Expanded Access to 
Investigational Drugs for 
Treatment Use  
Questions and Answers 
Guidance for Industry 
 
 
DRAFT GUIDANCE
 
 
  This guidance document is being distributed for comment purposes only. 
 
Comments and suggestions regarding this draft document should be submitted within 60 days of 
publication in the Federal Register of the notice announcing the availability of the draft 
guidance.  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.  All comments should be identified with the 
docket number listed in the notice of availability that publishes in the Federal Register. 
 
For questions regarding this draft document, contact (CDER) Dat Doan, 240-402-8926, or 
(CBER) Office of Communication, Outreach and Development, 800-835-4709 or 240-402-8010.  
 
 
 
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) 
 Office of Clinical Policy (OCLiP) 
Oncology Center for Excellence (OCE)  
 
 
 
November 2022 
Procedural 
                                                                     Revision 1 
 
37117902dftrev1-10-28-22 
   
Expanded Access to 
Investigational Drugs for Treatment Use  
Questions and Answers 
 
Guidance for Industry 
 
 
 
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 
10903 New Hampshire Ave., Bldg. 71, Room 3128 
Silver Spring, MD 20993-0002 
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) 
Office of Clinical Policy (OCLiP) 
Oncology Center for Excellence (OCE)  
 
November 2022 
Procedural 
Revision 1 
 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
TABLE OF CONTENTS 
 
 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
III.  QUESTIONS AND ANSWERS ....................................................................................... 4 
A.  Expanded Access for Treatment Use ........................................................................................... 4 
B.  Expanded Access Submission ....................................................................................................... 5 
C.  Individual (or Single) Patient Expanded Access ....................................................................... 14 
D.  Intermediate-Size Patient Population and Treatment INDs and Protocols............................ 18 
E.  Time Frame for Beginning Treatment Use Under an Expanded Access IND or Protocol ... 20 
F.  General Questions ........................................................................................................................ 21 
APPENDIX:  INFORMED CONSENT TEMPLATE FOR INDIVIDUAL PATIENT 
EXPANDED ACCESS................................................................................................................ 29 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
1  Expanded Access to Investigational Drugs for Treatment Use  
2  Questions and Answers 
3  Guidance for Industry1 
4   
5   
6  This draft guidance, when finalized, will represent the current thinking of the Food and Drug 
7  Administration (FDA or Agency) on this topic.  It does not establish any rights for any person and is not 
8  binding on FDA or the public.  You can use an alternative approach if it satisfies the requirements of the 
9  applicable statutes and regulations.  To discuss an alternative approach, contact the FDA staff responsible 
10  for this guidance as listed on the title page.   
11   
12   
13   
14   
15  I.  INTRODUCTION  
16   
17  This guidance provides information for industry, researchers, physicians, institutional review 
18  boards (IRBs), and patients about the implementation of FDAs regulations on expanded access 
19  to investigational drugs2 for treatment use under an investigational new drug application (IND) 
20  (21 CFR part 312, subpart I), which went into effect on October 13, 2009.3   FDA received 
21  numerous questions concerning implementation of the regulatory requirements for expanded 
22  access.  As a result, FDA issued the guidance for industry Expanded Access to Investigational 
23  Drugs for Treatment Use  Questions and Answers (June 2016, updated October 2017) (the 
24  2017 guidance), providing recommendations in a question-and-answer format, addressing the 
25  most frequently asked questions.  Since 2017, FDA has received additional questions concerning 
26  implementation of the regulatory and statutory requirements of expanded access to 
27  investigational drugs, including those added by the 21st Century Cures Act (Cures Act)4 and the 
28  FDA Reauthorization Act of 2017 (FDARA).5  When finalized, this guidance will replace the 
29  2017 guidance.  Significant changes from the 2017 version include additional recommendations 
30  related to IRB review, informed consent, and new requirements established by the Cures Act and 
31  FDARA related to sponsors making their policies for evaluating and responding to expanded 
32  access requests (i.e., expanded access policy) public and readily available.   
 
1 This guidance has been prepared by the Office of Medical Policy in 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 for Excellence (OCE) and in consultation with the Center for Devices and 
Radiological Health (CDRH) at the Food and Drug Administration.  
2 In this guidance, the terms investigational new drug, investigational drug, drug, and drug product refer to both 
human drugs and biological products regulated by CDER and CBER. 
 
3 Federal Register of August 13, 2009 (74 FR 40900). 
 
4 21st Century Cures Act (Cures Act), Public Law 114-255; 130 STAT.1033, December 13, 2016, Sec. 3032. 
 
5 See the FDA Reauthorization Act of 2017 (FDARA), Public Law 115-52; 131 STAT.1005, August 18, 2017, Sec. 
610. 
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33  In a separate guidance,6 FDA provides answers to questions concerning the implementation of 
34  the regulation on charging for investigational drugs under an IND (21 CFR 312.8).7  Also, in a 
35  separate guidance, FDA describes Form FDA 3926 (Individual Patient Expanded Access
36  Investigational New Drug Application (IND)) and the process for submitting expanded access 
37  requests for individual patient INDs.8   
38   
39  In general, FDAs guidance documents do not establish legally enforceable responsibilities. 
40  Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
41  as recommendations, unless specific regulatory or statutory requirements are cited. The use of 
42  the word should in Agency guidance means that something is suggested or recommended, but 
43  not required. 
44   
45   
46  II.  BACKGROUND 
47   
48  Expanded access refers to the use of an investigational drug when the primary purpose is to 
49  diagnose, monitor, or treat a patients disease or condition rather than to obtain the kind of 
50  information about the drug that is generally derived from clinical trials.  FDA has a long history 
51  of facilitating expanded access to investigational drugs for treatment use for patients with serious 
52  or immediately life-threatening diseases or conditions9 who lack satisfactory therapeutic 
53  alternatives.  Still, a patient cannot receive an investigational drug through the expanded access 
54  pathway unless the sponsor10 of the investigational drug agrees to provide such access.   
55   
 
6 See the revised draft guidance for industry Charging for Investigational Drugs Under an IND:  
Questions and Answers (August 2022).  When final, this guidance will represent FDAs current thinking 
on this topic.  We update guidances periodically.  For the most recent version of a guidance, check the 
FDA guidance web page at  https://www.fda.gov/RegulatoryInformation/Guidances/. 
  
7 See also 74 FR 40872, Federal Register of August 13, 2009. 
 
8 See the guidance for industry Individual Patient Expanded Access Applications: Form FDA 3926 (June 2016, 
updated June 2017). 
 
9 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)). 
 
10 The sponsor of an investigational drug (existing IND) typically is the pharmaceutical company or manufacturer of 
the drug. 
 
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56  FDA revised its IND regulations in 200911 by removing the existing regulations on treatment use 
57  and creating subpart I of part 312 to consolidate and expand the various provisions regarding 
58  expanded access to treatment use of investigational drugs.  
59   
60  Under FDAs current regulations, there are three categories of expanded access: 
61   
62    Expanded access for individual patients, including for emergency use (21 CFR 
63  312.310) 
64   
65    Expanded access for intermediate-size patient populations (generally smaller than 
66  those typical of a treatment IND or treatment protocol  a treatment protocol is 
67  submitted as a protocol to an existing IND by the sponsor of the existing IND)12  (21 
68  CFR 312.315) 
69   
70    Expanded access for widespread treatment use through a treatment IND or 
71  treatment protocol (designed for use in larger patient populations) (21 CFR 
72  312.320) 
73   
74  The regulations describe criteria that must be met to authorize expanded access use, requirements 
75  for expanded access submissions, and safeguards that are intended to protect patients and 
76  preserve the ability to develop meaningful data about the safety and effectiveness of the drug 
77  through clinical trials or drug development.  The regulations were also intended to facilitate the 
78  availability, when appropriate, of investigational new drugs for treatment use while protecting 
79  patient safety and avoiding interference with the development of investigational drugs for 
80  marketing under approved applications.  
81   
82  The Cures Act added section 561A to the Federal Food, Drug, and Cosmetic Act (FD&C Act) to 
83  include new requirements regarding expanded access.  Under section 561A of the FD&C Act, 
84  the manufacturer or distributor of one or more investigational drugs for the diagnosis, 
85  monitoring, or treatment of one or more serious diseases or conditions is required to make its 
86  policy for evaluating and responding to expanded access requests (expanded access policy) 
87  public and readily available, such as by posting the policy on a publicly available website.13  The 
88  manufacturer or distributor is required to include their contact information, procedures for 
89  submission of expanded access requests, general criteria for evaluation and response, the 
90  anticipated time frame for acknowledgement of such requests, and a hyperlink or other reference 
91  to the record in ClinicalTrials.gov that contains information about availability of the drug under 
92  expanded access.14  
93   
 
11 Federal Register of August 13, 2009 (74 FR 40900). 
 
12 For information on the types of regulatory submissions that can be used to obtain expanded access, including 
treatment INDs or treatment protocols, see Q6 in this guidance. 
 
13 21 U.S.C. 360bbb-0(b). 
 
14 21 U.S.C. 360bbb-0(c). 
 
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94  FDARA amended the FD&C Act to require that the expanded access policy for an 
95  investigational drug be posted by the earlier of (1) the first initiation of a phase 2 or phase 3 
96  study with respect to such investigational drug or (2) within 15 days after the drug receives a fast 
97  track, breakthrough, or regenerative advanced therapy designation.15  However, the posting of 
98  the expanded access policy does not guarantee access to the investigational drug under expanded 
99  access.16  When a sponsor provides expanded access to its drug, it does so voluntarily.  FDA 
100  cannot compel a sponsor to provide expanded access to its drug. 
101   
102  FDA expects that the public availability of this guidance will increase awareness and knowledge 
103  of the availability of expanded access and the procedures for obtaining investigational drugs for 
104  treatment use for patients with serious or immediately life-threatening diseases or conditions who 
105  lack satisfactory therapeutic alternatives. 
106      
107   
108  III.  QUESTIONS AND ANSWERS  
109   
110  A.  Expanded Access for Treatment Use   
111   
112  Q1.  What is expanded access? 
113   
114  The terms expanded access, access, and treatment use are used interchangeably to refer to the use 
115  of an investigational drug when the primary purpose is to diagnose, monitor, or treat a patients 
116  disease or condition.  The terms compassionate use and preapproval access are also occasionally 
117  used in the context of the use of an investigational drug to treat a patient.  Although the terms 
118  compassionate use and preapproval access have been used informally in the United States and 
119  are also used outside the United States, they are not defined or described in FDA regulations.  
120  This has led to some confusion or lack of clarity about the meaning of the terms (e.g., whether 
121  they refer to all expanded access or to a type of expanded access, such as individual patient 
122  expanded access).  For this reason, the terms compassionate use and preapproval access will not 
123  be used in this document. 
124   
125  The main distinction between expanded access and the use of an investigational drug in the usual 
126  studies covered under an IND is that expanded access uses are not primarily intended to obtain 
127  information about the safety or effectiveness of a drug.  Expanded access, access, and treatment 
128  use may also refer to (1) use in situations when a drug has been withdrawn for safety reasons but 
129  there exists a patient population for whom the benefits of the withdrawn drug continue to 
130  outweigh the risks; (2) use of a similar, but unapproved drug (e.g., foreign-approved drug 
131  product) to provide treatment during a drug shortage of the approved drug; (3) use of an 
132  approved drug where availability is limited by a risk evaluation and mitigation strategy (REMS) 
133  for diagnostic, monitoring, or treatment purposes by patients who cannot obtain the drug under 
134  the REMS; or (4) use for other reasons. 
135   
 
15 21 U.S.C. 360bbb-0(f). 
 
