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欧盟发布GMP远程检查指南,中国药企首次接受远程检查!

发布时间:2020-12-15  浏览:

欧盟发布GMP远程检查指南

  近日,EMA发布了《GMP/GDP和PMF 远程评估指南(Guidance related toGMP/GDP and PMF distant assessments)》,EMA表示:在国家或国际危机如 COVID-19疫情期间,可能因多种原因无法执行现场GMP/GDP 检查,如旅行限制、健康风险,或当地或国家药监发布的其它限制/指南。在此情况下,生产商、进口商和分销商符合GMP/GDP 的义务并不会被豁免,监管机构对其合规情况进行持续核查对于确保保护公众健康有着重要意义。在此情形下,同时考虑到国家和欧洲法规要求,远程评估不失为确定是否符合GMP/GDP 原则和指南的一种恰当方法,而本文列出执行远程评估的特殊考量要点。文件中指出,必要时所有类型的检查均可考虑执行远程评估。可对任何类型的场所,任何剂型按各案仔细评估之后进行远程评估,同时考虑相关的生产活动和产品的关键程度。

  自2020年11月25日以来,欧盟药监机构已对浙江京新制药公司、天津天士力药业有限公司(天津市北辰区汀江西路3号工厂天津市北辰区普吉河东路2号工厂)进行了远程检查。

  以浙江京新制药公司为例。在2020年11月25日,浙江京新药业正式接受了德国的官方远程审计,检查官通过现场连线视频对生产车间现场、设备设施验证、清洁验证报告、产品共线生产评估等进行审查,最后对公司在检查前递交的各项数目资料和视频现场的审查回复给出积极评价,最终顺利进行了远程审计。

  然而,和浙江京新相比,奥地利的Lupuca Pharma GmbH则没有这样幸运。该公司与2020-05-14接受奥地利当局的远程检查。经过官方远程审计,Lupuca Pharma GmbH被警告;其主要缺陷涉及供应商审计、变更管理、偏差管理、设备确认、计算机化系统验证等方面。

  EMA《GMP/GDP和PMF 远程评估指南》翻译如下:

  Guidance related to GMP/GDP and PMF distant assessments
  GMP/GDP和PMF 远程评估指南

  A. GMP/GDP distantassessment guidance (version1)
  第一部分:GMP/GDP远程评估指南(第一版)

  1. Introduction & Scope
  概述与范围

  1.1. Introduction
  概述

  During national orinternational crises such as the COVID-19 pandemic, on-site GMP/GDP inspectionsmay not be possible for a number of reasons such astravel restrictions, risk to health, or other restrictions/guidance issued by local or national authorities. Duringthese situations, the obligation of manufacturers,importers and distributors to comply with GMP/GDP is not waived and the ongoingverification of compliance by Supervisory Authorities is important toensure the protection of public health.
  在国家或国际危机如 COVID-19疫情期间,可能因多种原因无法执行现场GMP/GDP 检查,如旅行限制、健康风险,或当地或国家药监发布的其它限制/指南。在此情况下,生产商、进口商和分销商符合GMP/GDP 的义务并不会被豁免,监管机构对其合规情况进行持续核查对于确保保护公众健康有着重要意义。

  In thesecircumstances, taking into account national and European legislation, distantassessments can represent a suitablemeans of determining compliance with the principles and guidelines of GMP/GDPand the purpose of this document is to provide supplementaryguidance and points for consideration to inspectors relatingto the particulars of performing distant assessments.
  在此情形下,同时考虑到国家和欧洲法规要求,远程评估不失为确定是否符合GMP/GDP 原则和指南的一种恰当方法,而本文的目的则是提供补充指南,以及列出执行远程评估的特殊考量要点。

  If a member statedecides to use this guidance beyond the current COVID-19 pandemic, the IWGshould be informed.
  如果成员国决定在 COVID-19疫情以外使用本指南,应通知IWG。

  1.2. Scope
  范围

  In the context ofthis guidance, “distant assessment” can be defined as follows: “Assessment ofthe compliance of a site with the Union GMP/GDPprinciples performed by officials of Union Competent Authorities on the basis of documents and interviews and supported bytechnology for communicating, accessing systems,sharing and reviewing documents and other information, without the inspectorsbeing physically present at the sites where theactivities subject to the assessment have taken place and where the inspection would ordinarily be hosted”.
  在本指南中,“远程评估”可定义如下: “由EU 药监基于文件和面谈, 不实际亲临受检现场和通常主持检查的地方, 在通讯、 访问系统、共享和审核文件和其它信息的技术支持下执行的对现场 GMP/GDP原则符合性的评估”。

  This guidance isapplicable to manufacturers, importers, distributors and quality controllaboratories based in the EU/EEAand manufacturers and quality control laboratories in third countries, and isrelevantto Humanand Veterinary Medicinal Products, Investigational Medicinal Products, andActive Substances.
  本指南适用于与人药和兽药、临床试验用药品和活性物质有关的在 EU/EEA境内的生产商、进口商、分销商和 QC实验室,以及第三国生产商和QC 实验室。

  Thisguidance is not intended for use or to replace on-site inspections outside ofcrisis situations.
  本指南无意用于或取代危机情况以外的现场检查。

  2.Planning/Feasibility Assessment
  规划/可行性评估

  2.1.Manufacturing site/dosage form considerations
  生产场所/剂型考量

  Distantassessments can be considered for all types of inspections as necessary and canbe performed for all types of sites and dosage forms following a carefulcase-by-case evaluation, taking into account the criticality of themanufacturing activities and the product(s) concerned.
  必要时所有类型的检查均可考虑执行远程评估。可对任何类型的场所,任何剂型按各案仔细评估之后进行远程评估,同时考虑相关的生产活动和产品的关键程度。

