有相關(guān)成員國及上市許可持有人詳細(xì)說明其持異議的理由。
Article 29(3), (4) and (5) of Directive 2001/83/EC shall apply to the matter of disagreement referred to in paragraph 1.
歐盟理事會指令 2001/83/EC 第二十九條第 3 款、第 4 款及第 5 款的規(guī)定，適用于第 1 款所述的爭議事項。
CHAPTER IIa
第二章 a 節(jié)
VARIATIONS TO PURELY NATIONAL MARKETING AUTHORISATIONS
純國別上市許可的變更
Article 13a
第十三條 a
Notification procedure for minor variations of type IA
IA 類微小變更的申報程序
Where a minor variation of type IA is made, the holder shall submit to the competent authority a notification containing the elements listed in Annex IV. This notification shall be submitted within 12 months following the implementation of the variation as an annual update for all minor variations of type IA or be submitted as part of grouping in accordance with Article 13d(2), first subparagraph, points (b) and (c), or as part of super-grouping of variations in accordance with Article 7a.
實施 IA 類微小變更的，上市許可持有人應(yīng)向成員國主管機關(guān)提交申報材料，材料內(nèi)容需包含本條例附件四所列要素。該申報材料可作為所有 IA 類微小變更的年度更新文件，在變更實施后 12 個月內(nèi)提交；或依據(jù)第十三條 d 第 2 款第 1 項 (b) 目和 (c) 目規(guī)定，作為合并申報的組成部分提交；或依據(jù)第七條 a 規(guī)定，作為超合并申報的組成部分提交。
The notification shall be submitted immediately after the implementation of the variation in the case of minor variations requiring immediate notification for the continuous supervision of the medicinal product concerned.
對于為實現(xiàn)藥品持續(xù)監(jiān)管而需即時申報的微小變更，應(yīng)在變更實施后立即提交申報材料。
By way of derogation from the first subparagraph, in justified cases, the competent authority of the Member State may accept the immediate submission of the notification after the implementation of the variation.
有悖于本條第 1 款的規(guī)定，在具備正當(dāng)理由的情形下，成員國主管機關(guān)可同意持有人在變更實施后立即提交申報材料。
Within 30 days following receipt of the notification, the measures provided for in Article 13e shall be taken.
成員國主管機關(guān)應(yīng)在收到申報材料后 30 日內(nèi)，采取第十三條 e 規(guī)定的相關(guān)措施。
Article 13b
第十三條 b
Notification procedure for minor variations of type IB
IB 類微小變更的申報程序
The holder shall submit to the competent authority a notification containing the elements listed in Annex IV.
上市許可持有人應(yīng)向成員國主管機關(guān)提交申報材料，材料內(nèi)容需包含本條例附件四所列要素。
If the notification fulfils the requirement laid down in the first subparagraph, the competent authority shall acknowledge receipt of a valid notification.
若申報材料符合前款規(guī)定的要求，成員國主管機關(guān)應(yīng)出具有效申報材料的接收回執(zhí)。
If within 30 days following the acknowledgement of receipt of a valid notification, the competent authority has not sent the holder an unfavourable opinion, the notification shall be deemed accepted by the competent authority.
若成員國主管機關(guān)在出具有效申報材料接收回執(zhí)后 30 日內(nèi)，未向持有人發(fā)出負(fù)面意見，則該申報材料視為已獲主管機關(guān)認(rèn)可。
Where the notification is accepted by the competent authority, the measures provided for in Article 13e shall be taken.
若申報材料獲成員國主管機關(guān)認(rèn)可，應(yīng)采取第十三條 e 規(guī)定的相關(guān)措施。
Where the competent authority is of the opinion that the notification cannot be accepted, it shall inform the holder, stating the grounds on which its unfavourable opinion is based.
若成員國主管機關(guān)認(rèn)為申報材料不可接受，應(yīng)書面通知持有人，并闡明作出負(fù)面意見的依據(jù)。
Within 30 days following the receipt of the unfavourable opinion, the holder may submit to the competent authority an amended notification in order to take due account of the grounds laid down in that opinion.
持有人可在收到負(fù)面意見后 30 日內(nèi)，針對意見中提出的問題修訂申報材料，并提交至成員國主管機關(guān)。
If the holder does not amend the notification in accordance with the second subparagraph, the notification shall be deemed rejected.
若持有人未按前款規(guī)定修訂申報材料，則該申報材料視為已被主管機關(guān)駁回。
Where an amended notification has been submitted, the competent authority shall assess it within 30 days following its receipt and the measures provided for in Article 13e shall be taken.
若持有人提交了修訂后的申報材料，成員國主管機關(guān)應(yīng)在收到材料后 30 日內(nèi)完成評估，并采取第十三條 e 規(guī)定的相關(guān)措施。
This Article shall not apply where a type IB variation request is submitted in a grouping that includes a variation type II and does not contain an extension. In such case, the prior approval procedure in Article 13c shall apply.
若 IB 類變更與 II 類變更合并申報，且申報內(nèi)容不包含許可范圍拓展，則不適用本條規(guī)定，應(yīng)遵循第十三條 c 規(guī)定的預(yù)先批準(zhǔn)程序。
This Article shall not apply where a type IB variation request is submitted in a grouping that includes an extension. In such case, the procedure in Article 19 shall apply.
若 IB 類變更與許可范圍拓展合并申報，則不適用本條規(guī)定，應(yīng)遵循第十九條規(guī)定的程序。
Article 13c
第十三條 c
'Prior Approval' procedure for major variations of type II
II 類重大變更的預(yù)先批準(zhǔn)程序
The holder shall submit to the competent authority an application containing the elements listed in Annex IV.
上市許可持有人應(yīng)向成員國主管機關(guān)提交申請材料，材料內(nèi)容需包含本條例附件四所列要素。
If the application fulfils the requirements laid down in the first subparagraph, the competent authority shall acknowledge receipt of a valid application.
若申請材料符合前款規(guī)定的要求，成員國主管機關(guān)應(yīng)出具有效申請材料的接收回執(zhí)。
Within 60 days following the acknowledgement of receipt of a valid application, the competent authority shall conclude the assessment.
成員國主管機關(guān)應(yīng)在出具有效申請材料接收回執(zhí)后 60 日內(nèi)，完成評估工作。
The competent authority may reduce the period referred to in the first subparagraph, having regard to the urgency of the matter, or may extend it to 90 days for variations listed in Annex V or for grouping of variations in accordance with Article 13d (2), first subparagraph, point (c).
針對本條例附件五所列變更，或依據(jù)第十三條 d 第 2 款第 1 項 (c) 目規(guī)定合并申報的變更，成員國主管機關(guān)可根據(jù)事項的緊急程度縮短前款所述期限，或延長至 90 日。
Within the periods referred to in paragraph 2, the competent authority may request the holder to provide supplementary information within a time limit set by the competent authority. In this case the procedure shall be suspended until such supplementary information has been provided and the competent authority may extend the period referred to in paragraph 2.
在第 2 款所述的期限內(nèi)，成員國主管機關(guān)可要求持有人在其指定的期限內(nèi)補充相關(guān)信息。出現(xiàn)該情形時，審批程序自提出補充信息要求之日起暫停，直至收到補充信息為止，且主管機關(guān)可相應(yīng)延長第 2 款所述的審批期限。
Within 30 days after the conclusion of the assessment, the measures provided for in Article 13e shall be taken.
評估工作完成后 30 日內(nèi)，應(yīng)采取第十三條 e 規(guī)定的相關(guān)措施。
This Article shall not apply where a type II variation request is submitted in a grouping that includes an extension. In such case, the procedure in Article 19 shall apply.
若 II 類變更與許可范圍拓展合并申報，則不適用本條規(guī)定，應(yīng)遵循第十九條規(guī)定的程序。
Article 13d
第十三條 d
Grouping of variations to purely national marketing authorisations
純國別上市許可的變更合并申報
Where several variations are notified or applied for, a separate notification or application in accordance with Articles 13a, 13b, 13c, or 19 as appropriate shall be submitted to the competent authority in respect of each variation sought.
若同時申報多項變更，應(yīng)根據(jù)實際情況分別依據(jù)第十三條 a、第十三條 b、第十三條 c 或第十九條的規(guī)定，就每項擬申報的變更單獨向成員國主管機關(guān)提交申報材料。
By way of derogation from paragraph 1 the following shall apply:
有悖于第 1 款規(guī)定，下列情形適用合并申報規(guī)則：
(a) where the same minor variation (s) of type IA to the terms of one or more marketing authorisations owned by the same holder are notified at the same time to the same competent authority, a single notification as referred to in Article 13a may cover all such variations;
(a) 若同一持有人針對其持有的一項或多項上市許可，向同一成員國主管機關(guān)同時申報相同的 IA 類微小變更，可依據(jù)第十三條 a 的規(guī)定，提交一份申報材料涵蓋所有此類變更；
(b) where several variations to the terms of the same marketing authorisation are submitted at the same time to the same competent authority, a single submission may cover all such variations provided that the variations concerned fall within one of the cases listed in Annex III;
(b) 若針對同一上市許可，向同一成員國主管機關(guān)同時申報多項變更，且相關(guān)變更均屬于本條例附件三所列情形之一，則可提交一份申報材料涵蓋所有此類變更；
(c) where the same variation (s) to the terms of one or more marketing authorisations owned by the same holder are submitted at the same time to the same competent authority and they are not covered under subparagraph (a) or (b), a single submission may cover all such variations provided that the competent authority agrees to such single submission.
