英国脱欧专题：EMA集中审评程序框架内人药兽药有关问答（中英）20170531 - 药群论坛

Questions and Answers related to the United Kingdom's withdrawal from the EuropeanUnion with regard to the medicinal products for human and veterinary use within theframework of the Centralised Procedure

On 2 May 2017, the European Commission and EMA published a Notice to marketing authorisation holders of centrallyauthorised medicines products for human and veterinary use, stating: “The United Kingdom submitted on 29 March 2017 the notification of its intention to withdraw from the Union pursuant to Article 50 of the Treaty on European Union. This means that unlessthe withdrawal agreement establishes another date or the period is extended by the European Council in accordance with Article 50(3) ofthe Treaty on European Union, all Union primary and secondary law ceases to apply to the United Kingdom from 30 March 2019, 00:00h(CET). The United Kingdom will then become a 'third country'.”

2017年5月2日，EC和EMA发布了一份给人药和兽药集中审评药品上市许可持有人的通知，其中讲到：“英国于2017年3月29日根据欧盟协定第50条提交了正式通知告知其脱离欧盟的意向。这意味着除非脱欧协议设立其它日期，或EC根据欧盟协定第50（3）条延长期限，否则所有欧盟基本法和二级法将自2019年3月30日零点（CET时间）开始停止适用于英国。届时英国将会成为一个“第三国”。”

In this regard, marketing authorisation holders of centrally authorised medicinal products for human and veterinary use are reminded of certain legal consequences that need to be considered in a timely manner. Preparing for the consequences ofthe UK’s withdrawal from the Union is not just a matter for European and national administrations, but also for private parties.

鉴于此，在此提醒人药和兽药集中审评药品上市许可持有人应及时考虑某些法律后果。为英国脱欧做好准备不仅仅是欧洲和国家行政管理机构的事情，也是私人各方的问题。

This first list of Questions and Answers (Q&As) has been drafted jointly by the European Commission and EMA andconcerns information related to establishment requirements within the Union (EEA). The Q&As will be further updated and complemented in the near future.

本次首次列出的问答是由EC和EMA联合起草的，其中内容是关于EEA境内场所要求的信息。问答会进一步更新，并在近期进行补充。

According to Article 2 of Regulation (EC) No 726/2004 the marketing authorisation holder must be established in the Union.Through the EEA Agreement this is extended to include also Norway, Iceland and Liechtenstein.

For centrally authorised medicinal products the marketing authorisation holder will therefore normally need to transfer itsmarketing authorisation to a holder established in the Union (EEA) (see Commission Regulation (EC) 2141/96 and EMA Q&Aon transfer). This means that the addressee of the marketing authorisation decision changes to the new addressee.

对于集中审评药品来说，上市许可持有人则通常要将其上市许可证转让给EEA境内的持有人（参见欧盟EC2141/96以及EMA上市许可转让问答）。这意味着上市许可决策将受件人更改为新的受件人。

For designated orphan medicinal products the holder will therefore need to transfer its designation to a holder establishedin the Union (EEA) (see Checklist for sponsors applying for the transfer of Orphan Medicinal Product (OMP) designation and the corresponding template) or it will need to change its place of establishment to a Member State of the Union (or EEA)and submit the corresponding documentation through a change of name and/or address of the orphan designation holderprocedure provided the legal entity remains the same (see Guideline on the format and content of applications fordesignation as orphan medicinal products and on the transfer of designations from one sponsor to another, 27.03.2014).

对于已指定的孤独药品，持有人需要将其转让给EEA境内的持有人（参见申请孤独药品（OMP）指定的发起人清单以及相应的模板），或者如果法定实体保持不变（参见孤儿药申报内容和格式，以及发起人变更转让指南，2014-03-27），则需要变更其场所位置至成员国境内（或EEA境内），并且通过孤儿药持有人程序变更持有人名称和/或地址提交相应的文件.

If the sponsor/applicant is established in the UK, the MUMS incentives would no longer be applicable with effect from thedate of the UK’s withdrawal from the Union, as a sponsor/applicant established within a third country cannot seek andreceive MUMS/limited market classification in the Union (EEA). However, MUMS/limited market classification is connectedto the product/indication and therefore transferable together with the product.

如果发起人/申报人位于英国，则MUMS激励自英国脱欧之日开始将不再适用，因为第三国的发起人/申报人是不能寻求和接收EEA内MUMS/有限市场分类的。但是，MUMS/有限市场分类是与药品/适应症相关联的，因此，是可以连同品种一起转让的。

To formally acknowledge the transfer, the EMA requires a letter from the original sponsor/applicant officially informing the EMA of the transfer of the classification product and the MUMS/limited market classification from the originalsponsor/applicant to a sponsor/ applicant established in the Union (EEA). This letter should state the MUMS outcome letterdocument reference number.

