Institutional Review Board 
(IRB) Review of Individual 
Patient Expanded Access 
Submissions for Investigational 
Drugs and Biological Products 
Guidance for IRBs and Clinical 
Investigators  
 
 
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) Dat Doan, 240-402-8926. 
 
 
 
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) 
Oncology Center of Excellence (OCE) 
Office of Clinical Policy (OCLiP) 
 
September 2023 
Good Clinical Practice (GCP) 
53692460fnl   
Institutional Review Board 
(IRB) Review of Individual 
Patient Expanded Access 
Submissions for Investigational 
Drugs and Biological Products 
Guidance for IRBs and Clinical 
Investigators 
 
Additional copies are available from: 
Office of Communications, Division of Drug Information  
Center for Drug Evaluation and Research 
Food and Drug Administration 
10001 New Hampshire Ave., Hillandale Bldg., 4th Floor  
Silver Spring, MD 20993-0002  
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353 
Email: druginfo@fda.hhs.gov  
https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs  
and/or 
Office of Communication, Outreach and Development  
Center for Biologics Evaluation and Research 
 Food and Drug Administration 
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Phone: 800-835-4709 or 240-402-8010 
Email: ocod@fda.hhs.gov 
https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances     
 
 
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) 
Oncology Center of Excellence (OCE) 
Office of Clinical Policy (OCLiP) 
 
 September 2023 
Good Clinical Practice (GCP) 
  Contains Nonbinding Recommendations 
TABLE OF CONTENTS 
 
 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
III.  RECOMMENDATIONS ON IRB PROCEDURES AND FACTORS TO 
CONSIDER FOR INDIVIDUAL PATIENT EXPANDED ACCESS SUBMISSIONS
............................................................................................................................................. 4 
  Contains Nonbinding Recommendations 
Institutional Review Board (IRB) Review of Individual Patient Expanded 
Access Submissions for Investigational Drugs and Biological Products  
Guidance for IRBs and Clinical Investigators1 
 
 
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  
 
This guidance provides recommendations to institutional review boards (IRBs) and clinical 
investigators regarding the key factors and procedures IRBs should consider when reviewing 
individual patient expanded access submissions, including for reviews conducted by a single 
member of the IRB, to fulfill its obligations under 21 CFR part 56.  Although FDA has issued 
guidance on expanded access requests, including expanded access for individual patients,2 the 
Agency is aware that IRBs seek further clarity on this topic.   
 
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 
the word should in Agency guidance means that something is suggested or recommended, but 
not required.   
 
 
 
1 This guidance has been prepared by the Center for Drug Evaluation and Research (CDER) in cooperation with the 
Center for Biologics Evaluation and Research (CBER), the Office of Clinical Policy (OCLiP), and the Oncology 
Center of Excellence (OCE) at the Food and Drug Administration. 
 
2 See the draft guidance for industry Expanded Access to Investigational Drugs for Treatment Use:  Questions and 
Answers (November 2022).  When final, this guidance will represent FDAs current thinking on this topic.  See also 
the guidance for industry Individual Patient Expanded Access Applications:  Form FDA 3926 (October 2017) and 
the information sheet guidance for sponsors, clinical investigators, and IRBs Waiver of IRB Requirements for Drug 
and Biological Product Studies (October 2017).  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. 
  1  Contains Nonbinding Recommendations 
II.  BACKGROUND 
 
Expanded access refers to the use of an investigational drug3 when the primary purpose is to 
diagnose, monitor, or treat a patients disease or condition rather than to obtain the kind of 
information about the drug that is generally derived from clinical trials.4  This pathway, 
sometimes called compassionate use, allows a patient with a serious or immediately life-
threatening disease or condition5 to gain access to an investigational drug or biological product 
when there is no comparable or satisfactory alternative therapy; the potential patient benefit  
justifies the potential risks to the patient, and those risks are not unreasonable in the context of 
the disease or condition to be treated; and the requested use will not interfere with clinical 
investigations that could support marketing approval.6  For an investigational drug or biological 
product to be provided through the expanded access pathway, the sponsor of the investigational 
drug or biological product must agree to provide such access.  Although the drug requested under 
individual patient expanded access is investigational, use of that drug through individual patient 
expanded access is for the primary purpose of diagnosing, monitoring, or treating a patients 
disease or condition, rather than generating scientific data intended to characterize the safety and 
effectiveness of a drug.7   
 
Under FDA regulations, there are three categories of expanded access submissions:  individual 
(also known as single) patient, including for emergency use; intermediate-size for intermediate-
size patient populations; and treatment for larger populations.8  This guidance only applies to 
IRB review of individual patient expanded access submissions as outlined in 21 CFR 312.310.9   
 
This guidance does not address IRB review of intermediate-size and treatment expanded 
access submissions, as outlined in 21 CFR 312.315 and 312.320, respectively.   
 