  On-siteinspections should be conducted when circumstances permit following the distantassessment; the scheduling should be based on risk management principles andpriority should be given to sites which have never been inspected on-sitebefore by an EEA inspectorate or by an MRA partner authority, and to sterilemanufacturing processes.
  在情况允许时,远程评估之后应执行现场检查,计划应基于风险管理原则,应优先评估从未被EEA 检查组或由 MRA伙伴机构现场检查过的场所,优先评估无菌生产工艺。

  2.2.Distant assessments requested by the CHMP/CVMP and coordinated by EMA
  由 CHMP/CVMP申请并由 EMA协调的远程评估

  TheSupervisory Authority and inspectorate (if different) together with EMA shouldmake a case-by-case decision on whether a distant assessment is considered appropriateand feasible. For pre-approval distant assessments, the Rapporteurs should alsobe informed, and the criticality of the product should be taken intoconsideration.
  监管机构和检查组(如不同)应与 EMA一起根据各案决定远程评估是否恰当可行。对于批准前远程评估,还要通知主审国,同时要考虑药品的关键程度。

  Distantassessments should follow the applicable procedures that already exist forcoordinating, preparing and conducting GMP inspections requested by the CHMP orCVMP, respectively, and should take into consideration the present guidance.
  远程评估应遵守适用现有协调、准备和执行分别由 CHMP或 CVMP 申请的 GMP 检查的程序,同时考虑当前指南。

  Ifit is not deemed feasible to carry out or continue with a distant assessment,the inspection team shall communicate this to EMA without delay and the mostsuitable course of actions should be determined in each case together with theEMA product team and the Rapporteurs (e.g. adjust procedure timelines to facilitatean on-site inspection when restrictions are lifted).
  如果认为执行或继续远程评估不可行,则检查组应立即与 EMA就此进行沟通,并根据各案与 EMA产品组和主审国(例如,调整程序时间表以便于在限制解除之后进行现场检查)确定最适合的措施。

  2.3.Distant assessments coordinated by member states
  由成员国协调的远程评估

  IndividualNational Competent Authorities (NCAs) can determine on a case-by-case basiswhether a distant assessment is required, feasible and appropriate for sites ontheir national inspection programmes.
  各 NCA 可根据各案确定是否需要执行远程评估,确定其国家检查计划里的场所执行远程评估的可行性和恰当性。

  2.4.IT and other practical considerations
  IT和其它实际考虑

  Followinga decision to perform a distant assessment, early contact should be made withthe site todetermine the feasibility. Although it is envisaged thatmanufacturers, importers, and distributors generally have the necessaryresources and IT capabilities to support distant assessments, there are a numberof practical items that require consideration in order to determine the scopeof the distant assessment, and to ensure it is a suitable means of assessingthe required areas to allow for a decision to be made regarding GMP/GDPcompliance. At a minimum, the following should be considered:
  在决定执行远程评估之后,应与受检现场进行早期确定可行性。虽然设想是生产商、进口商和分销商通常具备必要的资源和 IT 能力来支持远程评估,但有大量实践问题需要考虑,以确定远程评估的范围,确保有合适的手段来评估所需评估的区域,使得能够做出 GMP/GDP 合规性的结论。最少要考虑以下方面:

  1. Theuse of appropriate platforms to allow for the timely provision of data such aslarge electronic documents (e.g. access to secure cloud servers or the use of Eudralinkor other secure NCA platforms).
  1. 使用适当的平台,以便及时提供数据如较大的电子文档(例如,访问安全的云服务器或使用Eudralink 或其它安全的 NCA 平台)

  Theuse of teleconference/videoconference or alternative to allow for real timediscussions with company personnel and Subject Matter Experts (SMEs).
  2. 使用电话会议/视频会议,或其它方式与公司人员和 SME进行实时讨论

  3.Thecapability for the live sharing of screens displaying computerised systems usedat the site, or the feasibility of providing remote (read-only) access toinspectors to computerised systems.
  3. 实时分享现场所用计算机化系统屏幕显示的能力,或者是为检查员提供计算机化系统远程(只读)访问的可行性

  4. The provision of live camera footage or video recordings (e.g. smart glasses,mobile cameras, drones or cameras in place) to allow for a remote review ofmanufacturing operations, equipment, facilities and relevant documentation suchas logbooks, if applicable.
  4. 提供直播摄像头录影或视频录像(例如,现场智能眼镜、手机相机、无人机或相机)对生产操作、设备、设施和相关文件如日志(如适用)进行远程审核

  5. Thetime zones of the site and the location of the inspector(s).
  5. 现场与检查员所在地区的时区

  6. Thelanguage of the site. The inspector(s) may require access to a translator forparts of or all of the remote inspection.
  6. 现场所用语言。检查员可能会要求翻译部分或所有远程检查内容

  Theoutcome of these considerations may highlight whether any additional resourcesare required by either the site or the inspectorate(s) conducting the distantassessment.
  这些考虑的衡量结果可能会提醒受检现场或执行远程评估的检查组是否需要其它资源。

  Itis preferable for the site to host and manage the communication platform andconsider its security requirements. In cases where the site does not have orcannot obtain the appropriate capabilities, the inspectorate(s) could considerhosting the communication platform.
  最好是由受检现场主持和管理通讯平台,考虑其安全性要求。如果受检现场没有或者不能获得适当的能力,则检查组可以考虑主持通讯平台。

  Anexample of an optimal communication platform could include the following:
  优化通讯平台的例子可以包括以下内容:

   Alive videoconference platform which has the following capabilities:
   实时视频会议平台,具备以下能力:

   -Break-out rooms/conferences to facilitate separate channels of discussionbetween different inspectors and the site.
   -独立房间/会议以便不同检查员和现场采用不同频道分头讨论

   -Screen sharing to display site applications/electronic systems.
   -屏幕共享展示现场应用程序/电子系统

