Expanded Access 

Program Report

May 2018
EA Program Report i May 2018

Table of Contents

Executive Summary ........................................................................................................................ 2

Section 1: Background/FDA’s EA Program ................................................................................... 5

1.1 Background ......................................................................................................................... 5

1.2 Report Focus―Obtaining Expanded Access ...................................................................... 6

1.3 Report Organization .......................................................................................................... 10

Section 2: Objectives and Methodology ....................................................................................... 11

2.1 Research Objectives .......................................................................................................... 11

2.2 Research Methodology ..................................................................................................... 11

Section 3: Findings ....................................................................................................................... 13

Section 4: Recommendations for FDA and Other Stakeholders to Consider ............................... 22

Section 5: Snapshot of the Stakeholder Roles and the EA Process .............................................. 27

4.1 Stakeholder Roles ............................................................................................................. 27

4.2 Process .............................................................................................................................. 29

Glossary ........................................................................................................................................ 33

Table of Figures

Figure 1 – High level flow chart for a “typical” single patient EA request .................................... 9

Figure 2 – EA requests for CDER, CBER and CDRH ................................................................. 14

Figure 3 – Turnaround time for CDER and CBER EA requests .................................................. 15

Figure 4 – Turnaround time for CDRH EA requests .................................................................... 16

Figure 5 – Mapping of recommendations to the findings they address ........................................ 26

Figure 6 – Patients' view of the EA program stakeholder ecosystem ........................................... 27

Figure 7 – High-level view of the EA process .............................................................................. 29
EA Program Report 2 May 2018

Executive Summary

Since the 1970s, the U.S. Food and Drug Administration (FDA) has facilitated making 

investigational drugs available to patients with serious diseases or conditions when there is no 

comparable or satisfactory alternative therapy to diagnose, monitor, or treat the patient's disease 

or condition. The FDA’s Expanded Access (EA) process was formalized through regulation in 

1987 (drugs and biologics)1 and 1996 (devices)2, and EA was further codified in law in 19973. 

The EA program provides a process for patients to obtain authorization to use an investigational 

medical product for treatment use that has not been FDA approved4 for use outside of a clinical 

trial setting.

5 Over the last five years, FDA’s Center for Drug Evaluation and Research (CDER), 

Center for Biologics Evaluation and Research (CBER) and Center for Devices and Radiological 

Health (CDRH) authorized approximately 9,000 applications through the EA program. FDA’s 

EA authorization rate is consistently high—approximately 99% across all application types. As 

part of FDA’s commitment to continuous operational improvement of the EA program, the 

Agency commissioned an independent assessment of the EA program that considered 

stakeholder perspectives from across the healthcare ecosystem. The assessment’s key goals were 

to better understand the current EA program’s performance and identify ways to improve it. 

This report summarizes the results of that independent assessment. The findings reflect the 

perspectives of patients and their advocates/caregivers, physicians, health system representatives, 

payers, institutional review boards (IRBs), manufacturers, and FDA staff. Those perspectives 

were sourced through a variety of quantitative and qualitative methods. The report’s principal 

findings on the overall EA process across the ecosystem are as follows: 

• External stakeholders’ overall perceptions of FDA’s EA program—and FDA’s role, 

in particular—are positive. Stakeholders across the healthcare ecosystem highlighted

FDA’s commitment to expediting the review of EA applications, their collaborative 

nature, and their focus on continuous improvement. This perception echoed findings in 

the recent Government Accountability Office (GAO) report6 as well as numerous sources 

in the EA literature.

• Stakeholders report pain points across the physician/patient journey, which, if 

addressed, could meaningfully enhance the program. The reported pain points varied 

significantly based on the respondent’s level of experience with the program. Confusion 

 

1 Per 21 CFR 312 section I

2 Per 21 CFR part 812

3 FDA’s EA program is sometimes referred to as the “compassionate use” program. “Expanded access” involves use 

of an investigational medical product outside of a clinical trial.

4 “Approved” or “Approval” is used in this report to refer to the following: approval for a drug or device, licensing 

for a biologic, and marketing authorization for a medical device via the premarket approval, 510(k) or De Novo 

classification pathway and for a medical device that is exempt from premarket notification to be marketed in the US. 5 Food and Drug Administration Modernization Act of 1997 (FDAMA). 6 GAO, Investigational New Drugs: FDA Has Taken Steps to Improve the Expanded Access Program but Should 

Further Clarify How Adverse Events Data Are Used, July 11, 2017, GAO-17-564, Washington, D.C.: GAO.
EA Program Report 3 May 2018

with program navigation, multi-stakeholder coordination, and administrative burden were

the most frequently-cited pain points.

• Because EA operates in an inherently multi-stakeholder environment, the absence

of standard processes and policies for EA submission requests to FDA, 

manufacturers, IRBs, and payers creates confusion for many stakeholders. 

Stakeholders reported variability in policies related to requirements for applications 

submitted to the various parties involved in approval and authorization, in addition to 

variation in insurance coverage policies. The variation drives administrative burden, 

creates a degree of stakeholder confusion, and hinders easy program engagement and 

navigation. 

• A detailed review of how the EA program is managed within FDA pointed to 

additional, addressable opportunities. Opportunities are related to (1) improving

FDA’s public website content, (2) investing in resources to support patient/physician 

program navigation and (3) improving the systems (and data) used to manage the EA 

program. 

• Manufacturers report facing challenges particularly related to (1) uncertainty about 

how FDA uses data from EA, and (2) managing divergent requirements and 

guidance from ex-US health authorities. Some manufacturers report perceived 

uncertainty around how data from the EA program will be interpreted and possibly affect 

investigational products either still under development or undergoing regulatory review, 

though recent studies suggest that drug development has not been harmed.7 Global 

challenges cited related principally to divergent practices and requirements (e.g., 

investigational product labeling) across health authorities.

A more detailed discussion of the report’s findings can be found in Section 3.

FDA and the other stakeholders in the ecosystem could consider several steps to strengthen the 

EA program. The following are high-level recommendations for FDA and other stakeholders to 

consider, organized around four guiding principles. These reflect many recommendations from 

recent literature. Detailed recommendations for consideration are discussed in Section 4.

1. Ensure patients continue to receive timely and medically appropriate access to 

investigational medical products through the EA program. Recommendations center on 

strengthening dialogue with manufacturers about the EA program across the product 

development lifecycle.

2. Make participating in the program minimally taxing for stakeholders (physicians, 

patients, FDA, and others). For example, FDA can place greater emphasis on crosspollinating known best practices (within FDA), to enhance stakeholders’ program 

experience.

 

7 Jonathan Jarow, Richard Moscicki, “Impact of Expanded Access on FDA Regulatory Action and Product 

Labeling,” Therapeutic Innovation & Regulatory Science, Volume 51, Issue No. 6 (2017): 1-3
EA Program Report 4 May 2018

3. Make the program easy for patients, physicians, and other stakeholders to understand 

and navigate. Recommendations focus on clarifying program language, enhancing online 

resources, and building program awareness and understanding in the community care 

setting8

4. Continue to integrate data from the program with medical product review to provide 

transparency and promote quality decision-making. Recommendations strive to help 

manufacturers understand how FDA may use data from EA and correct manufacturer 

misperceptions that data from EA harms product development, strengthen the use of data 

to manage and oversee the EA program, and further link EA data to the systems that 

support ongoing regulatory decision-making.

