FDA发布药品生产和生物研究监测设施远程交互评估指南!

近日，FDA发布了《行业指南：药品生产和生物研究监测设施远程交互评估》，该指南将适用于药品、生物制品的以下检查：

• 批准前检查(PAIs)和许可检查(PLIs) ：FDA 可以执行PAI 或PLI 来评估上市申请。FDA利用这些检查来确保为支持申请而指定或引用的任何设施能够按照CGMP要求进行拟议的生产操作，以核实与申请的一致性，并确认在申请中提交的数据是准确和完整的。

• 批准后检验(PoAIs) :PoAIs 侧重于特定药物及其生产操作的变化、工艺验证的评估、提交的任何变更申请，以及根据申请承诺和CGMP 要求执行的支持活动。

• 监督检查：监督药品质量检查用以检查整体操作，包括确保生产程序可以生产符合质量要求的药品，从而降低药品掺假或标签错误到达消费者和患者的风险。FDA使用监督检查来评估生产操作的CGMP 符合性。对活性药物成分和药品生产设施以及根据FD&C法案第503B 条在FDA注册的外包设施进行监督检查。

• 跟踪和符合性检查：当一个特定的药品质量问题或工厂问题引起FDA 的时，我们可以启动跟踪或符合性药品质量检查。例如，FDA可以进行检查以调查:(1)产品安全、有效性或由缺陷报告引起的质量问题;(2)由举报人提供的关于该工厂的信息;(3)在对其他工厂进行检查时发现本工厂有违法行为的;或者(4)工厂针对警告信或监管会议所采取的纠正措施。

• 生物研究监测(BIMO)检查: BIMO 程序是一个全面的，机构范围内的检查和数据审计程序，旨在监测受FDA监管的研究的实施和报告的所有方面。BIMO程序的目标是保护研究对象的权利、安全和福利;确认提交给FDA 的临床和非临床试验数据的准确性、可靠性和完整性;评估对FDA 临床和非临床试验法规的符合情况，包括知情同意和伦理审查的规定，以及某些上市后的要求。

全文翻译如下：

Remote Interactive Evaluations of Drug Manufacturing and Bioresearch Monitoring Facilities During the COVID-19Public Health Emergency

药品生产和生物研究监测设施远程交互评估

Guidance forIndustry

行业指南

April2021

2021年4月

U.S.Department of Health and Human Services

美国卫生与公众服务部

Food andDrug Administration

美国食品药品监督管理局

Center for Drug Evaluation andResearch

药物评价与研究中心

Center for Biologics Evaluation andResearch

生物制品评价与研究中心

Center for Veterinary Medicine

兽药中心

Table of Contents

目录

I. Introduction

介绍

II. Background

背景

III. Planning a Remote InteractiveEvaluation

远程交互评估的计划

A. Selecting and Notifying the Facility

工厂选择和通知

1.Specific Considerations for Pre-Approvaland Pre-License Inspections

批准前检查和许可检查的具体考虑

2.Specific Considerations for Post-ApprovalInspections

批准后检查的具体考虑

3.Specific Considerations for SurveillanceInspections

监督检查的具体考虑

4.Specific Considerations for Follow-Up andCompliance Inspections

跟踪行动和符合性检查的具体考虑

5.Specific Considerations for BioresearchMonitoring Inspections

生物研究监测检查的具体考虑

B. Preparing for a Remote InteractiveEvaluation

远程交互评估的准备

IV. Conducting a Remote InteractiveEvaluation

进行远程交互评估

A. TechnologicalRequirements

技术要求

B. RemoteInteractive Evaluation of Documents and Records

文件和记录的远程交互评估

V. Concluding a Remote InteractiveEvaluation

结束远程交互评估

VI. Impacts of Remote InteractiveEvaluations on Established Commitments and Timeframes

远程交互对既定承诺和时间框架的影响

A. Commitments for Pre-Approval and Pre-LicenseInspections

批准前检查和许可检查的承诺

B. Timeframes for All Inspection Types

所有检查类型的时间表

I．Introduction

介绍

FDA plays acritical role in protecting the United States from threats such as emerginginfectious diseases, including the Coronavirus Disease 2019 (COVID-19)pandemic. FDA is committed to providing timely guidance to support responseefforts to this pandemic.

FDA 在保护美国免受新发传染病等威胁方面发挥着关键作用，其中包括2019冠状病毒疾病(covid-19)大流行。FDA 致力于提供及时的指导，以支持应对这一流行病的工作。

FDA is issuing this guidance to describe how we will requestand conduct voluntary remote interactive evaluations at facilities2where drugs3aremanufactured, processed, packed, or held; facilities covered under FDA’s bioresearchmonitoring (BIMO) program; and outsourcing facilities registered under section503B of the Federal Food, Drug, and Cosmetic Act (FD&C Act) for theduration of the COVID-19 public health emergency.

FDA发布本指南，以说明我们将如何要求和进行自愿远程交互评估，这些评估包括2019冠状病毒毒疾病突发公共卫生事件期间进行药品生产、加工、包装或储存的设施; FDA生物研究监测(BIMO)计划所涵盖的设施; 以及根据联邦食品、药品和化妆品法案(FD & C)第503B 条注册的外包设施。

This policy is intended to remain in effect only for theduration of the public health emergency related to COVID-19 declared by theSecretary of Health and Human Services (HHS) on January 31, 2020, effective January27, 2020, including any renewals made by the HHS Secretary in accordance withsection 319(a)(2) of the Public Health Service Act (PHS Act) (42 U.S.C. 247d(a)(2)).