   Smartglasses or other mobile cameras which can be interfaced to the videoconferenceplatform to provide live footage of manufacturing operations, facilities andequipment.
   智能眼镜或其它手机相机,可接入视频会议平台提供生产操作、设施和设备的实时录像

   Accessto a secure cloud server to share documents.
   访问安全的云服务器查看共享文件

  2.5.Limited on-site inspections
  有限现场检查

  Dependingon the circumstances at the time, it may be possible to conduct a limitedon-site inspection of sites located in the EEA. This should only be consideredif it is compatible with travel restrictions, health measures, and otherrestrictions/guidance issued by local or national authorities at the time and shouldbe discussed with the site. The inspection could consist of a distantassessment of relevant documentation with a limited on-site inspection ofmanufacturing operations, facilities and equipment. The on-site inspection anddistant assessment should be considered together as parts of the same inspection.A single inspection report and inspection outcome (e.g. GMP certificate) shouldbe produced.
  根据当时环境的不同,可对 EEA 内现场执行有限的现场检查。这种情况仅在与旅行限制、健康措施和本地或国家机构当时发布的其它限制/指南没有冲突时才可考虑,并需与现场进行讨论。检查可以包括对相关文件进行远程评估,对生产操作、设施和设备进行有限的现场检查。现场检查和远程评估应作为同一检查的一部分一起进行考虑。应只制作一份检查报告和检查结果(例如 GMP 证书)。

  2.6.Distant assessment duration
  远程评估时长

  Theprinciples of the Union procedures A Model for Risk Based Planning for Inspectionsof Pharmaceutical Manufacturers and GDP Inspection Procedure (MedicinalProducts for Human Use) should be taken into account, as relevant, whendetermining the scope and duration required for the distant assessment.
  在决定远程评估的范围和时长时应考虑 EU程序“基于风险的药品生产商检查规划模式和GDP 检查程序(人药)”的原则(如相关)。

  Thepracticalities and potential challenges associated with distant assessmentsshould also be considered and could result in a longer duration compared to anequivalent on-site inspection. Aspects such as the communication process, sitetime zone and language, and location(s) of the inspectors should be taken intoaccount.
  亦应考虑远程评估的实践情况和潜在挑战,相比于同类现场检查,远程评估可能需要的时间更长。像通讯过程、现场时区和语言,以及检查员所在地方这些方面均应进行考虑。

  3.Preparation
  准备工作

  Inspector(s)should adequately prepare for the distant assessment and familiarise themselveswith the site to be inspected, in accordance with the Union procedures for Conductof Inspections of Pharmaceutical Manufacturers or Importers and GDPInspection Procedure (Medicinal Products for Human Use), as relevant.
  检查员应根据“基于风险的药品生产商检查规划模式和GDP 检查程序(人药)”(如有关)为远程评估进行充分准备,熟悉受检场所。

  3.1.Distant assessment plan
  远程评估计划

  Itis recommended that a plan is drafted in a manner similar to on-siteinspections, outlining the areas of the site to be reviewed by each inspector.It is also recommended to share relevant parts of the plan and timetable withthe site to facilitate the smooth running of the distant assessment and ensurethat site SMEs are available at the requested times.
  建议以类似于现场检查的方式起草计划,概述每个检查员要检查的现场区域。 还建议与受检现场共享计划和时间表的相关部分,以促进远程评估的顺利进行,并确保现场 SME 在要求的时间内有空。

  3.2.Announcement of distant assessment
  宣布远程评估

  Notificationof the intention to perform a distant assessment should be communicated to thesite in accordance with the standard timelines for on-site inspections. Inorder to prevent any delays during the distant assessment, consideration shouldbe given to requesting that electronic copies of documents and/or lists ofdocuments are provided to the inspector(s) in advance of the distant assessmentor, at least, are available for review from the start of the distantassessment.
  应当按照现场检查的标准时间表,将进行远程评估的意向通知给受检现场。为了防止在远程评估期间出现任何延误,应考虑要求在远程评估之前向检查员提供文件和/或文件的电子副本,或者至少从远程评估开始时应能够提供文件进行审查。

  3.3.Communication process for the distant assessment
  远程评估沟通流程

  Thecommunication platform and process for the provision of electronic copies ofdocuments and other information to the inspector(s) should be defined andagreed with the site in advance of the distant assessment. Consideration shouldbe given to the items listed in paragraph 2.4. IT and other practical considerations.
  在远程评估之前,应确定向检查员提供文件和其他信息的电子副本的通信平台和过程,并与现场达成一致。应考虑第2.4 段“IT和其他实际考虑” 中列出的项目。

  Ifthere are significant differences in the time zones of the inspector(s) and thesite, it is possible that site personnel may not always be available to respondto inspector queries in real time. In these cases, the inspector(s) shouldensure that they have sufficient documentation available for review when site personnelare not online, and related queries should be logged as documents are beingreviewed. In these circumstances, efforts should be made to ensure that thereis at least a sufficient over-lap time each day to hold discussions in realtime.
  如果检查人员和受检现场的时区存在显著差异,现场人员可能无法一直实时响应检查人员的查询。在这些情况下,检查员应确保他们有足够的文档可用于当现场人员不在线时进行检查, 文件被查阅时应有登记。在这种情况下,应努力确保每天至少有足够的重叠时间来进行实时讨论。

  Thecommunication process between inspectors should also be determined ifinspectors are based in different locations. To avoid duplication of review ordocument requests, consideration should be given to making all requests fordocuments and other information visible to all members of the inspection team.
  如果检查员位于不同的地点,则还应确定检查员之间的沟通过程。为了避免重复审阅或索取文件,应考虑使检查组的所有成员都可以看到所有文件索取要求和其他信息。