In summary, this report acknowledges and commends FDA on its efforts to manage and improve 

the EA program, facilitating rapid access to investigational therapies for patients in need while 

preserving the Agency’s ability to make informed regulatory decisions that protect and promote 

the public health. The findings and recommendations discussed in the following sections are 

designed to further the Agency’s public health mission through targeted program enhancements 

that have been informed by a broad range of healthcare ecosystem stakeholders.

 

8 In this report, the community care setting is defined as care delivered outside of an academic medical center 

(AMC) or AMC-affiliated facility. According to Joint Commission International, an academic medical center is 

integrated with medical school, offers education for medical students and postgraduate trainees, and is engaged in 

engaged in conduct human subject research. 
EA Program Report 5 May 2018

Section 1: Background/FDA’s EA Program

1.1 Background 

The U.S. Food and Drug Administration (FDA or “Agency”) regulates the development and 

approval for marketing of medical products in the United States of America (US) under authority 

from the Federal Food, Drug, and Cosmetic Act (FFDCA). For unapproved products, a clinical 

trial is generally the mechanism by which patients gain access to investigational products. 

However, in some cases, a clinical trial is not an option for a patient. In these cases, patients, in 

consultation with their physicians, may obtain access to unapproved therapies through FDA’s 

Expanded Access (EA) program.9

Since the 1970s, the U.S. Food and Drug Administration (FDA) has facilitated making 

investigational drugs available to patients with serious diseases or conditions when there is no 

comparable or satisfactory alternative therapy to diagnose, monitor, or treat the patient's disease 

or condition. The FDA’s Expanded Access (EA) process was formalized through regulation in 

1987 (drugs and biologics)10 and 1996 (devices)11, and EA was further codified in law in 199712. 

The EA program provides a pathway for patients, acting through their physician, to obtain 

investigational new drugs, biologics or devices that would otherwise be unavailable outside of a 

clinical trial setting to address a serious condition or disease for which there are no satisfactory 

alternatives.

13 Over the past five years, FDA received approximately 9,000 EA requests and 

authorized 99% of those requests. 

FDA is committed to continuous improvements and updates to the program. For example, FDA 

recently streamlined the required supporting documentation for EA requests for drugs and 

biologics, reducing administrative burden for sponsors (typically physicians) to complete the

required form by about 90%, from 8 hours to 45 minutes. The Agency also simplified the 

requirements for IRB review for single patient EA requests for investigational drugs and 

biologics so that a single member, such as the IRB Chair, can provide concurrence rather than 

requiring full board approval, which promotes consistency across all EA programs.14,15

 

9 The EA program is sometimes referred to as the “compassionate use” program. 10 Per 21 CFR 312 section I 11 Per 21 CFR part 812 12 FDA’s EA program is sometimes referred to as the “compassionate use” program. “Expanded access” involves 

use of an investigational medical product outside of a clinical trial.

13 FDAMA. 14 Scott Gottlieb, FDA Commissioner, “Expanded Access: FDA Describes Efforts to Ease Application Process,”

FDA Voice. FDA, Original publication October 3, 2017, 

https://blogs.fda.gov/fdavoice/index.php/2017/10/expanded-access-fda-describes-efforts-to-ease-applicationprocess/ (accessed February 5, 2018). 15 Expanded Access for Medical Devices, 

https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/InvestigationalDevi

ceExemptionIDE/ucm051345.htm (accessed April 17, 2018).
EA Program Report 6 May 2018

Additionally, FDA has released guidance on how it uses safety data generated from using an 

investigational drug or biologic through EA pathways.16

This independent assessment was undertaken in 2017 and 2018 to better understand the 

program’s current performance and identify areas for additional improvement. Because the EA 

program has multiple stakeholders, the assessment sought to build on existing reviews of the 

program by taking a comprehensive look at the healthcare ecosystem. Accordingly, the report 

integrates perspectives from patients and their advocates/caregivers, healthcare providers and the 

health systems that support healthcare providers, payers, IRBs, manufacturers, and FDA staff. 

The report presents many of these perspectives, and combined with quantitative and qualitative 

insights about program performance, identifies opportunities to strengthen the program. The 

report concludes with specific recommendations for FDA and other stakeholders to consider as 

they work to continually enhance this important public health program. 

1.2 Report Focus―Obtaining Expanded Access

For clarity, this report focuses on applications (alternately termed “requests”) submitted to FDA 

to obtain access to investigational products through the EA program. The EA program (described 

in detail in Section 5) provides patient access to an investigational product (i.e., drug, biologic or 

device) outside of a clinical trial to treat or diagnose a serious or immediately life-threatening 

disease or condition in the absence of a comparable or satisfactory alternative therapy.

17

Expanded access to drugs and biologics is authorized through the submission of a new protocol 

to either an existing or new investigational new drug application (IND). This can be for (1) a 

single patient, (2) an intermediate size patient population, or (3) a larger treatment population. 

These pathways are defined in the following way: 

• A single-patient protocol to a new or existing IND is used to request treatment for a 

single patient.

− When there is an emergency that requires treatment before a written submission 

can be made to FDA, the sponsoring physician may request and obtain 

authorization from FDA by telephone or other means of rapid communication. 

− The sponsor must then follow up with a written submission of the emergency 

protocol to a new or existing IND within 15 days of FDA’s authorization. 

• An intermediate-size patient population protocol to a new or existing IND is used for 

more than one patient but a population smaller than the typical treatment protocol to a 

new or existing IND (discussed further below). This type of protocol may be used when 

the investigational drug or biologic is not being developed for marketing (e.g., if 

 

16 FDA Center for Drugs Evaluation Research (2017). Guidance for Industry: Expanded Access to Investigational 

Drugs for Treatment Use – Questions and Answers (FDA Maryland). 17 FFDCA 21 USC, Section 360bbb, “Expanded access to unapproved therapies and diagnostics,” 

http://uscode.house.gov/view.xhtml?req=(title:21%20section:360bbb%20edition:prelim. 
EA Program Report 7 May 2018

development has been discontinued), or when the product is being developed but the 

sponsor is not yet actively pursuing marketing approval with due diligence. 

• A treatment protocol to a new or existing IND is used for widespread treatment use or to 

bridge the gap between the completion of clinical trials and marketing of the product. 

Investigational devices may be obtained through FDA’s EA program via three pathways: (1) 

emergency use, (2) single patient (also called “compassionate use” with or without an 

investigational device exemption [IDE]

18), and (3) treatment IDEs. These pathways are defined 

in the following way: 

• Emergency use is an immediate need, as determined by the physician, to use an 

unapproved device to treat life-threatening or serious diseases or conditions when there is 

no generally acceptable alternative and there is no time to obtain FDA approval due to 

the immediate need. Under these circumstances, the unapproved device may be used for 

treatment without prior notification to or approval by FDA. FDA expects the physician to 

make the determination that the patient’s circumstances meet these criteria, to assess the 

potential for benefit from the use of the unapproved device, and to have substantial 

reason to believe that benefits will exist. If there is an existing IDE for the device, the 

IDE sponsor must notify the FDA of the emergency use within five days19 through 

submission of an IDE report. If there is no IDE, the physician should submit a follow-up 

report to FDA describing the device used, patient’s outcome and the patient protection 

measures followed. 