(c) 若同一持有人針對其持有的一項或多項上市許可，向同一成員國主管機關(guān)同時申報相同的變更，且相關(guān)變更不屬于 (a) 項或 (b) 項所述情形，經(jīng)成員國主管機關(guān)同意，可提交一份申報材料涵蓋所有此類變更。
The submission referred to in points (b) and (c) shall be made by means of the following:
前述 (b) 項和 (c) 項所述的合并申報材料，應(yīng)通過以下方式提交：
(i) a single notification in accordance with Article 13b where at least one of the variations is a minor variation of type IB and the remaining variations are minor variations;
(i) 若變更中至少包含一項 IB 類微小變更，其余均為微小變更，依據(jù)第十三條 b 提交一份申報材料；
(ii) a single application in accordance with Article 13c where at least one of the variations is a major variation of type II and none of the variations is an extension;
(ii) 若變更中至少包含一項 II 類重大變更，且無任何變更屬于許可范圍拓展，依據(jù)第十三條 c 提交一份申報材料；
(iii) a single application in accordance with Article 19 where at least one of the variations is an extension.
(iii) 若變更中至少包含一項許可范圍拓展，依據(jù)第十九條提交一份申報材料。
Article 13e
第十三條 e
Measures to close the procedures of Articles 13a to 13c
終止第十三條 a 至第十三條 c 相關(guān)程序的措施
Where reference is made to this Article, the competent authority shall take the following measures:
凡援引本條規(guī)定時，成員國主管機關(guān)應(yīng)采取以下措施：
(a) it shall inform the holder as to whether the variation is accepted or rejected;
(a) 通知上市許可持有人該變更申請是否獲批；
(b) where the variation is rejected, it shall inform the holder of the grounds for the rejection;
(b) 若變更申請被駁回，需向上市許可持有人說明駁回理由；
(c) where necessary, it shall amend the decision granting the marketing authorisation in accordance with the accepted variation within the time limit laid down in paragraph 1 of Article 23.
(c) 必要情況下，于第二十三條第 1 款規(guī)定的期限內(nèi)，根據(jù)獲批的變更內(nèi)容修訂上市許可的批準(zhǔn)決定。
Article 13f
第十三條 f
Human influenza vaccines
人用流感疫苗
By way of derogation from Article 13c, the procedure laid down in paragraphs 2 to 4 shall apply to the examination of variations concerning changes to the active substance for the purposes of the annual update of a human influenza vaccine.
有悖于第十三條 c 的規(guī)定，針對人用流感疫苗年度更新所需的活性成分變更審查，適用本條第 2 款至第 4 款規(guī)定的程序。
The holder shall submit to the competent authority an application containing the elements listed in Annex IV.
上市許可持有人應(yīng)向成員國主管機關(guān)提交申請材料，材料內(nèi)容需包含本條例附件四所列要素。
If the application fulfils the requirements laid down in the first subparagraph, the competent authority shall acknowledge receipt of a valid application.
若申請材料符合前款規(guī)定的要求，成員國主管機關(guān)應(yīng)出具有效申請材料的接收回執(zhí)。
The competent authority shall assess the application submitted. Where deemed necessary, the competent authority may request additional data to the holder in order to complete its assessment.
成員國主管機關(guān)應(yīng)對提交的申請材料進(jìn)行評估。如認(rèn)為有必要，可要求持有人補充相關(guān)數(shù)據(jù)，以完成評估工作。
The competent authority shall adopt a decision within 45 days from the receipt of a valid application and shall take the measures provided for in Article 13e.
成員國主管機關(guān)應(yīng)在收到有效申請材料后 45 日內(nèi)作出審批決定，并采取第十三條 e 規(guī)定的相關(guān)措施。
The 45-day period referred to in the first subparagraph shall be suspended from the moment when the additional data referred to in paragraph 3 is requested until the data is submitted.
前款所述的 45 日期限，自提出第 3 款所述的補充數(shù)據(jù)要求之日起暫停計算，直至收到補充數(shù)據(jù)為止。
CHAPTER III
第三章
VARIATIONS TO CENTRALISED MARKETING AUTHORISATIONS
集中上市許可的變更
Article 14
第十四條
Notification procedure for minor variations of type IA
IA 類微小變更的申報程序
Where a minor variation of type IA is made, the holder shall submit to the Agency a notification containing the elements listed in Annex IV. This notification shall be submitted within 12 months following implementation of the variation as an annual update for all minor variations of type IA or be submitted as part of grouping in accordance with Article 7(2), first subparagraph, points (b) and (c), or as part of super-grouping of variations in accordance with Article 7a.
實施 IA 類微小變更的，上市許可持有人應(yīng)向歐洲藥品管理局提交申報材料，材料內(nèi)容需包含本條例附件四所列要素。該申報材料可作為所有 IA 類微小變更的年度更新文件，在變更實施后 12 個月內(nèi)提交；或依據(jù)第七條第 2 款第 1 項 (b) 目和 (c) 目規(guī)定，作為合并申報的組成部分提交；或依據(jù)第七條 a 規(guī)定，作為超合并申報的組成部分提交。
The notification shall be submitted immediately after the implementation of the variation in the case of minor variations requiring immediate notification for the continuous supervision of the medicinal product concerned.
對于為實現(xiàn)藥品持續(xù)監(jiān)管而需即時申報的微小變更，應(yīng)在變更實施后立即提交申報材料。
By way of derogation from the first subparagraph, in justified cases, the Agency may accept the immediate submission of the notification of the variation.
有悖于本條第 1 款的規(guī)定，在具備正當(dāng)理由的情形下，歐洲藥品管理局可同意持有人在變更實施后立即提交申報材料。
Within 30 days following receipt of the notification, the measures provided for in Article 17 shall be taken.
歐洲藥品管理局應(yīng)在收到申報材料后 30 日內(nèi)，采取第十七條規(guī)定的相關(guān)措施。
Article 15
第十五條
Notification procedure for minor variations of type IB
IB 類微小變更的申報程序
The holder shall submit to the Agency a notification containing the elements listed in Annex IV.
上市許可持有人應(yīng)向歐洲藥品管理局提交申報材料，材料內(nèi)容需包含本條例附件四所列要素。
If the notification fulfils the requirement laid down in the first subparagraph, the Agency shall acknowledge receipt of a valid notification.
若申報材料符合前款規(guī)定的要求，歐洲藥品管理局應(yīng)出具有效申報材料的接收回執(zhí)。
If within 30 days following the acknowledgement of receipt of a valid notification the Agency has not sent the holder an unfavourable opinion, its opinion shall be deemed favourable.
若歐洲藥品管理局在出具有效申報材料接收回執(zhí)后 30 日內(nèi)，未向持有人發(fā)出負(fù)面意見，則視為其出具了正面意見。
Where the opinion of the Agency on the notification is favourable, the measures provided for in Article 17 shall be taken.
若歐洲藥品管理局對申報材料出具正面意見，應(yīng)采取第十七條規(guī)定的相關(guān)措施。
Where the Agency is of the opinion that the notification cannot be accepted, it shall inform the holder, stating the grounds on which its unfavourable opinion is based.
若歐洲藥品管理局認(rèn)為申報材料不可接受，應(yīng)書面通知持有人，并闡明作出負(fù)面意見的依據(jù)。
Within 30 days of receipt of the unfavourable opinion, the holder may submit to the Agency an amended notification in order to take due account of the grounds laid down in that opinion.
持有人可在收到負(fù)面意見后 30 日內(nèi)，針對意見中提出的問題修訂申報材料，并提交至歐洲藥品管理局。
Where an amended notification has been submitted, the Agency shall assess it within 30 days following its receipt and the measures provided for in Article 17 shall be taken.
若持有人提交了修訂后的申報材料，歐洲藥品管理局應(yīng)在收到材料后 30 日內(nèi)完成評估，并采取第十七條規(guī)定的相關(guān)措施。
This Article shall not apply where a type IB variation request is submitted in a grouping that includes a variation type II and does not contain an extension. In such case, the prior approval procedure in Article 16 shall apply.
若 IB 類變更與 II 類變更合并申報，且申報內(nèi)容不包含許可范圍拓展，則不適用本條規(guī)定，應(yīng)遵循第十六條規(guī)定的預(yù)先批準(zhǔn)程序。
This Article shall not apply where a type IB variation request is submitted in a grouping that includes an extension. In such case, the procedure in Article 19 shall apply.
若 IB 類變更與許可范圍拓展合并申報，則不適用本條規(guī)定，應(yīng)遵循第十九條規(guī)定的程序。
Article 16
第十六條
'Prior Approval' procedure for major variations of type II
II 類重大變更的預(yù)先批準(zhǔn)程序
The holder shall submit to the Agency an application containing the elements listed in Annex IV.
上市許可持有人應(yīng)向歐洲藥品管理局提交申請材料，材料內(nèi)容需包含本條例附件四所列要素。
If the application fulfils the requirements laid down in the first subparagraph, the Agency shall acknowledge receipt of a valid application.
若申請材料符合前款規(guī)定的要求，歐洲藥品管理局應(yīng)出具有效申請材料的接收回執(zhí)。
The Agency shall issue an opinion on the valid application referred to in paragraph 1 within 60 days following its receipt.
