Considerations for the 
Conduct of Clinical Trials of 
Medical Products During 
Major Disruptions Due to 
Disasters and Public Health 
Emergencies 
Guidance for Industry, Investigators, 
and Institutional Review Boards 
 
This guidance is for immediate implementation. 
 
FDA is issuing this guidance for immediate implementation in accordance with 21 CFR 
10.115(g)(2).  Submit one set of either electronic or written comments on this guidance at any 
time.  Submit electronic comments to https://www.regulations.gov.  Submit written comments to 
the Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.  You should identify all comments with the docket number 
listed in the notice of availability that publishes in the Federal Register.  For questions regarding 
this document, contact (CDER) Office of Medical Policy, CDEROMP@fda.hhs.gov, 301-796-
2500. 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
Center for Biologics Evaluation and Research (CBER) 
Center for Devices and Radiological Health (CDRH) 
Oncology Center of Excellence (OCE) 
Office of Clinical Policy (OCLiP) 
 
September 2023 
Emergencies
 
     
   
Considerations for the Conduct of Clinical 
Trials of Medical Products During Major 
Disruptions Due to Disasters and Public 
Health Emergencies
 
 
Guidance for Industry, Investigators, and 
Institutional Review Boards 
 
Additional copies are available from: 
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Center for Drug Evaluation and Research 
Food and Drug Administration 
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and/or 
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 Food and Drug Administration 
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Email: ocod@fda.hhs.gov 
https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances     
and/or 
Office of Policy 
Center for Devices and Radiological Health 
Food and Drug Administration 
10903 New Hampshire Ave., Bldg. 66, Room 5431 
Silver Spring, MD 20993-0002 
Email: CDRH-Guidance@fda.hhs.gov 
https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/guidance-documents-medical-
devices-and-radiation-emitting-products  
  
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
Center for Biologics Evaluation and Research (CBER) 
Center for Devices and Radiological Health (CDRH) 
Oncology Center of Excellence (OCE) 
Office of Clinical Policy (OCLiP) 
 
September 2023 
Emergencies 
     
  Contains Nonbinding Recommendations 
TABLE OF CONTENTS 
 
 
 
I.  INTRODUCTION.............................................................................................................. 1 
II.  BACKGROUND ................................................................................................................ 2 
III.  DISCUSSION ..................................................................................................................... 2 
A.  Considerations for Continuing Trials .......................................................................... 2 
B.  Policies and Procedures to Account for Potential Disruptions to Trials ................... 4 
C.  For All Trials That Are Impacted by a Disaster or PHE ........................................... 4 
APPENDIX:  Questions and Answers......................................................................................... 6 
 
 
 
     
  Contains Nonbinding Recommendations 
Considerations for the Conduct of Clinical Trials of Medical 
Products During Major Disruptions Due to Disasters and Public 
Health Emergencies  
Guidance for Industry, Investigators, and Institutional Review 
Boards1 
 
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on 
this topic.  It does not establish any rights for any person and is not binding on FDA or the public.  You 
can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.  
To discuss an alternative approach, contact the FDA office responsible for this guidance as listed on the 
title page.   
 
 
 
 
I.  INTRODUCTION 
 
Disasters and public health emergencies (PHEs) have the potential to cause major disruptions in 
the conduct of clinical trials for medical products.2  Such events can include (but are not limited 
to) hurricanes, earthquakes, military conflicts, infectious disease outbreaks, or bioterrorist 
attacks.  FDA is issuing this guidance to provide general considerations to assist sponsors, 
institutional review boards (IRBs), and clinical investigators in assuring the safety of trial 
participants,3 maintaining compliance with good clinical practice (GCP), and minimizing risks to 
trial integrity during disasters and PHEs that may lead to major disruption of clinical trial 
conduct and operations.  The appendix to this guidance further explains these general 
considerations in a question-and-answer format.  
 
In general, FDAs guidance documents do not establish legally enforceable responsibilities.   
Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
as recommendations, unless specific regulatory or statutory requirements are cited.  The use of 
 
1 This guidance has been prepared by the Center for Drug Evaluation and Research, the Center for Biologics 
Evaluation and Research, the Center for Devices and Radiological Health, the Oncology Center of Excellence, and 
the Office of Clinical Policy at the Food and Drug Administration.  
2 We note that disasters and PHEs, as those terms are used in this guidance, may include natural catastrophes (e.g., 
significant earthquakes) and other unanticipated, significant disruptions with the potential to substantially impact the 
conduct of clinical trials for medical products, including situations where the Secretary of the Department of Health 
and Human Services has declared a PHE under section 319 of the Public Health Service Act or has declared that 
circumstances exist justifying the authorization of medical products for emergency use under section 564(b) of the 
Federal Food, Drug, and Cosmetic Act (FD&C Act). 
3 In this guidance, the terms trial participant, participant, and subject are interchangeable. 
1 
  Contains Nonbinding Recommendations 
the word should in Agency guidance means that something is suggested or recommended, but 
not required. 
 
 
II.  BACKGROUND 
 
FDA recognizes that disasters and PHEs can cause major disruptions to the conduct of clinical 
trials of medical products.  For example, disasters or PHEs can lead to population quarantines, 
trial site closures, travel limitations, interruptions to the supply chain for the investigational 
product (IP),4 or other challenges related to the type of disaster or PHE (e.g., site personnel or 
trial participants infected during an outbreak).  These challenges can create difficulties in 
complying with protocol-specified procedures, including administering or using the IP or 
adhering to protocol-specified visits and laboratory or diagnostic testing.   
 
FDA is aware that not all trials can be initiated or continued during disasters and PHEs, and for 
some trials, there may be no alternative to stopping the trial earlier than planned in order to 
safeguard participants and trial staffs safety.  The determination of whether to continue a trial 
should be based first and foremost on ensuring that participants will continue to be able to 
participate safely.  The determination should also consider whether the key objectives of the trial 
can still be met, with appropriate trial modifications implemented.  FDA outlines the following 
general considerations to assist sponsors in ensuring the safety of trial participants, maintaining 
compliance with GCP, and minimizing risks to trial integrity.  The appendix further explains 
these general considerations by providing answers to questions that the Agency has received 
about conducting clinical trials during major disruptions. 
 
 
III.  DISCUSSION 
 
A.  Considerations for Continuing Trials 
 
  Ensuring the safety of trial participants is paramount.  Sponsors should consider 
above all whether participants can safely continue in the trial, including necessary 
modifications and risk mitigation steps to ensure safety.  Sponsors should also 
consider whether the trial can continue to meet its key objectives with 
modifications that adequately address the disaster or PHE circumstances.  Study5 
decisions might include those regarding continuing trial recruitment, continuing 
use of the IP for participants already in the trial, and the need to change 
participant monitoring during the trial.  In all cases, it is critical that trial 
participants, IRBs/independent ethics committees (IECs), and regulatory agencies 
are kept informed of changes to the design and conduct of the study as 
appropriate. 
 
4 In this guidance, the term investigational product refers to investigational human drugs and biological products, as 
well as investigational medical devices. 
5 In this guidance, the terms trial and study are interchangeable.  
2 
  Contains Nonbinding Recommendations 
 
  Sponsors should consider whether the protection of a participants safety, welfare, 
and rights is best served by continuing a study participant in the trial as per the 
protocol, discontinuing the administration or use of the IP, modifying the 
assessments or assessment schedule, or discontinuing participation in the trial.  
Such decisions will depend on specific circumstances, including the nature of the 
IP, the ability to conduct appropriate safety monitoring, the potential impact of the 
disaster or PHE on the IP supply chain, and the nature of the disease or condition 
under study in the trial.  Sponsors should work with the investigators conducting 
the trial to assess the individual participants situation and risk profile when 
considering their status in the trial.  
 
  Screening procedures (e.g., testing for an infectious disease) that may be 
mandated by the health care system in which a clinical trial is being conducted 
may not need to be included as an amendment to the protocol if the sponsor does 
not plan to incorporate the data collected as part of a new research objective.  
 
  Changes to the protocol or investigational plan to eliminate apparent immediate 
hazards or to protect the life and well-being of research participants in an 
emergency may be implemented without IRB approval or before filing an 
amendment to the investigational new drug application (IND) or investigational 
device exemption (IDE) but are required to be reported afterwards.6  FDA 
encourages sponsors and investigators to work with their IRBs to prospectively 
define procedures as early as possible in response to major disruptions to ensure 
participant safety and to prioritize reporting of deviations necessitated by the 
impact of a disaster or PHE. 
 
  The implementation of alternative processes for the conduct of the study should 
be consistent with the protocol to the extent possible, and sponsors and clinical 
investigators should document the reason for any contingency measures 
implemented.  Sponsors and clinical investigators should document how the 
disaster or PHE led to the changes in study conduct and the duration of those 
changes, indicate which trial participants were impacted, and document how those 
trial participants were impacted. 
 
  There may be gaps in data capture, data loss, and difficulties in finalizing and 
locking datasets because of the disaster or PHE.  If changes in the protocol will 
lead to amending data management, prespecified analyses, and/or statistical 
analysis plans, the sponsor should consider making such amendments in 
consultation with the applicable FDA review division.  Before locking the 
database, sponsors should address how protocol deviations related to the disaster 
or PHE will be handled for the prespecified analyses in the statistical analysis 
plan. 
 