16 21 U.S.C. 360bbb-0(d). 
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136  Q2.    Are there safeguards in place for expanded access use of an unapproved drug?   
137   
138  A licensed physician under whose immediate direction an investigational drug is administered or 
139  dispensed for an expanded access use is considered an investigator ( 312.305(c)(1)).  An 
140  individual or entity that submits an expanded access IND or protocol under 21 CFR part 312, 
141  subpart I, is considered a sponsor ( 312.305(c)(2)).  A licensed physician who submits an IND 
142  for expanded access use and under whose immediate direction an investigational drug is 
143  administered or dispensed is considered a sponsor-investigator ( 312.305(c)(3)).  The sponsors, 
144  investigators, and sponsor-investigators must comply with the responsibilities set forth in 21 
145  CFR part 312, subpart D, to the extent they are applicable to the expanded access use 
146  ( 312.305(c)).  For all expanded access INDs, investigators are responsible for reporting adverse 
147  events to the sponsor, ensuring that the informed consent requirements in part 50 (21 CFR part 
148  50) are met, ensuring that an IRB review of the expanded access use is obtained in a manner 
149  consistent with the requirements of part 56 (21 CFR part 56), and maintaining accurate case 
150  histories and drug disposition records and retaining records in a manner consistent with the 
151  requirements of  312.62 ( 312.305(c)(4)).  For all expanded access INDs, sponsors are 
152  responsible for: 
153    complying with expedited IND safety reporting requirements under  312.32 
154    submitting to FDA annual reports (when the IND or protocol continues for 1 year or 
155  longer) under  312.33 
156    ensuring that licensed physicians are qualified to administer the investigational drug for 
157  the expanded access use 
158    providing licensed physicians with the information needed to minimize the risk and 
159  maximize the potential benefits of the investigational drug 
160    maintaining an effective IND for the expanded access use, and  
161    maintaining adequate drug disposition records and retaining records in a manner 
162  consistent with the requirements of  312.57 ( 312.305(c)(5)) 
163   
164  B.  Expanded Access Submission 
165   
166  Q3.  What types of regulatory submissions can be used to obtain expanded access to a 
167  drug under the three expanded access categories? 
168   
169  For each category of expanded access, there are two types of regulatory submissions that can be 
170  made: (1) an expanded access protocol submitted as a protocol amendment to an existing IND 
171  (i.e., an expanded access protocol) or (2) a new IND submission, which is separate and distinct 
172  from any existing INDs and is intended only to make a drug available for treatment use under 
173  expanded access (i.e., an expanded access IND). 
174   
175  A sponsor or physician may contact the appropriate FDA review division for consultation 
176  regarding the most appropriate type of submission.  Additional information about expanded 
177  access, including contact information for review divisions, may be found on FDAs website at 
178  https://www.fda.gov/news-events/expanded-access/fdas-expanded-access-contact-information. 
179   
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180  Q4.  When should an expanded access protocol submission be used?                                                       
181   
182  An expanded access protocol submission should be used only if the sponsor seeking expanded 
183  access has an existing IND in effect  typically, such a sponsor is a pharmaceutical company or 
184  manufacturer of the drug with an existing IND under which the sponsor is developing the drug 
185  for marketing.  When there is an existing IND in effect, FDA generally encourages the 
186  submission of an expanded access protocol rather than a new expanded access IND because 
187  having all expanded access use and clinical trial use consolidated under a single IND may 
188  facilitate the administrative and review processes, making it less burdensome for sponsors and 
189  FDA. 
190   
191  Q5.  When should a new expanded access IND submission be used? 
192   
193  A new expanded access IND submission for expanded access generally should be used when (1) 
194  there is no existing IND in effect for the drug or, more commonly, (2) there is an existing IND in 
195  effect for the drug, but the sponsor of the existing IND is not seeking to be the sponsor of the 
196  expanded access use (e.g., for an individual patient use, the sponsor of the existing IND may 
197  prefer that a patients physician take on the role of sponsor-investigator and submit a separate 
198  individual patient IND).  
199   
200  Q6.  How does FDA categorize and subcategorize expanded access submissions? 
201   
202  FDA categorizes expanded access submissions as either expanded access INDs or expanded 
203  access protocols.  In addition, there are three different sub-categories of expanded access, and for 
204  individual patient expanded access, FDA distinguishes between emergency and non-emergency 
205  individual patient expanded access.   
206   
207  This results in the following sub-categorization of expanded access submissions: 
208   
209  Individual Patient Expanded Access, Including for Emergency Use  
210   
211  (1)  Individual patient expanded access IND 
212  (1a) Individual patient expanded access IND for emergency use 
213   
214  (2)  Individual patient expanded access protocol 
215  (2a) Individual patient expanded access protocol for emergency use  
216   
217  Intermediate-Size Patient Populations 
218   
219  (1)  Intermediate-size patient population expanded access IND 
220  (2)  Intermediate-size patient population expanded access protocol 
221   
222  Treatment IND or Treatment Protocol (expanded access for widespread use) 
223   
224  (1)  Treatment IND 
225  (2)  Treatment protocol 
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226    
227  Individual Patient Expanded Access, Including for Emergency Use (also referred to as 
228  single patient expanded access) 
229   
230  (1) Individual patient expanded access IND (also referred to as single patient IND): 
231  Expanded access to an investigational drug for treatment use by a single patient 
232  submitted under a new IND.  Unless FDA notifies the sponsor (e.g., the patients 
233  physician17) that treatment may begin earlier, there is a 30-day period from the date 
234  FDA receives the IND before treatment with the drug may begin ( 312.305(d)(1)).  
235  See Q9 for IRB requirements. 
236   
237  (1a) Individual patient expanded access IND for emergency use: A subset of 
238  individual patient INDs that provides expanded access to an investigational drug for 
239  treatment use by a single patient in an emergency situation (e.g., a situation that 
240  requires a patient to be treated before a written submission can be made, treatments 
241  expected to have a rapid effect in resolving an acute clinical emergency) submitted 
242  under a new IND ( 312.310(d)).  Treatment uses intended for chronic 
243  administration to slow progression of disease generally are not appropriate as 
244  emergency expanded access requests. For emergency access to a single patient IND, 
245  treatment is initially requested and authorized by telephone (or other means of 
246  electronic communication) and may start immediately upon FDA authorization, and 
247  the licensed physician or sponsor must agree to submit a written submission (IND) 
248  within 15 working days of the initial authorization ( 312.310(d)(2)).   
249   
250  (2) Individual patient expanded access protocol (also referred to as single patient 
251  protocol):  Expanded access to an investigational drug for treatment use by a single 
252  patient, submitted as a protocol to an existing IND by the sponsor of the existing 
253  IND.  There is no 30-day period before treatment with the drug may begin, but the 
254  protocol must be submitted to FDA and have IRB approval consistent with 21 CFR 
255  part 56 (see  312.305(c)(4)) before treatment may begin.18  Additionally, FDA may 
256  put the protocol on clinical hold if any issues (e.g., safety issue with use of 
257  investigational drug) are identified during FDAs review of the protocol. 
258   
259  (2a) Individual patient expanded access protocol for emergency use:  An emergency 
260  use protocol is a subset of individual patient protocols that provides expanded access to 
261  an investigational drug for treatment use by a single patient in an emergency situation 
262  where authorization to treat is being requested before written submission of a protocol 
263  to an existing IND by the sponsor of the existing IND ( 312.310(d)).  Treatment is 
264  initially requested and authorized by telephone (or other rapid means of communication) 
265  and may start immediately upon FDA authorization, with a requirement for a written 
266  submission (protocol) to FDA within 15 working days of the initial authorization 
267  ( 312.310(d)(2)). 
 
17 Both physicians and sponsors can submit individual patient expanded access INDs.  However, in FDAs 
experience, licensed physicians typically submit these requests. 
 