 
3 In this guidance, the terms investigational new drug, investigational drug, drug, and drug product refer to human 
drugs, including biological products, regulated by CDER and CBER. 
 
4 See the draft guidance for industry Expanded Access to Investigational Drugs for Treatment Use:  Questions and 
Answers. 
 
5 For the purpose of expanded access to investigational drugs for treatment use, immediately life-threatening disease 
or condition means a stage of disease in which there is reasonable likelihood that death will occur within a matter of 
months or in which premature death is likely without early treatment.  Serious disease or condition means a disease 
or condition associated with morbidity that has substantial impact on day-to-day functioning.  Short-lived and self-
limiting morbidity will usually not be sufficient, but the morbidity need not be irreversible, provided it is persistent 
or recurrent.  Whether a disease or condition is serious is a matter of clinical judgment, based on its impact on such 
factors as survival, day-to-day functioning, or the likelihood that the disease, if left untreated, will progress from a 
less severe condition to a more serious one (21 CFR 312.300(b)).   
 
6 See 21 CFR 312.300 and 312.305. 
 
7 See 21 CFR 312.300.  See also the draft guidance for industry Expanded Access to Investigational Drugs for 
Treatment Use:  Questions and Answers. 
 
8 See 21 CFR 312.310, 312.315, and 312.320. 
 
9 See 21 CFR 312.310. 
  2  Contains Nonbinding Recommendations 
An individual patient expanded access request can be submitted to FDA by a licensed physician 
as a new investigational new drug application (IND) or by a sponsor of an existing IND as a 
protocol amendment, either on an emergency10 or non-emergency use basis.11  A request for 
emergency individual patient expanded access does not require prior IRB review, but the IRB 
must be notified within 5 working days of treatment initiation.  Generally, once an 
investigational drug is used in an emergency situation without prior IRB approval, any 
subsequent uses of the investigational drug at that same institution would require prior IRB 
review and approval.  An institution or physician that expects subsequent use of the 
investigational drug should request review and approval by the appropriate IRB after the initial 
emergency use.  However, when prior IRB review and approval is not feasible for a subsequent 
expanded access emergency use at a particular institution, FDA does not intend to deny the 
subsequent request for emergency use based on lack of time to obtain prospective IRB review, 
provided that use will be reported to the IRB within 5 working days of initiation of treatment.12  
For non-emergency expanded access requests for individual patients, prior IRB review and 
approval is required before treatment begins.13   
 
A licensed physician who submits a non-emergency individual patient expanded access request 
may request from FDA a waiver14 of the requirement for full IRB review.15  Upon request, FDA 
intends to allow for waivers of the requirement for full IRB review and approval for individual 
patient expanded access requests when the physician obtains concurrence from the IRB 
chairperson or another designated IRB member before treatment begins.16  A waiver of the 
requirement for full IRB review would also extend to any changes or amendments to the original 
treatment plan or for continuing review of the individual expanded access request.   
 
IRB review of an expanded access submission for an individual patient, including review by a 
designated single member of the IRB under a waiver, should focus on the key factors needed to 
assess the risks and benefits of treatment for the particular patient involved.  As discussed above, 
FDA is aware that IRBs are seeking clarity regarding the key factors and procedures they should 
 
10 FDA considers an emergency situation to be, for example, a situation that requires a patient to be treated before a 
written submission to the IRB can be made and in which the treatment is expected to have a rapid effect in resolving 
an acute clinical emergency.   
 
11 See 21 CFR 312.310 
 
12 See the draft guidance for industry Expanded Access to Investigational Drugs for Treatment Use:  Questions and 
Answers and 21 CFR 56.104(c). 
 
13 See 21 CFR 312.305(c)(4) and 56.103. 
 
14 See 21 CFR 56.105. 
 
15 See 21 CFR 56.108(c). 
 
16 FDA intends to consider a completed Form FDA 3926 with the box in Field 10.b checked and the form signed by 
the physician to be a request for a waiver.  Form FDA 3926, which is a streamlined alternative to Form FDA 1571, 
was created specifically for physician-submitted individual patient expanded access INDs, including those for 
emergency use.  A physician submitting an individual patient expanded access IND using Form FDA 1571 may 
include a separate waiver request with the application.  See the draft guidance for industry Expanded Access to 
Investigational Drugs for Treatment Use:  Questions and Answers.  
  3  Contains Nonbinding Recommendations 
consider when reviewing individual patient expanded access requests, including IRB reviews 
conducted by single members, to fulfill their obligations under 21 CFR part 56.  Below, FDA 
provides recommendations to IRBs on those key factors and procedures to consider.   
 