6 See 21 CFR 56.108(a)(4), 56.104(c), 312.30(b)(2)(ii), and 812.35(a)(2). 
3 
  Contains Nonbinding Recommendations 
 
B.  Policies and Procedures to Account for Potential Disruptions to Trials 
 
  Sponsors, clinical investigators, and IRBs should consider establishing and 
implementing policies and procedures, or revising existing policies and 
procedures, to describe approaches to be used to protect trial participants and 
manage study conduct during possible disruption of the study.  Changes to 
policies and procedures may address many issues, including the informed consent 
process; which participants can continue on the IP; study visits and procedures; 
data collection; study monitoring; adverse event reporting; study oversight; and 
changes in investigator(s), site staff, and/or monitor(s) due to travel restrictions, 
quarantine measures, or other safety measures.  Policies and procedures should be 
compliant with applicable (regional or national) laws and regulations for the 
management and control of the disaster or PHE.  Depending on the nature of the 
changes described above, a protocol amendment or IDE supplement may be 
required under the applicable regulations.7   
 
C.  For All Trials That Are Impacted by a Disaster or PHE 
 
Sponsors should provide a description of the impacts on study conduct of the disaster or PHE in 
a study-specific document with references to appropriate sections of the clinical study report: 
 
1.  Contingency measures implemented to manage study conduct during disruption of the 
study as a result of disaster- or PHE-related control measures 
 
2.  Specific challenges faced by the sponsor of the clinical trial as a result of the disaster or 
PHE 
 
3.  A listing of all participants affected by the disaster or PHE-related study disruption by 
unique trial participant number identifier and by investigational site and a description of 
how the individuals participation was altered, including missed visits and assessments 
related to the disaster or PHE 
 
4.  Analyses and corresponding discussions that address the impact of implemented 
contingency measures (e.g., trial participant discontinuation from IP and/or study, 
alternative procedures used to collect critical safety and/or efficacy data) on the safety 
and efficacy results reported for the study 
 
Robust efforts by sponsors, investigators, and IRBs or IECs to maintain the safety of trial 
participants and study data integrity are expected, and such efforts should be documented.  FDA 
recognizes that protocol modifications might occur, including unavoidable protocol deviations 
 
7 See 21 CFR 312.30(b) and 812.35(a).  Under applicable Federal regulations, investigators who are conducting 
research with Schedule I controlled substances under the Controlled Substances Act must request prior approval 
from the Drug Enforcement Administration when seeking to conduct research beyond that which is described in the 
approved protocol (see 21 CFR 1301.18).  
4 
  Contains Nonbinding Recommendations 
due to the disaster or PHE, or control measures implemented in response to the disaster or PHE.  
Efforts to minimize impacts on trial integrity and to document the reasons for protocol deviations 
will be important.   
5 
  Contains Nonbinding Recommendations 
APPENDIX:  Questions and Answers 
 
Q1.  Deciding whether to suspend, continue, or initiate trials ......................................................7 
Q2.  Managing protocol deviations and amendments ...................................................................8 
Q3.  Submitting changes to IND and IDE protocol.......................................................................9 
Q4.  Capturing data on protocol and process deviations .............................................................10 
Q5.  Conducting remote (virtual) clinic visits .............................................................................10 
Q6.  Remote clinical outcome assessments .................................................................................11 
Q7.  Use of alternative laboratory or imaging centers ................................................................14 
Q8.  Use of video conferencing for trial visits ............................................................................15 
Q9.  Delivering low-risk IPs to home .........................................................................................16 
Q10.  Disposal of unused IP ..........................................................................................................16 
Q11.  Changing site for delivering high-risk IP ............................................................................17 
Q12.  Alternative monitoring approaches .....................................................................................18 
Q13.  Remote site monitoring visits ..............................................................................................20 
Q14.  Obtaining informed consent for patients who are physically isolated ................................21 
Q15.  Collecting electronic signatures and part 11 compliance ....................................................23 
Q16.  Challenges and temporary waivers for eCTDs ....................................................................24 
Q17.  Shipping IP to local provider  Form FDA 1572 and accountability .................................25 
Q18.  Use of commercial versus IPs .............................................................................................26 
Q19.  Scheduling of meetings with review divisions ....................................................................27 
Q20.  Postmarketing requirements for drugs, biologics, and devices ...........................................27 
Q21.  Reporting serious adverse events for approved drugs used to treat conditions related to a 
disaster or PHE ....................................................................................................................29 
Q22.  Reporting serious adverse events associated with conditions related to a disaster or PHE in 
a trial not related to the condition ........................................................................................30 
Q23.  Exclusion criteria for investigational medical products ......................................................31   
6 
  Contains Nonbinding Recommendations 
Q1.  What are some of the key factors that a sponsor should consider when deciding 
whether to suspend or continue an ongoing study or to initiate a new study during a 
disaster or public health emergency (PHE)? 
 
Central to any decision should be ensuring that the safety of clinical trial participants can be 
maintained.  Sponsors should assess whether the protection of a participants safety, welfare, and 
rights is best served by continuing a study participant in the trial as per the protocol or by 
discontinuing participation in the trial.  Such decisions will depend on specific circumstances, 
including the nature of the investigational product (IP), the ability to conduct appropriate safety 
monitoring, the potential impact on the IP supply chain, each participants underlying risk profile 
and situation during the disaster or PHE, and the nature of the disease or condition under study in 
the trial.  As part of this assessment, sponsors should carefully consider the following aspects of 
clinical trial conduct when deciding how or whether to proceed with a clinical trial: 
 
  Assessing whether the limitations imposed by the disaster or PHE on protocol 
implementation pose new safety risks to trial participants, and whether it is 
feasible to mitigate these risks by amending study processes and/or procedures.   
 
  Assessing the availability of technology to communicate effectively and 
consistently with participants. 
 
  Assessing the continued availability of the clinical investigator/sub-investigators 
to provide oversight of the trial and properly assess and manage safety issues that 
may emerge.   
 
  Assessing whether there will be sufficient clinical trial support staff given the 
evolving situation and its impact on staff availability.  Important questions to be 
considered include:  Are there appropriately trained staff that could be available to 
handle the expected tasks?  Are there adequate equipment and materials for 
clinical trial support staff? 
 
  Assessing whether clinical investigator sites will remain open to trial participants 
for required in-person assessments or whether the clinical investigator has the 
ability to provide required in-person assessments at an acceptable alternate 
location(s) or whether such protocol-specified, in-person assessments can instead 
be conducted virtually.   
 
  Assessing the continued availability of clinical trial supplies and continued 
operations of vendors, especially related to supply of the IP and/or to clinical trial 
supplies that are essential to maintaining appropriate safety monitoring or other 
key trial procedures.  This should include consideration of product stability (shelf 
life) if the administration schedule is revised or if the clinical site is unable to 
properly store the product for the needed duration. 
 
  Assessing the continued availability of and support for information technology 
systems and any other technological tools that are needed to support the trial.  
7 
  Contains Nonbinding Recommendations 
Important questions to be considered include:  Are current contingency plans 
adequate for the types of disruptions that might be anticipated?  What other plans 
can be put in place to minimize disruptions to trial conduct?   
 
  Assessing whether there will be continued operations of and adequate 
communications with institutional review board (IRB) or independent ethics 
committee (IEC) and data monitoring committee (DMC) staff, if applicable, to 
support trial needs. 
 
  Assessing whether it is feasible to conduct the trial in light of any contingency 
and/or safety measures implemented by Federal, State, or local authorities.  
 
Involvement of a studys DMC, if one has been established, can provide support for the 
assessments discussed above.  Since a primary responsibility of the DMC is ensuring the safety 
of trial participants, the DMCs assessment of the impact of modifications of trial conduct during 
a disaster or PHE is important to consider.   
 
The risks and benefits of continuing a trial are likely different than a decision to initiate a trial.  
Given an evolving situation, with likely increasing impacts on investigators, staff, and supply 
chains, sponsors should carefully consider the ability to effectively mitigate risks such that 
patient safety and trial integrity are assured.  In addition, it is important to consider whether 
initiation of the trial could interfere with public safety measures implemented by Federal, State, 
or local authorities.  
 
Q2.  How should sponsors manage protocol deviations and amendments to ongoing trials 
during a disaster or PHE? 
 
FDA recognizes that during disasters or PHEs, sponsors of clinical trials may need to modify 
protocol-specified procedures.  As is discussed in the main body of this guidance, for protocol 
deviations necessitated by the impact of a disaster or PHE, the sponsor should document the 
specific protocol deviation and the reason for the deviation.  The sponsor can document protocol 
deviations using its standard processes or, given the larger expected number of such deviations in 
disaster or PHE circumstances, use alternative documentation approaches.  For example, if visits 
are to be conducted by telephone or video contact rather than at the investigational site as 
specified in the protocol, documentation that provides a listing of all study visits (e.g., listing 
study reference number, patient ID, date of visit) that are deviations from the protocol because of 
the disaster or PHE generally would be acceptable.  Protocol deviations should be included in 
final study reports and may also be included in annual reports.  
 
For changes in protocol conduct, under the investigational new drug application (IND) 
regulations, protocol amendments that are necessary to prevent apparent immediate hazards to 
trial participants can be immediately implemented with subsequent submission and formal 
approval by the IRB and notification to FDA through filing a protocol amendment to the IND.1 
 
 
1 See 21 CFR 56.108(a)(4) and 312.30(b)(2)(ii). 
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  Contains Nonbinding Recommendations 
For studies under an IND, 21 CFR 312.30(b) specifies that sponsors must submit a protocol 
amendment to the IND describing any change in a Phase 1 protocol that significantly affects the 
safety of trial participants or any change in a Phase 2 or 3 protocol that significantly affects the 
safety of trial participants, the scope of the investigation, or the scientific quality of the study.  
Pausing enrollment in a trial to decrease potential exposure to an emerging disease or condition 
related to the disaster or PHE would not generally be expected to significantly affect trial 
participant safety, the scope of the investigation, or the scientific quality of the study; therefore, 
submitting a protocol amendment would not be required under the regulation for such a pause.   
 
Prior to IRB approval of an amendment and submission to the FDA, clinical investigators must 
document as protocol deviations any modifications to protocol-specified procedures.2  
Consolidating several protocol modifications in a single protocol amendment generally will be 
considered acceptable but should be submitted expeditiously.   
 