18 See  312.305(d)(2) and 312.30(a).  
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268   
269  In an emergency situation (either an individual patient expanded access IND for emergency 
270  use (1a) or individual patient expanded access protocol for emergency use (2a)) when there 
271  is not sufficient time to secure IRB review before beginning treatment, the emergency use of 
272  the investigational drug must be reported to the IRB within 5 working days of emergency 
273  use, as required under  56.104(c).  However, the sponsor-investigator should also be aware 
274  of their institutions policy regarding IRB review before administration of drug in such cases. 
275   
276  Contact information for emergency use INDs and protocols is located on FDAs expanded 
277  access website at https://www.fda.gov/news-events/expanded-access/fdas-expanded-access-
278  contact-information. 
279   
280  Intermediate-Size Patient Population Expanded Access 
281  Expanded access to an investigational drug can be provided under an intermediate IND or 
282  protocol if FDA determines that there is enough evidence that the drug is safe at the dose 
283  and duration proposed for expanded access use to justify a clinical trial of the drug in the 
284  approximate number of patients expected to receive the drug under expanded access, and 
285  there is at least preliminary clinical evidence of effectiveness of the drug, or of a plausible 
286  pharmacologic effect of the drug to make expanded access use a reasonable therapeutic 
287  option in the anticipated patient population ( 312.315(b)). 
288   
289  (1) Intermediate-size patient population expanded access IND:  Expanded access to an 
290  investigational drug for use by more than one patient, but generally fewer patients 
291  than are treated under a typical treatment IND or protocol, submitted under a new 
292  IND.  Unless FDA notifies the sponsor that treatment may begin earlier, there is a 30-
293  day period from the date FDA receives the IND before treatment with the drug may 
294  begin ( 312.305(d)(1)).  IRB approval must also be obtained before treatment with 
295  the drug may begin ( 56.103(a)). 
296   
297  (2) Intermediate-size patient population expanded access protocol:  Expanded access 
298  to an investigational drug for use by more than one patient, but generally fewer 
299  patients than are treated under a typical treatment IND or protocol, submitted as a 
300  protocol to an existing IND by the sponsor of the existing IND.  There is no 30-day 
301  period before treatment with the drug may begin, but the protocol must be submitted 
302  to FDA and have IRB approval before treatment with the drug may begin.  See 
303   312.305(d)(2) and 312.30(a). 
304   
305  For more information about intermediate-size patient population expanded access, see Q22 
306  and Q23. 
307   
308  Treatment IND or Treatment Protocol 
309   
310  Expanded access to an investigational drug can only be provided under a treatment IND or 
311  protocol if the drug is being investigated in a controlled clinical trial under an IND designed 
312  to support a marketing application for the expanded access use, or all clinical trials of the 
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313  drug have been completed, and the sponsor is actively pursuing, with due diligence, 
314  marketing approval of the drug for the expanded access use ( 312.320(a)). 
315   
316  (1) Treatment IND:  Expanded access to an investigational drug for treatment use by a 
317  large (widespread) population, submitted under a new IND.  Unless FDA notifies the 
318  sponsor that treatment may begin earlier, there is a 30-day period from the date FDA 
319  receives the IND before treatment with the drug may begin ( 312.305(d)(1)).  IRB 
320  approval must also be obtained, consistent with 21 CFR part 56, before treatment 
321  with the drug may begin. 
322   
323  (2) Treatment protocol: Expanded access to an investigational drug for treatment use 
324  by a large (widespread) population, submitted as a protocol to an existing IND by the 
325  sponsor of the existing IND.  Unlike other expanded access protocols submitted to 
326  existing INDs, there is a 30-day period from the date FDA receives the protocol 
327  before treatment with the drug may begin unless FDA notifies the sponsor that 
328  treatment may begin earlier ( 312.305(d)(2)(ii)).  IRB approval must also be obtained 
329  before treatment with the drug may begin ( 312.30(a)). 
330   
331  FDA recommends that the expanded access submission identify the relevant subcategory.  For 
332  clarity, the time frames mentioned previously for when treatment can begin under the different 
333  subcategories of expanded access are based on the sponsor having agreed to provide the drug for 
334  such use under expanded access.  See also Q24, Q25, and Q26. 
335   
336  Q7.  What information should be included in an expanded access submission? 
337   
338  An expanded access submission must include all information required by  312.305(b) and any 
339  additional information required for the particular category of expanded access (described in 
340   312.310(b) for individual patient submissions, in  312.315(c) for intermediate-size patient 
341  population submissions, and in  312.320(b) for treatment submissions), either within the 
342  submission itself or by reference to an existing IND. 
343   
344  In cases where the sponsor of an existing IND for the drug is not seeking to be the sponsor of the 
345  expanded access use, the sponsor of that existing IND may give the sponsor of the expanded 
346  access IND permission to reference content in the existing IND to satisfy certain requirements 
347  for an expanded access IND submission.  If permission is obtained, the expanded access IND 
348  sponsor should then provide to FDA a letter of authorization (LOA) from the existing IND 
349  sponsor (e.g., pharmaceutical company or drug manufacturer) that permits FDA to reference that 
350  IND. 
351   
352  FDA expects that reference to an existing IND will typically be used by an expanded access IND 
353  sponsor to satisfy the requirements to submit the information described in  312.305(b)(2)(v) 
354  (description of the manufacturing facility); in  312.305(b)(2)(vi) (chemistry, manufacturing, and 
355  controls information); and in  312.305(b)(2)(vii) (pharmacology and toxicology information). 
356   
357  IND submissions that reference an existing IND generally will include the information described 
358  in  312.305(b)(2)(ii), (iii), (iv), and (viii) and 312.305(b)(3) in the expanded access IND 
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359  submission.  As noted, the expanded access submission must also include the additional 
360  information, consistent with 21 CFR part 312, subpart I, that may be required for the specific 
361  category of expanded access.   
362   
363  See Q8 for information on the forms that are available to use for expanded access submissions. 
364   
365  Q8.  What forms are used for expanded access submissions? 
366   
367  The licensed physician19 acting as a sponsor-investigator may submit an individual patient IND 
368  using Form FDA 3926 (Individual Patient Expanded AccessInvestigational New Drug 
369  Application (IND)), which when completed (including attachments, if appropriate), constitutes 
370  the individual patient IND submission.   
371   
372  Individual patient INDs, including for emergency use, may also be submitted by a licensed 
373  physician acting as a sponsor-investigator using Form FDA 1571 (Investigational New Drug 
374  Application (IND)), which is a transmittal form that accompanies the IND and provides 
375  information to identify the type of submission and its contents.   
376   
377  For individual patient protocols submitted to an existing IND, to intermediate-size patient 
378  population INDs and protocols, and to treatment INDs and protocols, Form FDA 1571 should 
379  accompany the submission.  The most current version of all FDA forms can be downloaded from 
380  the FDA website at https://www.fda.gov/AboutFDA/ReportsManualsForms/Forms/default.htm. 
381   
382  The following table illustrates which form may be used for each type of submission: 
383   
384   
 
19 A licensed physician who submits FDA Form 3926 to request emergency expanded access for a patient is 
considered to be acting as a sponsor-investigator.  Licensed physician and physician are used interchangeably in this 
guidance. 
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Table 1. Acceptable Expanded Access Submission Forms 
      Form FDA 3926        Form FDA 1571 
Individual patient IND     
submitted by a licensed     
physician# 
*Individual patient IND for     
emergency use submitted by     
a licensed physician# 
Individual patient protocol   
 
Individual patient protocol   
 
for emergency use 
Intermediate-size patient   
 
population IND 
Intermediate-size patient   
 
population protocol 
Treatment IND     
Treatment protocol     
385  # In these cases, the licensed physicians may use either one of these forms to submit the IND to FDA 
386  * When using Form FDA 3926 for individual INDs for emergency use, the box in Field 10.b 
387  (Request for authorization to use alternative IRB review procedures) should not be selected. 
388   
389  Q9.  Is IRB review and approval required for all expanded access categories?  
390   
391  Except for emergency expanded access use when there is not sufficient time to secure 
392  prospective IRB review (see Q6), an investigator treating a patient with an investigational drug 
393  under expanded access is responsible for obtaining IRB review20 and approval consistent with 21 
394  CFR part 56 before treatment with the investigational drug may begin, regardless of whether the 
395  protocol is submitted in a new IND or to an existing IND ( 312.305(c)(4)).  Part 56 requires, 
396  among other things, that the IRB review the expanded access use at a convened IRB meeting at 
397  which a majority of the members are present (full IRB review) ( 56.108(c)).    
398   
399  Non-emergency individual patient expanded access IND:  Upon request, FDA intends to 
400  allow for waivers of the requirement for review and approval at a convened IRB meeting for 
401  individual patient expanded access INDs where the IRB chairperson or another designated IRB 
402  member provides concurrence before treatment use begins.  In this case, the review of individual 
403  patient expanded access use by an IRB chairperson (or designated IRB member) would follow a 
 
20 An institutional review board (IRB) means any board, committee, or other group formally designated by an 
institution to review, to approve the initiation of, and to conduct periodic review of biomedical research involving 
human subjects.  The primary purpose of IRB review is to ensure that the rights and welfare of human subjects are 
protected, including by determining that informed consent is obtained in accordance with and to the extent required 
by Federal requirements.  Institutions may have their own IRB to oversee human subjects research conducted within 
the institution or by the staff of the institution.  If the patients physician does not have access to a local IRB, an 
independent IRB may be used.  The Department of Health and Human Services Office for Human Research 
Protections maintains a database of registered IRBs.  Go to https://ohrp.cit.nih.gov/search/irbsearch.aspx?styp=bsc and 
click on Advanced Search. Enter your state to find registered IRBs in your area.  For more information, see  
https://www.fda.gov/news-events/public-health-focus/expanded-access. 
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404  different review pathway that is neither full board nor expedited, but rather one in which the IRB 
405  chair or designee reviews the relevant documents (as determined by the IRB), and then the 
406  decision to concur or not (and/or any questions and responses) is documented by the IRB chair or 
407  designee.  FDA concludes that such a waiver is appropriate for individual patient expanded 
408  access INDs for the initial submission, any amendments (e.g., for change in the use or duration 
409  of treatment) to the IND, and, if applicable, continuing review.  FDA intends to consider a 
410  completed Form FDA 3926 with the box in Field 10.b selected and the form signed by the 
411  physician to be a request for a waiver under  56.105 of the requirements in  56.108(c), which 
412  relates to full IRB review.  When a waiver is requested in this manner, the physician does not 
413  receive notice from FDA indicating that the waiver is granted.  Alternatively, the physician may 
414  request a waiver separately in an amendment to the IND.  When the request for waiver is 
415  accomplished by submission of a separate waiver request, FDA issues a response to the waiver 
416  request. 
417   
418  If a physician submits an individual patient expanded access IND using Form FDA 1571 and 
419  wishes to request a waiver from full IRB review, a separate waiver request under  56.105 of the 
420  requirements in  56.108(c) should be submitted with the application.  FDA issues a response to 
421  the waiver request in this situation. 
422   
423  If the initial protocol under an individual patient expanded access IND was reviewed and 
424  approved by the full IRB but the physician would like any amendments or the continuing review 
425  to be conducted by the IRB chairperson or the chairpersons designee instead, the physician may 
426  amend the IND with a correspondence that clearly indicates the intent of the amendment (to 
427  change the approach for continuing IRB review of the expanded access protocol) and that 
428  includes a request for waiver under  56.105 of the requirements in  56.108(c).  As described 
429  previously, FDA intends to consider a completed Form FDA 3926 with the box in Field 10.b 
430  selected and the form signed by the physician to be a request for such a waiver.  Alternatively, 
431  the physician may amend the IND with a separate request for waiver of continuing IRB review 
432  by the full IRB if Form 3926 is not used or if Field 10.b was not checked. 
433   
434  Emergency individual patient expanded access IND:  FDA authorization is required before 
435  initiation of treatment ( 312.310(d)).  However, emergency expanded access use is exempted 
436  from obtaining full IRB approval before initiation of treatment ( 56.104(c)) provided that the 
437  IRB is notified of the emergency expanded access use within 5 working days of emergency use.  
438  Following receipt of notification of such emergency use, the IRB should follow its documented 
439  standard operating procedure for review of emergency expanded access use.  A physician may 
440  choose to use Form FDA 3926 for submitting the emergency expanded access application.  In 
441  such emergency expanded access cases, the box in Field 10.b on Form FDA 3926 should be left 
442  unchecked because Field 10.b is intended for requesting a waiver to obtain concurrence by the 
443  IRB chairperson or by a designated IRB member, in lieu of full IRB review, before the treatment 
444  use begins for non-emergency individual patient expanded access.  
445   
446  Intermediate IND/Protocol and Treatment IND/Protocol: The Agency believes a waiver is 
447  not appropriate for intermediate and treatment INDs and protocols.  FDA Form 1571 requires a 
448  commitment that an IRB will be responsible for the initial and continuing review of the studies 
449  under an IND.  See  312.23(a)(1)(iv). 
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450   
451  Q10.  Is a physician participating in an expanded access protocol sponsored by another 
452  entity (e.g., manufacturer of the drug) required to obtain local IRB review and 
453  approval? 
454   
455  If the sponsor of the expanded access protocol (e.g., manufacturer of the drug) has obtained IRB 
456  review and approval of the protocol, the physician may not be required to obtain local IRB 
457  review and approval.  A physician associated with an institution should verify that the sponsor 
458  has obtained IRB approval of the protocol, and the physician should consult their institution on 
459  their policy in these situations. Some institutions may require that their physicians obtain 
460  approval from the institutions IRB as well.   
461   
462  Q11.  Can the same drug be used in an emergency situation at the same institution more 
463  than once?  If so, is prospective IRB review required for the subsequent expanded 
464  access emergency use? 
465   
466  There can be more than one expanded access emergency use of the same drug at the same 
467  institution.  For expanded access use authorized under the emergency procedures, the emergency 
468  use must be reported to the responsible IRB within 5 working days of initiation of treatment 
469  ( 56.104(c)).  Generally, once an investigational drug is used in an emergency situation without 
470  prior IRB approval, any subsequent uses of the investigational drug at that same institution 
471  would require prior IRB review and approval ( 56.104(c)).  An institution or physician that 
472  expects subsequent use of the investigational drug should request review and approval by the 
473  appropriate IRB after the initial emergency use.  However, when prior IRB review and approval 
474  is not feasible for a subsequent expanded access emergency use at a particular institution, FDA 
475  does not intend to deny21 the subsequent request for emergency use based on lack of time to 
476  obtain prospective IRB review, provided that use will be reported to the IRB within 5 working 
477  days of initiation of treatment ( 56.104(c)). 
478   
479  Q12.  Are expanded access submissions subject to the informed consent requirements? 
480   
481  Yes.  FDAs informed consent requirements apply to clinical investigations as described in 21 
482  CFR 50.1(a).  The term clinical investigation is defined in 21 CFR 50.3(c) to include any 
483  experiment that involves a test article and one or more human subjects and that is subject to 
484  requirements for prior submission to the Food and Drug Administration under section 505(i) or 
485  520(g) of the act . . . .  FDA considers expanded access use of an investigational drug to meet 
486  the definition of clinical investigation in 21 CFR 50.3(c) since an IND or protocol to an existing 
487  IND must be submitted to provide investigational drugs under expanded access ( 312.305(b)). 
488  Therefore, expanded access to an investigational drug for treatment use, including emergency 
489  use, requires informed consent as described in 21 CFR part 50, unless one of the exceptions 
490  found in part 50 applies.22   Investigators treating a patient or patients with an investigational 
 