• Single patient use requests (also termed ‘Compassionate Use’) are those non-emergency 

situations for which expanded access to an unapproved device may be warranted for a 

single use. This mechanism is termed an “investigational device compassionate use 

request” and is either approved under an existing IDE or authorized when an IDE does 

not exist before treatment can begin. In rare circumstances, a small group access protocol 

may be considered under this pathway. Prior FDA approval is needed before such use 

occurs. If there is an open IDE for the investigational device, the request is submitted as 

an IDE supplement by the IDE sponsor. If not, the request may be submitted to FDA by 

the physician or manufacturer as a standalone request. The physician should not treat the 

patient identified in the request until FDA approves use of the device under the proposed 

circumstances. 

• Treatment IDEs are applications for widespread use of an unapproved device to treat or 

diagnose a serious or immediately life-threatening disease or condition, and require prior 

FDA approval. The application may be submitted under an existing or as a new IDE.

20

 

18 An IDE allows a device that otherwise would be required to comply with a performance standard or to have 

premarket approval to be shipped lawfully for the purpose of conducting a clinical investigation, 21 CFR 812.1. 19 21 CFR 812.35(a)(2), “Changes effected for emergency use,” 

https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=812.35. 20 21 CFR 812.36. 
EA Program Report 8 May 2018

The high-level process for a “typical” EA request for a single patient, sponsored by a physician, 

is described in Figure 1, and in more detail in Section 5. 
EA Program Report 9 May 2018

Figure 1 – High level flow chart for a “typical” single patient EA request
EA Program Report 10 May 2018

Facilitating patient access to investigational products is a delicate undertaking that involves 

complex ethical, medical, and legal judgments. This report does not address those aspects of the 

program. Nor does the report discuss other pathways, including Personal Importation (in which a 

patient imports a medical product for personal use either in personally transported baggage or 

shipped by courier) 21 or Emergency Use Authorization (EUA) (which allows the broad use of an 

investigational medical product in response to a public health emergency).22

1.3 Report Organization

Following a brief description of the objectives and methodology used during the assessment, this 

report presents the findings (see Section 3) and recommendations (see Section 4). To clarify

what can be a complicated process, Section 5 describes the roles of stakeholders and the process 

for a “typical” EA request. 

 

21 Personal Importation. https://www.fda.gov/ForIndustry/ImportProgram/ImportBasics/ucm432661.htm (accessed 

April 16, 2018).

22 EUA. https://www.fda.gov/EmergencyPreparedness/Counterterrorism/ucm182568.htm (accessed April 16, 2018).
EA Program Report 11 May 2018

Section 2: Objectives and Methodology

This report presents the findings of an independent assessment of FDA’s EA program that was 

conducted on FDA’s behalf. The research objectives and approach undertaken are described in 

this section. More detailed information is available in the “Expanded Access Program Report: 

Addendum” document. 

2.1 Research Objectives

The following objectives guided the assessment: 

• Assess the current performance of FDA’s EA program; conduct analyses to establish a 

baseline for the program, and identify areas for improvement 

• Evaluate the experience of physician sponsors and best practices across interactions with 

FDA and opportunities for improvement 

• Convene stakeholders across the broader healthcare ecosystem to assess knowledge, 

interest, and use of the EA program, and form recommendations to improve awareness 

• Perform a user experience assessment of EA webpages focused on three websites: 

FDA.gov, ClinicalTrials.gov, and Reagan-Udall Foundation’s EA Navigator

• Make recommendations to improve the overall EA program, including identifying where 

FDA can directly affect change

2.2 Research Methodology

The findings and recommendations in Sections 3 and 4 resulted from extensive research 

involving a broad range of inputs, both quantitative and qualitative. The following is a brief 

description of those sources: 

• In-depth review of FDA-focused written materials – Relevant statutes (e.g., FFDCA

Section 561), Code of Federal Regulations (CFR) (e.g., 21 CFR parts 312 and 812), FDA 

Manual of Policies and Procedures (MAPPs) and Standard Operating Policy and 

Procedures (SOPPs), guidance documents, job aids, and review articles 

• Historical data – FDA-housed data from 2012 to 2016 on volume of applications, 

authorization or approval rate, and timeliness of review from each of the three medical 

product centers 

• Interviews with FDA experts –34 FDA staff with direct experience handling EA requests 

• Interviews with external stakeholders –29 interviews were conducted with physicians 

and health systems leaders, patients and patient advocacy groups, IRB representatives, 

and payer representatives (both public and private sector) 

• Focus groups with external stakeholders – Five focus groups with nine patients or 

representatives of patient advocacy groups 
EA Program Report 12 May 2018

• Survey of previous EA applicants – A survey of physician sponsors who submitted at 

least one EA application to FDA between 2011 and 2017, with 139 respondents 

• Evaluation of externally-facing websites – Formal user-centered design assessment of 

primary websites providing EA information (FDA homepage for EA23, 

ClinicalTrials.gov24, and Reagan-Udall Foundation’s EA Navigator25), complemented 

with Google Analytics website traffic data (e.g., number of visitors, search terms, 

navigation to and from the home page, and time spent on the page) from January to 

October 31, 2017 

• Social media listening – Raw user-generated posts from a wide variety of sources (e.g., 

Facebook, Twitter, patient fora), leveraging relevancy filtering and scoring to categorize 

population segments and extract directional insights around attitudes and sentiments on 

EA

• Analysis of incoming responses to CDER’s Division of Drug Information – Top 

questions about EA that CDER’s Division of Drug Information (DDI) received between 

January 2016 and November 2017, categorized by demographic 

 

23 https://www.fda.gov/NewsEvents/PublicHealthFocus/ExpandedAccessCompassionateUse/default.htm. 24 https://clinicaltrials.gov/. 25 http://navigator.reaganudall.org/. 
EA Program Report 13 May 2018

Section 3: Findings

This section focuses on pain points identified in the assessment and on articulating opportunities 

for improvement. The principal findings were informed by a thorough, multi-stakeholder 

analysis and a careful evaluation of recent literature on the FDA EA program. 

What follows is a summary of the main findings from the research conducted to generate this 

report, including a brief discussion of evidence supporting each finding. 

Finding 1: External stake-holders’ overall perceptions of the EA program—and FDA’s role 

in particular—are positive. 

These perceptions are from stakeholders across the healthcare ecosystem, and they echo findings 

in the recent GAO report26 as well as numerous sources in the broader literature. See the 

“Expanded Access Program Report: Addendum” document for an in-depth discussion of 

stakeholder experience and insights from their participation in the EA program. 