For studies under an investigational device exemption (IDE), 21 CFR 812.35(a) generally 
requires prior FDA approval before implementing changes to the investigational plan.  These 
requirements do not apply to changes made to protect the life or physical well-being of a trial 
participant in an emergency, including study-wide changes, but such deviations must be reported 
to FDA within 5 working days.3  In addition, under 21 CFR 812.35(a)(3), changes to the protocol 
that the sponsor determines, based on credible information, do not affect the validity of the 
results from the study; the likely patient risk-to-benefit relationship; the scientific soundness of 
the investigational plan; or the rights, safety, or welfare of the trial participants may be made 
without prior FDA approval if the sponsor reports the modifications to the Agency within 5 days 
of implementing the changes.  Because of the unique and evolving circumstances surrounding 
the impact of a disaster or PHE, we understand that it may be challenging to submit 5-day reports 
or notices within the required timeframe.  Sponsors may consolidate implemented changes when 
submitting 5-day reports or notices and should update the IDE as soon as possible.    
 
Q3.  With the rapid changes in clinical trial conduct that may occur due to a disaster or 
PHE, including multiple deviations to address patient safety, what is the 
recommended way for sponsors and investigators to capture these data? 
 
It is important to capture specific information for individual participants that explains the basis 
for missing protocol-specified information that includes the relationship to the disaster or PHE 
(e.g., from missed study visits or study discontinuations due to the event).  This information, 
summarized in the clinical study report, will be helpful to FDA.  If it is not possible to 
immediately capture this information in the case report form(s), sponsors may develop processes 
that enable systematic capture of these data across the sites in a manner that enables the 
appropriate analysis when the data are submitted to FDA.  Sponsors may also develop processes 
to capture site-level status, site-level or vendor-level protocol deviations, and process deviations. 
 
 
2 See 21 CFR 312.62. 
3 See 21 CFR 812.35(a)(2). 
9 
  Contains Nonbinding Recommendations 
Q4.  How should a sponsor submit a change in protocol that results from challenges 
related to a disaster or PHE? 
 
For IND studies, the sponsor should submit a formal amendment to its IND, with the following 
information added to the cover letter in the subject line:   
 
     PROTOCOL AMENDMENT  DISASTER OR PHE TYPE (e.g., HURRICANE, COVID-
19) 
 
     TITLE OF PROTOCOL 
 
Sponsors should summarize the major changes made to the protocol related to the disaster or 
PHE in the cover letter and should include a tracked changes version of the protocol to facilitate 
review.  As with other protocol amendments, sponsors may implement protocol amendments due 
to disasters or PHEs upon submission to FDA if approved by the IRB.4  Sponsors seeking FDA 
input prior to implementation should indicate that in the cover letter.    
 
For IDE studies, the sponsor should make a submission to its existing IDE, with the following 
information added to the cover letter in the subject line, as applicable: 
 
     CHANGE IN PROTOCOL SUPPLEMENT  DISASTER OR PHE TYPE (e.g., 
MILITARY CONFLICT or RADIATION EMERGENCY) or  
 
     NOTICE OF IDE CHANGE  DISASTER OR PHE TYPE (e.g., EARTHQUAKE or 
PANDEMIC), as applicable 
 
     TITLE OF PROTOCOL 
 
The submission to the IDE should contain a tracked changes version of the protocol to facilitate 
review.  
 
Q5.  Can a sponsor initiate virtual clinical trial visits for monitoring participants without 
contacting FDA if there is an assessment by the sponsor and investigator that these 
visits are necessary for the safety of trial participants, and it will not impact data 
integrity? 
 
FDA regulations allow for changes to be made to the protocol without prior FDA review or 
approval if the change is intended to eliminate an apparent immediate hazard or to protect the life 
and well-being of trial participants in an emergency.5  Therefore, changes in protocol conduct 
necessary to immediately assure patient safety, such as conducting telephone or video contact 
 
4 As noted in the response to Q2 above, changes to a protocol necessary to eliminate an apparent immediate hazard 
to trial participants may be implemented before FDA and IRB review and approval (see 21 CFR 56.108(a)(4) and 21 
CFR 312.30(b)(2)(ii)). 
5 See 21 CFR 56.108(a)(4), 312.30(b)(2)(ii), and 812.35(a)(2).  
10 
  Contains Nonbinding Recommendations 
visits for safety monitoring rather than on-site visits, can be immediately implemented with 
subsequent review by the IRB and notification to FDA.  Since this reflects a protocol deviation 
(until the amendment is approved), documentation of such deviations, as described above, would 
generally be acceptable (i.e., a document that lists each deviation, study reference ID, patient ID, 
and date).  For example, this could include documentation that all protocol-specified visits will 
be done by telephone contact rather than on-site visits and that procedures requiring in-person 
visits will either not be conducted or will be performed by other means (specified, as 
appropriate).  Since the change to telephone or video contact visits would likely result in some 
protocol-required procedures not being conducted (e.g., vital signs, blood samples for safety 
laboratory studies), it is critical that the sponsor evaluate the potential impact of alternative 
approaches on participant safety and consider how to mitigate risks to participants, including 
whether to discontinue the IP.6   
 
For IDE studies, sponsors are required to report deviations implemented to protect the life or 
physical well-being of a participant in an emergency to FDA within 5 working days after 
learning of the deviations.7  We recognize that challenges related to the disaster or PHE may 
make it difficult to meet this time frame.  Sponsors may consolidate implemented deviations 
when submitting 5-day reports and should update FDA as soon as possible. 
   
Q6.  What factors should sponsors consider when deciding whether to change their 
clinical trial protocol to include remote clinical outcome assessments during a 
disaster or PHE? 
 
Some clinical outcome assessments (COAs)8 can be conducted remotely in clinical trials, 
including COAs for performance outcome (PerfO), interview-based clinician-reported outcome 
(ClinRO),9 patient-reported outcome (PRO), and observer-reported outcome (ObsRO).  During a 
disaster or PHE, investigators might still be conducting in-person assessments on some trial 
participants, whereas remote assessments may be recommended for others to protect their safety 
or to respond to measures implemented by Government authorities to protect the public.  When 
 
6 See 21 CFR 312.23(a)(6) and 812.25(c). 
7 21 CFR 812.35(a)(2). 
8 In this guidance, a COA is an assessment of a clinical outcome (i.e., an outcome that describes or reflects how a 
patient feels, functions, or survives); a PerfO is a measurement based on a standardized task performed by a 
participant that is administered and evaluated by an appropriately trained individual or is individually completed; a 
ClinRO is a measurement by a trained health care professional after observing a trial participants health condition; a 
PRO is a measurement based on a report that comes directly from the participant about the status of a patients 
health condition without amendment or interpretation of the participants response by a clinician or anyone else; and 
an ObsRO is a measurement based on a report of observable signs, events, or behaviors related to a participants 
health condition by someone other than the participant or a health professional (e.g., a parent or caregiver).  See 
FDA-NIH Biomarker Working Group BEST (Biomarkers, Endpoints, and other Tools) Resource, available at 
https://www.ncbi.nlm.nih.gov/books/NBK326791.   
9 Non-interview-based ClinRO assessments, such as those reliant on diagnostic imaging or physical examination, 
present a distinct set of challenges and are not addressed in this guidance.   
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  Contains Nonbinding Recommendations 
deciding whether to change their clinical trial protocols to include remote COAs, sponsors 
should evaluate the general and specific considerations outlined below.    
 
General considerations regarding (1) prioritization of trial participant safety and privacy; (2) 
maintenance of data quality and integrity, including minimizing missing data; and (3) 
appropriate training for personnel and trial participants, which are discussed elsewhere in this 
guidance, are also common to all COAs.  Other general considerations that are common to all 
COAs include attention to (1) the potential for increased variability in trial data; (2) the 
feasibility of conducting a specific type of COA remotely, depending on the context of use; (3) 
documentation and audit trails; and (4) availability of technology and technical support required 
for remote assessment.  These considerations are explained in more detail below.  
 
Increased Variability in Data:  When switching from in-person to remote assessments, 
sponsors should perform remote assessments in a manner as similar as possible to those done in-
person, while protecting trial participant safety and privacy.  To the extent feasible, sponsors 
should ensure that the methods and conduct of remote assessments are consistent across sites, 
trial participants, and visits to minimize variability in the data.  For example, if a sponsor decides 
that video is their preferred method of remote assessment in a clinical trial, then using different 
methods to conduct assessments (e.g., both telephone and video in the same trial) may increase 
variability.  Maintaining consistency in assessment methods should be balanced, however, 
against the need to minimize missing data, and the decision to use different methods should be 
justified in study documentation. 
 
Feasibility of the Assessment Method Within the Context of Use:  Investigators should assess 
the feasibility of conducting a specific type of COA remotely, which will depend on 
corresponding trial goals and needs (e.g., ability to conduct the assessment in a way that captures 
all the data needed to evaluate the endpoint in the trial), given that not all assessments can 
provide an accurate assessment when done remotely.  
 
Documentation and Audit Trails:  Investigators should document and sponsors should include 
in the clinical trial datasets (1) data on variables related to the trial, (2) whether an assessment 
was conducted in-person or remotely (including type of technology used), and (3) the date of the 
assessment and the name of the person who conducted the assessment.  Sponsors also should 
ensure that remote data acquisition, transmission, and storage are secure and that the privacy of 
trial participants is protected.  When sponsors use electronic platforms to perform remote 
assessments that transmit data directly into trial records, these platforms should use automated 
audit trails.10 
 
Technology and Technological Support:  Sponsors planning to use remote electronic 
assessments as part of a clinical investigation should use appropriate technology and develop 
procedures for provision of technology and technical support to trial participants, investigators, 
and/or other trial personnel to facilitate those assessments.  For example, sponsors could develop 
 
10 See the guidance for industry Computerized Systems Used in Clinical Investigations (May 2007).  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. 
12 
  Contains Nonbinding Recommendations 
a plan to accommodate trial participants who are either already enrolled in a trial or may be 
enrolled in a trial in the future but who do not have access to appropriate communication 
technology (e.g., cell phones or Internet) by providing trial participants with these technologies. 
 