21 In this guidance, reference to a request being denied means that such a request is put on clinical hold 
( 312.42(b)(3)). 
 
22 See 21 CFR part 50.  
 
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491  drug under expanded access are responsible for ensuring that the informed consent requirements 
492  of part 50 are met ( 312.305(c)(4)).  One of the purposes of informed consent is to ensure that 
493  patients are informed that they will be treated with an investigational product and that there may 
494  be uncertainty about the safety and effectiveness of the product.  
495   
496  Q13.   What information should be included in the informed consent document for 
497  obtaining a patients consent for treatment under individual patient expanded 
498  access?  
499   
500  The consent form must contain information set out in  50.20 and 50.25 to allow the patient to 
501  make an informed decision about receiving experimental treatment.  For further information, see 
502  FDAs draft information sheet guidance for IRBs, clinical investigators, and sponsors Informed 
503  Consent  Information Sheet (July 2014).23  FDA is sharing a template (see the appendix) that 
504  investigators may find helpful for obtaining informed consent from patients for individual patient 
505  expanded access.  Physicians and institutions may use this template to model their forms for 
506  obtaining consent from patients under expanded access. 
507   
508  Q14.  Under the informed consent regulations, informed consent documents must include 
509  [a] statement that the study involves research.  Is that appropriate for informed 
510  consent documents used for expanded access? 
511   
512  It is acceptable for informed consent documents used for expanded access to contain a statement 
513  that treatment under expanded access involves research.  As an alternative and given that the 
514  drug used under expanded access is investigational, FDA considers a statement in the informed 
515  consent document indicating that although the primary use of the drug is for treatment, the drug 
516  is investigational and FDA has not determined that the drug is safe or effective for use in treating 
517  the disease or condition, to also satisfy the requirement under  50.25(a)(1) that the informed 
518  consent provide a statement that the use of the product involves research. 
519   
520  C.  Individual (or Single) Patient Expanded Access 
521   
522  Q15.  Who can make a submission for individual patient expanded access? 
523   
524  The sponsor of an existing IND under which a drug is being developed (e.g., a pharmaceutical 
525  company or manufacturer of the investigational drug) or a licensed physician may make an 
526  individual patient expanded access submission ( 312.310(b)(1)). 
527   
528  The sponsor of an existing IND can submit an individual patient expanded access protocol to its 
529  existing IND.  In this scenario, the sponsor of the existing IND is also the sponsor of the 
530  expanded access protocol, and the patients physician is the investigator for the expanded access 
 
23 When final, this guidance will represent FDAs current thinking on this topic. 
 
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531  protocol.24  The term investigator is used because the drug is investigational, but the term does 
532  not denote the licensed physicians or patients involvement in a clinical trial. 
533    
534  Although a sponsor of an existing IND could submit a new individual patient expanded access 
535  IND and cross reference the information in its existing IND, it is preferable for sponsors to 
536  submit an individual patient expanded access protocol to an existing IND.  Having all clinical 
537  trials and expanded access for a drug under a single IND eases the administrative burden and 
538  facilitates the review process, making it less burdensome for sponsors and FDA.  In this scenario, 
539  the sponsor of the existing IND is also the sponsor of the expanded access IND, and the patients 
540  physician is the investigator for the expanded access IND. 
541   
542  An individual patients physician can submit an individual patient expanded access IND for their 
543  patient.  In this scenario, when the patients physician submits an expanded access IND, the 
544  physician is both the sponsor and the investigatorin other words, the physician is considered a 
545  sponsor-investigator25 for the purposes of part 312.  The physician may satisfy some of the 
546  expanded access submission requirements by referring to information in an existing IND if the 
547  physician obtains permission from the sponsor of the existing IND (see Q7).  If the physician 
548  obtains this permission from the sponsor of the existing IND, the physician should provide to 
549  FDA the letter of authorization from the sponsor of the IND that permits FDA to reference the 
550  sponsors IND. 
551   
552  In cases where it is not possible to obtain a letter of authorization (e.g., the entity supplying the 
553  drug does not have an IND filed with FDA), the physician should contact the relevant FDA 
554  review division to determine what information is needed per  312.305 to support the expanded 
555  access submission.  The physician should also contact the FDA review division if the individual 
556  patient expanded access IND is for an approved drug where availability is limited by a REMS.  
557  The physician should then submit an individual patient expanded access IND to the appropriate 
558  FDA review division and may choose to use Form FDA 3926.26   Contact information for review 
559  divisions may be found on FDAs website at https://www.fda.gov/news-events/expanded-
560  access/fdas-expanded-access-contact-information. 
561   
562  If the sponsor of the existing IND (e.g., the pharmaceutical company or drug manufacturer) does 
563  not authorize reference to the IND, the physician sponsoring the expanded access IND must 
564  include in the IND all the information (e.g., relevant preclinical and chemistry, manufacturing, 
565  and controls information) required to support the expanded access IND ( 312.305 and 
566  312.310). 
 
24 For the purposes of this guidance, it is assumed that the patients physician is the same person as the investigator. 
The pharmaceutical company or drug manufacturer may designate the investigator role to a physician who may not 
be the physician of the patient.  In this scenario it is the responsibility of the sponsor-appointed investigator to 
collect all necessary information from the patients physician to make decisions about treatment and to fulfill the 
responsibilities of an investigator.  
 
25 See  312.305(c)(3).  
 
26 Form FDA 3926 and accompanying instructions are available on FDAs website at  
https://www.fda.gov/AboutFDA/ReportsManualsForms/Forms/default.htm. 
 