  Itis recommended that the communication platform is tested prior to thecommencement of the distant assessment to verify its functionality. If possible,IT support staff should be readily available to respond to any IT issues thatmay arise during the remote distant assessment. The site should also be awarethat if there are any unexpected delays in the provision of electronic copiesof documents to the inspector during the distant assessment, the inspector(s)should be informed immediately.
  建议在开始进行远程评估之前先对通信平台进行测试,以验证其功能。如果可能的话, IT支持人员应随时准备对远程评估中可能出现的任何 IT 问题做出响应。现场还应注意,如果在远距离评估期间向检查员提供文件的电子副本有任何意外的延误,应立即通知检查员。

  4.Conduct
  执行

  4.1.Opening Meeting
  首次会议

  Thedistant assessment should start with an opening meeting via videoconference,teleconference or alternative. In addition to covering the relevant itemslisted in the Union procedures for Conduct of Inspections of PharmaceuticalManufacturers or Importers and GDP Inspection Procedure (Medicinal Productsfor Human Use), as relevant, the inspector should consider outlining thefollowing:
  远程评估应从通过视频会议,电话会议或其他方式的首次会议开始。检查员除了要涵盖《欧盟药品生产商或进口商检查程序》和《 GDP 检查程序(人用药品)》中列出的相关项目外,还应考虑列出以下内容:

  1. Abrief overview of the process for communication and the distant assessmentplan/timetable.
  1. 简要介绍沟通过程以及远程评估计划/时间表

  2. Anyvideo/audio recording of the distant assessment by the inspectorate should beagreed between the site and the inspector(s). If part of the distant assessmentwill be recorded, the site should be given the opportunity to appropriatelyinform any personnel who may appear in such video footage in accordance withany relevant local legislation.
  2. 检查组如需对远程评估进行任何视频/音频录制均应获得受检现场和检查员的同意。如果录制远程评估的一部分,则应让受检现场有机会恰当地通知可能出现在录像中的人员

  4.2.Performing the distant assessment
  执行远程评估

  Relevantelements of the Union procedures for Conduct of Inspections ofPharmaceutical Manufacturers or Importers, the Outline of a Procedurefor Co-ordinating the Verification of the GMP Status of Manufacturers in ThirdCountries and GDP Inspection Procedure (Medicinal Products for HumanUse) should be considered to assess the compliance with GMP/GDP and withthe terms and conditions of authorisation(s) as applicable.
  在评估是否符合 GMP /GDP 和批准条款和条件(如适用)时应考虑“欧盟药品制造商或进口商检查程序”、“第三国生产商 GMP状态验证协调程序纲要” 和“GDP 检查程序(人药) ” 的有关内容。

  Ifa distant assessment of manufacturing operations, facilities and equipment isfacilitated through the use of cameras or video footage, it may be useful tohave the site schematics, drawings and/or process flow diagrams available forreference, as relevant, to help the orientation of the inspector(s).
  如果对生产操作、设备和设备进行远程评估时使用了照相机或摄像机录影来提供帮助,为检查员提供现场流程图、图纸和/或工艺流程图供参考(如相关)可能会有助于检查员确定方向位置。

  Inorder to facilitate the smooth running of the distant assessment, at the end ofeach day, the inspector may consider informing the site of the documentationintended to be reviewed the following day to give sufficient notice for thescanning and provision of the requested documents. As the inspector reviews anew topic (e.g. deviations, process validation etc.), it may also be helpful topromptly communicate this to the site.
  为了便于远程评估的顺利进行,检查员可以在每天结束时考虑将第二天要检查的文件通知现场,以便为扫描和提供所需文件提供足够的通知。当检查员检查新主题(例如偏差,过程验证等)时,及时将其传达给现场也可能会有所帮助。

  Inspectorsshould record notes on the documents being reviewed as per on-site inspections.Relevant documents, emails and other information received should be securelysaved or deleted as required.
  检查员应按现场检查方式在被检查的文件上记录备注。 所收到的相关文档、 电子邮件和其他信息应按要求安全地保存或删除。

  4.3.Closing meeting
  末次会议

  Thedistant assessment should end with a closing meeting via videoconference,teleconference or alternative and should cover the relevant items listed in theUnion procedures for Conduct of Inspections of Pharmaceutical Manufacturersor Importers and GDP Inspection Procedure (Medicinal Products for HumanUse), as relevant.
  远程评估应以电视会议、 电话会议或其他方式的闭幕会议结束,并应涵盖“欧盟药品制造商或进口商检查程序” 和“GDP 检查程序(人药) ” 中列出的相关项目。

  5.Post distant assessment activities
  远程评估结束后的工作

  5.1.Distant Assessment Report
  远程评估报告

  Distantassessment reports should be written in line with the Union formats of GMP/GDPinspection reports. Appropriate clarifying remarks should be included inrelevant sections of the report to make it clear that a distant assessment wasperformed and to indicate if physical aspects of the facility were assessed andthe methods used.
  远程评估报告应按照 GMP /GDP 检查报告的欧盟格式编写。报告的相关章节中应包含适当的澄清说明,以明确进行了远程评估,并指出是否对设施的物理方面进行了评估以及所使用的方法。

  5.2.GMP/GDP certificates
  GMP/GDP证书

  Ifthe outcome of the distant assessment is positive, GMP/GDP certificates shouldbe issued. For GMP distant assessments, the Type of Inspection on thecertificate should indicate Distant Assessment. If a limited on-siteinspection as per paragraph 2.5. was conductedthe Type ofInspection on the certificate should reflect the on-site inspection and aclarifying remark may be included to indicate that part of the inspection wasperformed as a distant assessment.
  如果远程评估的结果是肯定的,则应签发 GMP/ GDP 证书。 对于 GMP 远程评估,证书上的“检查类型”应指明“远程评估”。 如果是第 2.5 段所述的有限现场检查,则证书上检查类型应反映出现场检查,并注明有一部分检查是采用的远程评估。