Specific considerations for certain COA types are explained below. 
 
PerfO- and Interview-Based ClinRO-Specific Considerations:  For these types of 
assessments, sponsors should consider (1) appropriateness of remote assessment for the type of 
clinical data to be collected; (2) special investigator training to administer the PerfO or 
interview-based ClinRO assessments remotely; and (3) procedures for assessing and confirming 
the safety of trial participants, their privacy, and appropriate setting and resources to adequately 
complete the assessment.   
 
Recognizing that components of the PerfO and interview-based ClinRO assessment for some 
trials may specify visualization or in-person interactions with trial participants that may be 
difficult to replicate through remote interactions, sponsors should assess whether these 
components can be evaluated in an alternative way that still permits an accurate clinical 
assessment.  When components of the assessment cannot be accomplished in a remote encounter, 
investigators should document and sponsors should report in the clinical trial datasets any 
aspects of the assessment they are unable to accomplish remotely.  Sponsors should consider 
whether the information that can be collected remotely will be sufficient to reliably assess the 
clinical outcome and support robust conclusions for the study. 
 
PRO- and ObsRO-Specific Considerations:  For these types of assessments, sponsors should 
consider (1) potential for missing data when switching from in-person assessment to remote 
assessment; (2) whether switching from use of paper- or electronic-based PRO and ObsRO 
assessments completed independently to assessments administered verbally by another person 
may lead to bias of scores (e.g., if trial participants try to please the site staff by offering ratings 
that might not truly reflect their experience); and (3) that data collected with PROs and ObsROs 
through verbal administration should not be considered a substitute for required safety 
monitoring throughout the trial.11 
 
To minimize potential bias resulting from verbal administration of PRO and ObsRO 
assessments, sponsors should ensure interviewer training and use of an interview script.  
Sponsors may also consider using automated virtual interviewers or a trained, neutral third-party 
interviewer to administer the assessments remotely. 
 
The potential for missing data is also a limitation when switching from in-person to remote 
assessment using paper-based PRO or ObsRO assessments if the trial participant or observer 
fails to complete all or part of the questionnaire within a given timeframe.  To mitigate potential 
for missing data, sponsors should consider remote electronic capture of these assessments 
through technologies that can remind trial participants to complete the questionnaires and/or 
verbal administration at the time instructed (assuming appropriate steps are taken to minimize 
 
11 See 21 CFR 312.32(b), 312.56(c), and 812.46. 
13 
  Contains Nonbinding Recommendations 
bias from verbal administration).  Investigators should record which assessments were conducted 
by alternative means on a participant level.   
 
Q7.   I am a sponsor and would like to use an alternate laboratory or imaging center12 for 
protocol assessments.  What should I consider regarding when this approach would 
be appropriate and how to select alternate laboratories or imaging facilities? 
 
Given that trial participants may not be able to come to the investigational site for protocol-
specified visits at which laboratory tests or imaging would be conducted, sponsors should 
evaluate whether it is feasible to use alternative laboratories or imaging centers.  The suitability 
of such alternative arrangements may vary depending on whether the protocol-specified 
procedures are related to eligibility criteria, safety evaluations, or endpoint assessments. 
 
In general, if trial participants cannot access a clinical trial site, alternative sites may be used for 
laboratory tests or imaging assessments that focus on the safety of trial participants when such 
tests and assessments are routinely performed in those settings (e.g., routine chemistries, blood 
counts, chest radiographs).13   
 
However, if the results of laboratory tests or imaging assessments are the basis for evaluating 
important (e.g., primary or secondary) efficacy or safety endpoints, sponsors should consult with 
the relevant FDA review division before considering an alternative site.  For example, 
differences in laboratory measurements or imaging protocols may introduce increased variability 
in analyses, which should be considered. 
 
When baseline tests are necessary to characterize the eligible study population, potential 
variation in test performance or precision related to use of an alternative laboratory or imaging 
center may also warrant discussion with the relevant FDA review division.  For example, an 
inclusion criterion based on a commonly available, routine test performed as a safety screen 
(e.g., renal function on a metabolic panel) might be amenable to alternative laboratory collection 
with minimal impact on study results.  Using an alternative laboratory for tests related to other 
eligibility factors could be more likely to affect study integrity (e.g., laboratory tests to identify a 
tumor biomarker required for inclusion, genetic test to identify a marker that is a critical 
inclusion criterion).  It may be important for such assessments to be standardized at a single site 
or a few sites.  Based on the nature of laboratory tests conducted for the purpose of protocol 
assessments, the alternative laboratory conducting such tests for investigational purposes will 
likely be subject to certification and other requirements under the Clinical Laboratory 
 
12 For IND studies, this would be laboratories and imaging centers not listed on Form FDA 1572. 
13 If a local laboratory or imaging center will be used for certain patients and will not replace the laboratory and 
imaging center specified in Form FDA 1572 for all patients, these alternative facilities do not need to be listed on 
Form FDA 1572; it is sufficient to retain documentation of when such facilities were used for protocol specified 
tests.  The sponsor can accumulate these changes and submit this information to the IND, in for example, an 
information amendment or a protocol amendment.   
14 
  Contains Nonbinding Recommendations 
Improvement Amendments (CLIA).14  Alternative laboratory and imaging centers may also be 
subject to additional laws governing their operations.  Investigators should record which 
assessments were conducted by alternative means on a participant level.   
 
Q8.   We are instituting trial participant visits remotely through video conferencing.  Are 
there recommendations regarding best practices? 
 
With the increasing use of telemedicine in clinical practice, a number of resources may be 
available to provide recommendations on best practices.  FDA does not endorse any particular 
telemedicine best practices.  However, from an FDA regulatory perspective, important 
considerations for trial visits through video conferencing include:   
 
  The investigator or study personnel who will conduct remote visits should be 
trained on how to conduct real-time video conferencing visits (e.g., training on the 
use of telemedicine for remote clinical trial visits). 
 
  Procedures should be put in place to maintain a trial participants privacy, as 
would be done for a clinical visit.  
 
  Both the investigator and the trial participant should confirm their respective 
identities with one another before engaging in a real-time video conference visit 
according to an identity verification plan developed by the sponsor.15   
 
To provide the same information that would be documented during a face-to-face visit, the date 
of a real-time video conference visit should be documented in the trial records and, if specified in 
the protocol, the time of the visit.  Investigators should consider asking for the trial participants 
location during a video conference visit in case a medical emergency arises during the visit.   
 
FDA considers real-time video interactions, including telemedicine, as a live exchange of 
information between the trial personnel and trial participants.  These interactions are not 
considered electronic records and therefore are not subject to 21 CFR part 11.16  
 
 
14 For more information on the CLIA, see https://www.cms.gov/Regulations-and-
Guidance/Legislation/CLIA/Downloads/Research-Testing-and-CLIA.pdf. 
15 FDA does not endorse any specific identification method.  Sponsors may consider the National Institute of 
Standards and Technology (NIST) Special Publication 800-63A, Digital Identity Guidelines:  Enrollment and 
Identity Proofing Requirements, available at https://doi.org/10.6028/NIST.SP.800-63a.  
16 See 21 CFR 11.1(b).  See also the guidance for industry Part 11, Electronic Records; Electronic Signatures
Scope and Application (August 2003).  
15 
  Contains Nonbinding Recommendations 
Q9.  If patients are currently dispensed IP through a pharmacy at the clinical trial site 
for self-administration at home, can a sponsor switch that to home delivery without 
amending the protocol? 
 
Home delivery of IP that would not raise any new safety risks may be implemented to protect 
patients from risks associated with coming to clinical trial sites.  In all cases, requirements under 
FDA regulations for maintaining IP storage conditions in accordance with the investigational 
plan and for IP accountability remain; these requirements must be addressed and documented.17  
If the protocol indicates pharmacy dispensing for self-administration at home and this is changed 
to direct-to-patient shipments, then a protocol amendment18 or change to the investigational 
plan19 would be required to permit home delivery of the IP.  If the extent of home delivery is 
limited to certain participants and not the entire population described in the protocol, 
documenting the change in the mechanisms of distribution of IP administration through protocol 
deviations may also be acceptable.20  If the change in the mechanisms of IP distribution is then 
included in a submission to the existing IND or IDE, such a change may be part of a cumulative 
submission that includes a number of changes that accrue, rather than an urgent protocol 
change.21  Sponsors are also responsible for ensuring that home delivery does not compromise 
the quality of the product supplied. 
 
Q10.  How can the sponsor ensure proper disposal of unused investigational drug product 
if the participant cannot return to the study site?    
 