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567   
568  A patients physician may not submit an individual patient expanded access protocol to an 
569  existing IND for which the physician is not the sponsor. 
570   
571  Regardless of who sponsors an individual patient expanded access protocol or expanded access 
572  IND, the patient can obtain expanded access to the investigational drug only through treatment 
573  by a licensed physician ( 312.310). 
574   
575  Q16.  What are the roles of the patients physician and FDA in determining if expanded 
576  access for an individual patient is appropriate? 
577   
578  FDA may permit expanded access to a drug for an individual patient when the criteria in 
579   312.305(a) (applicable to all types of expanded access) and the criteria in  312.310(a) 
580  (specific to individual patient expanded access) are met.  For these criteria to be met, both the 
581  patients physician and FDA must make certain determinations. 
582   
583  The patients physician must determine that the probable risk to the patient from the 
584  investigational drug is not greater than the probable risk from the disease or condition 
585  ( 312.310(a)(1)).  The physician should make this determination based on the information about 
586  the drug available to the physician and the physicians knowledge of the patients clinical 
587  situation.  FDA acknowledges that there is often limited information available to physicians 
588  about the risks and benefits of an investigational drug and no practical way to provide the 
589  physician the information at FDAs disposal (information is typically proprietary and generally 
590  can only be disclosed to a member of the public on consent of the pharmaceutical company or 
591  drug manufacturer). 
592   
593  Therefore, as with all types of expanded access, FDA must determine, based on the information 
594  available to FDA, that the potential benefit justifies the potential risks of the treatment use with 
595  the drug and that those risks are not unreasonable in the context of the disease or condition to be 
596  treated ( 312.305(a)(2)).  FDA has access to considerably more information about the 
597  investigational drug than does the patients physician and evaluates the potential benefits and 
598  risks of therapy considering the information provided by the physician.  Therefore, FDA may 
599  reach a different conclusion than the physician, based on the information available to the Agency 
600  about the investigational drug.  As noted previously, in most cases, FDA will not be able to share 
601  the information about the investigational drug on which its conclusion is based.   
602   
603  To authorize the expanded access use, FDA must also determine (1) that the patient has a serious 
604  or life-threatening disease or condition and has no other comparable or satisfactory therapeutic 
605  options ( 312.305(a)(1)); (2) that providing expanded access will not interfere with 
606  development of the drug for the expanded access use ( 312.305(a)(3); see Q28)); and (3) that 
607  the patient cannot obtain the drug under another IND or protocol (e.g., in a clinical study of the 
608  drug) ( 312.310(a)(2)). 
609   
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610  Q17.  What are some of the reasons for FDA to deny a request for individual patient 
611  expanded access when previous requests for the same drug for the same or a similar 
612  use have been permitted? 
613   
614  Each request for individual patient expanded access to a drug should be treated as a unique 
615  clinical situation, and the risks and benefits should be evaluated based on that clinical situation.  
616  Even when there are two (or more) individual patient expanded access requests for patients with 
617  the same disease or condition, there may be significant differences in the clinical presentation of 
618  the disease or condition that make the risks acceptable for one patient, but not for another.  For 
619  example, a patient may have a different stage of the disease or different tumor type than previous 
620  patients who were permitted expanded access to the drug and, therefore, may have a different 
621  benefit-risk assessment.  Similarly, a patient may have a comorbid condition not present in 
622  previous patients who obtained expanded access that would make the risk unacceptable.  FDA 
623  may also become aware of new safety signals or information about effectiveness that changes the 
624  benefit-risk assessment such that the risk is no longer acceptable for the patient.  In cases such as 
625  these, individual patient expanded access for additional patients might be denied. 
626   
627  There also may be other reasons for denying expanded access.  For example, a patient seeking 
628  expanded access may be able to enroll in a clinical trial that was not accessible to a previous 
629  patient who was granted expanded access (e.g., because the previous patient did not meet the 
630  inclusion criteria for the trial, or the trial was geographically inaccessible to the previous patient).  
631   
632  FDA could also have become aware since authorizing previous requests for expanded access that 
633  expanded access is impeding the clinical development of the drug and, on that basis, place further 
634  requests for expanded access on clinical hold ( 312.42(b)(3)). 
635   
636  Q18.  How does FDA address individual patient expanded access applications for 
637  treatment with multiple courses of therapy or treatment of a chronic condition? 
638   
639  Under  312.310(c)(1), individual patient expanded access is generally limited to a single course 
640  of therapy for a specified duration.  However, as reflected in  312.310(c)(1), FDA may 
641  authorize multiple courses of therapy or chronic therapy for individual patient expanded access, 
642  including authorizing individual patient expanded access to treat a chronic disease or condition 
643  that requires extended treatment.  FDA generally authorizes such individual patient expanded 
644  access when the circumstances of the treatment are well defined and reasonable considering the 
645  available evidence to support use of the drug.  The patients physician (as the investigator) 
646  proposes the full course of treatment when filing the request for expanded access.  To fairly 
647  weigh the risks and benefits of a drug for use for individual patient expanded access, FDA 
648  believes the planned course of therapy should be well defined because it will usually be 
649  necessary to consider the planned dose and duration of therapy in relation to what is known 
650  about the occurrence of toxicity for that dose and duration of therapy.   
651   
652  FDA does not usually authorize expanded access for an unspecified duration at the discretion of 
653  the patients physician.  FDA typically authorizes expanded access for an extended duration for 
654  the treatment of a chronic condition when the patients condition and the information available 
655  about the safety of the drug supports an extended duration of treatment.  For example, FDA may 
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656  authorize expanded access of extended duration for a drug being developed to treat multiple 
657  sclerosis or other types of progressively debilitating neuromuscular disease if it is critical that the 
658  drug be administered chronically to slow the progression of the disease and if the information 
659  available about the safety of the drug supports an extended duration of treatment.  If expanded 
660  access use is authorized for an extended duration, FDA may require the sponsor to continue to 
661  monitor the individual patient expanded access use through the extended duration (see 
662   312.310(c)(3)).  
663   
664  Q19.   When should individual patient expanded access using the emergency procedures in 
665   312.310(d) be requested? 
666   
667  Section 312.310(d) states that FDA may authorize expanded access for an individual patient 
668  without a written submission if there is an emergency that requires the patient to be treated 
669  before a written submission can be made.  The licensed physician or sponsor, however, must 
670  agree to submit an expanded access IND or protocol within 15 working days of FDAs 
671  authorization of the use ( 312.310(d)(2)).  Under this regulation FDA considers it appropriate to 
672  request individual patient expanded access using the emergency procedures described in 
673   312.310(d) when treatment of the patient must occur within a very limited number of hours or 
674  must occur before the next business day after regular business hours.  FDA intends to authorize 
675  expanded access using the emergency procedures only when the situation is a true emergency.  If 
676  FDA determines that the situation is not a true emergency but qualifies for expanded access, FDA 
677  will accept it as a non-emergency individual patient IND once the application is officially 
678  submitted.  In such case, the sponsor can treat the patient when the IND goes into effect 30 days 
679  after FDA receives the IND (unless the IND is put on clinical hold, i.e., is not allowed to 
680  proceed) or on earlier notification by FDA ( 312.40 and 312.305(d)(1)).  
681   
682  Q20.  Can a pharmaceutical company or the drug manufacturer that is developing the 
683  drug for marketing request individual emergency expanded access to its 
684  investigational drug to treat multiple patients? 
685   
686  Yes.  A separate emergency use IND or protocol would need to be submitted for each patient to 
687  be treated.  The pharmaceutical company or drug manufacturer can submit multiple such 
688  emergency use INDs or protocols to its existing IND.  An amendment to a single patient IND to 
689  treat additional patients is not acceptable.  However, if multiple emergency expanded access 
690  requests for similarly situated patients are anticipated, FDA may request that a sponsor submit an 
691  intermediate-size patient population expanded access IND or protocol, as appropriate. 
692   
693  D.  Intermediate-Size Patient Population and Treatment INDs and Protocols 
694   
695  Q21.  Can there be more than one intermediate-size patient population expanded access 
696  IND or protocol for a particular drug for the same disease or condition? 
697   
698  When multiple patients with the same disease or condition seek expanded access to a particular 
699  drug and the relevant criteria for expanded access are met, FDA believes that it is generally most 
700  efficient to consolidate expanded access in a single intermediate-size patient population IND or 
701  protocol.  If the drug is being developed, FDA believes it is most efficient if the pharmaceutical 
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702  company or the drug manufacturer that is developing the drug for marketing is the sponsor of a 
703  single intermediate-size patient population expanded access protocol.  However, the regulations 
704  do not preclude the possibility of authorizing more than one intermediate-size patient population 
705  expanded access IND or protocol, with different sponsors or sponsor-investigators, for a drug for 
706  the same disease or condition.  Thus, there may be situations in which there are multiple 
707  intermediate-size patient population expanded access INDs or protocols for a drug for the 
708  treatment of the same disease or condition.  FDA expects these situations to arise infrequently. 
709   
710  Q22.  When is it appropriate to request expanded access for multiple patients using an 
711  intermediate-size patient population expanded access IND or protocol rather than a 
712  treatment IND or protocol? 
713   
714  FDA regulations do not impose specific numerical limitations for when an intermediate-size 
715  patient population expanded access IND or protocol (as opposed to a treatment IND or protocol) 
716  may be appropriate.  This determination generally depends on the following two factors: 
717   
718  1. Whether the drug is under development for marketing for the expanded access use 
719   
720  If the drug is not being developed for marketing and the expanded access IND or protocol 
721  is intended to treat more than a single patient, expanded access would be provided under 
722  an intermediate-size patient population expanded access IND or protocol rather than a 
723  treatment IND or protocol.  Expanded access to an investigational drug can only be 
724  provided under a treatment IND or protocol if the drug is being developed for marketing 
725  for the expanded access use.  When the investigational drug is being developed, 
726  intermediate-size patient population expanded access is used earlier in development than 
727  treatment INDs or protocols.  Also, if FDA determines clinical development of the drug 
728  is essentially complete (i.e., the clinical trials to support marketing approval of the 
729  investigational drug have ended) and the intent of the expanded access is to bridge the 
730  gap between completion of the clinical trials and marketing of the drug (to ensure that 
731  treatment is not interrupted and to expand treatment to additional patients), the expanded 
732  access, regardless of the number of patients expected to be treated, would generally be 
733  designated as a treatment IND or protocol. 
734   
735  2. Size of the patient population 
736   
737  The second factor important to a determination of whether expanded access is provided 
738  under an intermediate-size patient population expanded access IND or protocol (as 
739  opposed to a treatment IND or protocol) is the size of the patient population.  In general, 
740  intermediate-size patient population expanded access is intended to accommodate 
741  population sizes smaller than the large populations typical of treatment INDs or 
742  protocols.  However, as noted in the preceding paragraph, if FDA determines clinical 
743  development is complete and the intent of the expanded access IND or protocol is to 
744  bridge the gap between the completion of clinical trials and marketing, expanded access 
745  would generally be provided under a treatment IND or protocol, regardless of the 
746  intended size of the patient population.  Similarly, if the drug is not being developed for 
747  marketing for the expanded access use, expanded access would generally be provided 
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748  under an intermediate-size patient population IND or protocol, regardless of the size of 
749  the patient population (as long as it is intended to treat more than a single patient). 
750   
751  Separate single patient INDs may be combined into a single intermediate-size patient 
752  population protocol when feasible and practical, at the request of the sponsor or the FDA.  
753  Adding patients to an intermediate-size patient population protocol can reduce paperwork 
754  and simplify IRB review.  In such cases, any number beyond one patient might be 
755  reasonable. FDA may be consulted on how to consolidate single patient expanded access 
756  under an intermediate-size patient population expanded access protocol.  When a growing 
757  number of eligible patients might benefit from treatment access under an intermediate-
758  size patient population protocol, a treatment IND may be appropriate.  (See Q23.) 
759   
760  Q23.  The regulations in  312.315(d)(1)(iii) state that as enrollment in an intermediate-
761  size patient population expanded access IND or protocol increases, FDA may ask 
762  the sponsor to submit an IND or protocol for the use under  312.320 (i.e., to 
763  transition the intermediate-size patient population expanded access IND or protocol 
764  to a treatment expanded access IND or protocol).  When and how would FDA make 
765  such a determination and how would such a transition be carried out? 
766   
767  FDA anticipates that there would ordinarily be a seamless transition from intermediate-size 
768  patient population expanded access to expanded access under a treatment IND or protocol at the 
769  point when the evidence is sufficient to support the treatment IND or protocol, when there is 
770  adequate progress with drug development, and when the sponsor is willing to make the drug 
771  available to a potentially larger patient population under a treatment IND or protocol.  Although 
772  there will be a 30-day period for initiation of the new treatment IND or protocol, as required by 
773  the regulations, the review division can act sooner, and FDA may notify the sponsor that 
774  treatment may begin earlier ( 312.40 and 312.305(d)). 
775   
776  For such a transition, all patients currently receiving treatment with the investigational drug 
777  would continue treatment under the intermediate-size patient population expanded access IND or 
778  protocol, as appropriate, until they transition to the treatment IND or protocol (to ensure that 
779  treatment is not interrupted).  Once all patients in the intermediate-size patient population 
780  expanded access IND or protocol are receiving their treatment under the new treatment IND or 
781  protocol, the sponsor should request that the intermediate-size patient population expanded 
782  access IND or protocol be withdrawn. 
783   
784  E.  Time Frame for Beginning Treatment Use Under an Expanded Access IND 
785  or Protocol 
786   
787  For clarity, the time frames mentioned here for when treatment use can begin under the different 
788  subcategories of expanded access are based on the sponsor having agreed to provide the drug for 
789  such use under expanded access.   
790   
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791  Q24.  When can treatment begin under emergency use expanded access INDs or 
792  protocols? 
793   
794  For an emergency use, treatment may begin immediately upon authorization (usually provided 
795  by telephone or other rapid means of communication) by the FDA reviewing official 
796  ( 312.310(d) and 312.305(d)(2)(i)), with a requirement for a written submission 
797  (IND/protocol) to FDA within 15 working days of the initial authorization ( 312.310(d)(2)).  As 
798  explained in Q6 and Q9, FDA anticipates that for expanded access uses authorized under the 
799  emergency procedures, there typically will not be time to obtain prior IRB approval of the use.  
800  In such cases, the emergency use must be reported to the IRB within 5 working days of initiation 
801  of treatment ( 56.104(c)). 
802   
803  Q25.  When can treatment begin under expanded access INDs not for emergency use? 
804   
805  When an expanded access IND (not for emergency use) is submitted, the treatment use of the 
806  drug may begin when the IND goes into effect and IRB approval has been obtained consistent 
807  with 21 CFR part 56 (see  312.305(c)(4)).  As is true for any new IND, an expanded access IND 
808  goes into effect 30 days after FDA receives the IND (unless the IND is put on clinical hold, i.e., 
809  is not allowed to proceed) or on earlier notification by FDA ( 312.40 and 312.305(d)(1)). 
810   
811  Q26.  When can treatment begin under expanded access protocols not for emergency use? 
812   
813  For an individual patient or intermediate-size patient population expanded access protocol, 
814  expanded access to the drug can begin once the expanded access protocol has been submitted to 
815  FDA and has been approved by an IRB ( 312.305(d)(2)).  For a treatment protocol, however, 
816  expanded access may not begin until 30 days after FDA receives the protocol (or on earlier 
817  notification by FDA ( 312.305(d)(2)(ii)) and IRB approval has been obtained consistent with 21 
818  CFR part 56 (see  312.305(c)(4)). 
819   
820  F.  General Questions 
821   
822  Q27.  Can FDA require a sponsor to provide expanded access to its drug if FDA 
823  authorizes the expanded access? 
824   
825  No.  FDA cannot compel a sponsor to provide expanded access to its drug.  A sponsor provides 
826  expanded access to its drug voluntarily. 
827   
828  Q28.  How does FDA determine that authorizing expanded access to a drug will not 
829  interfere with clinical trials or drug development? 
830   
831  Under  312.305(a)(3), to authorize any category of expanded access, FDA must determine that 
832  expanded access to the drug for the requested use will not interfere with the initiation, conduct, 
833  or completion of clinical investigations that could support marketing approval of the expanded 
834  access use or otherwise compromise the potential development of the drug for the expanded 
835  access use.  Generally, to receive the drug under an expanded access IND or protocol, patients 
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836  should be ineligible or otherwise unable (e.g., geographically unable to access a study site) to 
837  enter ongoing clinical trials. 
838   
839  FDA believes that expanded access INDs or protocols that treat larger patient populations 
840  generally have high potential to interfere with clinical investigations or drug development 
841  because of their greater potential to interfere with recruiting patients for the clinical investigation 
842  or investigations.  For FDA to determine whether an expanded access use will interfere with 
843  clinical investigations or drug development, FDA may ask the sponsor to provide additional 
844  information if FDA cannot make a determination based on the information the sponsor 
845  previously provided.  For example, before authorizing a treatment IND for a drug for which 
846  clinical trials are ongoing, FDA may ask the sponsor to explain (1) how the sponsor will ensure 
847  that the treatment IND will not interfere with accrual of patients in the clinical trials and (2) how 
848  the sponsor will determine whether interference with clinical development is occurring, if such 
849  information is not provided in the expanded access submission.  More specifically, FDA may ask 
850  the sponsor to submit to its IND a comprehensive investigational plan with a timetable and 
851  milestones (if it has not done so already) so that FDA can periodically assess whether the 
852  treatment IND is affecting accrual of patients in the clinical trials or other parameters related to 
853  the pace of drug development.  If FDA then determines that the ongoing treatment IND is 
854  interfering with clinical trials or drug development or that the sponsor is not pursuing, with due 
855  diligence, marketing approval for the expanded access use, FDA could place the treatment IND 
856  on clinical hold ( 312.42(b)(3)(ii)). 
857   
858  The potential for expanded access to interfere with clinical trials/drug development is also high 
859  for rare disease drug development programs, where the number of subjects available for 
860  participation in a clinical trial are limited. This potential is highest early in development and 
861  decreases as development progresses.  In general, for rare disease drug development, well-
862  controlled clinical trials should be initiated before patients are treated with the drug under 
863  expanded access, and expanded access should be sought only for those patients who are truly not 
864  eligible for or are unable to participate in those well-controlled trials.  Sponsors developing drugs 
865  for the treatment of a rare disease should consider study designs that help to minimize barriers to 
866  trial participation such as broad inclusion criteria, virtual or at-home visits, or utilizing health 
867  facilities that may be closer in proximity to potential subjects. Once the trials required by FDA to 
868  support a marketing application have been completed, there is little risk for interference with 
869  drug development, and broader expanded access may be considered. 
870   
871  Q29.  What data and information must sponsors submit as follow-up for active expanded 
872  access INDs or protocols? 
873   
874  As with any IND, in all cases of expanded access, sponsors are responsible for complying with 
875  expedited IND safety reporting requirements under  312.32 and for submitting annual reports 
876  (when the IND or protocol continues for 1 year or longer) under  312.33 (see  312.305(c)).  To 
877  comply with expedited IND safety reporting requirements under  312.32(c)(1)(i), the sponsor 
878  must report a serious adverse event that occurs during treatment as a suspected adverse reaction 
879  only if there is evidence to suggest a causal relationship between the drug and the adverse event.  
880  Data and information on expanded access protocols submitted to an existing IND may be 
881  provided in the annual report for the IND.  At the conclusion of treatment for individual patient 
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882  expanded access, the regulations in  312.310(c)(2) specify that the sponsor must provide to 
883  FDA a written summary of the results of the expanded access use, including adverse effects.  
884  FDA considers adverse effects to have the same meaning as adverse events as defined in 
885   312.32(a).27  
886   
887  Q30.  Why does FDA review adverse event data for expanded access INDs? 
 888 
889  From a public health perspective, early identification of important adverse events is beneficial.  
890  For example, a relatively rare adverse event might be detected during expanded access use, or 
891  such use might contribute safety information for a population not exposed to the drug in clinical 
892  trials.  FDA is aware of a small number of cases in which clinical safety data from expanded 
893  access treatment were used to help assess the risks and benefits of the drug.  In a very small 
894  number of cases, adverse event information from expanded access has contributed to safety 
895  information reflected in the FDA-approved labeling for a drug product.  FDA is not aware of 
896  instances in which adverse event information from expanded access has prevented FDA from 
897  approving a drug.  FDA reviewers of these adverse event data understand the context in which 
898  the expanded access use was permitted and will evaluate any adverse event data obtained from 
899  an expanded access submission within that context.  For example, FDA reviewers recognize that: 
900   
901  (1) expanded access treatment generally occurs outside a controlled clinical trial setting 
902   
903  (2) patients who receive a drug through expanded access may have a more advanced stage of 
904  the disease or condition than patients participating in a clinical trial  
905   
906  (3) patients who receive a drug through expanded access may be receiving other therapies for 
907  their disease or condition at the same time as the drug they are receiving through 
908  expanded access 
909   
910  (4) patients who receive a drug through expanded access may have one or more 
911  comorbidities 
912   
913  All of these factors make it difficult to attribute a particular adverse event to the expanded access 
914  treatment.  Moreover, it is very rare for FDA to place an IND on clinical hold due to adverse 
915  events observed in expanded access treatment. 
916   
917  Q31.  Can FDA consider an IND or protocol submission to be an expanded access 
918  submission and identify and review it as such, even though the applicant does not 
919  identify it as an expanded access submission? 
920   
921  Yes.  For example, FDA intends to evaluate whether proposals for studies described as open-
922  label safety studies should be considered treatment INDs or protocols.  The goal of an open-label 
923  safety study is to better characterize the safety of a drug late in its development. 
924   
 