Physicians, especially those with direct experience submitting an EA application to FDA, 

reported positive impressions of the program. A survey of 139 physicians with direct experience 

submitting an EA application to FDA was conducted for this report and 94% of respondents 

reported a willingness to recommend the 

program to a colleague. Several cited specific 

staff members at FDA who educated them on

the EA process and provided input on their 

proposed protocol. Those interviewed (a group 

distinct from survey respondents) consistently 

agreed that FDA’s EA program is important for patients without other options who may benefit 

from investigational treatment. 

Similarly, patients and their advocates described the program as a crucial route to access 

investigational therapies when other alternatives have been exhausted. Those with direct prior 

experience (as patients, advocates, or caregivers) reported positive experiences with the EA

program in focus group discussions and in social media posts. Advocacy groups shared 

numerous examples of individuals and groups of patients receiving access to lifesaving 

investigational products when approved therapies were unsuccessful and the patients were 

otherwise ineligible for clinical trials. However, many advocacy groups underscored the 

importance of ensuring that the EA program does not hinder ongoing investigational product 

development (e.g., by diverting enrollment from clinical trials) and noted that this consideration 

was important in their tendency to support the program.

 

26 U.S. Government Accountability Office, Investigational New Drugs: FDA Has Taken Steps to Improve the 

Expanded Access Program but Should Further Clarify How Adverse Events Data Are Used, July 11, 2017, GAO17-564, Washington, D.C.: U.S. Government Accountability Office.
EA Program Report 14 May 2018

Manufacturers, patient advocates, IRB representatives, and physicians all noted that FDA has 

taken important steps to reduce the administrative burden associated with submitting requests 

and seems genuinely committed to facilitate medically appropriate access via the EA program. 

Several physicians interviewed pointed to the significantly streamlined application Form 3926, 

which is available for physicians to use for expanded access requests for single patient INDs in

CDER and CBER, while others lauded efforts by the Office of Health and Constituent Affairs 

(OHCA) and certain divisions to engage with the public and educate the community about the 

EA program and how to most effectively navigate it. 

Over the last four years, the EA program’s application volume has grown consistently across all 

three centers, with FDA receiving approximately 1,800 applications on average annually for the 

past five years. Figure 2 shows the growth in requests across centers for EA from 2012 to 2016. 

Figure 2 – EA requests for CDER, CBER and CDRH

Despite double-digit growth in volume, FDA’s review timelines consistently meet or exceed 

target turnaround times. Emergency requests for single patients are regularly reviewed by CDER 

and CBER in less than one day (in CDRH, emergency use does not require prior notification or 

authorization). Non-emergency requests for single patients take longer, between 8 days and 26 

days, depending on the center, against a target turnaround of 30 days. Intermediate-size patient 

population and treatment IND or protocol requests had a review duration in-line with typical 

IND review processes (i.e., less than or at 30 days). Treatment IDEs are rarely used for EA and 
EA Program Report 15 May 2018

are excluded from this analysis. Figure 3 and Figure 4 show the turnaround time in days by 

center for each type of EA request. 

Figure 3 – Turnaround time for CDER and CBER EA requests
EA Program Report 16 May 2018

Figure 4 – Turnaround time for CDRH EA requests

Finding 2: Stakeholders report pain points across the physician/patient journey, which, if 

addressed, could meaningfully enhance the program. 

The reported pain points varied significantly based on the respondent’s experience with the 

program, but what follows is a summary of areas consistently identified by stakeholders as 

exhibiting potential for improvement: 

1. Program awareness. Awareness of the EA program, especially in the community-based care 

setting (i.e., outside of an academic medical center), is low. This is further compounded by the 

relative absence of administrative personnel in the community setting with experience and 

knowledge to support application submission. This observation correlates with lower levels of 

participation in clinical research—interviews revealed that physicians who were not involved in 

clinical trials were often less aware of the newest therapies and less likely to have exposure to

those stakeholders (manufacturers, IRBs, and FDA) that play a vital role in facilitating EA. 

2. Administrative burden. Without 

dedicated staff to support clinical 

research, the administrative burden to 

apply for EA and comply with required 

monitoring and reporting falls on 

physicians and their administrative staff. 

Paperwork is reported to be the key hurdle, particularly for IRB approval and requesting 

manufacturer access to an investigational drug, biologic or device. Surveyed physicians 

estimated that the total time required to support an EA application (including submissions to all 
EA Program Report 17 May 2018

relevant stakeholders and other required coordination) can average nearly 30 hours for a single 

application (17.1 hours for the physician and 12.5 hours for his or her staff), which is not 

reimbursed by payers or other parties. Several stakeholders interviewed suggested that 

differences in working familiarity with EA applications and in resources available to support 

applications between academic and community settings of care drives disparity in access to 

investigational therapies through EA. 

3. Program navigation. Stakeholders indicated that navigating the program was challenging, 

especially for physicians without prior experience. All physicians who have undertaken EA

applications on behalf of their patients (regardless of setting) cited challenges associated with 

coordinating applications across the multi-step, 

multi-stakeholder process. The challenge of 

navigating the program was especially acute for

first-time applicants.

27 Survey respondents who 

had filed only one application reported more 

difficultly working with the manufacturer to 

request access and receive the product, finding and engaging an IRB to obtain approval, and 

completing required documentation during and after treatment. Interviews and survey responses

consistently mentioned frustration with the necessity of coordinating with multiple stakeholders,

i.e., the manufacturer, the IRB, FDA, the health system, and a patient’s insurance company.

4. Program informational resources. Respondents provided feedback that improvements are 

needed in the resources available on public websites that support the EA program. Specifically, 

stakeholders expressed frustration with the lack of richness, reliability (i.e., that the information

is accurate and up-to-date), and accessibility of information available through FDA websites. 

Although many cited the convenience of the CDRH website, stakeholders who interacted with 

the CDER and CBER materials noted the absence of a single location to retrieve relevant 

program information. 

Respondents also reported difficulty navigating to the required information; even FDA staff 

reported relying on a search engine to find specific information or materials rather navigating 

through the Agency’s internal resources. FDA’s webpages are long―some require 10 to 15 

minutes to read while website traffic analytics showed only an average of three minutes spent on 

FDA’s EA home page, suggesting limited engagement. Moreover, the EA home page averages a 

bounce rate28 of 62%, which suggests that when users search and land on the page, they are not 

finding what they need. In addition, Form FDA 3926 is inaccessible in many common web 

 

27 Estimated to be approximately 74% of physician sponsors, according to an analysis of FDA data. 28 This is typically the percentage of visitors to a website who navigate away (bounce away) from the site after 

viewing only one page. 
EA Program Report 18 May 2018

browsers.29 In fact, requesting the form because it was not available through the website was the 

second most common EA-related question CDER’s DDI received across all demographics. 

Physicians, payers, and patient groups cited the importance of the National Institutes of Health 

(NIH) website, ClinicalTrials.gov30 (which includes information about EA programs from 

manufacturers), in identifying treatments available through EA. Recent improvements to the 

ClinicalTrials.gov site, such as queries linking search terms like expanded access, compassionate 

use, and pre-approval access, have simplified the identification step. Physicians not already 

engaged in research with industry contacts cited the criticality of having EA-related information 

available in a central, searchable database. While manufacturers are required to submit 

information about their EA programs for drugs and biologics, including contact information, to 

ClinicalTrials.gov31, several stakeholder groups reported that navigating the site to view product 

availability through EA is difficult.