  Existingregulatory risk management principles should be used to determine the durationof the validity of GMP/GDP certificates issued following distant assessments.
  应使用现有的监管风险管理原则来确定在进行远程评估后颁发的 GMP/ GDP 证书的有效期限。

  5.3.Serious GMP/GDP non-compliance
  严重 GMP/GDP不符合

  Fornew sites, including pre-approval distant assessments requested by EMA, if anycritical deficiencies are identified during the distant assessment, therelevant application should be put on hold until an onsite inspection can beperformed.
  对于少数场所,包括由 EMA 申请的批准前远程评估,如果在远程评估期间发现有关键缺陷,则应搁置相关申报,直到执行现场检查。

  Forother types of distant assessments, if any critical deficiencies are identifiedduring the distant assessment, existing processes for on-site inspectionsshould be followed and a Statement of noncompliance may be issued ifapplicable.
  如果是其它类型的远程评估,如果在远程评估期间发现任何关键缺陷,则应执行现场检查的现有流程,适当时签发不符合声明。

  5.4.Planning of next Inspection
  下次检查的计划

  On-siteinspections should be conducted once circumstances permit. The principles ofthe Union procedures A Model for Risk Based Planning for Inspections ofPharmaceutical Manufacturers and GDP Inspection Procedure (MedicinalProducts for Human Use) should be used as relevant when recommending thenext interval, scope as well as duration and number of inspectors for the next inspectionof the site. A distant assessment may be considered a suitable justification torecommend a reduced interval until the next on-site inspection. The followingitems could also be taken into consideration:
  一旦情况许可即应执行现场检查。在提出下次检查时间、范围以及下次现场检查的时长和检查员人数建议时,如有相关应采用 EU 程序“基于风险的药品生产检查计划模式和 GDP检查程序(人用药)”的原则。远程评估可作为适当的评判手段,建议缩短到下次现场检查的时间间隔。同时亦应考虑以下情况:

  1. Therisk and complexity of the dosage form/active substance/manufacturing process.
  1. 剂型/活性成分/生产工艺的风险和复杂程度

  2. Thecompliance history.
  2. 合规历史

  3. Thetype of distant assessment (e.g. for-cause distant assessment or distantassessments to support an application for a new type of product or activity).
  3. 远程评估的类型(例如,有因远程评估或为支持新的产品类型或活动的申报而进行的远程评估)

  4. Thedate of the last inspection.
  4. 上次检查的时间

  B.PMF distant assessment guidance (version 2)
  B.PMF 远程评估指南(第 2 版)

  1.Introduction & Scope
  概述与范围

  1.1.Introduction
  概述

  Duringthe COVID-19 pandemic, on-site PMF inspections of plasma collection sites maynot be possible for a number of reasons such as travel restrictions within andbetween the boarders of countries, risk to health, or otherrestrictions/guidance issued by local or national authorities.
  在 COVID-19疫情期间,对血浆采集现场进行现场 PMF检查可能由于多个原因而无法执行,例如国内外旅行限制、健康风险,或当地或国家药监发布的其它限制/指南。

  Duringthese situations, the obligation of Blood Establishments to comply with GMP/GPis not waived and the ongoing verification of compliance by SupervisoryAuthorities is important to ensure the protection of public health andconsequentially the access to essential medicines.
  在此情况下,血液场所符合 GMP/GP 的义务并不会被豁免,监管机构对其合规情况进行持续核查对于确保保护公众健康和持续获得基本药物有着重要意义。

  Thisdocument provides guidance on conducting distant assessments of new plasmacollection centres operated by a parent company/blood establishment thatalready operates other centres that are included in the manufacturers’ PMFduring the COVID-19 pandemic to determine compliance of the centre with GMP/GP.In addition, an on-site inspection should be conducted as soon as circumstancespermit.
  本文指导的是由已经运营了其它中心的母公司/血液场所运营的新血浆采集中心,在 COVID-19疫情期间加到生产商的 PMF 中,需要确定新中心合规情况时执行远程评估。此外,一旦情况许可应尽快进行现场检查。

  Distantassessments should take into consideration the limitations imposed by using aremote process and recognise that such a remote process cannot completelyreplace an on-site inspection.
  远程评估应考虑使用远程方法带来的局限性,认识到此类远程方法并不能完全替代现场检查。

  Thepurposes of this document is to outline the requirements and specificities ofdistant assessments for PMF plasma collection centres outlining the points tobe considered during the preparation, conduct, and reporting phase in thiscontext.
  本文件的目的是列出远程 PMF 血浆采集中心的远程评估要求和标准,列出此情况下在准备、执行和报告阶段所要考虑的要素。

  1.2.Scope
  范围

  Ingeneral, Blood Establishments have access to appropriatetechnologies/platforms, electronic systems and virtual working environmentsfacilitating communication of remote staff. These may enable appropriatecommunication settings during distant assessments. In these circumstances, distantassessments can represent a suitable means of determining compliance with theprinciples and guidelines of GMP/GP.
  一般来说,血液机构可以使用适当的技术/平台、电子系统和虚拟工作环境,促进远程工作人员的交流。这些可以在远程评估期间启用适当的通信设置。在这种情况下,远程评估是确定是否符合 GMP/GP原则和指南的合适方法。

  Thisdocument is intended to provide guidance on the conduct of distant assessmentsduring the COVID-19 pandemic. It is applicable to new plasma collection centresoperated by a parent company/blood establishment that already operates othercentres that are included in the manufacturers’ PMF (as stipulated in theNotice to Stakeholders issued by the European Commission, Heads of MedicinesAgencies (HMA) and EMA and entitled “Questions and Answers on Regulatory Expectationsfor Medicinal Products for Human Use during the COVID-19 Pandemic”). Forcentres that have been previously inspected and for which a control measure mayalready have been performed, the time frame for reinspection can be extendedduring the COVID-19 pandemic by performing either another control measure inline with EMA recommendation EMA/INS/GMP/534269/2018 "Application of inspectionand control measures" or a distant assessment.
  本文件旨在为 COVID-19疫情期间进行远程评估提供指导。适用于由已经运营了其它中心的母公司/血液场所运营的新血浆采集中心(EC、 HMA 和 EMA 发布的干系人须知和“COVID-19疫情期间人药注册要求问答”中规定)。对于之前已接受过现场检查,已执行了控制措施的中心,在疫情期间可以通过按照 EMA 建议“EMA/INS/GMP/534269/2018检查和控制措施的应用”执行另一次控制措施,或者通过远程评估延长重新检查时间。