该政策仅在美国卫生与公众服务部(HHS)于2020年1月31日宣布的与COVID-19有关的公共卫生紧急事件期间有效，并于2020年1月27日生效，包括HHS秘书根据《公共卫生服务法》(PHS Act)第319(a)(2)条(42 U.S.C. 247d(a)(2)条)作出的任何延期。

1This guidance hasbeen prepared by the Center for Drug Evaluation and Research in cooperationwith the Center for Biologics Evaluation and Research, the Center forVeterinary Medicine, and the Office of Regulatory Affairs at the Food and DrugAdministration.

本指南由药物评价和研究中心与生物制品评价和研究中心、兽药中心和FDA监管事务办公室合作编写。

2In this guidance,the term facility covers persons, sites, and establishments subject toFDA drug manufacturing and bioresearch monitoring regulations and statutoryauthority.

在本指南中，术语“工厂”包括受 FDA 药物制造和生物研究监测法律法规监管的人员、场所和机构。

3In this guidance,the term drug includes biologics.

在本指南中，术语“药物”包括生物制品。

Given this public health emergency, and as discussed in theNotice in the Federal Register of March 25, 2020, titled “Process forMaking Available Guidance Documents Related to Coronavirus Disease 2019,” availableat https://www.govinfo.gov/content/pkg/FR-2020-03-25/pdf/2020-06222.pdf,this guidance is being implemented without prior public commentbecauseFDA has determined that prior public participation for this guidance is notfeasible or appropriate (see section 701(h)(1)(C) of the FD&C Act (21U.S.C. 371(h)(1)(C)) and 21 CFR10.115(g)(2)).This guidance document is being implemented immediately, but itremains subjectto comment in accordance with the Agency’s good guidance practices.

The contents of this document do not have the force andeffect of law and are not meant to bind the public in any way, unlessspecifically incorporated into a contract. This

本文件的内容不具有法律效力和法律效力，也不意味着以任何方式对公众具有约束力，除非特别纳入合同。这一点

document is intended only to provide clarity to the publicregarding existing requirements under the law. FDA guidance documents,including this guidance, should be viewed only as recommendations, unlessspecific regulatory or statutory requirements are cited. The use of the word shouldin Agency guidance means that something is suggested orrecommended, but not required.

文件旨在向公众提供有关法律现有要求的清晰信息。包括本指南在内的FDA 指导文件应仅被视为建议，除非引用了具体的法规或法定要求。在FDA指导意见中，“应该”一词的使用意味着建议，但不是必须。

II. Background

背景

There is currently an outbreak of respiratory disease causedby a novel coronavirus. The virushasbeen named “SARS-CoV-2” and the disease it causes has been named “CoronavirusDisease 2019” (COVID-19). On January 31, 2020, HHS issued a declaration of apublic health emergency related to COVID-19 and mobilized the OperatingDivisions of HHS.4In addition, on March 13, 2020,there was a Presidential declaration of a national emergency in responseto COVID-19.5During the COVID-19 public health emergency, FDA is limitingunnecessary contact by only conducting prioritized domestic facility inspectionsand those that are deemed mission-critical.6

在2019冠状病毒病(COVID-19)公共卫生紧急情况期间，FDA通过只对国内设施和被视为关键任务的设施进行优先现场检查来减少不必要的接触。

When an upcoming inspection is not mission-critical, is nota prioritized domestic inspection, or is impacted by travel restrictionsresulting from the public health emergency, we are using other available toolsand information to support regulatory decisions and oversight of facilities.FDA may also supplement a planned inspection with other available tools.Therefore, FDA has developed this guidance to describe various remote interactivetools we may request to use to conduct an evaluation. In this guidance, werefer to our use of any combination of these interactive tools as a remoteinteractive evaluation. FDA may request to conduct a remote interactiveevaluation prior to or following other types of regulatory oversight activities(e.g., an inspection or a request for records or other information).7

如果即将进行的检查对任务不是至关重要的，不是优先进行的国内检查，或者受到公共卫生紧急情况造成的旅行限制的影响，我们正在利用其他现有工具和信息来支持监管决定和对设施的监督。FDA也可以用其他可用的工具来补充计划中的现场检查。因此，FDA开发本指南，以描述我们可能要求使用的各种远程交互工具进行评估。在本指南中，我们将这些交互工具的任何组合称为远程交互评估。FDA可要求在其他类型的监管监督活动(例如，现场检查或要求记录/其他信息)之前或之后进行远程交互评估。

4Secretary of Health and Human Services, Determination that aPublic Health Emergency Exists (originally issued Jan. 31, 2020, andsubsequently renewed), available at https://www.phe.gov/emergency/news/healthactions/phe/Pages/default.aspx.

卫生与公众服务部部长，《确定存在公共卫生紧急情况》(最初于2020年1月31日发布，后续更新) ，可在https://www.phe. gov/Emergency/news/healthactions/phe/pages/default. aspx。

5Proclamation onDeclaring a National Emergency Concerning the Novel Coronavirus Disease(COVID-19) Outbreak (Mar. 13, 2020), available at https://trumpwhitehouse.archives.gov/presidential-actions/proclamation-declaring-national-emergency-concerning-novel-coronavirus-disease-covid-19-outbreak/.On February 24, 2021,there was a PresidentialDeclaration continuing the national emergency concerning the COVID-19 pandemicbeyond March 1, 2021. See Continuation of the National Emergency Concerning theCoronavirus Disease 2019 (COVID-19) Pandemic (February 24, 2021), available at https://www.federalregister.gov/documents/2021/02/26/2021-04173/continuation-of-the-national-emergency-concerning-the-coronavirus-disease-2019-covid-19-pandemic