Representatives from patient advocacy groups familiar with the Regan-Udall Foundation 

Expanded Access Navigator32 agreed that the website is a helpful resource. However, awareness 

was not universal. The anticipated expansion beyond oncology will likely increase awareness 

among patient groups focused on other therapeutic areas.

Separately, a formal usability analysis of FDA.gov, ClinicalTrials.gov and the Reagan-Udall 

Foundation Expanded Access Navigator, using heuristic evaluation was conducted. This 

evaluation benchmarked the sites against a validated framework of 12 industry-standard usability 

heuristics. The analysis evaluated website experience through the lens of three main visitor 

profiles—patients, health care personnel (HCP) and industry representatives—that potentially 

interact with these websites to gather information and complete tasks related to the EA program.

While the analysis has findings specific to each website, it identified consistent opportunities to 

improve the ease of navigating the websites, enhance clarity and usability of provided 

information, and provide access to user help and support. For additional details, see the 

“Expanded Access Program Report: Addendum” document. 

Finding 3: Because EA operates in an inherently multi-stakeholder environment, the 

absence of standard processes and policies for EA submission requests to FDA, 

manufacturers, IRBs, and payers creates confusion for many stakeholders.

Physicians repeatedly cited challenges with differences in application requirements for 

submission to FDA, manufacturers, IRBs, and payers, which drive substantial administrative 

workload for the physicians and their staff. Physicians interviewed pointed to the difficulty of 

 

29 There are instructions on how to access the form at the top of the FDA forms page where the form is housed 

(https://www.fda.gov/AboutFDA/ReportsManualsForms/Forms/default.htm). However, this text can be missed if the 

form is accessed directly through search results. 30 https://clinicaltrials.gov/ 31 Per 42 CFR 11.28

32 http://navigator.reaganudall.org/
EA Program Report 19 May 2018

identifying the correct contact for each manufacturer and the process for submitting a request. 

Furthermore, survey respondents cited manufacturer denial as the most frequent reason for not 

submitting an EA application to the Agency where the request was previously submitted to the 

manufacturer. 

For physicians practicing in a setting without ready access to an IRB, the process of identifying 

an IRB and covering the cost of an application, while often waived by the IRB, was frequently 

identified as a challenge by physicians and patient advocates alike. Since each IRB sets its own 

internal process, working with multiple IRBs requires the physician to learn a new process for 

each one. Physicians reported that IRBs that do not regularly review EA requests occasionally 

ask for supporting documentation that is not feasible in an EA setting (e.g., data that does not 

exist or is not available in a timely manner). IRB interviewees reported that unlike applications 

related to a manufacturer-sponsored trial (with standard forms and templates), they saw 

physicians struggle to develop the required documentation. 

There is also substantial variability in cost coverage from payers for treatments administered via 

EA. Although the investigational product itself is typically provided by manufacturers at no cost, 

interviews and published literature indicate that there is often associated expense for treatment 

administration and for monitoring progress and complications. Many payers (both public and 

private) report that they cover this associated care, but almost always on a case-by-case basis and 

often in accordance with clinical trial coverage policy, which can vary from standard coverages. 

According to the patient advocates who participated in focus groups, these varied policies cause 

financial uncertainty for patients who have often exhausted all other resources before becoming 

eligible for EA. Inconsistencies in policy also frequently require the physician or administrative 

staff to spend additional time engaging with payers to provide additional documentation and 

secure authorization. 

Finding 4: A detailed review of how the EA program is managed within FDA pointed to 

additional addressable opportunities. 

Interviewees from across the stakeholder spectrum consistently cited confusion in terminology as 

a primary barrier to understanding and effectively researching the EA program. For example, the 

terms “expanded access” and “compassionate use,” often used to refer to the EA program, mean 

different things to different stakeholders. The respondents said inconsistent terminology and 

definitions has created challenges in discussing topics with colleagues and introduced confusion 

about program intent and potential eligibility. Some patient advocacy groups reported that 

unclear definitions caused them to incorrectly assume that their communities did not have access 

to the program, for example, not understanding that the EA pathway can be used for treatment of 

a serious but not immediately life-threatening condition. 

Best practices and adaptations to enhance program effectiveness exist across FDA centers and 

divisions within centers, but are not systematically cross-pollinated to share learnings and elevate 

program execution. FDA’s recently established Expanded Access Coordinating Council (EACC) 

is an important first step toward formalizing a venue for sharing those practices, but more can be 

done to raise awareness of center- and division-level innovations and identify ways to 
EA Program Report 20 May 2018

systematically apply them. For example, teams within FDA have built robust and efficient 

processes for facilitating and reviewing requests, such as offering packets of information with 

detailed instructions, pre-populated template materials, and previously used protocols. However, 

standardization of the process should not be the primary goal—much of the observed variability 

is appropriate for the wide range of products regulated and makes the process nimble and 

efficient.

Finally, the richness and quality of data available to FDA—both on EA program performance 

and impact, and data related to outcomes—are highly variable across centers. Given (1) 

limitations in current systems and staff capacity, (2) modest availability of standard 

queries/reports, and (3) the scope of training for review teams, it is difficult to access and analyze 

data about EA. This variability complicates developing a comprehensive, timely picture of 

program performance and consistent, transparent program management. The variability also 

prevents FDA from routinely publishing facts about the program’s impact on public health, an 

activity that could help address persistent misunderstandings about the EA program. 

Finding 5: Manufacturers report facing challenges particularly related to (1) uncertainty 

about how FDA uses data from EA, and (2) managing divergent requirements and 

guidance from non-FDA, ex-US health authorities. 

A commonly reported, yet unsubstantiated, concern by manufacturers is that data from an EA

program could derail ongoing product development or compromise regulatory review. This 

concern was widespread among manufacturers 

interviewed, despite updated guidance on use 

of data for EA for drugs and biologics released 

in October 201733 that states that the data are 

considered in context,34 and despite literature 

showing that there have been no instances in 

which EA has led to a negative regulatory 

 

33 FDA CDER (2017). Guidance for Industry: Expanded Access to Investigational Drugs for Treatment Use – 

Questions and Answers (FDA Maryland). 34 From the FDA CDER (2017). Guidance for Industry: Expanded Access to Investigational Drugs for Treatment 

Use – Questions and Answers: “FDA reviewers of these adverse event data understand the context in which the 

expanded access use was permitted and will evaluate any adverse event data obtained from an expanded access 

submission within that context. For example, FDA reviewers recognize that: 1) expanded access treatment generally 

occurs outside a controlled clinical trial setting; 2) patients who receive a drug through expanded access may suffer 

from a more advanced stage of the disease or condition than patients participating in a clinical trial; 3) patients who 

receive a drug through expanded access may be receiving other therapies for their disease or condition at the same 

time as the drug they are receiving through expanded access; and 4) patients who receive a drug through expanded 

access may suffer from one or more comorbidities. All these factors make it difficult to link an expanded access 

treatment to a particular adverse event. Moreover, it is very rare for FDA to place an IND on clinical hold due to 

adverse events observed in expanded access treatment.”
EA Program Report 21 May 2018

decision regarding a drug application.35 Nevertheless, this uncertainty is cited as a top 

consideration for manufacturers’ participation in EA, even by companies experienced with the 

program. For those that do participate, interviews surfaced a wide range (40% to 95%) of 

manufacturer approval rates for EA requests. 