  Thisguidance is not intended for use or to replace on-site inspections duringnormal circumstances which are conducted in line with existing guidance.
  本指南不适用于或取代按照现有指南在正常情况下进行的现场检查。

  2.Planning/Feasibility Assessment
  计划/可行性评估

  Thepreparation of a distant assessment will be significantly more demandingcompared to on-site inspections. Following a request to perform a distantassessment, the intended extent of the distant assessment should becommunicated in a timely manner.
  与现场检查相比,远程评估准备工作的要求要高得多。在要求进行远程评估后,应及时告知远程评估的预期范围。

  Thedistant assessment feasibility will need to be assessed by the inspection team( e.g. whether the inspectee meets the technical requirements such as providingremote (read-only) access to electronic systems and maintain communication withand support to inspectors). The inspectee should provide detailed informationas requested by the inspectors to allow for the feasibility assessment. In thiscontext, appropriate mitigation strategies (e.g. for poor communication ornon-optimal system performances/interruptions) should also be considered.
  远程评估的可行性将需要由检查小组进行评估(例如,检查人员是否满足技术要求,例如远程(只读)访问电子系统,并与检查人员保持通信和支持)。受检方应按检查员的要求提供详细资料,以便进行可行性评估。在这种情况下,还应该考虑适当的应对策略(例如,针对通信不良或非最佳系统性能/中断)。

  Thepracticalities and potential challenges associated with distant assessmentscould result in a longer duration compared to an equivalent on-site inspection.Aside from aspects such as the communication processes, company time zone,language, and location(s) of the inspection team should be considered. Theprinciples of the EMA Guideline Application of inspection and controlmeasures to facilitate riskbased inspection planning of sites within the PlasmaMaster File (PMF) certification system should be taken into account, whendetermining the extent and duration required for the distant assessment.
  与相应的现场检查相比,远程评估的实用性和潜在挑战可能导致持续时间更长。除了沟通过程等方面,还应考虑公司时区、语言和检查组的位置。在确定远程评估所需的范围和持续时间时,应考虑 EMA 指南“应用检查和控制措施以便于血浆主文件(PMF)认证系统内基于风险的检查规划” 中的原则。

  2.1.Distant assessments requested by the CHMP and coordinated by EMA
  CHMP申请由 EMA协调的远程评估

  Theinspectorate together with EMA should make a case-by-case decision on whether adistant assessment is considered appropriate and feasible.
  检查组和 EMA 应就远距离评估是否合适和可行作出具体决定。

  Distantassessments should follow the applicable procedures that already exist forcoordinating, preparing and conducting PMF inspections requested by the CHMPand should take into consideration the present guidance. Similar to the processfor on-site inspections, multiple sites can be grouped for distant assessmentsunder one reference number. Procedure timelines should be agreed between the inspectorateand EMA taking into consideration that grouped distant assessments mightrequire a greater period of time than normally applied for the conduction ofon-site inspections.
  远程评估应遵守现有的协调、准备和执行由 CHMP申请的 PMF 检查的适用程序,并考虑现有指南。与现场检查的过程类似,可以将多个场址按一个编号组合进行远程评估。程序时间表应由检查组和 EMA 商定,同时考虑组合远程评估可能比通常执行现场检查需要更长的时间。

  Ifit is not deemed feasible to carry out or continue with a distant assessment,the inspection team shall communicate this to EMA without delay and the mostsuitable course of actions should be determined in each case (e.g. adjustinspection timelines to facilitate an on-site inspection when restrictions arelifted) together with the PMF coordinator. The PMF holder should also beinformed.
  如果认为执行或继续远程评估不可行,则检查组应与 EMA及时沟通, 与 PMF 协调员一起按具体情况对各案采取最适当的措施(例如,调查检查时间以便于在限制解除时进行现场检查) 。 还应通知 PMF 持有人。

  2.2.Distant assessments coordinated by member states
  成员国协调的远程评估

  IndividualNCAs can determine on a case by case basis whether a distant assessment isrequired, feasible and appropriate for sites on their national inspectionprogrammes during the COVID-19 pandemic.
  个别 NCA 可根据具体情况确定,在疫情期间,其国家检查规划的场址是否需要进行远程评估、是否可行和是否合适。

  2.3.IT and other practical considerations
  IT和其它实践考虑

  Theremay be many challenges for an organisation to support distant assessments. Itis fundamental to assess whether the inspectee has the necessary resources andIT capabilities to support distant assessments not only at the headquarter butalso at the collection/processing sites. A number of practical items requireconsideration in order to ensure the distant assessment is a suitable measure. Thefollowing items should be considered: 
  一个组织要支持远程评估可能会面临许多挑战。评估被检查者是否具有必要的资源和 IT能力支持总部和采集/加工场所的远程评估是至关重要的。为了确保远距离评估的恰当性,需要考虑许多实际项目。应考虑以下内容:

  1. Theuse of teleconference/videoconference or alternative to allow for real timediscussions with site personnel, especially at the collection sites.
  1. 使用电话会议/电视会议或其他方式可以与现场人员进行实时讨论,尤其是在采集现场

  2. Thecapability for the live sharing of screens displaying computerised systems usedat the site, or the provision of remote (read-only) access to inspectors tocomputerised systems, especially at the collection sites.
  2. 受检现场使用的计算机系统的屏幕实时共享的功能,或为检查员提供远程访问(只读) 计算机系统(特别是在采集现场)的功能