《关于新型冠状病毒疾病(covid-19)爆发的全国紧急状态宣言》(2019年3月13日) ，可在 https://trumpwhitehouse.archives.gov/presidential-actions/declaration-declaration-National-Emergency-Concerning-Novel-Coronavirus-Disease-covid-19-Outbreak/查阅。2021年2月24日，美国总统发表了一份宣言，宣布2021年3月1日之后，美国继续紧急应对2019冠状病毒疾病。参见2019年全国冠状病毒病紧急情况延续(covid-19)大流行(2021年2月24日) :https://www.federalregister.gov/documents/2021/02/26/2021-04173/Continuation-of-the-National-Emergency-Concerning-the-Coronavirus-Disease-2019-covid-19-Pandemic

6See the guidance for industry Manufacturing, SupplyChain, and Drug and Biological Product Inspections During COVID-19Public Health Emergency Questions and Answers (January 2021) for furtherinformation on FDA’s criteria for deeming inspections mission-criticalduring the COVID-19 public health emergency. (We update guidances periodically.For the most recent version of a guidance, check the FDA guidance web page at https://www.fda.gov/regulatory-information/search-fda-guidance-documents.)

请参阅工业制造业、供应链、药品和生物制品检验指南在2019冠状病毒毒疾病紧急问答期间(2021年1月)的进一步信息，了解 FDA 认为检验任务至关重要的标准在2019冠状病毒毒疾病紧急公共卫生期间。(我们定期更新指南。对于最新版本的指南，请查看FDA 指南：https://www.FDA. gov/regulatory-information/search-FDA-guidance-documents。)

III. Planning a Remote Interactive Evaluation

远程交互评估的计划

FDA may request to conduct a remote interactive evaluationwhenever a program officedeterminesit is appropriate based on mission needs and any travel limitations. FDAconducts inspections for many purposes and programs, and we will consider eachof those inspection program areas as possible candidates for a remoteinteractive evaluation. This policy applies to all drug inspection programsincluding, but not limited to:

FDA将要求在项目办公室根据任务需要和旅行限制决定是否合适时进行远程交互评估。FDA按照不同目的和程序进行检查，我们将考虑每一个检查计划领域进行可能的远程交互评估。本政策适用于所有药品检查项目，包括但不限于:

• Pre-Approval Inspections (PAIs) and Pre-License Inspections(PLIs): FDA may perform a PAI orPLI to assess a marketing application. FDA uses these inspections to ensurethat any facility named or referenced in support of an application can performthe proposed manufacturing operations in conformance with current goodmanufacturing practice (CGMP) requirements, to verify conformance with theapplication, and to confirm that data submitted in the application are accurateand complete.

• 批准前检查(PAIs)和许可检查(PLIs) :FDA 可以执行PAI 或PLI 来评估上市申请。FDA利用这些检查来确保为支持申请而指定或引用的任何设施能够按照CGMP要求进行拟议的生产操作，以核实与申请的一致性，并确认在申请中提交的数据是准确和完整的。

• Post-Approval Inspections (PoAIs): PoAIs focus on a specific drug and changes to its manufacturingoperations, the evaluation of process validation, any changes submitted to theapplication, and the execution of supporting activities according toapplication commitments and CGMP requirements.
  

• 批准后检验(PoAIs) :PoAIs 侧重于特定药物及其生产操作的变化、工艺验证的评估、提交的任何变更申请，以及根据申请承诺和CGMP 要求执行的支持活动。

• urveillance Inspections:Surveillance drug quality inspections examine overall operations,including controls that ensure manufacturing processes produce quality drugs,thereby reducing the risk of adulterated or misbranded drugs reaching consumersand patients. FDA uses surveillance inspections to evaluate the CGMP complianceof manufacturing operations. Surveillance inspections are performed at activepharmaceutical ingredient and drug product manufacturing facilities, as well asoutsourcing facilities that have registered with FDA under section 503B of theFD&C Act.
  

• 监督检查: 监督药品质量检查用以检查整体操作，包括确保生产程序可以生产符合质量要求的药品，从而降低药品掺假或标签错误到达消费者和患者的风险。FDA使用监督检查来评估生产操作的CGMP 符合性。对活性药物成分和药品生产设施以及根据FD&C法案第503B 条在FDA注册的外包设施进行监督检查。

• Follow-Upand Compliance Inspections: When a specificdrug quality problem or facility issue comes to FDA’s attention, we mayinitiate a follow-up or compliance drug quality inspection. For example, FDAmay conduct an inspection to investigate: (1) product safety, effectiveness, orquality concerns arising from defect reports; (2) information provided by aninformant about a facility; (3) violative activities involving a facility thatwere discovered during the inspection of another facility; or (4) correctiveactions undertaken by a facility in response to, for example, a warning letteror regulatory meeting.

• 跟踪和符合性检查：当一个特定的药品质量问题或工厂问题引起FDA 的时，我们可以启动跟踪或符合性药品质量检查。例如，FDA可以进行检查以调查:(1)产品安全、有效性或由缺陷报告引起的质量问题;(2)由举报人提供的关于该工厂的信息;(3)在对其他工厂进行检查时发现本工厂有违法行为的;或者(4)工厂针对警告信或监管会议所采取的纠正措施。

• Bioresearch Monitoring (BIMO) Inspections: The BIMO program is a comprehensive, Agency-wideprogram of inspections and data audits designed to monitor all aspects of theconduct and reporting of FDA-regulated research. The goals of the BIMO programare to protect the rights, safety, and welfare of research subjects; to verifythe accuracy, reliability, and integrity of clinical and nonclinical trial datasubmitted to FDA; and to assess compliance with FDA’s regulations governing theconduct of clinical and nonclinical trials, including regulations for informedconsent and ethical review, and certain postmarketing requirements.