FDA regulations outline sponsor and investigator responsibilities for storage conditions and 
accountability of investigational drug products, including disposition of unused IPs.22  Under 21 
CFR 312.59, the sponsor shall assure the return of all unused supplies of the investigational drug 
from each individual investigator.  The regulation further provides that the sponsor may 
authorize alternative disposition of unused supplies of the investigational drug, provided this 
alternative does not expose humans to risks from the drug.  The procedure for disposition is 
generally considered part of the investigational plan and is normally described in the study 
protocol as a study-specific plan for handling the IPs.  In most protocols, such plans involve the 
participant bringing the unused IP to the clinical trial site and then the investigator returning the 
unused IP to the sponsor or its designee.  During a disaster or PHE, if appropriate, a prepaid 
shipping package can be used by the participant to return IP back to a central location where it 
 
17 See 21 CFR 312.60, 312.62, 812.100 and 812.140. 
18 See 21 CFR 312.30(b). 
19 See 21 812.35(a). 
20 Investigators must not make any changes in the research without IRB approval, except where necessary to 
eliminate apparent immediate hazards to human subjects (21 CFR 56.108(a)(4), 312.66, and 812.35(a)).  An 
amendment to the protocol should be considered if a protocol deviation is not isolated or transient.  When impacting 
only a specific region or country, a country-specific amendment may be appropriate. 
21 See 21 CFR 312.30(b), 812.35(a), and 812.150(a)(4). 
22 See 21 CFR 312.57, 312.59, 312.60, and 312.62.   
16 
  Contains Nonbinding Recommendations 
can be accounted for and disposed of per the protocol, but this approach is not the only way to 
satisfy the regulatory requirements for disposition of unused IP.  Regardless of the chosen 
disposition method, sponsors and investigators must maintain adequate records regarding the 
disposition of the IP.23 
 
Sponsors may consider adopting alternative procedures for disposition of IP that permit sponsors 
and investigators to fulfill their requirements for maintaining adequate records of IP disposition 
(including documenting dates, quantity, and use by participants), provided such procedures do 
not expose humans to risks from the IP.24  For example, it may be possible to provide the 
participants with a way to dispose of the IP at their home (such as with a drug disposal pouch) 
and document such disposal through photo or video that can be transmitted to the investigator or 
sponsor.  FDA does not endorse a particular approach, but relevant considerations (e.g., 
environmental) associated with specific IPs should be considered when selecting a method for 
disposal.  FDA has provided a consumer update Where and How to Dispose of Unused 
Medicines25 that provides recommendations to consumers about how to safely dispose of unused 
FDA-approved medication at home.  Sponsors can consider whether any of those recommended 
methods of disposition are appropriate for approved drugs being studied for a new use in a 
clinical investigation.  As noted in the consumer update, FDA only recommends flushing 
medications that are on the FDA flush list, which currently does not include unapproved IP.   
 
Investigators proposing alternative disposition methods must obtain authorization of those 
methods from the sponsor of the trial.26  Additional restrictions may apply to IPs subject to the 
Controlled Substances Act.27 
 
Q11.  If participants are currently receiving an IP at the clinical trial site, can a sponsor 
switch to use at home? 
 
Sponsors should consider the safety risk to trial participants who would miss receiving an IP 
because of the inability to come to the clinical trial site during a disaster or PHE.  If a sponsor is 
considering providing alternative arrangements for administration of the IP (e.g., home nursing 
or alternative sites by trained but non-study personnel), the sponsor is expected to perform a risk 
assessment that considers the nature of the IP and the potential risks to both the trial participants 
and the health care providers (HCPs) responsible for administering the product at the alternative 
site.  This risk assessment should include evaluation of risk mitigation steps.  Based on this risk 
assessment, sponsors should consider consulting the appropriate FDA review divisions regarding 
alternative plans for the administration of IP that is usually administered in a health care setting.  
 
 
23 See 21 CFR 312.57 and 312.62.  
24 Sponsors should consider whether an information amendment should be submitted pursuant to 21 CFR 312.31. 
25 See https://www.fda.gov/consumers/consumer-updates/where-and-how-dispose-unused-medicines.  
26 See 21 CFR 312.59 and 21 CFR 312.62. 
27 See 21 CFR 312.58(b) and 312.69.  
17 
  Contains Nonbinding Recommendations 
Consulting FDA is strongly advised for complex IPs (e.g., cellular therapy and gene therapy 
products), where potentially altered storage and handling conditions could adversely affect 
product stability.  However, in all cases, applicable requirements for maintaining IP storage 
conditions in accordance with the investigational plan (before and after reconstitution, if 
applicable), IP reconstitution specifications per the investigators brochure, and IP accountability 
remain and must be addressed and documented.28  Storage conditions and IP accountability 
should be considered if the protocol is amended to permit alternative site infusions.  Defining 
circumstances when discontinuing IP administration, while continuing study participation, albeit 
with potentially delayed assessments, may be an appropriate option when suitable alternative 
arrangements for administration of the IP cannot be made.   
 
Q12.  Considering that there may be delays to on-site monitoring of clinical trials during a 
disaster or PHE, what are FDAs recommendations, including for remote 
monitoring, in such circumstances? 
 
FDA recognizes that study monitors may not be able to access the trial sites for on-site visits in a 
timely manner during a disaster or PHE.  Sponsors should work to find alternative approaches to 
maintain trial participant safety and trial data quality and integrity, such as enhanced central 
monitoring, telephone contact with the sites to review study procedures, or remotely tracking 
trial participant status and study progress where appropriate and feasible.   
 
Sponsors should carefully document situations where monitors were unable to access or had to 
delay monitoring of a clinical site.  Sponsors or monitors should also include in their 
documentation of protocol deviations, or other GCP non-compliance issues identified at clinical 
sites, whether delayed identification was due to postponed monitoring.  FDA recognizes that 
unique situations at clinical sites may occur due to contingency and safety measures 
implemented and will consider these circumstances when evaluating inspectional observations.    
 
FDA regulations require sponsors to monitor the conduct and progress of their clinical 
investigations.29  The regulations are not specific about how sponsors must conduct such 
monitoring and are therefore compatible with a range of approaches to monitoring that may vary 
depending on multiple factors.  Therefore, certain aspects of site monitoring visits can be done 
remotely if technically feasible.  FDA understands that during a disaster or PHE, there may be 
deviations from the timing of on-site monitoring visits set forth in the trial monitoring plan and 
procedures and that sponsors may consider ways to replace on-site monitoring visits with remote 
monitoring visits.  Further, there may be components of an on-site monitoring visit, as outlined 
in the trial monitoring plan, that cannot be completed remotely.   
 
During a disaster or PHE, traditional on-site monitoring might be difficult for reasons such as (1) 
sites may not be able to accommodate monitoring visits (e.g., due to staffing limitations or site 
closures) or (2) monitors may not be able to travel to trial sites.  When planned on-site 
 
28 See 21 CFR 312.60, 312.62, 812.100 and 812.140. 
29 See 21 CFR 312.50, 312.53(d), 312.56(a), 812.40, 812.43(d), and 812.46.  
18 
  Contains Nonbinding Recommendations 
monitoring visits are not possible, the reason should be documented and available for review by 
the sponsor and during FDA inspections. 
 
The sponsor should consider using a risk-based approach to prioritize sites for remote 
monitoring, including as many study sites as feasible (and with a frequency as close to that 
described in the site monitoring plan as feasible).30,31  The sponsors should also consider 
additional factors in any risk-based approach (e.g., underlying participant risk profile, type of 
medical product, ability to obtain the required data remotely).  The decision regarding which 
sites to prioritize for remote monitoring should be guided by centralized monitoring or other 
information available about site performance (e.g., frequency and severity of protocol deviations 
previously identified during monitoring visits or currently identified by centralized monitoring, 
number of randomized active trial participants, experience of site staff, known history of prior 
major audit or inspection findings).   
 
Remote monitoring should be focused on review of critical study site documentation and source 
data.  If the materials identified for review include participants medical records that are 
normally reviewed at the site (and such a review is consistent with the trial participants 
informed consent documents), then, to complete source document review, remote review of 
medical records may be explored.  When the study monitor cannot access the site to review 
critical source documents, requests for review of source documents that may include private 
health information should be consistent with requirements for source document validation and 
review as described in the current study monitoring plan or other appropriate study-specific 
document.  When remote monitoring processes and procedures have not previously been 
described by the sponsor, these processes and procedures should be established (e.g., in a revised 
study monitoring plan or in updates to existing sponsor policies and procedures). 
 
During remote monitoring, the study monitor should focus on trial activities that are essential to 
the safety of trial participants and/or data reliability.  Sponsors and monitors may wish to 
consider one or more of the following options to facilitate remote monitoring access to clinical 
site records: 
 
  If the site can provide appropriate resources and technical capabilities, consider 
establishing a secure remote viewing portal that would permit site staff to provide 
access to the sites study documentation and/or trial participants source 
documents for the study monitors review.  In addition, the potential for remote 
access to trial participants electronic health records can be explored with trial 
sites. 
 
 
30 See the guidance for industry A Risk-Based Approach to Monitoring of Clinical Investigations:  Questions and 
Answers (April 2023). 
31 See the guidance for industry Oversight of Clinical Investigations  A Risk-Based Approach to Monitoring 
(August 2013). 
19 
  Contains Nonbinding Recommendations 
  Sites could upload certified copies32 of source records to a sponsor-controlled 
electronic system or other cloud-based repository that contains appropriate 
security controls.  In the setting of a blinded or partially blinded study, if source 
documents may contain unblinded information, controls to protect the study blind 
should be in place prior to transfer of source documents (e.g., use of an unmasked 
study monitor to review source documents, restricted access to folders containing 
copies of source documents).  It is not necessary for the clinical site to have 
control of certified copies of source documents uploaded to such a repository; 
however, the clinical investigator should maintain control of the original source 
records. 
 
Regarding retention of copies of source documents used for remote review, it would not be 
necessary to retain the certified copies of source documents used for remote review, provided the 
clinical investigator retains the original source documents according to FDA regulations for the 
retention of records.33  
 
In addition, processes and procedures should be established for the handling of source document 
copies that were placed in temporary storage locations for remote review and that are no longer 
needed after the remote monitoring has concluded. 
 
Remote monitoring activities, including remote review of source documents, should be 
documented in the same level of detail as on-site monitoring activities, and any resulting actions 
to address issues identified from the remote source document review should be consistent with 
procedures and processes described in the study monitoring plan. 
 