  3. Theuse of appropriate platforms to allow for the timely provision of largeelectronic documents (e.g. access to secure cloud servers or the use ofEudralink or other secure NCA platforms). Methods used to share, and transferinformation should comply with an adequate standard of security as well as withIT policies of the inspectorate(s) and the site, especially for the exchange ofhighly confidential donor information.
  3. 使用适当的平台来及时提供大型电子文档(例如,访问安全的云服务器或使用 Eudralink或其他安全的 NCA 平台)。用于共享和传递信息的方法应符合适当的安全标准以及检查机构和受检现场的IT 策略,尤其是在交换高度机密的捐助者信息时。

  4. Thecommunication process between members of the inspection team, especially whennot in the same location.
  4. 检查团队成员之间的沟通过程,尤其是不在同一地点时

  5. Thetime zones of the site undergoing distant assessment and the location of theinspector(s).
  5. 进行远程评估的现场的时区和检查员的地点

  6. Thelanguage of the site. The inspector(s) may require access to a translator forparts of or all of the distant assessment.
  6. 工厂的语言。 检查员可能需要对部分或全部远程评估进行翻译

  7. Theoutcome of these considerations may highlight whether any additional resourcesare required by either the site or the inspectorate(s) conducting the distantassessment.
  7. 这些考虑的结果可能会突出显示进行远程评估的现场或检查机构是否需要任何其他资源。

  Itis preferable for the site to host and manage the communication platform andconsider its security requirements. In cases where the site does not have orcannot obtain the appropriate capabilities, the inspectorate(s) could considerhosting the communication platform.
  最好由现场提供和管理通信平台并考虑其安全要求。 如果受检现场不具备或无法获得适当的功能,则检查机构可以考虑提供通信平台。

  Anexample of an optimal communication platform could include the following:
  最佳通信平台的示例可以包括以下内容:

   Alive videoconference platform which has the following capabilities:
   直播视频会议平台, 具有以下功能

   -Break-out rooms/conferences to facilitate separate channels of discussionbetween members of the inspection team and the site.
   -分开房间/会议, 以便于检查组成员和现场单独进行讨论

   -Screen sharing to display site applications/electronic systems.
   -屏幕共享, 显示现场申报/电子系统

   Accessto a cloud server and other secure platforms in compliance with IT policies ofthe inspectorate(s) and the site to share documents including highlyconfidential donor information.
   访问符合检查组和受检现场 IT 政策的云服务器和其它安全的平台, 实现共享文件包括高度机密的捐献者信息

   Achat / instant-messaging platform should be considered, in case of soundinterferences.
   如果是语音会议, 可考虑使用聊天/即时通讯平台

  3.Preparation
  准备工作

  Inspector(s)should prepare adequately for the distant assessment and familiarise themselveswith the site to be inspected, taking into account the existing guidance.
  检查人员应对远距离评估进行充分准备,并在考虑现有指导的情况下熟悉要检查的现场。

  Aplan similar to an inspection plan for on-site inspections, outlining the areasof the site to be reviewed by each member of the inspection team may facilitatethe smooth running of the distant assessment and ensure that siterepresentatives are available at the requested times.
  制订与现场检查的检查计划相似的计划, 列出检查组的每个成员要检查的现场领域,可以促进远程评估的顺利进行,并确保在要求的时间有现场人员。

  3.1.Announcement of distant assessment
  宣布远程评估

  Notificationof the intention to perform a distant assessment should be communicated to thesite in accordance with the standard timelines for on-site inspections. Inorder to prevent any delays during the distant assessment, consideration shouldbe given to requesting that electronic copies of documents and/or lists ofdocuments are provided to the inspector in advance of the distant assessmentor, at least, are available for review from the start of the distantassessment.
  应当按照现场检查的标准时间表,将进行远程评估的意向通知给受检现场。为了防止在远程评估期间出现任何延误,应考虑要求在远程评估之前向检查员提供文件和/或文件的电子副本,或者至少从远程评估开始时应能够提供文件进行审查。

  Itshould be communicated that a subsequent on-site inspection is required inaddition to the distant assessment to be conducted when circumstances permit.
  应当告知,在情况允许的情况下,除了进行远程评估外,还需要进行后续的现场检查。

  3.2.Distant assessment agenda
  远程评估计划

  Adetailed agenda similar to on-site inspections should be submitted to theinspectee in advance. The agenda should list all (planned) sessions andanticipated time slots for items that need to be scheduled to facilitate thesmooth running of the distant assessment and ensure that relevant siterepresentatives are available at the requested times.
  应提前向受检方提交一份与现场检查相似的详细检查计划。 计划中应列出所计划的会议和需要安排的项目的预期时间段, 以便于远程评估顺利进行, 确保在所要求的时间内有相应的现场人员应答。

  3.3.Communication process for the distant assessment
  远程评估沟通过程

  Thecommunication platform and process for the provision of electronic copies ofdocuments and other information by the site to the inspector(s) should bedefined and agreed with the site in advance of the distant assessment.Consideration should be given to the items listed in paragraph 2.4. IT andother practical considerations.
  在远程评估之前,应确定向检查员提供文件和其他信息的电子副本的通信平台和过程,并与现场达成一致。应考虑第2.4 段“IT和其他实际考虑” 中列出的项目。

  Durationof daily sessions should be agreed between inspectors and inspectee, especiallyif there are significant differences in the time zones of the inspector(s) andthe site, and in adherence to procedures on both sides. A host should beassigned by the inspectee to coordinate and manage further requests and queriesduring the distant assessment.
  每天议程的时长应由检查员与受检方协定, 尤其是当检查员与受检现场有较大时差时,并遵守双方的程序。 应由受检方指定一个主持人协调和管理远程评估期间其它请求和查询。