• 生物研究监测(BIMO)检查: BIMO 程序是一个全面的，机构范围内的检查和数据审计程序，旨在监测受FDA监管的研究的实施和报告的所有方面。BIMO程序的目标是保护研究对象的权利、安全和福利;确认提交给FDA 的临床和非临床试验数据的准确性、可靠性和完整性;评估对FDA 临床和非临床试验法规的符合情况，包括知情同意和伦理审查的规定，以及某些上市后的要求。

7A remote interactiveevaluation is not the same as an inspection as described in section 704(a)(1)of the FD&C Act or a request for records or other information in advance ofor in lieu of an inspection, as described in section 704(a)(4) of the FD&CAct. Similarly, a remote interactive evaluation or a request under section704(a)(4) does not constitute an inspection for purposes of section 510(h)(3)of the FD&C Act. Section 704(a)(4) does not apply to every inspectionprogram covered by this guidance (e.g., section 704(a)(4) does not apply to theBIMO inspection program). Failure to cooperate with either an inspection or a704(a)(4) request for records or other information may constitute a limiting ofinspection and as a result, FDA may deem the relevant drugs manufactured atthese establishments adulterated. See the guidance for industry Circumstancesthat Constitute Delaying, Denying, Limiting, or Refusing a DrugInspection (October 2014) for further information.

远程交互评估不同于FD&C法案第704(a)(1)条所述的检查，也不同于FD&C第704(a)(4)条所述的在检查前或代替检查的记录或其他信息要求。同样，远程交互评估或根据第704(a)(4)条提出的请求，不构成为FD&C法案第510(h)(3)条目的而进行的检查。第704(a)(4)条并不适用于本指南所涵盖的每个检验程序(例如，第704(a)(4)条并不适用于 BIMO 检验程序)。不配合检查或不提供704(a)(4)所要求的记录或其他信息可能构成限制检查，因此，FDA可能认为在这些机构生产的有关药品掺假。有关进一步信息，请参阅FDA行业指南《拖延、拒绝、限制或拒绝药品检查》2014年10月。

A.Selecting and Notifying the Facility

选择和通知工厂

FDA will apply risk management methods and tools todetermine when to request a facility’s participation in a remote interactiveevaluation. In some cases, FDA may request records or request that a facilityparticipate in a remote interactive evaluation prior to an inspection; thisapproach could minimize risk associated with conducting inspections during thepandemic by reducing the number of FDA staff who have to travel and by reducingtime spent on-site for the inspection. We will not accept requests fromapplicants or facilities for FDA to perform a remote interactive evaluation.Such decisions depend on many factors and information not always known toapplicants or facilities, and it would be too burdensome on all parties toestablish a request-based program.

FDA将应用风险管理方法和工具来确定何时要求工厂参与远程交互评估。在某些情况下，FDA可能在检查之前要求记录或要求工厂进行远程交互评估;这种方法可以通过以下途径最大限度地降低在大流行期间进行检查的风险减少FDA 工作人员必须旅行的人数，减少现场检查的时间。我们不会接受申请人或工厂对FDA 进行远程交互评估的请求。这种决定基于申请人或工厂并不总是知道的许多因素和信息，并且对所有各方来说建立一个基于请求的程序太过沉重。

OnceFDA determines that a remote interactive evaluation is appropriate for aparticular facility or drug, we will notify the facility and applicant (whenappropriate) by electronic correspondence or phone call. We will use thefacility’s registration or application information to identify the facilitypoint of contact or U.S. agent. Correspondence or phone contact will include arequest for confirmation of the facility’s willingness and ability toparticipate in a remote interactive evaluation, including the use ofteleconference, livestream video, and screen sharing of data and documents. Therequest will indicate the name and address of the facility to be evaluated, thereason for the use of a remote interactive evaluation, and the names of FDAparticipants, if known.

一旦 FDA 确定远程交互评估适用于特定的工厂或药物，我们将通过电子通信或电话通知工厂和申请人(适当时)。我们将使用工厂的注册或申请信息来确定工厂的联系人或美国代理人。通信或电话联系将包括要求确认该工厂的意愿和能力，以参与远程交互评估，包括使用电话会议，直播视频和屏幕共享信息及文件。要求将指明需要评估的工厂的名称和地址，使用远程交互评估的原因，以及FDA 参与者的姓名(如知道)。

Following a facility’s agreement to be evaluated remotely,FDA will contact the facility to confirm the point of contact for the remoteinteractive evaluation, facilitate planning, and determine a facility’s abilityto transfer records and perform remote interactions with FDA staff. FDA willidentify the FDA lead for the remote interactive evaluation. FDA will also workwith facilities to procure information necessary to plan and coordinate theactivities for a remote interactive evaluation. The facility should meet theserequests or inform FDA of any challenges in meeting these requests as soon aspossible.

在工厂同意进行远程评估之后，FDA 将联系该工厂以确认远程交互评估的联系点，帮助计划，并确定工厂传输记录和与FDA 工作人员进行远程交互的能力。FDA将确定本次FDA远程交互评估的负责人。FDA还将与工厂合作，获取计划和协调远程交互评估活动所需的信息。工厂应该满足这些要求，或者在满足这些要求方面存在任何挑战，尽快通知FDA。

DecliningFDA’s request to perform a remote interactive evaluation could impede our abilityto make a timely regulatory decision (e.g., regarding adequacy of a clinicaltrial used in support of a pending application or adequacy of a drugmanufacturing operation described in the application).

拒绝 FDA 进行远程交互评估的要求可能会阻碍我们及时作出监管决定的能力(例如，用以支持待审申请的临床试验是否充分或申请中描述的药品生产操作是否充分)。

1.Specific Considerations forPre-Approval and Pre-License Inspections

批准前检查和许可检查的特殊考虑

When FDA cannot perform a PAI or PLI, or when we determineit would be useful tosupplement a plannedinspection, we will consider using tools other than inspection, selecting themost appropriate method to address the specific risks that justify the need forthe PAI or PLI. FDA may request a remote interactive evaluation to support anapplication action if we determine that: (1) remote interaction with thefacility will help us assess risks identified during application review; and(2) there are no data integrity or other issues that FDA determines require aninspection.