对于正式通知的转让，EMA要求原研发起人/申报人发一份正式的函件通知EMA其转让分类药品和MUMS/有限市场分类至EEA境内的发起人/申报人。此函件中应给出MUMS结论函文件的索引号。

For already authorised MUMS/limited market veterinary medicinal products it is important to note that a transfer ofmarketing authorisation does not include a transfer of an MUMS/limited designation as this is subject to a differentprocedure. Therefore, for those authorised MUMS/limited market veterinary medicinal products the marketing authorisationholder needs to transfer the marketing authorisation (see: “What if I am a marketing authorisation holder established inthe UK (H + V)?”) and separately the MUMS/ limited market classification (see above).

对于已经批准的MUMS/有限市场兽药产品，要重点注意的一点是上市许可证的转让并不包括MUMS/有限市场的转让，因为这是不同的程序。因此，对于已批准的MUMS/有限市场兽药产品，上市许可持有人需要分别转让其上市许可证（参见“如果我是英国境内的上市许可持有人，要怎么办（H+V）？”）和MUMS/有限市场分类（见上）。

According to Article 8 of Directive 2001/83/EC and Article 74 of Directive 2001/82/EC, the qualified person responsible forpharmacovigilance must reside and carry out his/her tasks in the Member State of the Union (EEA). The QPPV will therefore need to change his/her place of residence and carry out his/her tasks in the Union (EEA) or a new QPPV residing and carrying out his/her tasks in the Union (EEA) will need to be appointed. Changes in the QPPV, including contact details(telephone, and fax numbers, postal address and email address) may, for medicinal products for human use, be updated through the Article 57 database only (without the need for a variation) (see Variation Guideline C.I.8). Regarding medicinalproducts for veterinary use the changes should be updated through a variation (see Variation Guideline C.I.9).

根据法令2001/83/EC第8条和法令2001/82/EC第74条，负责药物警戒的授权人必须居住并在EEA成员国内执行其任务。QPPV因此需要变更其居住地，在EEA境内执行其造作，或者需要重新重写一名居住的EEA的新QPPV并在EEA境内执行其任务。QPPV变更，包括联系信息（电话号码、传真号码、邮件地址和电子邮箱地址）变更，对于人药，可能需要通过第57条数据库进行更新即可（不需要提交变更）（参见变更指南C.I.8）。至于兽药，则需要通过提交变更来修改（参见变更指南C.I.9）。

According to Commission Implementing Regulation (EU) No 520/2012, the PSMF must be located within the Union (EEA). Thesupervisory authority for pharmacovigilance is the competent authority of the Member State in which the pharmacovigilance system master file is located .The marketing authorisation holder will therefore need to change thelocation of the PSMF to a Member State within the Union (EEA). Changes to the location of the PSMF (street, city,postcode, country) may be updated through the Article 57 database only (without the need for a variation) (see VariationGuideline C.I.8).

根据欧洲很会实施法规EU 520/2012规定，PSMF必须位于EEA境内。药物警戒监管机构是药物警戒系统主文件所在成员国的合法监管机构。上市许可持有人因而需要变更其PSMF的所在地至EEA境内成员国。PSMF所在地变更（国家、邮编、城市、街道）可能仅需要通过第57条数据库更新（不需要提交变更）（参见变更指南C.I.8）。

Directive 2001/83/EC and Directive 2001/82/EC state that manufacturing authorisation holders are obliged to use, asstarting materials, only active substances that have been manufactured in accordance with the detailed guidelines onGMP for starting materials.

In addition, pursuant to Article 46b(2) of Directive 2001/83/EC, active substances for medicinal products for human useshall only be imported in the Union (EEA) if, inter alia, the active substances are accompanied by a written confirmationfrom the competent authority of the exporting third country which, as regards the plant manufacturing the exported active substance, confirms that the standards of good manufacturing practice and control of the plant are equivalent to those inthe Union (EEA).

另外，根据法规2001/83/EC第46b(2)，人药用活性物质应该只能从EEA境内进口，否则该活性物质应有出口国药监当局的书面证明签发给生产该出口活性物质的工厂，确认其GMP标准和工厂控制与EEA境内等同。

The competent authorities of the Union (EEA) shall ensure that the import of medicinal products into their territory issubject to an authorisation in accordance with Article 40(3) of Directive 2001/83/EC and Article 44(3) Of Directive2001/82/EC. The authorisation is granted when a number of conditions, as defined in Articles 41 and 42 of Directive2001/83/EC and Articles 45 and 46 of Directive 2001/82/EC, are fulfilled (e.g. availability of a qualified person within theUnion (EEA), GMP inspection).