Variations in policies across geographies and other non-FDA global health authorities add major 

complexity for manufacturers when seeking to remain compliant in responding to EA requests. 

Because countries have different regulations and importation requirements (for investigational 

products shipped across borders), manufacturers must track and comply with a challenging array 

of requirements (manufacturers especially mentioned variations in labeling requirements from 

country to country as a logistical challenge). 

Manufacturers also worry about how to navigate the line between publicizing their EA 

participation and any perception that they are marketing an unapproved product. Manufacturer 

interviewees frequently mentioned the difficulty with managing the tension of wanting to inform 

physicians whose patients could potentially benefit while remaining compliant with regulations 

governing the information that can be shared. 

 

35 Jonathan Jarow, Richard Moscicki, “Impact of Expanded Access on FDA Regulatory Action and Product 

Labeling,” Therapeutic Innovation & Regulatory Science, Volume 51, Issue No. 6 (2017): 1-3.
EA Program Report 22 May 2018

Section 4: Recommendations for FDA and Other 

Stakeholders to Consider

As the preceding analysis outlines, the EA program operates in a complex, multi-stakeholder 

environment. As such, addressing a number of the identified pain points (e.g., policy 

inconsistency, application burden) requires coordinated action on the part of a number of 

disparate stakeholders. What follows below is a set of recommendations for FDA to specifically 

consider, framed around actions that are within FDA’s remit to take if it chooses. Those 

recommendations are grouped around four broad principles to guide continuous improvement 

activity for the EA program moving forward. 

Principle 1: Ensure patients continue to receive timely and medically appropriate access to 

investigational medical products through the EA program. 

Recommendation 1: Consistently incorporate EA planning into manufacturer interactions. 

FDA could consistently engage with manufacturers on EA throughout the medical product 

development lifecycle to proactively assess and plan for potential EA applications, as 

appropriate. In many cases, FDA can anticipate circumstances when a product might be subject 

to an EA request. Such discussions could have numerous benefits, such as: 

• Supporting the development of robust, publicly accessible, product-level manufacturer 

policies for granting EA requests

• Prompting a dialogue that encourages planning for EA use (e.g., securing sufficient 

clinical supply), without compromising the critical importance of clinical trials

• Prospectively clarifying how data from EA might be used prior to and during application 

review 

The process could also facilitate more systematic identification of appropriate opportunities to 

use intermediate and treatment protocols (for drugs and biologics), and treatment IDEs (for 

devices). This may enable more timely access for patients, provide more robust data collection 

and monitoring, and reduce the administrative burden for all stakeholders. In the short term, 

review teams could pilot such conversations to explore what types of discussions are most 

helpful, with a long-term goal of standardized questions posed to manufacturers as part of 

sponsor interactions, as appropriate.

Principle 2: Make participating in the program minimally taxing for stakeholders (physicians, 

patients, FDA, and others). 

Recommendation 2: Systematically cross-pollinate best practices in FDA program 

execution and management. FDA could build on existing mechanisms, such as the EACC, to 

systematically cross-pollinate best practices to enhance program execution and management. 

Given that FDA is a de-centralized organization, intentionally seeking out and formalizing 

approaches to disseminate best practices in EA program execution and management across 

centers and divisions is essential. 
EA Program Report 23 May 2018

One example of an innovation that could be leveraged more broadly is the use of packets for 

frequently requested products. This may reduce administrative burden on physician sponsors and 

streamline the review of these applications. These packets include specific, step-by-step 

instructions on how to submit an EA application, along with a previously reviewed protocol and 

form with specific completion instructions. Physicians retain the ability to propose alternative 

protocols; however, these require additional review by FDA staff to ensure the risk-benefit 

profile is acceptable.

Principle 3: Make the program easy for patients, physicians, and other stakeholders to 

understand and navigate.

Recommendation 3: Clarify language used to describe the program, both internally and 

externally. By unifying the language (ideally for all centers) and choosing consistent 

terminology when communicating with external stakeholders, FDA can foster a broad and 

clearer understanding of the program. 

Recommendation 4: Enhance the use of EA in community medical centers through a 

systematic campaign to educate physicians and administrative personnel. Addressing the

lack of program awareness and limited understanding about the process among physicians will 

help to overcome a major barrier to EA in the community setting. While FDA will need to assess 

the most effective methods to build awareness and working familiarity with the EA program in 

the community setting, the following are examples of possible initiatives:

• Routinely presenting on the EA process at conferences organized by national societies, 

such as the American Society of Clinical Oncology (ASCO), the American Academy of 

Neurology (AAN), Infectious Diseases Society of America (IDSA), and selected regional 

conferences. 

• Delivering continuing medical education (CME) webinars in partnership with national 

societies and larger CME providers (e.g., MedScape). 

• Implementing an outreach campaign (e.g., FDA blogs) to build awareness with 

stakeholders and share known best practices with community health system 

administrators on how to support EA applications with limited resources.

Recommendation 5: Conduct a user-centered redesign of web-based materials.

Organizations involved in Expanded Access, including the FDA, National Institutes of Health 

(NIH), and the Reagan-Udall Foundation, could conduct user-centered redesigns of their 

Expanded Access web-based materials to enhance their relevance and impact. Redesigns could 

incorporate common features, as appropriate, to create a more consistent and easy navigation 

experience across the websites that support EA program engagement. Specific website-related 

recommendations, with a detailed discussion of the website analysis, findings, and suggestions,

are available in this report’s addendum. Two near-term improvements FDA could make are

fixing Form 3926 so it can be accessed from all popular web browsers, and offering step-by-step 

instructions on the FDA webpage on how to navigate the ClinicalTrials.gov site and interpret 

search results for EA. In the long-term, a mobile device app for physicians may be useful in 

preparing, submitting, and tracking EA applications.
EA Program Report 24 May 2018

Recommendation 6: Invest in the development of a central navigation and triage resource 

for EA applicants. Given the significance of EA application volume originating from 

physicians with limited EA program experience, a central navigation and triage capability at 

FDA that could interact with patients and physicians seeking information about how to engage 

with the EA program would be valuable. This system could facilitate connections to subject 

matter experts in the Centers when product or disease-specific questions or needs arise. It would 

serve as the “single point of entry” many stakeholders asked for, though would not replace 

existing connections stakeholders have within the Agency.

Principle 4: Continue to integrate data from the program with medical product review to 

provide transparency and promote quality decision-making.

Recommendation 7: Correct manufacturer misperceptions that data from EA harm 

product development. By bringing manufacturer attention to the recently released official 

agency guidance for drugs and biologics, FDA could increase manufacturer confidence that all 

data will be appropriately considered (i.e., in the context of an uncontrolled population, likely 

with advanced disease, and with many comorbidities), decreasing their reluctance to participate. 