当FDA无法执行PAI或PLI，或者当我们确定它可以作为所计划的检查的补充时，我们将考虑使用现场检查以外的工具，选择最合适的方法来解决特定的风险，以满足 PAI或PLI的需要。如果我们确定:(1)与工厂的远程交互将帮助我们评估申请审核过程中所识别出的风险;(2) FDA认为没有数据完整性或其他需要现场检查的问题。

Generally, FDA intends to request records and otherinformation under section 704(a)(4) of the FD&C Act, before initiating aremote interactive evaluation.

一般来说，FDA 将在启动远程交互评估之前，根据FD&c法案第704(a)(4)节要求记录和其他信息。

2.Specific Considerations forPost-Approval Inspections

批准后检查的特定考虑

When FDA cannot perform a PoAI, or when we determine itwould be useful to supplement a planned inspection, we will consider usingtools other than inspection to address the specific risks that justify the needfor the PoAI; we may determine that requesting a remote interactive evaluationis an appropriate alternative to conducting an inspection. FDA may request aremote interactive evaluation for PoAIs when: (1) a facility has an acceptableinspection history with no data integrity or other concerns that FDA determinesrequire an inspection; and (2) specific application considerations and CGMPmanufacturing risks that warrant a PoAI can be sufficiently assessed through aremote interactive evaluation.

如FDA 无法进行 PoAI，或者当我们确定在计划检查外进行补充时，我们将考虑使用现场检查以外的工具来处理具体的风险以满足PoAI 的需要;我们可以确定，要求进行远程交互评估是进行现场检查的适当替代办法。FDA可能会在以下情况要求远程交互评估:(1)工厂具有可接受的检查历史，没有数据完整性或FDA 认为需要进行现场检查的其他问题;(2)特定申报考量和CGMP 制造风险，可通过远程交互评估对PoAI 进行充分评估。

3.Specific Considerations forSurveillance Inspections

监督检查的具体考虑

The prioritization of facilities, domestic and foreign, forremote interactive evaluations will follow the same risk-based approachcurrently used by FDA for surveillance inspections.8

对国内和国外工厂进行远程交互评估的优先顺序将遵循FDA目前用于监督检查的同样基于风险的方法

Aremote interactiveevaluation does not constitute an inspection for purposes of section 510(h)(3)of the FD&C Act. However, FDA will use information gathered via a remoteinteractive evaluation to determine the scope, depth, and timing of a futureinspection.

远程交互评估不构成 FD&C 法案第510(h)(3)节的检查。然而，FDA 将使用通过远程交互评估收集的信息来确定未来检查的范围，深度和时间。

4.Specific Considerations for Follow-Upand Compliance Inspections

跟踪行动和符合性检查的具体考虑

Afollow-up orcompliance inspection examines operations, records, and other information thatrelate to the specific issue being addressed (e.g., drug quality control,facility, or manufacturing problem). FDA will determine whether a remoteinteractive evaluation is appropriate, such as when an inspection cannot beperformed due to travel restrictions or to supplement a planned inspection. Theuse of a remote interactive evaluation will depend on the nature of thefacility and the reason for the assignment, including, but not limited to,inspection history and any data integrity concerns.

跟踪或符合性检查用以检查操作、记录和其他与被处理的具体问题相关的信息(例如，药品质量控制、设施或制造问题)。FDA将确定远程交互评估是否适当，例如在因旅行限制而无法进行现场检查或需要在检查计划外进行补充时。远程交互评估的使用将取决于工厂的性质和分配任务的原因，包括但不限于检查历史和任何数据完整性问题。

8See, for example, the risk-based approach described in MAPP5014.1 Understanding CDER’s Risk-Based Site Selection Model,available at https://www.fda.gov/media/118214/download.

例如，参见 MAPP 5014.1《CDER 基于风险的工厂选择模型》中描述的基于风险的方法：https://www.fda.gov/media/118214/download 。

After issuance of a warning letter, holding a regulatorymeeting, or following an enforcement action (e.g., seizure or injunction), FDAusually will conduct an inspection to confirm that corrective actions have beenimplemented.

在发出警告信、召开监管会议或采取强制执行行动(如扣押或禁令)之后，FDA 通常会进行检查，以确认纠正行动已得到执行。

To evaluate defect reports (e.g., Field Alert Reports orBiological Product Deviation Reports), FDA may request a remote interactiveevaluation and/or make a request under section 704(a)(4) of the FD&C Act.

为了评估缺陷报告(例如，现场警报报告或生物产品偏差报告)，FDA可要求进行远程交互评估和/或根据FD&C法案第704(a)(4)条提出要求。

5.Specific Considerations forBioresearch Monitoring Inspections

生物研究监测检查的具体考虑

Selection of facilities for BIMO inspections is risk based.While some facility selection factors such as inspection history and time sincelast inspection may be common across BIMO programs, other factors are unique toeach BIMO program.

BIMO 检查的工厂选择是基于风险的。一些工厂选择因素，如检查历史和自上一次检查的时间，是通用的，而其他因素则是特定于每个BIMO程序。

FDA will consider BIMO facilities for remote interactiveevaluation according to existing risk- based facility selection methodologieswhen there are no data integrity or other concerns that FDA determines requirean inspection, and information to be evaluated can be accessed remotely.Generally, the information obtained from a remote interactive evaluation willbe used to assess the facility’s conduct, including data reliability and humansubject protections to determine the acceptability of BIMO studies for FDA’sapplication decision-making.