 
III.  RECOMMENDATIONS ON IRB PROCEDURES AND FACTORS TO 
CONSIDER FOR INDIVIDUAL PATIENT EXPANDED ACCESS SUBMISSIONS  
 
The recommendations in this section are intended to assist IRBs in complying with the 
requirements under 21 CFR part 56 when reviewing individual patient expanded access requests, 
including establishing procedures for such requests and factors to consider when assessing the 
risks and benefits of treatment with the investigational drug for the particular patient involved.   
 
FDA recommends that IRBs: 
 
  Consider establishing procedures for a single IRB member (an IRB chairperson or other 
designated IRB member) to review a non-emergency individual patient expanded access 
submission if the physician requests a waiver17 of the requirements for review by the full 
IRB.18  These procedures should reflect the information that the IRB deems relevant for a 
single IRB member review and should include procedures designed to ensure that the 
member documents the decision to concur or not concur with the treatment.   
 
  Focus the review of an individual patient expanded access submission on assessing the 
risks and benefits for the patient involved.  The information reviewed by the IRB must be 
adequate to assess whether risks to the patient have been minimized and that such risks 
are reasonable in relation to anticipated benefits.19  FDA regulations under 21 CFR 
56.111 outline the criteria for IRB approval of research.  In the context of an individual 
patient expanded access submission, FDA does not expect that a protocol will be 
necessary to provide the IRB with sufficient information to determine whether those 
criteria are satisfied.20  A thorough patient history and treatment plan, included in the 
Form FDA 3926 or in a separate document, can be sufficient to provide the information 
necessary for an IRB assessment.  Such information should include:  
 
-  The proposed daily dose, route, and frequency of administration of planned 
treatment; duration of planned treatment; criteria for discontinuation of treatment; 
and planned dose modifications for adverse events 
 
 
17 See 21 CFR 56.105. 
 
18 See 21 CFR 56.108(c). 
 
19 See 21 CFR 56.111(a)(1) and (a)(2). 
 
20 For individual expanded access protocol amendments submitted by sponsors to their existing INDs, the IRB is 
likely to receive a protocol for review. 
 
  4  Contains Nonbinding Recommendations 
-  The planned monitoring for adverse events, response to treatment, and changes in 
clinical status, as well as proposed modifications to the treatment plan to mitigate 
risks to the patient if appropriate 
 
-  The key details of the patients history, including diagnosis and summary of prior 
therapy (including response to such therapy); the reason for request, including an 
explanation of why the patient lacks other therapeutic options; and information 
regarding a patients relevant clinical characteristics (such as comorbid conditions 
and concomitant medications) that is necessary to assess the potential for 
increased risks of the drug 
 
-  A summary of known risks of the drug 
 
The following are also important components of IRB review of an expanded access submission 
for an individual patient: 
 
  Assess the qualifications of the physician submitting the individual patient expanded 
access request.21  
 
  When the request is for a pediatric patient, confirm that adequate provisions are included 
for soliciting age-appropriate assent from children and permission from a parent or 
guardian, as required under 21 CFR 50.55. 
 
  Confirm that the informed consent document contains the information required under 21 
CFR 50.25.  As described above, the primary purpose of expanded access is to use the 
drug to diagnose, monitor, or treat a patients disease or condition rather than to generate 
scientific information intended to characterize the safety and effectiveness of a drug.  21 
CFR 50.25(a)(1) requires that the informed consent include a statement that the use of the 
product involves research.  Given that the drug used under expanded access is 
investigational, FDA generally considers a statement in the informed consent document 
indicating that although the primary use of the drug is for treatment, the drug is 
investigational, and FDA has not determined that the drug is safe or effective for use in 
treating the patients disease or condition to satisfy this requirement.  
 
21 See 21 CFR 56.107(a) and 56.111 and the guidance for IRBs, clinical investigators, and sponsors IRB 
Responsibilities for Reviewing the Qualifications of Investigators, Adequacy of Research Sites, and the 
Determination of Whether an IND/IDE is Needed (August 2013).  
  5