Furthermore, FDA could clarify in the CDRH EA resources that in the absence of devicespecific guidance, reviewers will generally follow drug and biologic guidance, if appropriate. In 

the long term, FDA could develop guidance specific to devices. In addition, the Agency could 

clarify which circumstances would be appropriate for EA data to support label extensions or 

other claims, potentially changing how manufacturers view participation in the EA program.

FDA could also consider providing the industry guidance on how manufacturers can build 

awareness of their own EA programs while avoiding any challenges related to marketing 

unapproved products.

Recommendation 8: Ensure that FDA review staff are able to link EA applications within

regulatory systems so program data is more easily and appropriately considered in 

regulatory decision-making. FDA’s complex data architecture makes it challenging to link 

multiple INDs or other requests from physician sponsors to the manufacturer’s IND/IDE or 

pending marketing applications. Updating center systems to support EA application processing is 

a longer-term solution. In the near-term, providing review teams with additional training on 

system capabilities and creating standard reports that pull data from the existing systems and

include all associated EA use could be near-term workarounds.

Recommendation 9: Develop a common mechanism for tracking EA applications that 

enables each center to more actively manage the program. Medical product centers should 

have accessible, near real-time data on application volume, timelines, origin of requests, 

disposition, and products involved in EA. In addition to giving FDA greater transparency into 

program performance, such tracking and reporting would also help FDA communicate more 

effectively to external stakeholders about program performance and the public health impact of 

the program. Program performance could be further communicated to stakeholders through 

periodic public meetings or publication of a brief annual report. 
EA Program Report 25 May 2018

While many recommendations may take several years to realize their full impact, FDA has the 

opportunity to begin work against all the recommendations in the relatively near term. Across all 

recommendations, opportunities to consider for near-term potential impact include: (1) beginning 

to pilot conversations with manufacturers about EA where appropriate, (2) clarifying the 

terminology used to describe the EA program in FDA’s web-based resources, (3) posting 

instructions on how to navigate ClinicalTrials.gov, (3) fixing Form FDA 3926 so it is accessible 

from all web browsers, (4) publicizing the October 2017 CDER/ CBER guidance on the use of 

data from EA for drugs, (5) clarifying in the CDRH EA resources that in the absence of devicespecific guidance, reviewers will generally follow drug and device guidance, if appropriate (6) 

improving FDA reviewer training on system capabilities, and (7) creating standard reports of 

operational data to aid program management.

Figure 5 summarizes the recommendations and the findings they address.
EA Program Report 26 May 2018

Figure 5 – Mapping of recommendations to the findings they address 
EA Program Report 27 May 2018

Figure 6 – Patients' view of the 

EA program stakeholder 

Section 5: Snapshot of the Stakeholder Roles and the EA 

Process

4.1 Stakeholder Roles 

The process of obtaining access to investigational products via the FDA’s EA program requires 

interaction among seven principal stakeholders: FDA, patients, physicians, manufacturers, IRBs, 

and payers, and health systems. The following are high-level descriptions of the role each 

stakeholder plays in relation to an EA application. Additional detail is available in the addendum 

to this report. 

FDA

FDA staff are involved in EA work across the Agency, including in CBER, CDER, and CDRH 

and in the Office of the Commissioner (OC). FDA fields inquiries from patients, healthcare 

providers, and manufacturers on the EA program. Once a healthcare provider or manufacturer 

submits an application, FDA works with the sponsor (i.e., the submitting physician or 

manufacturer) to triage, coordinate, review, and authorize the request. This can involve backand-forth discussion with the sponsor. After a patient is treated, FDA receives reports on 

progress and safety, and considers that information in the context of the ongoing development 

program, as needed.

Patients

This analysis considers patients to be all patients who are 

prospective, current, or former users of FDA’s EA program. 

Their caregivers are also included in this group for the 

purposes of this report. Patients participating in the EA 

program have a life-threatening or serious condition, have 

exhausted all other approved treatment options, and do not 

qualify for participation in or have access to ongoing clinical 

trials for their condition. There is wide variation across patient 

populations in the level of knowledge, empowerment, and savvy in 

navigating the healthcare system. Their interactions with 

other program stakeholders is illustrated in Figure 6

Physicians 

Licensed physicians are responsible for treating patients and play a central role in identifying 

appropriate treatments and coordinating the required interactions across stakeholders to obtain 

treatment through the EA program. Physicians who interact with the program come from a wide 

range of specialties, the most common being hematology/oncology, infectious disease, and 

pulmonology. Physicians work in a range of settings, though it is estimated that as many as 95% 
EA Program Report 28 May 2018

of physicians that submit EA applications are in an academic setting as opposed to a communitybased practice (based on the physician survey). 

Manufacturers

For this assessment, a manufacturer is the owner of the drug, biologic or device that is being 

requested for EA use. Manufacturers range from large, multinational pharmaceutical companies, 

to small biotechnology startups, to individual researchers in an academic setting. They differ 

markedly in terms of available resources (both financial and other types of resources), level of 

experience with the EA process, and relative progress in the development process (e.g., early 

stage, awaiting marketing approval). Manufacturers do not have a legal obligation to provide 

medical products through EA; however, in compliance with the 21st Century Cures Act, 

manufacturers of investigational drugs for serious diseases must publicly post their company 

policy for EA. The policy includes contact information, the process to make a request, and the 

criteria for consideration of the requests. Manufacturers can also post this information on the 

Reagan-Udall Expanded Access Patient Navigator website. FDA cannot compel a manufacturer 

to provide an unapproved medical product through the EA program. 

IRBs

Per 21 CFR part 56.102, an IRB is any board, committee or group formally designated by an 

institution to review, approve initiation, and conduct periodic reviews of biomedical research 

involving human subjects. The primary purpose of the reviews is to assure the protection of the 

human subjects’ rights and welfare. An IRB can be associated with a hospital or academic 

institution or a private organization. The requirements and other expectations for the IRB’s role

in the use of an unapproved medical product through the EA process are described by the FDA 

regulations and institutional policies. 

Payers 

Payers are private healthcare insurance companies and public insurance programs (e.g., 

Medicare, Medicaid, and Veterans Health Administration [VHA]) that may or may not cover the 

costs associated with treatments administered under EA. Each payer sets coverage policies for 

treatment costs, which may include professional fees for administration and subsequent 

monitoring, IRB review of the protocol, treatment of complications, and in some cases, the cost 

of the investigational product. 

Health systems

Health systems typically play a supportive role in EA and can play a significant role in 

supporting a physician sponsor. Health systems can be academic medical centers, communitybased hospitals, or outpatient settings of care. They may include system administrators who set 

policy and manage a physician’s practice; clinical research staff, including pharmacists and 

research coordinators; and the support staff who help physicians with administrative tasks. The 

health system typically provides infrastructure for administrative support, and may operate a 

research pharmacy to manage shipments of investigational medical products for hospitalized 
EA Program Report 29 May 2018

patients. They also coordinate billing for any eligible procedures carried out in concert with 

administering the investigational therapy.