27 Adverse event means any untoward medical occurrence associated with the use of a drug in humans, whether or 
not considered drug related. 
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925  However, in practice, many studies that are described as open-label safety studies have 
926  characteristics that appear to be more consistent with treatment INDs or protocols.  If an IND or 
927  protocol describes an open-label study that provides for broad expanded access to an 
928  investigational drug in the later stages of development, but lacks planned, systematic data 
929  collection and a design adequate to meaningfully evaluate a safety issue, FDA will generally 
930  consider the submission to be a treatment IND or protocol.  In the event that a protocol is not 
931  submitted as an expanded access protocol but is designated as such by FDA, the review division 
932  will notify the sponsor of the designation. 
933   
934  Q32.  What is the difference between an expanded access protocol and a continuation or 
935  open-label safety protocol? 
936   
937  A continuation protocol (also referred to as an extension trial) describes a trial in which patients 
938  are allowed to remain on an investigational drug or to cross over to an investigational drug from 
939  placebo or active control following conclusion of the randomized phase of a trial.  An open-label 
940  safety study is an unblinded study in which safety data are collected.  The primary purpose of 
941  both continuation and open-label safety protocols, in contrast to expanded access protocols, is to 
942  obtain safety data on the investigational drug.  The conduct of continuation and open-label safety 
943  protocols differs from that of expanded access protocols in that (1) participation in open-label 
944  safety and continuation protocols is usually limited to specific, named institutions/centers; (2) 
945  participating investigators in continuation or open-label safety protocols are already identified 
946  and trained to collect appropriate safety data; and (3) in the case of a continuation trial, 
947  participants are typically limited to those in the original randomized, controlled trial.  
948   
949  A protocol for which the primary intent is treatment of patients and for which enrollment is 
950  limited to patients who participated in the clinical trials to support approval of the investigational 
951  drug is considered a continuation protocol and not an expanded access protocol, even though the 
952  primary intent is treatment.  For such protocols, access to the investigational drug is not 
953  expanded beyond those patients who participated in the clinical trials.  The design and 
954  requirements for a continuation protocol for which the primary purpose is treatment of patients
955  and not collection of additional safety or other datawill generally be much simpler with fewer 
956  requirements than those for a continuation protocol for which the primary purpose is collection 
957  of additional safety or other data.   
958   
959  Q33.  If a sponsor continues to provide its investigational drug for treatment use under its 
960  IND to a patient who was enrolled in a clinical trial but who does not continue to 
961  meet inclusion criteria, is that considered expanded access (i.e., is the sponsor 
962  expected to make an expanded access submission to continue to provide the drug to 
963  that patient)? 
964   
965  In general, if a patient is already enrolled in a clinical trial (designed to further the development 
966  of or determine the safety and/or effectiveness of an investigational drug) and the patients 
967  results are to be included in the analysis of the investigational drug, the continued treatment of 
968  that patient with the investigational drug is not considered expanded access, even if the patient 
969  does not continue to meet all the study inclusion criteria or the patients treatment deviates from 
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970  the study protocol.  This is commonly known as a protocol exception and would be covered 
971  under the existing IND. 
972   
973  Q34.  If a sponsor provides its investigational drug for treatment use under its IND to a 
974  patient who does not meet inclusion criteria for their trial and is not enrolled in the 
975  trial, is that considered expanded access? 
976   
977  In general, if a patient is not enrolled in a clinical trial but is provided access to the 
978  investigational drug for the purposes of treating the patient, treatment of that patient with the 
979  investigational drug is considered expanded access to the investigational drug, and the 
980  requirements for expanded access apply. 
981   
982  Q35.  How can manufacturers and distributors comply with the requirement to make 
983  their expanded access policies readily available to the public? 
 984 
985  The enactment of the Cures Act added section 561A to the FD&C Act.28  This section requires a 
986  manufacturer or distributor of one or more investigational drugs for the diagnosis, monitoring, or 
987  treatment of one or more serious diseases or conditions to make its policy for evaluating and 
988  responding to expanded access requests submitted under section 561(b) of the FD&C Act  (i.e., 
989  expanded access policy) readily available to the public, such as by posting the policy on a 
990  publicly available website (e.g., the manufacturers website, the Reagan-Udall Foundation 
991  Expanded Access Navigator web page (see Q37)).29  Manufacturers and distributors of 
992  investigational medical devices are not required to comply with section 561A of the FD&C Act. 
993    
994  The expanded access policy must include all of the following:30 
995   
996    Contact information for the manufacturer or distributor to facilitate communication about 
997  expanded access requests submitted under section 561(b) of the FD&C Act 
998   
999    Procedures for submitting expanded access requests 
1000   
1001    The general criteria the manufacturer or distributor will use to evaluate individual 
1002  patients expanded access requests and for responses to such requests 
1003   
1004    The length of time the manufacturer or distributor expects will be needed to acknowledge 
1005  receipt of such requests 
1006   
 