歐洲藥品管理局應(yīng)在收到第 1 款所述有效申請材料后 60 日內(nèi)，出具相關(guān)意見。
The Agency may reduce the period referred to in the first subparagraph, having regard to the urgency of the matter, or may extend it to 90 days for variations listed in Annex V or for grouping of variations in accordance with Article 7 (2), first subparagraph, point (c).
針對本條例附件五所列變更，或依據(jù)第七條第 2 款第 1 項 (c) 目規(guī)定合并申報的變更，歐洲藥品管理局可根據(jù)事項的緊急程度縮短前款所述期限，或延長至 90 日。
Within the period referred to in paragraph 2, the Agency may request the holder to provide supplementary information within a time limit set by the Agency. The procedure shall be suspended until such time as the supplementary information has been provided. In this case the Agency may extend the period referred to in paragraph 2.
在第 2 款所述的期限內(nèi)，歐洲藥品管理局可要求持有人在其指定的期限內(nèi)補充相關(guān)信息。審批程序自提出補充信息要求之日起暫停，直至收到補充信息為止。出現(xiàn)該情形時，歐洲藥品管理局可相應(yīng)延長第 2 款所述的審批期限。
Article 9(1) and (2) of Regulation (EC) No 726/2004 shall apply to the opinion on the valid application.
歐盟委員會條例（EC）第 726/2004 號第九條第 1 款和第 2 款的規(guī)定，適用于針對有效申請材料出具的意見。
Within 15 days from the adoption of the final opinion on the valid application, the measures provided for in Article 17 shall be taken.
針對有效申請材料的最終意見出具后 15 日內(nèi)，應(yīng)采取第十七條規(guī)定的相關(guān)措施。
This Article shall not apply where a type II variation request is submitted in a grouping that includes an extension. In such case, the procedure in Article 19 shall apply.
若 II 類變更與許可范圍拓展合并申報，則不適用本條規(guī)定，應(yīng)遵循第十九條規(guī)定的程序。
Article 17
第十七條
Measures to close the procedures of Articles 14 to 16
終止第十四條至第十六條相關(guān)程序的措施
Where reference is made to this Article, the Agency shall take the following measures:
凡援引本條規(guī)定時，歐洲藥品管理局應(yīng)采取以下措施：
(a) it shall inform the holder of the outcome of the assessment;
(a) 通知上市許可持有人評估結(jié)果；
(b) where the variation is rejected, it shall inform the holder of the grounds for the rejection;
(b) 若變更申請被駁回，需向上市許可持有人說明駁回理由；
(c) where the outcome of the assessment is favourable and the variation affects the terms of the Commission decision granting the marketing authorisation, the Agency shall transmit to the Commission its opinion and the grounds for its opinion as well as the revised versions of the documents set out in Article 9 (4) of Regulation (EC) No 726/2004.
(c) 若評估結(jié)果為正面，且該變更將影響歐盟委員會作出的上市許可批準(zhǔn)決定條款，則歐洲藥品管理局應(yīng)向歐盟委員會提交其意見、意見依據(jù)，以及歐盟委員會條例（EC）第 726/2004 號第九條第 4 款所列文件的修訂版本。
In the cases identified under paragraph 1, point (c), the Commission, having regard to the opinion from the Agency and within the time limit provided for in Article 23(1a), shall amend where necessary the decision granting the marketing authorisation. The Union Register of Medicinal Products provided for in Article 13(1) of Regulation (EC) No 726/2004 shall be updated accordingly.
對于第 1 款 (c) 項所述情形，歐盟委員會應(yīng)參考?xì)W洲藥品管理局的意見，在第二十三條第 1a 款規(guī)定的期限內(nèi)，對上市許可批準(zhǔn)決定作出必要修訂。同時，應(yīng)相應(yīng)更新歐盟委員會條例（EC）第 726/2004 號第十三條第 1 款規(guī)定的歐盟藥品注冊簿。
Article 18
第十八條
Human influenza and human coronavirus vaccines
人用流感疫苗與人用冠狀病毒疫苗
By way of derogation from Article 16, the procedure laid down in paragraphs 2 to 6 of this Article shall apply to the examination of variations concerning changes to the active substance for the purposes of the annual update of a human influenza or human coronavirus vaccine.
有悖于第十六條的規(guī)定，針對人用流感疫苗或人用冠狀病毒疫苗年度更新所需的活性成分變更審查，適用本條第 2 款至第 6 款規(guī)定的程序。
For annual updates of human coronavirus vaccines that procedure shall only apply after a public announcement of the Agency. The announcement shall be published on the Agency’s webportal and include the timeframe for application.
針對人用冠狀病毒疫苗的年度更新，前述程序僅在歐洲藥品管理局發(fā)布公開公告后方可適用。該公告需在歐洲藥品管理局門戶網(wǎng)站發(fā)布，并明確申請時限。
The holder shall submit to the Agency an application containing the elements listed in Annex IV.
上市許可持有人應(yīng)向歐洲藥品管理局提交申請材料，材料內(nèi)容需包含本條例附件四所列要素。
If the application fulfils the requirements laid down in the first subparagraph, the Agency shall acknowledge receipt of a valid application and inform the holder that the procedure starts from the date of such acknowledgement.
若申請材料符合前款規(guī)定的要求，歐洲藥品管理局應(yīng)出具有效申請材料的接收回執(zhí)，并通知持有人程序自回執(zhí)出具之日起正式啟動。
The Agency shall assess the application submitted. Where deemed necessary, the Agency may request additional data to complete its assessment.
歐洲藥品管理局應(yīng)對提交的申請材料進(jìn)行評估。如認(rèn)為有必要，可要求補充相關(guān)數(shù)據(jù)以完成評估工作。
Within 55 days from the receipt of a valid application, the Agency shall adopt an opinion. The Agency’s opinion on the application shall be transmitted to the holder. Where the Agency’s opinion is favourable, the Agency shall also transmit to the Commission its opinion and the grounds for its opinion as well as the revised versions of the documents set out in Article 9(4) of Regulation (EC) No 726/2004.
歐洲藥品管理局應(yīng)在收到有效申請材料后 55 日內(nèi)出具意見，并將該意見送達(dá)持有人。若意見為正面，歐洲藥品管理局還應(yīng)向歐盟委員會提交其意見、意見依據(jù)，以及歐盟委員會條例（EC）第 726/2004 號第九條第 4 款所列文件的修訂版本。
The 55-day period referred to in paragraph 4 shall be suspended from the moment when the additional data referred to in paragraph 3 is requested until the data is submitted.
前款所述的 55 日期限，自提出第 3 款所述的補充數(shù)據(jù)要求之日起暫停計算，直至收到補充數(shù)據(jù)為止。
Having regard to the favourable opinion of the Agency, the Commission shall amend where necessary the decision granting the marketing authorisation. The Union Register of Medicinal Products provided for in Article 13(1) of Regulation (EC) No 726/2004 shall be updated accordingly.
歐盟委員會應(yīng)參考?xì)W洲藥品管理局的正面意見，對上市許可批準(zhǔn)決定作出必要修訂。同時，應(yīng)相應(yīng)更新歐盟委員會條例（EC）第 726/2004 號第十三條第 1 款規(guī)定的歐盟藥品注冊簿。
CHAPTER IV
第四章
SECTION 1
第一節(jié)
Special procedures
特殊程序
Article 19
第十九條
Extensions of marketing authorisations
上市許可范圍拓展
An application for an extension of a marketing authorisation shall be evaluated in accordance with the same procedure as for the initial marketing authorisation to which it relates.
上市許可范圍拓展的申請，應(yīng)依據(jù)其對應(yīng)的初始上市許可所適用的程序開展審評。
An extension shall either be granted a marketing authorisation in accordance with the same procedure as for the granting of the initial marketing authorisation to which it relates or be included in that marketing authorisation.
上市許可范圍拓展事項，既可依據(jù)其對應(yīng)的初始上市許可所適用的程序單獨獲批上市許可，也可納入該初始上市許可的范疇。
Article 20
第二十條
Worksharing procedure
分工審評程序
By way of derogation from Articles 7(1) and Articles 9, 10, 13b, 13c, 13d, 15 and 16 the holder shall follow the worksharing procedure laid down in paragraphs 3 to 9 of this Article in the following cases:
有悖于第七條第 1 款及第九條、第十條、第十三條 b、第十三條 c、第十三條 d、第十五條、第十六條的規(guī)定，上市許可持有人在下列情形下，應(yīng)遵循本條第 3 款至第 9 款規(guī)定的分工審評程序：
(a) for marketing authorisations referred to in Chapters II and III, where a minor variation of type IB, a major variation of type II, or a group of variations as provided for in Article 7 (2)(b) or (c) that does not contain any extension relates to several marketing authorisations owned by the same holder;
(a) 針對第二章和第三章所述的上市許可，若同一持有人就其持有的多項上市許可，申報一項 IB 類微小變更、一項 II 類重大變更，或申報一項符合第七條第 2 款 (b) 項或 (c) 項規(guī)定且不包含許可范圍拓展的合并變更；
(b) for purely national marketing authorisations referred to in Chapter IIa, where a minor variation of type IB, a major variation of type II, or a group of variations as provided for in Article 13d (2)(b) or (c) that does not contain any extension relates to several marketing authorisations owned by the same holder;
(b) 針對第二章 a 節(jié)所述的純國別上市許可，若同一持有人就其持有的多項上市許可，申報一項 IB 類微小變更、一項 II 類重大變更，或申報一項符合第十三條 d 第 2 款 (b) 項或 (c) 項規(guī)定且不包含許可范圍拓展的合并變更；
(c) for purely national marketing authorisations referred to in Chapter IIa, where a minor variation of type IB, a major variation of type II, or a group of variations as provided for in Article 13d (2)(b) or (c) that does not contain any extension relates to one marketing authorisation that is owned by the same holder in more than one Member State.