Q13.  During a disaster or PHE, some sponsors have used remote monitoring to oversee 
study conduct at clinical trial sites, including remote review of source data.  Should 
data that have been remotely monitored be re-monitored during an on-site 
monitoring visit once the disaster- or PHE-related restrictions that prevented on-site 
monitoring visits have been lifted?   
 
FDA regulations require sponsors to monitor the conduct and progress of their clinical 
investigations.34  These regulations are not specific about how sponsors must conduct such 
monitoring and are therefore compatible with a range of approaches that may vary depending on 
multiple factors.  The guidances for industry Oversight of Clinical Investigations  A Risk-Based 
Approach to Monitoring (August 2013) and A Risk-Based Approach to Monitoring of Clinical 
 
32 FDA guidance on good clinical practice, developed with the International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use (ICH), defines a certified copy as [a] copy (irrespective of the 
type of media used) of the original record that has been verified (i.e., by a dated signature or by generation through a 
validated process) to have the same information, including data that describe the context, content, and structure, as 
the original.  See the ICH guidance for industry E6(R2) Good Clinical Practice:  Integrated Addendum to ICH 
E6(R1) (March 2018). 
33 See 21 CFR 312.62 and 812.140(a). 
34 See 21 CFR 312.50, 312.53(d), 312.56(a), 812.40, 812.43(d), and 812.46.  
20 
  Contains Nonbinding Recommendations 
Investigations:  Questions and Answers (April 2023) clarify that sponsors can use a variety of 
approaches to fulfill their responsibilities for monitoring clinical investigations; these guidance 
documents also describe monitoring activities that reflect modern, risk-based approaches, 
including remote monitoring when appropriate.  
 
The decision as to whether remote monitoring conducted for a given site or clinical investigation 
was adequate or should be followed up with additional on-site monitoring visits should be based 
on the sponsors ongoing risk assessment.  The sponsor may determine that on-site follow-up of 
remote monitoring activities is appropriate based on a risk assessment (e.g., sites with certain 
data anomalies or a higher frequency of errors, important protocol violations, or dropouts relative 
to other sites).  As with on-site monitoring, remote monitoring should be focused on critical data 
and processes for human subject protection and trial integrity, such as the sites conduct of key 
study procedures and documentation related to important efficacy endpoints and safety 
assessments. 
 
Q14.  How do I obtain signed informed consent from a hospitalized patient who is in 
isolation during the disaster or PHE and is physically inaccessible because policies 
prevent trial staff from entering the patients room due to a disaster or PHE? 
 
FDA regulations generally require that the informed consent of a trial participant be documented 
by the use of a written consent document that typically includes the elements of informed 
consent, as described under 21 CFR 50.25, and that has been approved by the IRB and signed 
and dated by the trial participant or their legally authorized representative at the time of consent 
(21 CFR 50.27(a)).  When feasible, we recommend a traditional method of obtaining and 
documenting informed consent using a signed paper copy of the consent form or use of 
electronic informed consent.35,36  If neither of these approaches are possible, the following 
procedures would be considered to satisfy FDAs informed consent documentation 
requirement.37   
 
Method 1:  A photograph of the signed informed consent document can be transmitted to 
the trial staff 
 
1.  An unsigned consent form is provided to the patient (e.g., by a health care worker who 
has entered the room).  
 
2.  The investigator or designee arranges a telephone call or video conference call with the 
patient (and, if desired and feasible, additional individuals requested by the patient (e.g., 
next of kin)).   
 
 
35 See the guidance for institutional review boards, investigators, and sponsors Use of Electronic Informed Consent:  
Questions and Answers (December 2016).   
36 See Q15. 
37 The procedures suggested do not apply to the exception from general informed consent requirements under 21 
CFR 50.23 or the exception from informed consent requirements for emergency research under 21 CFR 50.24. 
21 
  Contains Nonbinding Recommendations 
3.  To ensure that prospective participants are approached in a consistent fashion, a standard 
process should be used that will accomplish the following: 
 
  Identification of who is on the call. 
 
  Review of the informed consent document with the patient by the investigator 
or designee and response to any questions the patient may have.  
 
  Verbal confirmation by the patient that their questions have been answered, 
that they would like to participate in the trial, and that they have signed and 
dated the informed consent document that is in their possession. 
 
4.  The patient (or an individual in the room) takes a photograph of the signed informed 
consent document and sends it to the investigator/designee. 
 
5.  A trial team member enters the photograph into the trial records along with an attestation 
that states how that photograph was obtained and that it is a photograph of the informed 
consent document signed by the patient.  
 
Method 2:  A witness can attest to the signature or a recording can be obtained, but a 
photograph of the signed informed consent document cannot be transmitted  
 
1.  An unsigned consent form is provided to the patient (e.g., by a health care worker 
who has entered the room). 
 
2.  The investigator or designee arranges a three-way telephone call or video 
conference call with the patient, a witness who is not otherwise connected with 
the clinical investigation, and, if desired and feasible, additional individuals 
requested by the patient (e.g., next of kin).  Alternatively, in lieu of using a 
witness, a recording of the conversation can be made.38 
 
3.  To ensure that prospective participants are approached in a consistent fashion, a 
standard process should be used that will accomplish the following: 
 
  Identification of who is on the call. 
 
  Review of the informed consent document with the patient by the investigator 
or designee and response to any questions the patient may have. 
 
  Verbal confirmation by the patient that their questions have been answered, 
that they would like to participate in the trial, and that they have signed and 
dated the informed consent document that is in their possession. 
 
38 If an investigator wants to record the telephone or video conference call, the investigator or designee should 
ensure that the recording is done in a manner consistent with applicable State and local laws and that all parties 
agree to being recorded. 
22 
  Contains Nonbinding Recommendations 
 
4.  When using a witness, documentation in the trial records includes (1) a signed and 
dated attestation by the witness who participated on the call that the patient 
confirmed their agreement to participate in the trial and signed the informed 
consent document and (2) a signed and dated attestation by the investigator or 
designee stating why the informed consent document signed by the patient was 
not retained (e.g., due to potential contamination of the document by infectious 
material). 
 
When using a recording in lieu of a witness, documentation in the trial records includes 
(1) the recording of the conference call and (2) a signed and dated attestation by the 
investigator or designee who participated on the call stating why the informed consent 
document signed by the patient was not retained (e.g., due to potential contamination of 
the document by infectious material). 
 
When either method 1 or 2 is used to document informed consent, the resulting documentation 
should be (1) collected and archived, as either original paper copies or appropriately certified 
electronic copies (e.g., using a validated process for scanning paper copies)39 and (2) retained 
according to applicable FDA record retention requirements as part of the trial record.40 
 
If the patient is unable to provide informed consent and there is a legally authorized 
representative, investigators must obtain written consent from the patients legally authorized 
representative in accordance with 21 CFR 50.27(a). 
 
Q15.  What considerations apply to the electronic systems used to generate electronic 
signatures on electronic clinical trial records, including informed consent 
documents, during a disaster or PHE? 
 
Electronic systems41 used to generate electronic signatures42 on electronic clinical trial records, 
including informed consent documents, generally must comply with the requirements outlined in 
 
39 See footnote 32. 
40 See 21 CFR 312.57, 312.62, and 812.140. 
41 For the purposes of this guidance, the term electronic systems means systems, including hardware and software, 
that create, modify, maintain, or transmit electronic records. 
42 For the purposes of this guidance, the term electronic signature means a computer data compilation of any symbol 
or series of symbols executed, adopted, or authorized by an individual to be the legally binding equivalent of the 
individuals handwritten signature (21 CFR 11.3(b)(7)). 
23 
  Contains Nonbinding Recommendations 
FDA regulations under 21 CFR part 11 (part 11).43,44  
 
FDA is aware that there are multiple commercial off-the-shelf (COTS) software systems 
providing electronic signature services for electronic clinical trial records.  FDA does not certify 
individual electronic systems or methods to obtain part 11-compliant electronic signatures on 
electronic records, but COTS vendors may be able to provide sponsors and other regulated 
entities with information regarding whether their systems are part 11-compliant.  Sponsors and 
other regulated entities should work with COTS vendors to ensure compliance with part 11.  For 
further information regarding part 11 compliance, see the guidance for industry Part 11, 
Electronic Records; Electronic SignaturesScope and Application (August 2003) and the 
additional recommendations proposed in the draft guidance for industry Electronic Systems, 
Electronic Records, and Electronic Signatures in Clinical Investigations Questions and Answers 
(March 2023).45   
 
When a part 11-compliant electronic system used to create electronic signatures is not available, 
regulated entities must have an alternate means of obtaining required signatures46 (e.g., 
handwritten47 wet ink signatures executed on documents, handwritten stylus or finger-drawn 
signatures executed on electronic documents that are then printed or appropriately witnessed).  
Alternative methods for obtaining signatures on informed consent documents are described in 
Q14 of this guidance.  When handwritten methods are used, the sponsor and other regulated 
entities should ensure that all records containing original handwritten signatures are (1) collected 
and archived, as either original paper copies or appropriately certified electronic copies (e.g., 
using a validated process for scanning paper copies) and (2) retained according to applicable 
FDA record retention requirements.48  
  
Q16.   I am a sponsor of commercial INDs, and electronic common technical document 
(eCTD) requirements cannot be met due to a disaster or PHE.  Whom do I contact 
for assistance? 
 