EEA境内的药监机构应确保进口至其境内的制剂根据法令2001/83/EC第40（3）条和法令2001/82/EC第44（3）条经过批准。当满足法令2001/83/EC第41和42条和法令2001/82/EC第45和46条所要求的一系列条件时（即，在EEA内有授权人、GMP检查），可以颁发许可。

For centrally authorised medicinal products the marketing authorisation holder will therefore need to specify an authorised importer established in the Union (EEA) and submit the corresponding variation (see Variation Guideline B.II.b.2).

In addition, in accordance with Article 51(1)(b) of Directive 2001/83 and Article 55(1)(b) of Directive 2001/82 the marketing authorisation holder will need to specify a site of batch control in the Union (EEA) where each production batch canundergo upon importation a full qualitative analysis, a quantitative analysis of at least all the active substances and all theother tests or checks necessary to ensure the quality of medicinal products in accordance with the requirements of the marketing authorisation.

另外，根据法令2001/83/EC第51（1）（b）条和法令2001/82/EC第55（1）（b）条，上市许可持有将需要在EEA境内指定一个批检测场所，在该场所执行逐批进口全检，至少要对所有活性物质进行定量分析，加上其它所有检测或必要的检查，以确保药品质量符合上市许可的要求。

For centrally authorised medicinal products the marketing authorisation holder will need to change the location of itscurrent UK based site of batch control to a location established in the Union (EEA) and submit the corresponding variation(see Variation Guideline B.II.b.2).

对于集中审评的药品，上市许可持有人则需要更改其目前执行批检验的英国地址，改为EEA内的位置，并且提交相应的变更（参见变更指南B.II.b.2）。

In accordance with Article 51(1) of Directive 2001/83/EC and Article 55(1) of Directive 2001/82/EC, the qualified person ofthe manufacturing and importation authorisation holder is responsible to certify that each batch of medicinalproduct intended to be placed on the EEA market was manufactured in accordance with EU GMP requirements and the marketing authorisation.

根据法令2001/83/EC第51（1）条和法令2001/82/EC第55（1）条，生产和进口许可持有人的授权人负责认证每批要在EEA销售的药品是根据EU GMP要求和上市许可证内容进行生产的。

For centrally authorised medicinal products the marketing authorisation holder will therefore need to transfer its current UKbased site of batch release to a location established in the Union (EEA) and submit the corresponding variation (see Variation Guideline B.II.b.2).

对于集中审评药品，上市许可持有人因而需要转移其当前在英国的批放行至EEA境内，并且提交相应的变更（参见变更指南B.II.b.2）。

· to apply for SME status once the company has established a legal entity in the Union (EEA). For proof ofestablishment, the SME office requires a copy of the certificate of incorporation in the company’s commercial register.In such cases, the SME declaration can be submitted in the name of the newly established subsidiary with details of the parent company to be declared.

· 一旦公司在EEA境内设立了法定实体即可申请SME状态。关于公司的证明，SME办公室要求提交一份公司商务登记时公司证照副本。在此情形下，可以使用新设定的分支机构的名义提交SME声明，在其中具体说明要声明的母公司情况。

· to indirectly benefit from the SME incentives through an Union (EEA) established SME regulatory consultancy. SMEregulatory consultancies may seek to benefit from the provisions of the SME Regulation on behalf of non-EEA based clients, only if both they and the client meet the SME criteria (i.e. fall below headcount and financial thresholds). In thiscase, both the regulatory consultancy and the non-EEA based company should submit SME declarations. If successful,the regulatory consultancy would receive an SME notification and the non-EEA based company would be listed in anannex to that notification as an SME client company. It is not possible for an SME regulatory consultancy to beconsidered eligible if they are acting on behalf of non-SME clients, as this would be contrary to the objectives of the SME Regulation.

· 通过EEA内的SME法规顾问从SME激励政策中间接获得受益。SME法规顾问可以从代表非EEA客户依照SME法规条款获得救济，但需要顾问和其客户均符合SME标准（即，员工数和财务额低于标准）。在些情形下，法规顾问和非EEA公司应提交SME声明。如果成功，则法规顾问将会收到SME通知，非EEA公司会被列在该通知的一份附录中作为SME客户公司。如果一个SME法规顾问在代表非SME客户，则该SME法规顾问会被认为不符合要求，因为这会违背了SME法规的目标。