28 See 21 U.S.C. 360bbb-0. 
 
29 See 21 U.S.C. 360bbb-0(a) and (b). 
 
30 See 21 U.S.C. 360bbb-0(c).   
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
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  Contains Nonbinding Recommendations 
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1007    A hyperlink or other reference to the clinical trial record containing information about 
1008  expanded access availability for the drug that is required to be submitted to 
1009  ClinicalTrials.gov 31  
1010   
1011  FDA recommends that the pharmaceutical company or the drug manufacturer that is developing 
1012  the drug for marketing make its expanded access policy publicly available, rather than the 
1013  distributor.  Posting the expanded access policy on its own website will fulfill the requirement of 
1014  making the policy available to the public.32  If a pharmaceutical company or the drug 
1015  manufacturer is developing multiple investigational drugs, it may have one general expanded 
1016  access policy that applies to all applicable products and should make such general policy 
1017  publicly available.  However, if it has different expanded access policies for different 
1018  investigational drugs, each expanded access policy should be made publicly available with 
1019  reference to the products to which the policy applies. 
1020   
1021  If a pharmaceutical company or the drug manufacturer that is developing the drug for marketing 
1022  makes its expanded access policy publicly available and mentions specific drugs for which 
1023  expanded access is available and provides a link to the relevant information on ClinicalTrials.gov 
1024  to comply with the requirements of the Cures Act, FDA does not intend to consider this to be 
1025  promotion of an investigational drug or evidence of a new intended use unless the posted policy 
1026  represents in a promotional context that the investigational new drug is safe or effective for a use 
1027  for which it is under investigation.33   
1028   
1029  Q36.  When is the manufacturer or distributor required to make its expanded access 
1030  policy publicly available?  
1031   
1032  FDARA amended section 561A(f) of the FD&C Act34 to require that the manufacturer or 
1033  distributor of investigational drugs for the diagnosis, monitoring, or treatment of one or more 
1034  serious diseases or conditions make the expanded access policy public and readily available by 
1035  one of the following timelines, whichever is earlier: 
1036   
1037    At the first initiation of a phase 2 or phase 3 study; or 
1038   
1039    Fifteen days after the drug receives a designation as a breakthrough therapy, fast track 
1040  product, or regenerative advanced therapy 
 
31 A reference to the record in ClinicalTrials.gov may not be available if the trial is not required to be registered at 
ClinicalTrials.gov.  In addition, if the party responsible for registering that clinical trial is not both the sponsor of the 
applicable trial and the manufacturer of the investigational drug product being studied, that responsible party is not 
required to submit information on the availability of its investigational drug product for expanded access.  For 
further information, refer to the Frequently Asked Questions section on the ClinicalTrials.gov website 
(https://clinicaltrials.gov/ct2/manage-recs/faq). 
 
32 See 21 U.S.C. 360bbb-0(b). 
 
33 See 21 CFR 201.128 and 21 CFR 312.7(a). 
 
34 See 21 U.S.C. 360bbb-0(f). 
 
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  Contains Nonbinding Recommendations 
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1041   
1042  FDA recommends that the pharmaceutical company or the drug manufacturer that is developing 
1043  the drug for marketing, rather than the distributor, make its expanded access policy publicly 
1044  available.  FDA interprets initiation of a phase 2 or phase 3 study to be when enrollment 
1045  begins.  At the initiation of the phase 2 or 3 trial, it is the responsibility of the pharmaceutical 
1046  company or the drug manufacturer that is developing the drug for marketing to identify whether 
1047  the investigational drug is intended to treat a serious disease or condition and to make the 
1048  expanded access policy public and readily available to comply with the requirement.  An FDA 
1049  designation of fast track, breakthrough therapy, or regenerative advanced therapy indicates that 
1050  the drug is intended to treat a serious disease or condition.  The requirement of making 
1051  expanded access policies public and readily available by the specified timelines does not 
1052  preclude posting the policies at an earlier point in time. 
1053   
1054  Q37.  Where can patients and health care providers get information about the availability 
1055  of drugs under expanded access?    
1056   
1057  Information about the availability of expanded access to an investigational drug may be  found 
1058  on the website of the relevant drug manufacturer or distributor.  The information may also be 
1059  found on other publicly available websites.  The Reagan-Udall Foundations (RUF)35 Expanded 
1060  Access Navigator website (https://navigator.reaganudall.org/expanded-access-navigator) has a 
1061  Company Directory web page (https://navigator.reaganudall.org/company-directory) that 
1062  includes (1) a list of pharmaceutical companies and drug manufacturers developing 
1063  investigational drugs for marketing and (2) information about the availability of their drugs 
1064  under expanded access (e.g., hyperlinks to the companys own publicly available website 
1065  describing its expanded access policy, contact information, and information on the expected time 
1066  frame for acknowledgement of such requests).   
1067   
1068  Information about the availability of investigational drugs under expanded access may also be 
1069  available at ClinicalTrials.gov under certain circumstances.  If the party responsible for 
1070  registering that trial is both the sponsor of the trial and the manufacturer of the investigational 
1071  drug product being studied, that responsible party is also required to submit certain information 
1072  on the availability of its investigational product for expanded access, including the type of 
1073  expanded access being offered, to ClinicalTrials.gov.36  This information on expanded access is 
1074  then included on the ClinicalTrials.gov website.  However, not all clinical trials must be 
1075  registered on ClinicalTrials.gov.  If information about expanded access availability for a 
1076  particular investigational drug is not included on ClinicalTrials.gov, physicians or patients may 
 
35 The Reagan-Udall Foundation for the Food and Drug Administration is an independent 501(c)(3) organization 
created by Congress to advance the mission of the FDA to modernize medical, veterinary, food, food ingredient, 
and cosmetic product development, accelerate innovation, and enhance product safety.  See 
https://reaganudall.org/about-us.  
 
36 See 42 CFR 11.28(a)(2)(ii)(H) and (c).  In general, a sponsor-investigator of a single patient IND who obtains a 
letter of authorization from another sponsor to cross-reference manufacturing information would not be considered 
responsible for submitting information on the availability of the product for expanded access on ClinicalTrials.gov 
because the sponsor-investigator is not the manufacturer of the investigational product.  
 
27 
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1077  wish to contact the sponsor (or manufacturer of the investigational drug, if different from the 
1078  sponsor) about possible availability.   
1079     
1080  Q38.  May treatment with two or more investigational drugs be requested and authorized 
1081  under a single expanded access IND or protocol, or may an individual patient 
1082  participate in more than one expanded access IND or protocol (e.g., be enrolled in 
1083  two different treatment INDs)? 
1084   
1085  Yes.  A single expanded access IND or protocol may involve treatment with more than one 
1086  investigational drug, and a patient may be enrolled in more than one expanded access IND or 
1087  protocol.  When expanded access to two or more investigational drugs is appropriate to treat a 
1088  single disease and the relevant criteria are met, it is most efficient to provide expanded access to 
1089  the multiple investigational drugs under a single expanded access IND or protocol, rather than to 
1090  provide expanded access by having a patient enroll in two or more separate expanded access 
1091  INDs or protocols (one for each drug).  Management of the patients disease, treatment, and the 
1092  collection of information about the therapy is likely to be better coordinated under a single 
1093  expanded access IND or protocol. 
1094   
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  Contains Nonbinding Recommendations 
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1095  APPENDIX:  INFORMED CONSENT TEMPLATE FOR INDIVIDUAL PATIENT 
1096  EXPANDED ACCESS1 
1097   
1098  Disclaimer:  The purpose of this informed consent template is to assist investigators with 
1099  preparing an informed consent document for the treatment of a single patient with an 
1100  investigational drug under the expanded access program.  However, this template is not a 
1101  substitute for the Federal Food, Drug, and Cosmetic Act (FD&C Act) or the Code of Federal 
1102  Regulations (CFR) and does not necessarily contain all information required to ensure 
1103  compliance in a given situation.  Investigators are responsible for ensuring that the informed 
1104  consent requirements of 21 CFR part 50 are met (21 CFR 312.305(c)(4)) unless one of the 
1105  exceptions found in part 50 applies. 
1106   
1107  1.  Introduction 
1108   
1109  Provide the following information: 
1110   
1111    The name of the disease or condition for which the investigational drug will be provided 
1112  for treatment. 
1113   
1114    A statement that the patient does not have any alternative Food and Drug Administration 
1115  (FDA)-approved medical product (e.g., drug/biologic)2 available to them for treatment. 
1116   
1117    The name of the investigational drug/biologic.  
1118   
1119    An explanation that the product is investigational, is not approved by FDA as safe and 
1120  effective, and that the treatment will be considered an experimental treatment.  A statement 
1121  that the treatment may only proceed under FDAs expanded access program, with FDA 
1122  authorization.   
1123    
1124    A statement that the patients participation in the program is voluntary and that the patient 
1125  may change their decision to participate.  Provide the name of the person the patient may 
1126  contact in case the patient changes their decision. 
1127   
1128    A statement that refusal to participate will involve no penalty or loss of benefits to which 
1129  the patient is otherwise entitled and that the patient may discontinue participation at any 
1130  time without penalty or loss of benefits to which the patient is otherwise entitled. 
1131   
1132    A recommendation to read the form carefully and discuss with others before making any 
1133  decision. 
1134   
1135    The name of the staff whom the patient can contact if the patient has questions. 
1136     
 