4.2 Process 

At a very high level, the process of obtaining an investigational product through the EA program 

has four main steps: (1) identification, (2) application, (3) treatment, and (4) follow-up. Specific 

aspects of each step vary based on the type of product being requested, the FDA center 

reviewing the application, and the type of EA application submitted. Figure 7 shows the highlevel EA process steps with the associated participants and activities.

Figure 7 – High-level view of the EA process

This process is most representative for a single patient request initiated by a physician, i.e., a 

single patient protocol to a new or existing IND (for a drug or biologic) or compassionate use 

without an IDE (for a device).

36 The following is a description of each process step. 

Step 1: Identification 

 

36 Requests for treatment or intermediate INDs/protocols or treatment IDEs follow a well-documented review 

process relevant to the medical product.
EA Program Report 30 May 2018

• Patients reach a point in their clinical care when there is no generally acceptable 

alternative treatment—either because they have exhausted all available approved 

therapies and/or they are not candidates for open clinical trials. 

• Patients or caregivers typically search for available treatment options through a 

physician, but they may also initiate the research themselves, most commonly through 

online resources. It is during this time that patients and physicians often learn about the 

EA program as a potential avenue. 

− Patients and caregivers will occasionally reach out to manufacturers to check if 

they have products that are available through EA, or to FDA to generally 

understand how to proceed. 

− Because of confidentiality constraints, FDA cannot give patients or physicians 

direct contact information for manufacturers with INDs and IDEs without specific 

approval; however, the Agency can provide general information on where to 

search (e.g., ClinicalTrials.gov, literature reviews). 

− Manufacturers provide information about their EA policy through various sources 

and may answer physician or patient questions. 

• Physicians typically work with their health system (if applicable) and an IRB to 

understand any local requirements. At this point, patients and physicians typically contact 

payers to understand coverage options (e.g., for the treatment itself or any aftereffects).

Step 2: Application

• If a potentially appropriate product has been identified and the physician believes the 

patient is a good candidate, the physician can present the treatment option to the patient 

and outline the potential risks and benefits associated with the product to support 

informed consent. 

• For drugs and biologics, should the patient decide to proceed, the physician asks the 

manufacturer for access to the medical product and a letter of authorization to crossreference the existing IND (if a separate IND submission is needed). If the manufacturer 

agrees to provide the medical product, the physician prepares the application for 

submission to FDA. For devices, if there is an IDE for the device, the FDA application 

process is led by the investigational device sponsor, and is submitted as a supplement to 

the IDE. If there is not an IDE, a physician can submit the required documentation. 

• The physician must notify an IRB about the pending EA request, which is typically done 

in parallel to the FDA application. IRB approval is required before treatment unless it is 

an emergency application,37 in which case the physician only needs to notify the IRB 

within five days following treatment. Health system policies vary regarding IRB review 

for EA; for example, some require IRB approval before emergency use.

 

37 For devices with no IDE, concurrence from the IRB chair and compliance with institutional policies is expected 

before treatment, but there are no specific regulations and it is understood that this may be a time-sensitive situation.
EA Program Report 31 May 2018

• With the agreement of the manufacturer and in parallel with IRB review, the physician 

submits the completed application to FDA. 

− For drugs and biologics, applicants can use Form 1571 and 1572, which are used 

for all IND applications. Alternatively, physician sponsors can use Form 3926 for 

single patient requests. Form 3926 is an abbreviated form released in 2017 that 

streamlines the application to an estimated 45-minute completion time. Typically, 

sponsors need to submit the patient’s clinical history, rationale for the treatment 

with the investigational product, the proposed treatment plan (i.e., protocol), and 

the relevant patient protection measures (e.g., IRB concurrence/approval, 

informed consent documents, and institutional clearance, as required), and a copy 

of their curriculum vitae (CV). 

− For devices, applicants need to provide similar information, as well as an 

independent assessment from an uninvolved physician that the EA request is 

appropriate, though no specific form is required. 

• FDA evaluates the application and determines whether to authorize or deny the request. 

As part of the review, the Agency will collaborate with the coordinating physician to 

update documentation and refine the protocol, as needed. 

Step 3: Treatment

• If FDA authorizes the request, FDA documents the decision internally and notifies the 

physician of the authorization, and explains follow-up requirements. 

• The physician communicates that decision to the manufacturer to initiate shipment of the 

investigational product. 

• If the investigational product needs to be imported into the US for use, the manufacturer 

must ensure proper labeling and documentation for the product to pass U.S. Customs and 

Border Protection (CBP) inspection. 

• The physician obtains and documents informed consent from the patient. 

• The physician then treats the patient per the approved protocol. The payer may reimburse 

costs related to the treatment, which is determined on a case-by-case basis. In most cases, 

the manufacturer provides the unapproved medical product free-of-charge, though it is 

permitted to charge reasonable costs consistent with the conditions of the EA process 

used. 

Step 4: Follow up

• During the follow-up step, the physician documents the treatment outcome and adverse 

events, as needed or required by the authorized protocol. 

• The physician notifies the relevant parties (e.g., FDA, manufacturer, IRB) about 

treatment status, as appropriate. Adverse events typically must be reported to FDA and 

the IRB at intervals specified by regulations and policy. 

• The patient continues to receive treatment per the protocol until the treatment has been 

completed or is withdrawn. 
EA Program Report 32 May 2018

− For drugs and biologics, the physician must submit annual reports for as long as 

the IND is open, and is required to submit a follow-up report before the IND can 

be withdrawn or closed. 

− For devices, a follow-up report with the patient outcome and IRB approval 

documentation, if not previously submitted, is expected within 45 days of using 

the device. If EA is approved under an open IDE, safety information is also 

submitted as part of the IDE annual report. 

• If the payer grants coverage for the treatment, they generally decide whether to continue 

to pay for the associated care.
EA Program Report 33 May 2018

Glossary

AAN American Academy of Neurology 

ASCO American Society of Clinical Oncology 

CBER Center for Biologics Evaluation and Research 

CBP U.S. Customs and Border Protection 

CDER Center for Drug Evaluation and Research

CDRH Center for Devices and Radiological Health

CFR Code of Federal Regulations 

CME Continuing medical education 

CMS Centers for Medicare & Medicaid Services

CTO Chief Technology Officer

CV Curriculum vitae

DDI Division of Drug Information 

EA Expanded Access

EACC Expanded Access Coordinating Committee 

EUA Emergency Use Authorization 

FDA Food and Drug Administration 

FDAMA Food and Drug Administration Modernization Act of 1997 

FFDCA Federal Food, Drug, and Cosmetic Act 

GAO Government Accountability Office 

HHS U.S. Department of Health and Human Services 

IDE Investigational device exemption

IDSA Infectious Diseases Society of America

IND Investigational new drug application

IRB Institutional Review Board

IDSA Infectious Diseases Society of America

MAPP Manual of Policies and Procedures 

NIH National Institutes of Health
EA Program Report 34 May 2018

OC Office of the Commissioner

OHCA Office of Health and Constituent Affairs 

SOPP Standard Operating Policy and Procedure

US United States of America

VHA Veterans Health Administration