当没有数据完整性或FDA认为需要现场检查的其他问题，且需要评估的信息可以远程访问时，FDA将根据现有的基于风险的工厂选择方法考虑用于远程交互评估的BIMO设施。通常，从远程交互评估中获得的信息将用于评估工厂的操作，包括数据可靠性和人体受试者保护，以确定FDA申请决策中的BIMO研究的可接受性。

B.Preparing for a Remote InteractiveEvaluation

准备远程交互评估

Once the facility confirms its willingness and ability toparticipate in a remote interactive evaluation, FDA will schedule a briefvirtual meeting to discuss logistics, responsibilities, and expectations.Discussion topics may include, but are not limited to, the following:

一旦该工厂确认参与远程交互评估的意愿和能力，FDA将安排一个简短的虚拟会议来讨论后勤、责任和期望。讨论主题可能包括，但不限于以下内容:

•Objectives and scope of the remoteinteractive evaluation.

远程交互评估的目标和范围。

• Introduction of the FDA remote interactive evaluation teamand the remote interactive evaluation lead.

FDA远程交互评估团队和远程交互评估负责人的介绍。

• Identification of the facility point of contact and allother participants (e.g., sponsor or contract research organization, monitor,remote ancillary operations).

确定工厂接触点和所有其他参与者(例如，申报人或合同研究机构、监测方、远程辅助操作)。

• Schedule of virtual interactions and the anticipatedduration of the remote interactive evaluation.

虚拟交互的时间表和远程交互评估的预期持续时间。

•FDA’s expectations during the livestreamingwalkthroughs of the facility.

FDA在工厂直播检查期间的要求。

• Time zone differences and translation services (i.e., spokenand written translation), if applicable. Virtual interactions, including remoteobservation of manufacturing operations or livestream assessment of data,usually will occur during the facility’s normal business hours.

时差和翻译服务(即口头和书面翻译) ，如适用。虚拟交互，包括远程观察生产操作或直播评估数据，通常会发生在工厂的正常工作时间。

• Methods for sharing requested information, including sharingdocuments and the use of video-streaming technology.

共享所需信息的方法，包括共享文件和使用视频流技术。

• Technological limitations that could impair or prevent FDA’sremote interactive evaluation of the facility.

可能影响或妨碍FDA 对工厂进行远程交互评估的技术限制。

• Check of the internet connection throughout the facility toverify that the signal strength is adequate to support livestreaming video andaudio during the actual remote interactive evaluation.

检查整个工厂的互联网连接，以确认在实际的远程交互评估期间，信号强度足以支持直播视频和音频。

IV. Conducting a Remote Interactive Evaluation

进行远程交互评估

When facilities agree to participate in a remote interactiveevaluation, FDA expects them to cooperate with the same level of transparencyas they would during an FDA inspection. We expect appropriate staff to beavailable at scheduled times for interviews and other virtual interactions, andwe expect the facility to be operational to the extent possible for FDA toevaluate areas and operations of interest (e.g., manufacturing, laboratory,packaging). If a facility is unable to support video or other virtualinteractions, or if FDA determines that the video or any other virtual interactionduring the remote interactive evaluation does not permit a sufficientexamination of the facility or of a corrective action, FDA may terminate theremote interactive evaluation and instead perform an inspection or use otheravailable tools.

当工厂同意参与远程交互评估，FDA 希望他们能像在 FDA 现场检查时一样，以同样的透明度合作。我们希望有合适的工作人员在预定的时间进行对话和其他虚拟互动，我们希望该工厂能够对FDA评估的相关区域和操作(如生产、实验室、包装)的可能范围进行操作。如果工厂不能支持视频或其他虚拟互动，或者如果 FDA 发现远程交互评估期间的视频或任何其他虚拟互动都不能充分对工厂或纠正行动进行检查，FDA可终止远程交互评估，而进行现场检查或使用其他可用的工具。

As part of a remote interactive evaluation, FDA may:

作为远程交互评估的一部分，FDA 可以:

• Requestand review documents, records, and other information (electronic systems).9

要求和审查文件，记录和其他信息(电子系统)

•Use livestreamand/or pre-recorded video to examine facilities, operations, and data and otherinformation.10

使用直播和/或预先录制的视频来检查设施、操作、数据和其他信息。

• Through the facility’s point of contact, schedule interviewsand meetings to address any questions or concerns.

通过工厂的联系点，安排对话和会议来解决任何问题或点。

• Evaluate a facility’s corrective actions (e.g., in responseto a previous inspection or evaluation, or to the current remote interactiveevaluation). An inspection instead of a remote interactive evaluation may benecessary to verify the adequacy of some corrective actions, or if evaluatingthe corrective actions remotely would unreasonably extend the duration of theremote interactive evaluation.

评估工厂的纠正措施(例如，对先前的检查或评估或当前的远程交互评估的响应)。为了确认某些纠正措施的充分性，或者如果对纠正措施进行远程评估会不合理地延长远程交互评估的持续时间，可能需要进行现场检查而不是远程交互评估。

• Provide verbal updates to the facility on observations andoutstanding issues, whenever feasible.

在可行的情况下，向工厂提供关于观察项和未决问题的口头更新。

FDA will not issue a Form FDA 482, Notice of Inspection, toannounce or open a remote interactive evaluation.

FDA将不会发布FDA 482表，检查通知，以宣布或启动远程交互评估。

A.Technological Requirements

技术要求

The qualityof the remote connection (e.g., connectivity, image quality, cameras used)should be adequate for FDA to remotely review, observe, examine, and evaluatethe information requested. To the extent practicable, technologies employedalso should allow access for remotely viewing and evaluating operations at thefacility, as necessary (e.g., aseptic practices, equipment cleaning and set up,material weighing and dispensing, instrument set up, sampling, testing). FDAunderstands that there may be temporary connection issues during the virtualinteraction, and we expect either party to resolve the issue in a timelymanner.