Commercial sponsors may qualify for a short-term waiver from the eCTD requirements under 
section 745A of the Federal Food, Drug, and Cosmetic Act (FD&C Act) in unique and rare 
circumstances and for a limited duration.  During a disaster or PHE, rare circumstances may 
 
43 See 21 CFR 11.1(b), 11.10, and 11.30.  See also the guidance for industry Part 11, Electronic Records; Electronic 
SignaturesScope and Application (August 2003) and the draft guidance for industry Electronic Systems, 
Electronic Records, and Electronic Signatures in Clinical Investigations Questions and Answers (March 2023).  
When final, this guidance will represent FDAs current thinking on this topic.     
44 For electronic records that are not subject to part 11, sponsors and other regulated entities should rely on their 
internal business practices to determine acceptable electronic signature methods and controls.   
45 When final, this guidance will represent FDAs current thinking on this topic.   
46 See 21 CFR 50.27(a). 
47 See 21 CFR 11.3(b)(8) for the definition of a handwritten signature. 
48 See 21 CFR 312.57, 312.62, and 812.140. 
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  Contains Nonbinding Recommendations 
arise in which a sponsor cannot meet eCTD requirements (e.g., if computer operations are 
impacted).  For information on requesting a short-term waiver from eCTD requirements, see 
section III.E of the guidance for industry Providing Regulatory Submissions in Electronic 
Format  Certain Human Pharmaceutical Product Applications and Related Submissions Using 
the eCTD Specifications (eCTD guidance) (February 2020). 
 
Companies experiencing technical difficulties with transmission of their electronic submissions 
to FDA should consult FDAs electronic submission staff for technical assistance, rather than 
submitting a waiver request, as described in section III.E of the eCTD guidance. 
 
Q17.  During a disaster or PHE, participants may no longer be able to travel to a central 
location for administration of an investigational drug that is scheduled on a 
recurring basis.  Can the IP be shipped to a local HCP who is not a sub-investigator 
to administer the product to a participant while still maintaining integrity of the 
trial?  If so, what else would be needed regarding trial monitoring and IRB 
oversight? 
 
Specific circumstances for a given clinical trial would affect the feasibility and appropriateness 
of shipping IP to locations other than clinical trial sites as specified under an IND, as well as 
administering the IP.  Depending on how the IP(s) being evaluated in the trial are administered, it 
would be important that any alternative location have appropriately trained personnel and 
oversight by physicians with sufficient experience regarding the class of products involved to 
assure trial participant safety comparable to administration at a trial site.   
 
In this guidance, local HCPs who are administering drugs in a manner that does not differ from 
their normal clinical practices would not be considered sub-investigators and need not be listed 
on Form FDA 1572.49  FDA recommends that these HCPs be listed in site records, such as a log 
of activities delegated by the investigator.  Any changes to a trial protocol to permit HCPs to 
administer the investigational drug generally must be reviewed and approved by an IRB.50 
 
The above paragraph describes administration of the IP by local HCPs who are practicing 
medicine within their scope of practice.  In contrast, if a sponsor will be asking local HCPs to 
perform study-specific research procedures or assessments that represent a direct and significant 
contribution to the clinical data for the study (e.g., assessing drug response for a patient or 
performing a procedure unique to the study and not part of routine medical care), these HCPs 
would be considered sub-investigators that must be listed on Form FDA 1572.51  
 
 
49 For the definition of a sub-investigator, see 21 CFR 312.3(b); for the requirement to list sub-investigators on the 
FDA Form 1572, see 21 CFR 312.53(c)(1)(viii). 
50 As noted in the response to Q2 above, changes to a protocol necessary to eliminate an apparent immediate hazard 
to trial participants may be implemented before FDA and IRB review and approval (see 21 CFR 56.108(a)(4) and 21 
CFR 312.30(b)(2)(ii)). 
51 21 CFR 312.53(c)(1)(viii). 
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  Contains Nonbinding Recommendations 
IP may be shipped from a central distribution site directly to an HCP, provided that such 
shipping is done under the supervision of the investigator using procedures that ensure 
accountability and product quality (i.e., that storage conditions, as defined in the protocol, for the 
IP were maintained during shipping, and the drug packaging was intact upon receipt).   
 
If the HCP administering the IP is not considered a sub-investigator, the investigator should 
ensure that they can obtain records regarding administration of the IP by requesting that the trial 
participants provide consent to allow access to medical records from their local HCPs involving 
trial-related data, such as measuring vital signs, and results of evaluations of any symptoms or 
signs occurring with receiving the product.  Communicating to the HCP the intent to request 
such records in advance may facilitate this process.   
 
Consulting the appropriate FDA review division on plans for alternative administration is also 
recommended as per Q11 above. 
 
Q18.  If a trial participant is unable to receive the IP from the trial site but the medical 
product is legally marketed in the United States for other uses, can the participant 
or HCP secure the product commercially?  Can the sponsor reimburse trial 
participants for their out-of-pocket expenses in getting the product commercially? 
 
If the product under investigation in a clinical trial is legally marketed and the study does not 
require blinding, then local sourcing of the product would be acceptable to FDA (e.g., by having 
the local physician write a prescription for the product instead of shipping the product directly to 
the participant).  Depending on the circumstances for providing the commercially obtained drug 
to the participant, the sponsor may need to submit a request to charge for the investigational drug 
under 21 CFR 312.8(a)(3) and satisfy other applicable requirements under 21 CFR 312.8.  FDA 
also would not object if the sponsor reimburses the participant for any costs incurred by 
commercially purchasing the product or for charges related to the use of the product (e.g., 
charges related to an infusion).   
 
Per FDA regulations under 21 CFR 312.6, the immediate package of an investigational new drug 
intended for human use must include a label with the statement Caution: New DrugLimited 
by Federal (or United States) law to investigational use.  Per FDA regulations under 21 CFR 
812.5, an investigational device or its immediate package for human use must include a label 
with the statement CAUTIONInvestigational device.  Limited by Federal (or United States) 
law to investigational use.  FDA recognizes that a commercially obtained product will not have 
this statement on its container.  In the setting of a disaster or PHE, where alternative 
arrangements are being made to provide a commercially obtained investigational drug to a 
participant who is unable to come to the trial site, FDA does not intend to object to the labeling 
of the investigational drug because it does not include the statement required under 21 CFR 
312.6 and the sponsor has not obtained a waiver of that requirement under 21 CFR 312.10.  In 
addition, FDA similarly does not intend to object to the labeling of a commercially obtained 
investigational device because it does not include the statement required under 21 CFR 812.5 
and the sponsor has not obtained a waiver under 21 CFR 812.10. 
 
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  Contains Nonbinding Recommendations 
Q19.  Throughout the guidance, FDA recommends that sponsors consult with the review 
division for certain changes to ongoing clinical trials.  For drugs and biological 
products, is this a reference to scheduling a Type A or Type 1 meeting?  How should 
sponsors contact FDA regarding device clinical trials? 
 
As stated in our guidance for industry and review staff Best Practices for Communication 
Between IND Sponsors and FDA During Drug Development (December 2017), review division 
regulatory project managers (RPMs) are the primary point of contact for communications 
between a sponsor and FDA.  Both FDA and sponsors use various communication methods to 
focus discussions to exchange information and resolve issues efficiently.  For example, telephone 
communication between a sponsor and FDA RPM may be more effective for time-sensitive 
matters.  FDA staff try to respond to sponsor questions promptly, while balancing FDA public 
health priorities and other work obligations.  Note that to ensure participant safety, responses to 
safety-related inquiries will be prioritized over other inquiries.  More generally, FDA 
understands that many questions that arise regarding changes in trial conduct due to a disaster or 
PHE will need to be addressed expeditiously.  RPMs will work with sponsors to determine the 
best path forward to answer their questions for certain changes in an expedited manner.   
 
To discuss urgent issues related to IDEs managed in CDRH, sponsors should contact the lead 
reviewer.  For IDEs managed in CBER, sponsors should contact the RPM.  For FDA feedback 
on a proposed future IDE study or regarding modifications to ongoing studies that are not urgent 
(such as a statistical analysis plan to address missing data), a Pre-Submission is recommended.  
For additional information on Pre-Submissions, please refer to the guidance for industry 
Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission 
Program (June 2023). 
 
For general questions regarding FDA policy on clinical trial conduct during a disaster or PHE, 
sponsors should contact CTconductquestions@fda.hhs.gov. 
 
Q20.  How are drug and biological product clinical trials required as postmarketing 
requirements (PMRs) affected during disasters or PHEs?  What about required 
postmarket device studies? 
 
The information in this guidance applies to all clinical trials, including those postmarketing 
clinical trials that FDA requires an applicant52 to conduct53 for drugs and biological products.  
 
52 After a company submits a marketing application (e.g., new drug application (NDA), biologics license application 
(BLA), premarket approval application (PMA), De Novo classification request, or premarket notification (510(k)) 
for review, the company is referred to as the applicant.  The person who initiates a clinical investigation is referred 
to as the sponsor (see 21 CFR 312.3 and 812.3(n)). 
53 Specifically, this response is intended to apply to studies or clinical trials required under 505(o)(3) of the FD&C 
Act (21 U.S.C. 355(o)(3)), confirmatory trials for drugs approved under the accelerated approval pathway (21 
U.S.C. 356(c)(2)(A)), deferred pediatric studies (21 U.S.C. 355B), and postmarketing studies required for drugs and 
biological products developed under the Animal Rule (see 21 CFR 314.610(b)(1) and 610.91(b)(1)); see also the 
FDA guidance for industry Product Development Under the Animal Rule (November 2015). 
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  Contains Nonbinding Recommendations 
Many of the considerations outlined in this guidance may also be relevant to postmarket device 
studies.54   
 
Applicants who are required to complete postmarketing clinical trials for drugs or biological 
products follow a timetable that includes due dates for completing certain milestones in the trial.  
FDA encourages applicants to inform FDA as soon as possible if they experience delays due to a 
disaster or PHE that may affect the applicants ability to meet the applicable interim,55 trial 
completion, and/or final report submission milestones.  These applicants should propose feasible 
revised milestones for interim, trial completion, and/or final report submission milestones.56 
  
For postmarket device studies, the approved postapproval study protocol or postmarket 
surveillance plan generally includes due dates for completing certain study milestones.  Due 
dates for certain milestones may also be listed expressly in the order requiring the postmarket 
study.  Applicants required to complete such studies should similarly inform FDA as soon as 
possible of delays due to a disaster or PHE that may affect the applicants ability to meet those 
milestones and propose feasible revised milestones.57   
 
Applicants with PMRs or required postmarket device studies should also provide an explanation 
to FDA of how the disaster or PHE impacts the ability to meet the original milestones.  FDA will 
evaluate the facts and circumstances of the explanation provided, as well as the conduct of the 
applicant, in determining whether the applicant is in compliance with the applicable authority 
requiring the postmarketing trial or postmarket device study after an original milestone has been 
missed.   
 