(c) 針對第二章 a 節(jié)所述的純國別上市許可，若同一持有人就其在多個成員國持有的同一項上市許可，申報一項 IB 類微小變更、一項 II 類重大變更，或申報一項符合第十三條 d 第 2 款 (b) 項或 (c) 項規(guī)定且不包含許可范圍拓展的合并變更。
Variations covered under (a), (b) or (c) may be subject to the same worksharing procedure.
前述 (a) 項、(b) 項或 (c) 項所述的變更，可適用同一分工審評程序。
The reference authority or, in the case of purely national marketing authorisations, the competent authority may refuse to process a submission under the worksharing procedure where the same change (s) to different marketing authorisations require the submission of individual supportive data for each medicinal product concerned or a separate product-specific assessment.
若針對不同上市許可的同一變更，需為每個相關(guān)藥品單獨提交支持性數(shù)據(jù)或開展單獨的產(chǎn)品專項評估，則參考主管機關(guān)（對于純國別上市許可則為成員國主管機關(guān)）可拒絕采用分工審評程序處理該申報。
The holder shall submit to all relevant authorities an application containing the elements listed in Annex IV, with an indication of the preferred reference authority.
上市許可持有人應(yīng)向所有相關(guān)主管機關(guān)提交申請材料，材料內(nèi)容需包含本條例附件四所列要素，并注明擬選擇的參考主管機關(guān)。
The coordination group shall choose a reference authority. If the application fulfils the requirements laid down in the first subparagraph, that reference authority shall acknowledge receipt of a valid application.
協(xié)調(diào)小組應(yīng)選定一家參考主管機關(guān)。若申請材料符合前款規(guī)定的要求，該參考主管機關(guān)應(yīng)出具有效申請材料的接收回執(zhí)。
Where the chosen reference authority is the competent authority of a Member State which has not granted a marketing authorisation for all the medicinal products affected by the application, the coordination group may request another relevant authority to assist the reference authority in the evaluation of that application.
若選定的參考主管機關(guān)為某成員國主管機關(guān)，且該機關(guān)未為此次申報所涉的全部藥品授予上市許可，則協(xié)調(diào)小組可要求另一家相關(guān)主管機關(guān)協(xié)助該參考主管機關(guān)開展審評工作。
The reference authority shall issue an opinion on a valid application as referred to in paragraph 3 within a period that corresponds to the assessment period of the highest type of variation included following acknowledgement of receipt of a valid application in the case of minor variations of type IB or major variations of type II.
對于第 3 款所述的有效申請材料，若申報內(nèi)容包含 IB 類微小變更或 II 類重大變更，參考主管機關(guān)應(yīng)在自出具有效申請材料接收回執(zhí)之日起、與所包含變更類型中最高級別的審評周期相對應(yīng)的期限內(nèi)，出具相關(guān)意見。
The reference authority may reduce the period referred to in paragraph 4, having regard to the urgency of the matter, or may extend it to 90 days for variations listed in Annex V or for grouping of variations in accordance with Article 7(2), first subparagraph, point (c), or Article 13d(2), first subparagraph, point (c).
針對本條例附件五所列變更，或依據(jù)第七條第 2 款第 1 項 (c) 目、第十三條 d 第 2 款第 1 項 (c) 目規(guī)定合并申報的變更，參考主管機關(guān)可根據(jù)事項的緊急程度縮短第 4 款所述期限，或延長至 90 日。
Within the period referred to in paragraph 4, the reference authority may request the holder to provide supplementary information within a time limit set by the reference authority. In this case:
在第 4 款所述的期限內(nèi)，參考主管機關(guān)可要求持有人在其指定的期限內(nèi)補充相關(guān)信息。出現(xiàn)該情形時：
(a) the reference authority shall inform the other relevant authorities of its request for supplementary information;
(a) 參考主管機關(guān)應(yīng)將補充信息的要求通報其他相關(guān)主管機關(guān)；
(b) the procedure shall be suspended until such supplementary information has been provided;
(b) 審評程序自提出補充信息要求之日起暫停，直至收到補充信息為止；
(c) the reference authority may extend the period referred to in paragraph 4 to 90 days.
(c) 參考主管機關(guān)可將第 4 款所述期限延長至 90 日。
Where the reference authority is the Agency, Article 9(1) and (2) of Regulation (EC) No 726/2004 shall apply to the opinion referred to in paragraph 4.
若參考主管機關(guān)為歐洲藥品管理局，則歐盟委員會條例（EC）第 726/2004 號第九條第 1 款和第 2 款的規(guī)定，適用于第 4 款所述的意見出具工作。
The Agency’s opinion on the application shall be transmitted to the holder and the Member States, together with the assessment report. Where the outcome of the assessment is favourable and the variation affects the terms of a Commission decision granting the marketing authorisation, the Agency shall also transmit to the Commission its opinion and the grounds for its opinion as well as the revised versions of the documents set out in Article 9 (4) of Regulation (EC) No 726/2004.
歐洲藥品管理局應(yīng)將其針對申請材料出具的意見及評估報告，一并送達(dá)持有人及各成員國。若評估結(jié)果為正面，且該變更將影響歐盟委員會作出的上市許可批準(zhǔn)決定條款，則歐洲藥品管理局還應(yīng)向歐盟委員會提交其意見、意見依據(jù)，以及歐盟委員會條例（EC）第 726/2004 號第九條第 4 款所列文件的修訂版本。
Where the Agency issues a favourable opinion, the following shall apply:
若歐洲藥品管理局出具正面意見，則適用以下規(guī)定：
(a) if the opinion recommends the variation to the terms of a Commission decision granting the marketing authorisation, the Commission shall, having regard to the final opinion and within the time limits provided for in Article 23 (1a), amend the decision accordingly, provided that the revised versions of the documents set out in Article 9 (4) of Regulation (EC) No 726/2004 have been received. The Union Register of Medicinal Products provided for in Article 13 (1) of Regulation (EC) No 726/2004 shall be updated accordingly;
(a) 若該意見建議修訂歐盟委員會的上市許可批準(zhǔn)決定條款，則歐盟委員會應(yīng)參考最終意見，在第二十三條第 1a 款規(guī)定的期限內(nèi)作出相應(yīng)修訂，但前提是已收到歐盟委員會條例（EC）第 726/2004 號第九條第 4 款所列文件的修訂版本。同時，應(yīng)相應(yīng)更新歐盟委員會條例（EC）第 726/2004 號第十三條第 1 款規(guī)定的歐盟藥品注冊簿；
(b) the Member States concerned shall, within 60 days following receipt of the final opinion of the Agency, approve that final opinion, inform the Agency thereof and, where necessary, amend the marketing authorisations concerned accordingly, provided that the documents necessary for the amendment of the marketing authorisation have been transmitted to the Member States concerned.
(b) 相關(guān)成員國應(yīng)在收到歐洲藥品管理局最終意見后 60 日內(nèi)，對該意見予以批準(zhǔn)，并將批準(zhǔn)情況通報歐洲藥品管理局；同時，在收到修訂上市許可所需文件的前提下，對相關(guān)上市許可作出必要修訂。
Where the reference authority is the competent authority of a Member State:
若參考主管機關(guān)為某成員國主管機關(guān)，則適用以下規(guī)定：
(a) it shall send its opinion to the holder and to all relevant authorities;
(a) 該主管機關(guān)應(yīng)將其出具的意見送達(dá)持有人及所有相關(guān)主管機關(guān)；
(b) without prejudice to Article 13 and within 30 days following receipt of the opinion, the relevant authorities shall approve that opinion and inform the reference authority;
(b) 在不影響第十三條規(guī)定的前提下，相關(guān)主管機關(guān)應(yīng)在收到該意見后 30 日內(nèi)，對該意見予以批準(zhǔn)，并將批準(zhǔn)情況通報參考主管機關(guān)；
(c) the concerned marketing authorisations shall be amended accordingly within 30 days following the approval of the opinion, provided that the documents necessary for the amendment of the marketing authorisation have been transmitted to the Member States concerned.
(c) 在收到修訂上市許可所需文件的前提下，相關(guān)上市許可應(yīng)在該意見獲批后 30 日內(nèi)完成相應(yīng)修訂。
Upon request from the reference authority, the Member States concerned shall provide information related to the marketing authorisations affected by the variation for the purpose of verifying the validity of the application and of issuing the opinion on the valid application.
應(yīng)參考主管機關(guān)的要求，相關(guān)成員國應(yīng)提供與此次變更所涉上市許可相關(guān)的信息，以核查申請材料的有效性，并為針對有效申請材料出具意見提供支持。
Where harmonisation of a section of the summary of product characteristics of a purely national marketing authorisation has been achieved through a worksharing procedure, any subsequent variation submission affecting the harmonised section shall be transmitted simultaneously to all Member States concerned.