远程连接的质量(例如，连接，图像质量，使用的照相机)应该足以让 FDA 远程审查，观察，检查和评估所要求的信息。在可行的范围内，所采用的技术也应允许在必要时远程查看和评估工厂的操作(例如，无菌操作、设备清洗和装配、物料称量和调配、仪器设置、取样、检验)。FDA 理解在虚拟交互过程中可能存在暂时的连接问题，我们希望任何一方及时解决这个问题。

9Some remoteinteractive evaluations will be preceded by a request for records and otherinformation for those facilities covered by FDA’s authority under section704(a)(4) of the FD&C Act, when appropriate. FDA requests, including requestsfor records, during a remote interactive evaluation are considered voluntaryunless a section 704(a)(4) request is sent to the facility.

在进行一些远程交互评估之前，FDA将根据FD&C法案第704(a)(4)条的规定，酌情要求提供有关这些工厂的记录和其他信息。在远程交互评估期间，FDA的要求，包括记录要求，被认为是自愿的，除非第704(a)(4)节的要求被发送到工厂。

10For a remoteinteractive evaluation supporting a pending biologics license application, FDAusually will expect a facility to provide for livestream video of themanufacturing operations described in the application.

对于支持待审生物制品许可证申请的远程交互评估，FDA通常希望有一个工厂提供申请中描述的生产操作的直播视频。

For security reasons, FDA will use its ownIT platforms and equipment11 to host virtual interactionsduring remote interactive evaluations (e.g., videoconferences, livestreamingvideo of the facility and operations in the facility). FDA currently uses thefollowing conferencing platforms:

出于安全原因，FDA将使用其自己的IT平台和设备在远程交互评估期间主持虚拟交互(例如，视频会议、工厂的直播视频和设施中的操作)。FDA目前使用以下会议平台：

•FDA Microsoft Teams（一款会议软件）

•FDA Zoom forGovernment（一款会议软件）

•FDA Adobe Connect（一款会议软件）

B.Remote Interactive Evaluation ofDocuments and Records

文件和记录的远程交互评估

FDA will usually request and review documents and otherinformation in advance of a remote interactive evaluation12to ensurethe livestream interactions are as efficient as possible. However, we mayrequest additional documents and other information, including video recordings,at any time during the remote interactive evaluation to address questions andto explain observations. Documents and other information requested during aremote interactive evaluation are expected to be provided within a reasonabletimeframe, similar to requests for documents or other information made duringan inspection.

FDA通常会在远程交互评估之前要求并审核文件和其他信息，以确保直播交互尽可能有效。但是，我们可能在远程交互评估期间的任何时候要求额外的文件和其他信息，包括视频、录音，以解决问题和解释观察项。远程交互评估期间要求提供的文件和其他资料要求在合理的时限内提供，与检查期间要求提供的文件或其他资料类似。

FDA expects all documents requested during the remoteinteractive evaluation to be provided in electronic format or accessible byscreen sharing during a live interaction so that the documents can be assessedefficiently. FDA will provide a secure means to send requested informationduring a remote interactive evaluation. For electronic documents and otherinformation, facilities should identify any limitations and ensure thatencrypted and password-protected files can be accessed by FDA. Documentssubmitted during a remote interactive evaluation should be in English. However,if translation is needed during a livestream interaction, the facility may needto provide a translator.

FDA希望远程交互评估期间要求提供的所有文件都以电子格式提供，或在实时交互期间通过屏幕共享访问，以便能够有效地评估文件。FDA将提供一个安全的手段，在远程交互评估期间发送要求的信息。对于电子文档和其他信息，工厂应该识别任何限制，并确保加密和密码保护的文件可以被FDA 访问。在远程交互评估期间提交的文件应是英文的。然而，如果在直播交互中需要翻译，工厂可能需要提供一名翻译。

FDArecognizes that some facilities maintain documents in paper format and not allelectronic systems will be accessible for direct viewing. Thus, when such afacility agrees to participate in a remote interactive evaluation, they shouldconsider taking steps to enable FDA’s remote viewing and verification of thefacility’s documents, procedures, and electronic systems. Requested documentsmaintained in paper format should be scanned as searchable Portable DocumentFormat (PDF) files when possible.

FDA 认识到，一些工厂以纸质格式保存文件，且并不是所有的电子系统都可以直接访问查看。因此，当这些工厂同意参与远程交互评估，他们应考虑采取步骤，使FDA 可以远程查看和确认工厂的文件，程序和电子系统。如有可能，以纸质格式保存的文件应扫描为可检索的PDF)文件。

11FDA is not able tosupply equipment to a facility to enable FDA’s remote interactive evaluation.Additionally, FDA is not able to accept equipment or devices from a facilityfor our use in conducting a remote interactive evaluation.

FDA无法向工厂提供设备或仪器，使FDA 可以进行远程交互评估。此外，FDA不接受使用来自工厂的设备或仪器进行远程交互评估。

12Generally, for manufacturingfacilities, such requests for records or other information prior to the remoteinteractive evaluation will be made under section 704(a)(4) of the FD&CAct.

一般而言，对于生产工厂，在远程交互评估之前对记录或其他信息的要求将根据FD&C法案第704(a)(4)条提出。

V.Concluding a Remote InteractiveEvaluation

结束远程交互评估

Upon completion of a remote interactive evaluation, FDA willhave a closeout meeting with the facility’s management. During this meeting,FDA will usually present a written list of observations, if any, and describeand discuss any observations in sufficient detail to enable understanding andfoster an appropriate response.13This written list ofobservations will not be a final Agency action or decision. FDA will not issuea Form FDA 483, Inspectional Observations. As with an inspection, FDAencourages facilities to respond during the discussion and/or provide responsesin writing to the observations within 15 U.S. business days.