Additional considerations for drug and biological product PMRs include: 
 
  PMRs Under Section 505(o)(3) of the FD&C Act:  FDA will continue to make 
good cause determinations on a case-by-case basis for all missed milestones, 
including those where the applicant asserts that its failure to meet a PMR interim, 
 
54 For devices subject to premarket approval, FDA may require postapproval studies as a condition of approval (21 
CFR 814.82(a)(2)).  FDA may also require manufacturers to conduct postmarket surveillance studies of certain 
Class II and Class III devices under section 522 of the FD&C Act (21 U.S.C. 360l).   
55 Interim milestones refer to those due dates scheduled to occur between the final protocol submission and trial 
completion milestones. 
56 Although a revised trial completion date may be acknowledged by FDA, for drugs and biological product PMRs, 
the original projected completion date will continue to be displayed on the FDAs Postmarket Requirements and 
Commitments web page.  In the case of Pediatric Research Equity Act postmarketing requirements, if a deferral 
extension is granted and the final report submission date has been deferred, the new final report submission date will 
replace the original or previously granted final report submission date. 
57 See the guidance for industry and FDA staff Postmarket Surveillance Under Section 522 of the Federal Food, 
Drug, and Cosmetic Act (October 2022).  See also the guidance for industry and FDA staff Procedures for Handling 
Post-Approval Studies Imposed by PMA Order (October 2022). 
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  Contains Nonbinding Recommendations 
trial completion, and/or final report submission milestone is related to the disaster 
or PHE.58  
 
  Deferred Pediatric Study PMRs Under the Pediatric Research Equity Act 
(PREA):59  If circumstances involving a disaster or PHE have affected an 
applicants ability to complete a PREA PMR, applicants may request a deferral 
extension of the timeline for a deferral granted by FDA.  If an applicant has not 
obtained a deferral extension and fails to submit required PREA studies by the 
final report submission date listed in the PREA PMR, FDA is required to issue a 
noncompliance letter to the applicant.60 
 
  PMRs Under Accelerated Approval:  For confirmatory trials, if an applicant 
misses an interim, trial completion, and/or final report submission milestone, 
FDA will review the applicants explanation for the delay, as well as assess the 
trials progress before the disaster or PHE, before determining whether or not the 
applicant has been compliant with its milestone obligations.   
 
  Annual Status Reports of PMRs:  Applicants must continue to follow the annual 
reporting requirements for PMRs61 and should document in their annual status 
report the disaster or PHE-related reasons for missing interim, trial completion, 
and/or final report submission milestones, the reasons for the non-compliance 
with the milestones, and any steps taken to address factors specific to the disaster 
or PHE.  
 
Q21.  My company is the holder of an approved marketing application for an FDA-
approved drug for a specific indication and is also the sponsor of an IND for the 
same drug being investigated for a new indication to prevent conditions related to a 
disaster or PHE.  If I receive a spontaneous report of a serious adverse event (SAE) 
that occurred with the approved drug being used in clinical practice for the 
prevention of the disease or condition related to the disaster/PHE, do I report that 
event to the IND?   
 
Reports of SAEs that occur in clinical practice with the use of an approved drug or biological 
product, whether or not the use is included in the approved labeling for that product, must be 
reported in accordance with the applicable postmarketing reporting requirements under 21 CFR 
314.80 and 600.80.  Reports of SAEs for approved vaccines are submitted to the Vaccine 
 
58 See the FDA guidance for industry Postmarketing Studies and Clinical TrialsImplementation of Section 
505(o)(3) of the Federal Food, Drug, and Cosmetic Act (October 2019). 
59 Section 505B(a)(4)(B) of the FD&C Act governs the process and timelines required for requests for a deferral 
extension for deferred pediatric studies required under section 505B of the FD&C Act (21 U.S.C. 355c) (often 
referred to as PREA PMRs).   
60 See section 505B(d)(1) of the FD&C Act (21 U.S.C. 355c(d)(1)). 
61 See section 506B of the FD&C Act (21 U.S.C. 356b) and 21 CFR 314.81(b)(2)(vii) and 601.70(b). 
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  Contains Nonbinding Recommendations 
Adverse Events Reporting System (VAERS), while reports of SAEs for other approved drugs 
and biological products are submitted to the FDA Adverse Event Reporting System (FAERS).62    
 
Serious adverse events that occur during a clinical trial under an IND for an approved drug or 
biological product being investigated for a new use to treat or prevent a disaster- or PHE-related 
disease or condition must be reported as an IND safety report per FDA regulations under 21 CFR 
312.32 if (1) they are unexpected and (2) the sponsor determines that there is a reasonable 
possibility that the drug caused the SAE.  
 
Regardless of whether an SAE occurs in the course of clinical practice or during a clinical trial 
and regardless of where it is first reported, an NDA or BLA holder who is also the sponsor of an 
IND investigating the same drug for treatment or prevention of a disaster- or PHE-related disease 
or condition is responsible for monitoring the safety of its drug and evaluating all accumulating 
safety data.63  If accumulating safety data, including use in clinical practice, indicates a new 
potential serious risk associated with the drug, an IND safety report will need to be filed to the 
IND, and updates will likely need to be made to the investigator brochure and/or the informed 
consent document.64  For more information, see the guidance for industry and investigators 
Safety Reporting Requirements for INDs and BA/BE Studies (December 2012). 
 
Q22.  If a trial participant experiences an SAE that may be associated with a disease or 
condition related to the disaster or PHE, should that be reported as an IND safety 
report?  Should these events be reported to the IRB?  
 
Under 21 CFR 312.32, a sponsor must report to FDA any SAE that is both unexpected and for 
which there is a reasonable possibility that the drug caused the SAE (i.e., there is evidence to 
suggest a causal relationship between the drug and the adverse event).  
  
Participants in a clinical trial may be diagnosed with a PHE- or disaster-related disease or 
condition and experience SAEs associated with the disease or condition that are not causally 
related to the investigational drug.  However, it is possible that such SAEs could be causally 
related to the investigational drug.  Establishing a potential causal relationship likely requires 
more than a single or even a few cases.   
 
FDA had provided additional information about aggregate safety assessment and reporting for 
INDs in the guidance for industry and investigators Safety Reporting Requirements for INDs and 
BA/BE Studies (December 2012) and has proposed recommendations in the draft guidance for 
 
62 For more information, see the Vaccine Adverse Event Reporting System, available at 
https://vaers.hhs.gov/reportevent.html, and the FDA Adverse Event Reporting System (FAERS) Public Dashboard, 
available at https://www.fda.gov/drugs/questions-and-answers-fdas-adverse-event-reporting-system-faers/fda-
adverse-event-reporting-system-faers-public-dashboard. 
63 See 21 CFR 312.32(b). 
64 See 21 CFR 312.32(c).  
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  Contains Nonbinding Recommendations 
industry Sponsor ResponsibilitiesSafety Reporting Requirements and Safety Assessment for 
IND and Bioavailability/Bioequivalence Studies (June 2021).65 
 
Where an IND safety report is required to be submitted to FDA under 21 CFR 312.32, the 
investigator must also send that IND safety report to the IRB.66  The IRB may have additional 
reporting requirements regarding the disaster or PHE that apply during the clinical trial. 
 
Q23.  Certain clinical trial protocols have an exclusion criterion for receipt of another 
investigational medical product.  If a participant receives a vaccine or other medical 
product authorized under an emergency use authorization (EUA), would FDA 
consider this receipt of an investigational medical product? 
 
When a medical product is being used under an EUA, it is an authorized (though not an approved 
or cleared)67 medical product for use in clinical care that has met the statutory criteria under 
section 564 of the FD&C Act.68  The product is not being studied under an IND or IDE when 
used pursuant to an EUA, and FDA therefore does not consider an individuals receipt of the 
product under an EUA as receipt of an IP.  In contrast, when the same product is used in a 
clinical investigation under an IND or IDE, the products safety and/or effectiveness is being 
studied for investigational uses, and FDA would consider receipt in this situation to be receipt of 
an IP.  
 
In the design of a clinical investigation, there may be valid scientific reasons to have an 
exclusion (and even a discontinuation of study treatment) criterion for receipt of a medical 
product  a monoclonal antibody or vaccine, for example  whether that product was used 
under an EUA or not.  These scientific reasons may include risks to an individual if they enroll 
or continue to receive study treatment in a clinical trial after receiving (or having received) the 
excluded product or the potential impact of the use of the excluded product on trial objectives, 
such as confounding the determination of effectiveness of the product under investigation. 
 
65 When final, this guidance will represent FDAs current thinking on this topic. 
66 See 21 CFR 312.53(c)(1)(vii) and 312.66.  See also the guidance for clinical investigators, sponsors, and IRBs 
Adverse Event Reporting to IRBs  Improving Human Subject Protection (January 2009). 
67 In this guidance, approved or cleared, with respect to devices, refers to FDA permitting the marketing of a device 
via the premarket approval, premarket notification (510(k)), De Novo classification, or Humanitarian Device 
Exemption (HDE) pathways. 
68 See section 564(k) of the FD&C Act (21 U.S.C. 360bbb-3(k)); see also guidance for industry Emergency Use 
Authorization of Medical Products and Related Authorities (January 2017). 
31