若某純國別上市許可的藥品特性概要中某一部分內(nèi)容，已通過分工審評程序?qū)崿F(xiàn)協(xié)調(diào)統(tǒng)一，則此后針對該協(xié)調(diào)統(tǒng)一部分提出的任何變更申報，均應(yīng)同時提交至所有相關(guān)成員國。
In justified cases, in accordance with the guidelines referred to in Article 4(1), when agreed by the competent authorities of the Member States and the Agency, the holder may choose to follow the worksharing procedure laid down in paragraphs 3 to 9 for the marketing authorisations referred to in Chapters II, IIa and III, where a minor variation of type IB, a major variation of type II, or a group of variations where at least one of the variations is a minor variation of type IB or a major variation of type II that does not contain any extension, relates to several marketing authorisations owned by several holders in more than one Member State.
在具備正當(dāng)理由的情形下，依據(jù)第四條第 1 款所述指南，經(jīng)各成員國主管機關(guān)及歐洲藥品管理局同意，若多家持有人就其在多個成員國持有的多項上市許可，申報一項 IB 類微小變更、一項 II 類重大變更，或申報一項合并變更（其中至少包含一項 IB 類微小變更或一項 II 類重大變更，且不包含許可范圍拓展），則針對第二章、第二章 a 節(jié)及第三章所述的上市許可，持有人可選擇遵循本條第 3 款至第 9 款規(guī)定的分工審評程序。
Article 21
第二十一條
Public health emergency
公共衛(wèi)生緊急狀態(tài)
By way of derogation from Chapters I, II, IIa and III, where a public health emergency at Union level is recognised by the Commission pursuant to Regulation (EU) 2022/2371 of the European Parliament and of the Council ( 1 ) the relevant authorities, or in the case of centralised marketing authorisations, the Commission may, where certain pharmaceutical, non-clinical or clinical data are missing, exceptionally and temporarily accept a variation to the terms of a marketing authorisation for a human vaccine pertaining to the pathogen causing the public health emergency.
有悖于第一章、第二章、第二章 a 節(jié)及第三章的規(guī)定，若歐盟委員會依據(jù)歐洲議會和歐盟理事會《（歐盟）2022/2371 號條例》認(rèn)定歐盟層面進(jìn)入公共衛(wèi)生緊急狀態(tài)，則相關(guān)主管機關(guān)（對于集中上市許可，則為歐盟委員會）可在部分藥學(xué)、非臨床或臨床數(shù)據(jù)缺失的情形下，破例且臨時批準(zhǔn)針對引發(fā)該公共衛(wèi)生緊急狀態(tài)的病原體的人用疫苗上市許可條款的變更。
The relevant authority may request the holder to provide supplementary information in order to complete its assessment within a time limit set by it.
相關(guān)主管機關(guān)可要求上市許可持有人在其指定的期限內(nèi)補充相關(guān)信息，以完成評估工作。
Variations may be accepted pursuant to paragraph 1 only if the benefit-risk balance of the medicinal product is favourable.
僅當(dāng)該藥品的獲益 - 風(fēng)險比為正向時，方可依據(jù)第 1 款的規(guī)定批準(zhǔn)相關(guān)變更。
Where a variation is accepted pursuant to paragraph 1, the holder shall submit the missing pharmaceutical, non-clinical and clinical data within a time limit set by the relevant authority.
若相關(guān)變更依據(jù)第 1 款獲得批準(zhǔn)，上市許可持有人應(yīng)在相關(guān)主管機關(guān)指定的期限內(nèi)，提交缺失的藥學(xué)、非臨床及臨床數(shù)據(jù)。
In the case of centralised marketing authorisations, the missing data and the time limit for submission or compliance shall be specified in the conditions to the marketing authorisation. Where the marketing authorisation has been granted in accordance with Article 14-a of Regulation (EC) No 726/2004 this may be done as part of the specific obligations referred to in paragraph 4 of that Article.
對于集中上市許可，上述缺失的數(shù)據(jù)及提交或合規(guī)的時限應(yīng)在上市許可的附加條件中予以明確。若該上市許可系依據(jù)《（EC）第 726/2004 號條例》第 14a 條授予，則前述要求可納入該條例第 4 款所述的特定義務(wù)范疇。
Article 22
第二十二條
Urgent safety restrictions
緊急安全限制措施
Where, in the event of a risk to public health in the case of medicinal products, the holder takes urgent safety restrictions on its own initiative, it shall forthwith inform all relevant authorities and, in the case of a centralised marketing authorisation, the Agency.
若藥品出現(xiàn)公共健康風(fēng)險，上市許可持有人主動采取緊急安全限制措施的，應(yīng)立即通知所有相關(guān)主管機關(guān)；對于集中上市許可，還應(yīng)同時通知歐洲藥品管理局。
If the relevant authority or, in the case of a centralised marketing authorisation, the Agency has not raised objections within 24 hours following receipt of that information, the urgent safety restrictions shall be deemed accepted.
若相關(guān)主管機關(guān)（對于集中上市許可，則為歐洲藥品管理局）在收到該通知后 24 小時內(nèi)未提出異議，該緊急安全限制措施即視為獲得批準(zhǔn)。
In the event of a risk to public health in the case of medicinal products, relevant authorities or, in the case of centralised marketing authorisations, the Commission may impose urgent safety restrictions on the holder.
若藥品出現(xiàn)公共健康風(fēng)險，相關(guān)主管機關(guān)可對持有人采取緊急安全限制措施；對于集中上市許可，歐盟委員會可實施前述限制措施。
Where an urgent safety restriction is taken by the holder or imposed by a relevant authority or the Commission, the holder shall submit the corresponding application for variation within 15 days following the initiation of that restriction.
無論緊急安全限制措施由持有人主動采取，還是由相關(guān)主管機關(guān)或歐盟委員會強制實施，持有人均應(yīng)在該措施啟動后 15 日內(nèi)，提交對應(yīng)的變更申請。
SECTION 2
第二節(jié)
Amendments to the decision granting the marketing authorisation and implementation
上市許可批準(zhǔn)決定的修訂與變更的實施
Article 23
第二十三條
Amendments to the decision granting the marketing authorisation
上市許可批準(zhǔn)決定的修訂
Amendments to the decision granting the marketing authorisation resulting from the procedures laid down in Chapters II and IIa shall be made:
依據(jù)第二章和第二章 a 節(jié)規(guī)定的程序作出的上市許可批準(zhǔn)決定修訂，應(yīng)按以下時限完成：
(a) in the case of major variations of type II, within two months following receipt of the information referred to in Article 11 (1)(c) and Article 13e (a), provided that the documents necessary for the amendment of the marketing authorisation have been transmitted to the Member States concerned;
(a) 對于 II 類重大變更，自收到第十一條第 1 款 (c) 項和第十三條 e (a) 項所述信息后兩個月內(nèi)完成，但前提是已向相關(guān)成員國提交修訂上市許可所需的文件；
(b) in the other cases, within six months following receipt of the information referred to in Article 11 (1)(c) and Article 13e (a), provided that the documents necessary for the amendment of the marketing authorisation have been transmitted to the Member States concerned.
(b) 對于其他情形，自收到第十一條第 1 款 (c) 項和第十三條 e (a) 項所述信息后六個月內(nèi)完成，但前提是已向相關(guān)成員國提交修訂上市許可所需的文件。
1a. Amendments to the decision granting the marketing authorisation resulting from the procedures laid down in Chapter III shall be made:
1a. 依據(jù)第三章規(guī)定的程序作出的上市許可批準(zhǔn)決定修訂，應(yīng)按以下時限完成：
(a) within two months following receipt of the information referred to in Article 17 (1)(c) for the following variations:
(a) 對于下列變更，自收到第十七條第 1 款 (c) 項所述信息后兩個月內(nèi)完成：
(i) variations related to the addition of a new therapeutic indication or to the modification of an existing one;
(i) 新增或修改現(xiàn)有治療適應(yīng)癥的變更；
(ii) variations related to the addition of a new contraindication;
(ii) 新增禁忌癥的變更；
(iii) variations related to a change in posology;
(iii) 變更給藥劑量方案的變更；
(vi) variations related to changes to the active substance of a seasonal, pre-pandemic or pandemic vaccine against human influenza;
(vi) 季節(jié)性、大流行前或大流行期人用流感疫苗活性成分變更的相關(guān)變更；
(viii) other type II variations that are intended to implement changes to the decision granting the marketing authorisation due to a significant public health concern;
(viii) 因重大公共健康問題需修訂上市許可批準(zhǔn)決定的其他 II 類變更；
(ix) variations related to changes to the active substance of a human coronavirus vaccine, including replacement or addition of a serotype, strain, antigen or coding sequence or combination of serotypes, strains, antigens or coding sequences;
(ix) 人用冠狀病毒疫苗活性成分變更的相關(guān)變更，包括血清型、毒株、抗原或編碼序列的替換或新增，或上述各類物質(zhì)組合的變更；
(x) variations related to the replacement or addition of a serotype, strain, antigen or coding sequence or combination of serotypes, strains, antigens or coding sequences of a human vaccine that has the potential to address a public health emergency;
(x) 可能應(yīng)對公共衛(wèi)生緊急狀態(tài)的人用疫苗的血清型、毒株、抗原或編碼序列的替換或新增，或上述各類物質(zhì)組合的相關(guān)變更；
(b) within 12 months following receipt of the information referred to in Article 17 (1)(c) in the other cases.