  Thecommunication process between inspectors should also be determined ifinspectors are based in different locations. To avoid duplication of review ordocument requests, consideration should be given to making all requests fordocuments and other information visible to all members of the inspection team.
  如果检查员位于不同的地点,则还应确定检查员之间的沟通过程。为了避免重复审阅或索取文件,应考虑使检查组的所有成员都可以看到所有文件索取要求和其他信息。

  Itis recommended that the communication platform is tested prior to thecommencement of the distant assessment to verify its functionality. IT support staffshould be readily available to respond to any IT issues that may arise. Anyunexpected delays in the provision of electronic copies of documents to theinspector during the distant assessment should be communicated to theinspector(s) immediately.
  建议在开始进行远程评估之前先对通信平台进行测试,以验证其功能。 IT支持人员应随时准备应对可能出现的任何 IT问题。在远距离评估期间,向检查员提供文件电子副本的任何意外延迟都应立即通知检查员。

  4.Conduct
  执行

  4.1.Opening Meeting
  首次会议

  Thedistant assessment should start with an opening meeting via videoconference,teleconference, or alternative.
  远程评估应从通过视频会议,电话会议或其他方式的首次会议开始。

  Inaddition to taking into consideration the relevant items listed in existingguidance, the inspector should consider outlining the following:
  除了要考虑现有指南中所列的相关条款之外, 检查员还应考虑列出以下内容:

  1. particularitiesof a distant assessment setting so that the scope and logistics are understoodby all parties involved
  1. 远程评估的特殊设置, 涉及各方应了解其范围与逻辑性

  2. Abrief overview of the process for communication.
  2. 简要介绍沟通过程以及远程评估计划/时间表

  3. Theinspectee should provide a list of attendees for the opening meeting
  3. 受检方应提交一份首次会议的出席者名单

  4. Video/audiorecording of the distant assessment is forbidden. It shall be guaranteed to theinspector to get photos of buildings, rooms and equipment if necessary. Thisshall be attached to the distant assessment report.
  4. 远程评估期间禁止录制视频/音频。 应保证检查员获得厂房、 房间和设备(必要时) 的图片。 这些图片应附在远程评估报告中。

  4.2.Performing the distant assessment
  执行远程评估

  Relevantelements of existing guidance should be considered to assess the compliancewith GMP/GP and with the terms and conditions of the Plasma Master File.
  应考虑现有指南的相关要素,以评估其对 GMP/ GP 以及 PMF 项目和条件的遵守情况。

  Essentialcomponents of the distant assessment include interviews, presentations (by theinspectee) relating to the topics requested by inspectors in the agenda, anddocumentation review. Where electronic systems for data management are used, itis necessary to have remote (read-only) access to these systems.
  远程评估的基本组成部分包括谈话,与检查员在议程中要求的主题相关的演讲(由受检方进行)和文件审查。在使用数据管理用电子系统时,必须具有对这些系统的远程(只读)访问权限。

  Inorder to facilitate the smooth running of the distant assessment, at the end ofeach day, the inspector may consider informing the site of the documentationintended to be reviewed the following day to give sufficient notice for thescanning and provision of the requested documents. As the inspector reviews anew topic (e.g. deviations, process validation etc.), it may also be helpful topromptly communicate this to the site.
  为了便于远程评估的顺利进行,检查员可以在每天结束时考虑将第二天要检查的文件通知现场,以便为扫描和提供所需文件提供足够的通知。 当检查员检查新主题(例如偏差,过程验证等)时,及时将其传达给站点也可能会有所帮助。

  4.3.Closing meeting
  末次会议

  Thedistant assessment should end with a closing meeting covering the relevantitems taking into account existing guidance.
  远程评估结束时应有末次会议, 其中要覆盖现有指南中所列的相关项目。

  Itshould also be communicated that an additional on-site inspection is requiredwhen circumstances permit.
  还应说明在情况允许时会进行另外的现场检查。

  5.Post distant assessment activities
  远程评估之后的活动

  5.1.Distant Assessment Report
  远程评估报告

  Distantassessment reports should be written taking into account the Union formats ofGMP/GDP inspection reports. Appropriate clarifying remarks should be includedin the relevant sections of the report to make it clear that a distantassessment was performed and to indicate that physical aspects of the facilitywere not assessed. 
  编制远程评估报告时应考虑欧盟的GMP/GDP 检查报告格式。报告的相关章节中应包含适当的澄清说明,以明确进行了远程评估,并指出是否对设施的物理方面进行了评估以及所使用的方法。

  Existingregulatory risk management principles should be used to determine the durationof the validity of GMP/GDP certificates issued following distant assessments.
  应使用现有的监管风险管理原则来确定在进行远程评估后颁发的 GMP/ GDP 证书的有效期限。

  5.2.Statements of Next Inspection (SONI)
  下次检查声明(SONI

  Ifthe outcome of the distant assessment is satisfactory, a SONI should be issuedtaking into consideration the EMA Guideline Application of inspection andcontrol measures to facilitate risk-based inspection planning of sites withinthe Plasma Master File (PMF) certification system stating the recommended dateof next inspection. The Subject on the certificate should indicate Distant Assessmentand a clarifying remark (as per the Questions and Answers issued by theEuropean Commission, HMA and EMA referenced in paragraph 1.1. )that on-site inspections will resume as soon as circumstancespermit should be added and any exceptions indicated.
  如果远程评估的结果令人满意, 则应签发 SONI, 同时考虑 EMA 申报指南中的检查和控制措施, 以便于 PMF认证系统中基于风险的现场检查规划,说明下次检查日期建议。 证书的主题应该写明远程评估, 并注明(按 1.1 节中引用的EC、 MHA 和 EMA 签发的问答) 一旦情况允许将恢复现场检查, 如有例外情况亦应写明。

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