在远程交互评估完成后，FDA 将与工厂的管理层举行末次会议。在会议上，FDA通常会提交一份书面清单13。这份书面意见清单并不是FDA的最后行动或决定。FDA 将不会发布 FDA 483 检查缺陷表。与现场检查一样，FDA 鼓励工厂在讨论期间作出响应，并/或在15个美国工作日内以书面形式对观察结果作出回复。

Depending onthe purpose and outcome of the remote interactive evaluation, the informationand documentation collected may be used to, among other regulatory purposes:

根据远程交互评估的目的和结果，所收集的信息和文件可用于，以及其他监管目的:

• Support FDA’s assessment of pending applications, includingwhether to approve an application

支持FDA 对待审申请的评估，包括是否批准申请

•Preclude the need for an inspectionin follow-up to a reported concern or defect

排除对报告问题或缺陷的进行跟踪检查的必要性

• Support a regulatory meeting, warning letter, import alert,recall activities, or enforcement action

支持监管会议、警告信、进口警报、召回活动或执法行动

• Rank or prioritize a facility for an inspection,particularly a surveillance CGMP inspection

对工厂的检查进行排序或分级，特别是CGMP 监督检查

•Justify a follow-up or complianceinspection or any other surveillance activity

对后续行动或符合性检查或任何其他监督活动进行论证

After the remote interactive evaluation concludes, FDA willprovide a copy of the final remote interactive evaluation report to thefacility. A remote interactive evaluation report and any written list ofobservations may be subject to a disclosure request under the Freedom ofInformation Act.

在远程交互评估结束后，FDA 将向工厂提供一份远程交互评估最终报告的副本。一份远程交互评估报告和任何书面意见清单都可以根据《信息自由法》提出披露要求。

If FDA determines that an inspection will be necessary basedon the outcome of the remote interactive evaluation, we will use theinformation obtained from the remote interactive evaluation to prepare for andconduct the inspection.

如果 FDA 根据远程交互评估的结果确定有必要进行现场检查，我们将使用从远程交互评估中获得的信息来准备和进行现场检查。

VI. Impacts of Remote Interactive Evaluations on EstablishedCommitments and Timeframes

远程交互评估对既定承诺和时间框架的影响

In general, the use of remote interactive evaluations shouldhelp FDA operate within normal timeframes (i.e., in a similar manner as aninspection) as outlined below, especially for higher priority activities inspite of challenges related to the COVID-19 pandemic.

一般而言，使用远程交互评估应有助于FDA在下文概述的正常时间框架内(即以类似于检查的方式)开展工作，特别是在2019冠状病毒毒疾病大流行带来挑战的情况下开展更高优先级的活动。

13If the remoteinteractive evaluation, including the review of any records before or duringthe evaluation, is intended to supplement a scheduled inspection, then FDAusually will combine any observations from the remote interactive evaluation(s)into a single written list of observations issued at the close of theinspection, which would be issued on a Form FDA 483, Inspectional Observations.

如果远程交互评估，包括在评估之前或评估期间对任何记录的审查，是为计划检查的补充，那么FDA 通常将远程交互评估的任何意见合并为检查结束时发布的单一意见书面清单，该清单将以FDA 483检查缺陷表发布。

FDA intends to use information from a remote interactiveevaluation to meet user fee commitments and to update FDA’s relevant internaldatabases. FDA expects that a remote interactive evaluation will generallyenable us to meet a user fee goal date. However, FDA will notify applicants ifwe expect to miss a user fee goal date.

FDA将使用来自远程交互评估的信息来满足用户收费承诺，并更新FDA 的相关内部数据库。FDA希望远程交互评估通常能够使我们满足用户费用目标日期。然而，如果我们预计将错过用户费用目标日期，FDA将通知申请者。

A.Commitments for Pre-Approval andPre-License Inspections

批准前检查和许可检查的承诺

FDA will adhere to existing response timeframes applicableto inspections.

FDA 将遵守适用于检查的现有响应时间框架。

• Any responses or corrective actions submitted to the FDA inresponse to the observations identified during the remote interactiveevaluation will be considered in the application assessment if provided within15 U.S. business days of FDA’s communication. FDA may defer consideration ofresponses or corrective actions in the current review cycle if received after15 days.

• 根据远程交互评估中发现的意见向FDA 提交的任何答复或纠正行动，如果在FDA 通知后15个美国工作日内提交，将在申请评估中予以考虑。如果在15天后收到，FDA 可能会推迟考虑当前审查周期中的回复或纠正行动。

• Responses received after 15 U.S. business days will beconsidered in the next application user fee cycle, should the applicationreceive a complete response action and the facility requires re-evaluation.
  

• 在15个美国工作日之后收到的回复将在下一个申请用户收费周期中考虑，如果申请收到完整的回复行动，并且该工厂需要重新评估。

B.Timeframes for All Inspection Types

所有检查类型的时间表

FDA generally intends to use existing timelines establishedfor reporting on and evaluating the outcome of an inspection for the remoteinteractive evaluation.

FDA通常将使用现有的时间表来报告和评估远程交互评估的检查结果。

Any responses or corrective actions submitted to the FDA inresponse to the issues identified during the remote interactive evaluation willbe considered with respect to further regulatory action if provided within 15U.S. business days of FDA’s communication of the observations.

针对远程交互评估期间发现的问题向FDA提交的任何答复或纠正行动，如果在FDA通报意见后15个美国工作日内提交，将考虑采取进一步的监管行动。