(b) 對于其他情形，自收到第十七條第 1 款 (c) 項所述信息后 12 個月內(nèi)完成。
The Agency shall determine the variations referred to in point (a)(viii) and provide reasons for such determination.
歐洲藥品管理局應(yīng)確定 (a)(viii) 項所述的變更范疇，并就該確定說明理由。
Where the decision granting a marketing authorisation is amended as a result of one of the procedures laid down in Chapters II, IIa, III and IV, the relevant authority or, in the case of centralised marketing authorisations, the Commission shall notify the amended decision without delay to the holder.
若上市許可批準(zhǔn)決定依據(jù)第二章、第二章 a 節(jié)、第三章及第四章規(guī)定的任一程序完成修訂，相關(guān)主管機關(guān)應(yīng)立即將修訂后的決定通知持有人；對于集中上市許可，由歐盟委員會履行前述通知義務(wù)。
Article 23a
第二十三條 a
Compliance with the paediatric investigation plan
兒科研究計劃的合規(guī)性
The statement indicating compliance with the agreed completed paediatric investigation plan provided for under Article 28 (3) of Regulation (EC) No 1901/2006 shall be included within the technical dossier of the marketing authorisation.
依據(jù)《（EC）第 1901/2006 號條例》第 28 條第 3 款規(guī)定的、證明符合已商定且完成的兒科研究計劃的聲明，應(yīng)納入上市許可的技術(shù)檔案。
The relevant authority shall provide the holder with a confirmation that the statement is included in the technical dossier within 30 days after the relevant assessment has been concluded.
相關(guān)主管機關(guān)應(yīng)在相關(guān)評估完成后 30 日內(nèi)，向持有人出具該聲明已納入技術(shù)檔案的確認(rèn)函。
Article 24
第二十四條
Implementation of variations
變更的實施
Minor variations of type IA may be implemented any time before completion of the procedures laid down in Articles 8, 13a and 14.
IA 類微小變更可在第八條、第十三條 a 及第十四條規(guī)定的程序完成前的任意時間實施。
Where a notification concerning one or several minor variations of type IA is rejected, the holder shall cease to apply the concerned variation (s) immediately after receipt of the information referred to in Articles 11 (1)(a), 13e (a), and 17 (1)(a).
若一項或多項 IA 類微小變更的申報被駁回，持有人應(yīng)在收到第十一條第 1 款 (a) 項、第十三條 e (a) 項及第十七條第 1 款 (a) 項所述信息后，立即停止實施相關(guān)變更。
Minor variations of type IB may only be implemented in the following cases:
IB 類微小變更僅可在下列情形下實施：
(a) for variations submitted in accordance with the procedures laid down in Chapter II, after the competent authority of the reference Member State has informed the holder that it has accepted the notification pursuant to Article 9, or after the notification is deemed accepted pursuant to Article 9 (2);
(a) 依據(jù)第二章規(guī)定程序申報的變更，自參考成員國主管機關(guān)依據(jù)第九條通知持有人申報已獲批準(zhǔn)，或依據(jù)第九條第 2 款申報被視為獲批后；
(b) for variations submitted in accordance with the procedures laid down in Chapter IIa, after the relevant authority has informed the holder that it has accepted the notification pursuant to Article 13b, or after the notification is deemed accepted pursuant to Article 13b (2);
(b) 依據(jù)第二章 a 節(jié)規(guī)定程序申報的變更，自相關(guān)主管機關(guān)依據(jù)第十三條 b 通知持有人申報已獲批準(zhǔn)，或依據(jù)第十三條 b 第 2 款申報被視為獲批后；
(c) for variations submitted in accordance with the procedures laid down in Chapter III, after the Agency has informed the holder that its opinion referred to in Article 15 is favourable, or after that opinion is deemed favourable pursuant to Article 15 (2);
(c) 依據(jù)第三章規(guī)定程序申報的變更，自歐洲藥品管理局依據(jù)第十五條通知持有人其意見為正面，或依據(jù)第十五條第 2 款其意見被視為正面后；
(d) for variations submitted in accordance with the procedure laid down in Article 20, after the reference authority has informed the holder that its opinion is favourable.
(d) 依據(jù)第二十條規(guī)定程序申報的變更，自參考主管機關(guān)通知持有人其意見為正面后。
Major variations of type II may only be implemented in the following cases:
II 類重大變更僅可在下列情形下實施：
(a) for variations submitted in accordance with the procedures laid down in Chapter II, 30 days after the competent authority of the reference Member State has informed the holder that it has accepted the variation pursuant to Article 10, under the condition that the documents necessary for the amendment to the marketing authorisation have been provided to the Member States concerned. Where an arbitration procedure has been initiated in accordance with Article 13, the holder shall not implement the variation until the arbitration procedure has concluded that the variation is accepted;
(a) 依據(jù)第二章規(guī)定程序申報的變更，自參考成員國主管機關(guān)依據(jù)第十條通知持有人變更已獲批準(zhǔn)后 30 日，但前提是已向相關(guān)成員國提交修訂上市許可所需的文件。若依據(jù)第十三條啟動了仲裁程序，則持有人需待仲裁程序裁定變更獲批后，方可實施該變更；
(b) for variations submitted in accordance with the procedures laid down in Chapter IIa, after the competent authority has informed the holder that it has accepted the variation pursuant to Article 13c;
(b) 依據(jù)第二章 a 節(jié)規(guī)定程序申報的變更，自相關(guān)主管機關(guān)依據(jù)第十三條 c 通知持有人變更已獲批準(zhǔn)后；
(c) for variations submitted in accordance with the procedures laid down in Chapter III, after the Agency has informed the holder that its opinion referred to in Article 16 is favourable, unless the variation is one referred to in Article 23 (1a)(a).
(c) 依據(jù)第三章規(guī)定程序申報的變更，自歐洲藥品管理局依據(jù)第十六條通知持有人其意見為正面后，但第二十三條第 1a 款 (a) 項所述的變更除外。
Variations referred to in Article 23 (1a)(a) may only be implemented after the Commission has amended the decision granting the marketing authorisation and notified the holder thereof;
第二十三條第 1a 款 (a) 項所述的變更，僅可在歐盟委員會修訂上市許可批準(zhǔn)決定并通知持有人后實施；
(d) for variations submitted in accordance with the procedure laid down in Article 20, 30 days after the reference authority has informed the holder that its opinion is favourable, under the condition that the documents necessary for the amendment to the marketing authorisation have been provided to the Member States concerned; unless an arbitration procedure has been initiated in accordance with Article 13, or unless the procedure concerns a variation to a centralised marketing authorisation as referred to in Article 23 (1a)(a).
(d) 依據(jù)第二十條規(guī)定程序申報的變更，自參考主管機關(guān)通知持有人其意見為正面后 30 日，但前提是已向相關(guān)成員國提交修訂上市許可所需的文件；但依據(jù)第十三條啟動仲裁程序的情形，或該程序涉及第二十三條第 1a 款 (a) 項所述集中上市許可變更的情形除外。
Where an arbitration procedure has been initiated in accordance with Article 13, or where the worksharing procedure concerns a variation to a centralised marketing authorisation as referred to in Article 23 (1a)(a), the holder shall not implement the variation until the arbitration procedure has concluded that the variation is accepted, or until the Commission Decision amending the decision granting the marketing authorisation has been adopted.
若依據(jù)第十三條啟動了仲裁程序，或該分工審評程序涉及第二十三條第 1a 款 (a) 項所述的集中上市許可變更，則持有人需待仲裁程序裁定變更獲批，或歐盟委員會通過修訂上市許可批準(zhǔn)決定的決議后，方可實施該變更。
An extension may only be implemented after the relevant authority or, in the case of extensions to a centralised marketing authorisation, the Commission has amended the decision granting the marketing authorisation and notified the holder accordingly.
上市許可范圍拓展，僅可在相關(guān)主管機關(guān)修訂上市許可批準(zhǔn)決定并通知持有人后實施；對于集中上市許可的范圍拓展，需在歐盟委員會完成前述修訂及通知后實施。
Urgent safety restrictions and variations which are related to safety issues shall be implemented within a time frame agreed by the holder and the relevant authority and, in the case of a centralised marketing authorisation, the Agency.
緊急安全限制措施及與安全性相關(guān)的變更，應(yīng)在持有人與相關(guān)主管機關(guān)商定的時限內(nèi)實施；對于集中上市許可，應(yīng)在持有人與歐洲藥品管理局商定的時限內(nèi)實施。
By way of derogation from the first subparagraph, urgent safety restrictions and variations related to safety issues which concern marketing authorisations granted in accordance with Chapter 4 of Directive 2001/83/EC shall be implemented within a time frame agreed by the holder and the competent authority of the reference Member State, in consultation with the other relevant authorities.
有悖于前款規(guī)定，針對依據(jù)《2001/83/EC 號指令》第四章授予的上市許可的緊急安全限制措施及安全性相關(guān)變更，應(yīng)在持有人與參考成員國主管機關(guān)（經(jīng)與其他相關(guān)主管機關(guān)協(xié)商）商定的時限內(nèi)實施。
Article 24a
第二十四條 a
Application of national provisions on variations to purely national marketing authorisations
成員國法規(guī)對純國別上市許可變更的適用
Member States that, in accordance with Article 23b (4) of Directive 2001/83/EC, may continue to apply their national provisions on variations to certain purely national marketing authorisations are listed in Annex VI to this Regulation.
依據(jù)《2001/83/EC 號指令》第 23b 條第 4 款的規(guī)定，可繼續(xù)對特定純國別上市許可的變更適用本國法規(guī)的成員國，列于本條例附件六。
CHAPTER V
第五章
FINAL PROVISIONS
最終條款
Article 25
第二十五條
Continuous monitoring
持續(xù)監(jiān)測
Where requested by a relevant authority, the holder shall supply without delay any information related to the implementation of a given variation.
應(yīng)相關(guān)主管機關(guān)的要求，持有人應(yīng)立即提供與特定變更實施情況相關(guān)的所有信息。
Article 27
第二十七條
Repeal and transitional provision
條例廢止與過渡條款
Regulations (EC) No 1084/2003 and (EC) No 1085/2003 are hereby repealed.
《（EC）第 1084/2003 號條例》及《（EC）第 1085/2003 號條例》特此廢止。
References to the repealed Regulations shall be construed as references to this Regulation.
此前對已廢止條例的援引，應(yīng)視為對本條例的援引。
By way of derogation from paragraph 1, Regulations (EC) Nos 1084/2003 and 1085/2003 shall continue to apply to valid notifications or applications for variations which are pending at the date referred to in the second subparagraph of Article 28.
有悖于第 1 款規(guī)定，對于在第二十八條第二款所述日期仍處于待審狀態(tài)的有效變更申報或申請，《（EC）第 1084/2003 號條例》及《（EC）第 1085/2003 號條例》繼續(xù)適用。
Article 28
第二十八條
Entry into force
生效日期
This Regulation shall enter into force on the 20th day following its publication in the Official Journal of the European Union.
本條例自在《歐盟官方公報》發(fā)布后第 20 日起生效。
It shall apply from 1 January 2010.
本條例自 2010 年 1 月 1 日起適用。
By way of derogation from the second subparagraph, the recommendations on unforeseen variations provided for in Article 5 may be requested, delivered and published from the date of entry into force referred to in the first subparagraph.
有悖于第二款規(guī)定，第五條所述的關(guān)于意外變更的建議，可自第一款所述的生效日期起提出、出具并發(fā)布。
This Regulation shall be binding in its entirety and directly applicable in all Member States.
本條例整體具有約束力，并直接適用于所有成員國。
ANNEX I
附件一
Extensions of marketing authorisations
上市許可范圍拓展
Changes to the active substance(s):
活性成分的變更：
(a) replacement of a chemical active substance by a different salt/ester complex/derivative, with the same therapeutic moiety, where the efficacy/safety characteristics are not significantly different;
(a) 化學(xué)活性成分替換為含相同治療母核的不同鹽類 / 酯類復(fù)合物 / 衍生物，且藥品的有效性與安全性特征無顯著差異；
(b) replacement by a different isomer, a different mixture of isomers, of a mixture by an isolated isomer (e.g. racemate by a single enantiomer), where the efficacy/safety characteristics are not significantly different;
(b) 活性成分替換為不同異構(gòu)體、不同異構(gòu)體混合物，或由異構(gòu)體混合物替換為單一異構(gòu)體（如外消旋體替換為單一對映體），且藥品的有效性與安全性特征無顯著差異；
(c) replacement of a biological active substance with one of a slightly different molecular structure where the efficacy or safety characteristics are not significantly different, with the exception of the following:
(c) 生物活性成分替換為分子結(jié)構(gòu)略有差異的同類成分，且藥品的有效性與安全性特征無顯著差異，但以下情形除外：
— changes to the active substance of a seasonal, pre-pandemic or pandemic vaccine against human influenza;
— 季節(jié)性、大流行前或大流行期人用流感疫苗的活性成分變更；
— replacement or, upon agreement of the relevant authorities, addition of a serotype, strain, antigen or coding sequence or combination of serotypes, strains, antigens or coding sequences for a human coronavirus vaccine;
— 人用冠狀病毒疫苗的血清型、毒株、抗原或編碼序列的替換，或經(jīng)相關(guān)主管機關(guān)同意后新增上述物質(zhì)，以及上述各類物質(zhì)組合的變更；
— replacement or, upon agreement of the relevant authorities, addition of a serotype, strain, antigen or coding sequence or combination of serotypes, strains, antigens or coding sequences, for a human vaccine other than for human influenza or coronavirus that has the potential to address a public health emergency in the Union;
— 除流感疫苗和冠狀病毒疫苗外，可能應(yīng)對歐盟公共衛(wèi)生緊急狀態(tài)的人用疫苗，其血清型、毒株、抗原或編碼序列的替換，或經(jīng)相關(guān)主管機關(guān)同意后新增上述物質(zhì)，以及上述各類物質(zhì)組合的變更；
(d) modification of the vector used to produce the antigen or the source material, including a new master cell bank from a different source, where the efficacy/safety characteristics are not significantly different;
(d) 生產(chǎn)抗原所用載體或原料的變更（包括采用不同來源的新主細(xì)胞庫），且藥品的有效性與安全性特征無顯著差異；
(e) a new ligand or coupling mechanism for a radiopharmaceutical, where the efficacy/safety characteristics are not significantly different;
(e) 放射性藥品采用新的配體或偶聯(lián)機制，且藥品的有效性與安全性特征無顯著差異；
(f) change to the extraction solvent or the ratio of herbal drug to herbal drug preparation where the efficacy/safety characteristics are not significantly different.
(f) 植物藥提取溶劑或植物藥與植物藥制劑配比的變更，且藥品的有效性與安全性特征無顯著差異。
Changes to strength, pharmaceutical form and route of administration:
規(guī)格、劑型及給藥途徑的變更：
(a) change of bioavailability;
(a) 生物利用度的變更；
(b) change of pharmacokinetics e.g. change in rate of release;
(b) 藥代動力學(xué)特征的變更（如釋放速率的變更）；
(c) change or addition of a new strength/potency;
(c) 規(guī)格 / 效價的變更或新增；
(d) change or addition of a new pharmaceutical form;
(d) 劑型的變更或新增；
(e) change or addition of a new route of administration ( 2 ).
(e) 給藥途徑的變更或新增（標(biāo)注 2）。
ANNEX II
附件二
Classification of variations
變更的分類
The following variations shall be classified as minor variations of type IA:
下列變更應(yīng)歸類為 IA 類微小變更：
(a) variations of purely administrative nature that are related to the identity and contact details of:
(a) 與以下主體的身份信息及聯(lián)系方式相關(guān)的純行政性變更：
— the holder;
— 上市許可持有人；
— the manufacturer or supplier of any starting material, reagent, intermediate, active substance used in the manufacturing process or finished product;
— 生產(chǎn)過程所用起始物料、試劑、中間體、活性成分及成品的生產(chǎn)商或供應(yīng)商；
(b) variations related to the deletion of any manufacturing site, including for an active substance, intermediate or finished product, packaging site, manufacturer responsible for batch release, site where batch control takes place;
(b) 撤銷任何生產(chǎn)場地（包括活性成分、中間體、成品的生產(chǎn)場地）、包裝場地、負(fù)責(zé)批次放行的生產(chǎn)商及批次檢驗場地的相關(guān)變更；
(c) variations related to minor changes to an approved physico-chemical test procedure, where the updated procedure is demonstrated to be at least equivalent to the former test procedure, appropriate validation studies have been performed and the results show that the updated test procedure is at least equivalent to the former;
(c) 對已批準(zhǔn)的理化檢驗方法進(jìn)行微小修訂，且經(jīng)證明修訂后的方法與原方法至少等效，同時已完成適當(dāng)?shù)尿炞C研究，驗證結(jié)果顯示修訂方法與原方法至少等效的相關(guān)變更；
(d) variations related to changes in the specifications of the active substance or of an excipient in order to comply with an update of the relevant monograph of the European Pharmacopoeia or of the national pharmacopoeia of a Member State, where the change is made exclusively to comply with the pharmacopoeia and the specifications for product specific properties are unchanged;
(d) 為符合《歐洲藥典》或成員國國家藥典相關(guān)各論的更新要求，對活性成分或輔料的質(zhì)量標(biāo)準(zhǔn)進(jìn)行變更，且該變更僅為滿足藥典要求、產(chǎn)品專屬性質(zhì)的質(zhì)量標(biāo)準(zhǔn)未發(fā)生改變的相關(guān)變更；
(e) variations related to changes in the packaging material not in contact with the finished product, which do not affect the delivery, use, safety or stability of the medicinal product;
(e) 與成品非接觸性包裝材料的變更，且該變更不影響藥品的配送、使用、安全性及穩(wěn)定性的相關(guān)變更；
(f) variations related to the tightening of specification limits, where the change is not a consequence of any commitment from previous assessment to review specification limits and does not result from unexpected events arising during manufacture;
(f) 收緊質(zhì)量標(biāo)準(zhǔn)限度的變更，且該變更并非源于既往審評中承諾的質(zhì)量標(biāo)準(zhǔn)限度復(fù)核要求，也非源于生產(chǎn)過程中發(fā)生的意外事件的相關(guān)變更；
(g) variations related to changes to a medical device that is an integral part of or in exclusive use with the medicinal product which have no impact on the quality, safety or efficacy of the medicinal product.
(g) 作為藥品組成部分或?qū)９┧幤放涮资褂玫尼t(yī)療器械的變更，且該變更對藥品的質(zhì)量、安全性及有效性無影響的相關(guān)變更。
The following variations shall be classified as major variations of type II:
下列變更應(yīng)歸類為 II 類重大變更：
(a) variations related to the addition of a new therapeutic indication or to the modification of an existing one;
(a) 新增治療適應(yīng)癥或修改現(xiàn)有治療適應(yīng)癥的相關(guān)變更；
(b) variations related to significant modifications of the summary of product characteristics due in particular to new quality, pre-clinical, clinical or pharmacovigilance findings;
(b) 因新的質(zhì)量、非臨床、臨床或藥物警戒相關(guān)發(fā)現(xiàn)，對產(chǎn)品特性概要進(jìn)行重大修訂的相關(guān)變更；
(c) variations related to changes outside the range of approved specifications, limits or acceptance criteria;
(c) 超出已批準(zhǔn)質(zhì)量標(biāo)準(zhǔn)、限度或驗收標(biāo)準(zhǔn)范圍的變更；
(d) variations related to substantial changes to the manufacturing process, formulation, specifications or impurity profile of the active substance or finished medicinal product which may have a significant impact on the quality, safety or efficacy of the medicinal product;
(d) 對活性成分或成品的生產(chǎn)工藝、處方、質(zhì)量標(biāo)準(zhǔn)或雜質(zhì)譜進(jìn)行重大變更，且可能對藥品質(zhì)量、安全性及有效性產(chǎn)生顯著影響的相關(guān)變更；
(f) variations related to the introduction of a new design space, where the design space has been developed in accordance with the relevant European and international scientific guidelines;
(f) 引入新的設(shè)計空間，且該設(shè)計空間的制定符合相關(guān)歐洲及國際科學(xué)指南要求的相關(guān)變更；
(fa) variations related to the introduction of a post approval change management protocol where the protocol has been developed in accordance with the relevant European and international scientific guidelines;
(fa) 引入上市后變更管理方案，且該方案的制定符合相關(guān)歐洲及國際科學(xué)指南要求的相關(guān)變更；
(j) variations related to changes to the active substance of a seasonal, pre-pandemic or pandemic vaccine against human influenza;
(j) 季節(jié)性、大流行前或大流行期人用流感疫苗活性成分的相關(guān)變更；
(l) variations related to the replacement or, upon agreement of the relevant authorities, addition of a serotype, strain, antigen or coding sequence or combination of serotypes, strains, antigens or coding sequences for a human coronavirus vaccine;
(l) 人用冠狀病毒疫苗的血清型、毒株、抗原或編碼序列的替換，或經(jīng)相關(guān)主管機關(guān)同意后新增上述物質(zhì)，以及上述各類物質(zhì)組合的相關(guān)變更；
(m) variations related to the replacement or, upon agreement of the relevant authorities, addition of a serotype, strain, antigen or coding sequence or combination of serotypes, strains, antigens or coding sequences of a human vaccine that has the potential to address a public health emergency;
(m) 可能應(yīng)對公共衛(wèi)生緊急狀態(tài)的人用疫苗，其血清型、毒株、抗原或編碼序列的替換，或經(jīng)相關(guān)主管機關(guān)同意后新增上述物質(zhì)，以及上述各類物質(zhì)組合的相關(guān)變更；
(n) variations related to changes to a medical device that is an integral part of or in exclusive use with the medicinal product which may have a significant impact on the quality, safety or efficacy of the medicinal product.
(n) 作為藥品組成部分或?qū)９┧幤放涮资褂玫尼t(yī)療器械的變更，且該變更可能對藥品的質(zhì)量、安全性及有效性產(chǎn)生顯著影響的相關(guān)變更。
ANNEX III
附件三
Cases for grouping variations referred to in Article 7(2)(b) and Article 13d(2)(b)
第七條第 2 款 (b) 項及第十三條 d 第 2 款 (b) 項所述的變更合并情形
One of the variations in the group is an extension of the marketing authorisation.
合并變更中包含一項上市許可范圍拓展。
One of the variations in the group is a major variation of type II; all other variations in the group are variations which are consequential to this major variation of type II.
合并變更中包含一項 II 類重大變更，且其余所有變更均為該 II 類重大變更引發(fā)的后續(xù)變更。
One of the variations in the group is a minor variation of type IB; all other variations in the group are minor variations which are consequential to this minor variation of type IB.
合并變更中包含一項 IB 類微小變更，且其余所有變更均為該 IB 類微小變更引發(fā)的后續(xù)變更。
All variations in the group relate solely to changes of administrative nature to the summary of product characteristics, labelling and package leaflet or insert.
合并變更中的所有變更均僅涉及產(chǎn)品特性概要、標(biāo)簽、說明書的行政性修改。
All variations in the group are changes to an Active Substance Master File, Vaccine Antigen Master File or Plasma Master File.
合并變更中的所有變更均為活性成分主文件、疫苗抗原主文件或血漿主文件的變更。
All variations in the group relate to a project intended to improve the manufacturing process and the quality of the medicinal product concerned or its active substances, including related administrative changes.
合并變更中的所有變更均與旨在改進(jìn)相關(guān)藥品或其活性成分的生產(chǎn)工藝及質(zhì)量的項目相關(guān)，包括相關(guān)的行政性變更。
All variations in the group are changes affecting the quality of a human pandemic influenza or coronavirus vaccine.
合并變更中的所有變更均為影響人用大流行流感疫苗或冠狀病毒疫苗質(zhì)量的變更。
All variations in the group are changes to the pharmacovigilance system referred to in Article 8(3), point (ia) of Directive 2001/83/EC.
合并變更中的所有變更均為《2001/83/EC 號指令》第八條第 3 款 (ia) 項所述藥物警戒體系的變更。
All variations in the group are consequential to a given urgent safety restriction and submitted in accordance with Article 22.
合并變更中的所有變更均為特定緊急安全限制措施引發(fā)的后續(xù)變更，且依據(jù)第二十二條提交。
All variations in the group relate to the implementation of a given class labelling.
合并變更中的所有變更均與實施特定分類標(biāo)簽相關(guān)。
All variations in the group are consequential to the assessment of a given periodic safety update report.
合并變更中的所有變更均為特定定期安全性更新報告的審評引發(fā)的后續(xù)變更。
All variations in the group are consequential to a given post-authorisation study conducted under the supervision of the holder.
合并變更中的所有變更均為上市許可持有人開展的特定上市后研究引發(fā)的后續(xù)變更。
All variations in the group are consequential to a specific procedure or condition carried out pursuant to Article 14(8) of Regulation (EC) No 726/2004 or Article 22 of Directive 2001/83/EC.
合并變更中的所有變更均為依據(jù)《（EC）第 726/2004 號條例》第十四條第 8 款或《2001/83/EC 號指令》第二十二條實施的特定程序或附加條件引發(fā)的后續(xù)變更。
ANNEX IV
附件四
Elements to be submitted
應(yīng)提交的材料
A list of all the marketing authorisations affected by the notification or application.
受本次申報影響的所有上市許可清單。
A description of all the variations submitted, including:
本次申報的所有變更的說明，包括：
(a) in the case of minor variations of type IA, the date of implementation for each variation described;
(a) 若為 IA 類微小變更，列明每項變更的實施日期；
(b) in the case of minor variations of type IA which do not require immediate notification, a description of all minor variations of type IA made in the last 12 months to the terms of the concerned marketing authorisation (s) and which have not been already notified.
(b) 若為無需即時申報的 IA 類微小變更，說明過去 12 個月內(nèi)對相關(guān)上市許可條款作出的、尚未申報的所有 IA 類微小變更。
All necessary documents as listed in the guidelines referred to in point (b) of Article 4(1).
第四條第 1 款 (b) 項所述指南中列明的全部必要文件。
Where a variation leads to or is the consequence of other variations to the terms of the same marketing authorisation, a description of the relation between these variations.
若某項變更導(dǎo)致同一上市許可條款的其他變更，或系其他變更引發(fā)的后續(xù)變更，需說明這些變更之間的關(guān)聯(lián)。
In the case of variations to centralised marketing authorisations, the relevant fee provided for in Council Regulation (EC) No 297/95 ( 3 ).
若為集中上市許可的變更，需繳納《歐盟理事會（EC）第 297/95 號條例》（標(biāo)注 3）規(guī)定的相關(guān)費用。
In the case of variations to marketing authorisations granted by the competent authorities of Member States:
若為成員國主管機關(guān)授予的上市許可的變更：
(a) a list of those Member States with an indication of the reference Member State if applicable;
(a) 相關(guān)成員國清單，如適用需注明參考成員國；
(b) the relevant fees provided for in the applicable national rules in the Member States concerned.
(b) 相關(guān)成員國適用法規(guī)規(guī)定的相關(guān)費用。
ANNEX V
附件五
Variations concerning a change to or addition of therapeutic indications.
涉及治療適應(yīng)癥變更或新增的相關(guān)變更
ANNEX VI
附件六
List of Member States referred in Article 24a
第二十四條 a 所述的成員國清單
the Republic of Bulgaria,
保加利亞共和國
the Federal Republic of Germany.
德意志聯(lián)邦共和國
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