1 This template consists of instructions (in italics) to create the template and includes some example language (below 
the instructions) for each element.  Once the template is finalized, delete the instructions from the template. 
 
2 In these examples, drug is used as a reference.  In your document, use drug or biologic, as appropriate.  
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1137  Examples: 
1138   
1139    You are diagnosed with disease X. 
1140   
1141    For your condition, there is no drug approved by the Food and Drug Administration (FDA) 
1142  for use in routine medical care in the United States.  OR The Food and Drug 
1143  Administration (FDA)-approved drug or drugs available for your treatment did not work 
1144  for you.  OR You cannot tolerate the side-effects of the drug or drugs approved by the 
1145  Food and Drug Administration (FDA) for treatment of your condition.  
1146   
1147    Your doctor would like to treat you with drug Y. 
1148   
1149    Drug Y is an investigational drug.  It is NOT approved by FDA for the treatment of your 
1150  disease.  However, for your case, FDA authorized Dr. Z to treat you with the 
1151  investigational drug Y under FDAs expanded access program, OR Dr. Z has requested or 
1152  will request FDAs permission to treat you with the investigational drug Y under FDAs 
1153  expanded access program. 
1154   
1155    Whether or not you take this investigational drug is up to you.  If you choose not to receive 
1156  the investigational drug, it will not result in penalty or loss of benefits to which you are 
1157  otherwise entitled.  
1158   
1159    You can choose to take the investigational drug now but change your mind later.  Tell your 
1160  doctor right away about your decision if you change your mind later.  It will not result in 
1161  any penalty or loss of benefits to which you are otherwise entitled.   
1162   
1163  Read this document carefully.  You may want to discuss your options with your doctors, family, 
1164  friends, and others before deciding on whether to receive the treatment.  Please ask questions about 
1165  anything you do not understand.  You will find a contact information table at the end of the 
1166  document. 
1167   
1168  2.  What are the potential benefits of receiving the treatment? 
1169   
1170  List potential benefits of the investigational drug/biologic, if any.  Include a statement to reflect 
1171  that the anticipated benefit may be uncertain or that the disease may worsen with the treatment. 
1172   
1173  Examples: 
1174   
1175    There is a chance that the investigational drug Y may (1) improve . . ., (2) reduce . . ., etc.  
1176  However, there is no guarantee that it will happen in your case. 
1177   
1178    Dr. Z would like to treat you with the investigational drug because she believes that it may 
1179  benefit you.  However, there is no guarantee that you will benefit from this investigational 
1180  treatment.  It is possible that you will receive no benefit other than receiving the standard 
1181  care (regularly seen by a doctor, evaluated for your condition, etc.) associated with 
1182  receiving this treatment, or it could worsen your condition. 
  30  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
1183    We do not know if this investigational drug will help you.  Your condition may get better, 
1184  stay the same, or possibly get worse.  
1185   
1186  3.  What are the potential risks of this treatment?  
1187    
1188  Provide a list of reasonably foreseeable risks or side effects of the investigational drug/biologic.  
1189  Include frequency, if known.  Include information on risks that are more likely to occur and those 
1190  that are serious.  Discuss any potential risks from the medical procedures necessary to administer 
1191  the drug/biologic, if appropriate.  Provide specific instructions for whom the patient should 
1192  contact if experiencing serious side effects. 
1193   
1194  Examples: 
1195   
1196    There is a risk that the investigational drug Y makes your condition worse. 
1197   
1198    The following are serious side effects that have been reported for the investigational 
1199  drug Y:  
1200   
1201    Serious injury to your kidneys that could lead to dialysis 
1202    Significant disability  
1203   
1204    The following are side effects that are more likely to occur:  
1205   
1206    Vomiting 
1207    Diarrhea 
1208    Lack of appetite 
1209   
1210    The investigational drug needs to be administered via [W] route of administration during 
1211  [X procedure].  Risks of [X procedure] may include headache, pain or numbness in the legs 
1212  and lower back, and bleeding into the spinal canal where the main nerve that goes down 
1213  your back is located.  The doctors who will perform the [X procedure] are specifically 
1214  trained and very experienced in performing this procedure. 
1215   
1216    There may be side effects of the investigational drug Y that we do not know about.   
1217   
1218    These effects could be immediate and short term, or your future health may be 
1219  affected in ways that we currently do not understand. 
1220   
1221    If you experience side effects listed above or any other adverse effects, contact the staff 
1222  listed in the contact information table. 
1223   
1224    In case of emergency, contact the staff listed in the contact information table or get 
1225  emergency medical help immediately. 
1226   
1227     
  31  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
1228  4.  How long will you be treated with the investigational drug/biologic? 
1229   
1230  Describe the length of time the treatment will last (e.g., hours, days, weeks, months, years, or until 
1231  a certain event), as well as long-term follow-up, if appropriate.  Include number of visits or 
1232  treatments as applicable. 
1233   
1234  Examples: 
1235   
1236    You will receive the investigational drug approximately every 2 months (68 weeks) for up 
1237  to 1 year. 
1238   
1239    After you complete this treatment, you will still need to come to the clinic for follow-up 
1240  visits for at least the next year. 
1241   
1242  5.   If you do not accept this treatment, what are the other choices? 
1243   
1244  Explain that to provide an investigational drug/biologic under expanded access, the doctor should 
1245  determine there is no available comparable or satisfactory alternative therapy to diagnose, 
1246  monitor, or treat the disease or condition and that the doctor has made such a determination.   
1247   
1248  Examples: 
1249   
1250    Dr. Z determined that there are no other drugs approved to treat your disease. 
1251    
1252    There are no other drugs approved for your disease or clinical trials that you could enroll 
1253  in.  However, you can discuss other options with Dr. Z, such as not taking any 
1254  investigational drug.  
1255   
1256  6.  What are the procedures associated with the treatment? 
1257   
1258  Describe in chronological order the procedures that are necessary as part of receiving the 
1259  treatment.  Use a table, if needed, to organize the information.  If describing every procedure will 
1260  make the document too lengthy or detailed, include the information as an addendum. 
1261   
  32  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
1262  Examples: 
1263   
Date (chronological  Description of therapy;  Duration 
order)/Frequency  dose, route of 
administration 
Approximately every 2  Administer drug Y in  90 minutes 
months (i.e., 68 weeks)  your vein (10 mg/kg) 
1264   
Date (chronological  Procedure for  Purpose 
order)/Frequency  assessment 
Day 1  Collect blood samples  Routine laboratory 
tests 
Month 4  CT scan to take a picture  If there is any change 
of your X   in the size of the tumor 
1265   
1266  7.  Can your doctor stop the treatment without your permission? 
1267   
1268  Provide a list of reasons for which the doctor may stop the treatment without the patients consent.  
1269  Explain that the patient will be notified if this happens. 
1270   
1271  Examples: 
1272   
1273  In certain situations, your doctor may need to stop the investigational drug without your permission 
1274  if: 
1275   
1276    Your condition gets worse. 
1277   
1278    The investigational drug is no longer safe for you. 
1279   
1280    New information suggests that this investigational drug does not work. 
1281   
1282    You become pregnant. 
1283   
1284    New information suggests that another investigational drug is better. 
1285   
1286    FDA tells your doctor that your treatment should be stopped.  This may happen if FDA 
1287  receives new information about the investigational drug that your doctor may not know 
1288  because it is confidential.  
1289   
1290    The investigational drug is no longer available from the manufacturer. 
1291   
1292  If your doctor stops your treatment, we will tell you as soon as possible. 
1293   
1294  8.  What is the cost of the treatment?  
1295   
1296  Explain that the patient may incur expenses for the treatment with the investigational 
1297  drug/biologic.  Explain to the best of your knowledge what costs the patient is likely to need to 
  33  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
1298  cover and that insurance may not cover all costs.  Because the coverage of treatment with an 
1299  investigational drug/biologic could be complex, it may be appropriate to recommend that the 
1300  patient consult their insurer about reimbursement before initiating the treatment.  
1301   
1302  Examples: 
1303   
1304    You or your insurance company will be charged for the treatment.  You will be responsible 
1305  for any costs your insurance does not cover.  Contact your insurance company if you have 
1306  any questions about these costs or what out-of-pocket expenses you may have. 
1307   
1308    The [INSTITUTION] will pay for the treatment, including treatment of any side effect, 
1309  adverse reaction, illness, or injury to you resulting from the treatment. 
1310   
1311    If you receive this treatment, your insurance may not cover the cost of some of the tests and 
1312  visits to see your doctor that are related to receiving this investigational drug.  Contact your 
1313  insurance company to learn more about the coverage if you decide to receive the treatment. 
1314     
1315    Dr. Zs research funds will pay for some items and services related to your treatment.  
1316  However, you and your insurer will be responsible for the remaining costs.  Please contact 
1317  the person listed in the contact information table to learn more about the coverage by 
1318  research fund. 
1319   
1320    If you need financial assistance to cover the cost of your treatment, please contact the 
1321  staff listed in the contact information table for more information. 
1322   
1323  9.  What happens if you are injured from the treatment? 
1324   
1325  Provide the following information about treatment-related injuries: 
1326   
1327  Describe any compensation and medical treatments available to the patient if injury occurs. 
1328   
1329  Provide the names and contact information of the staff whom the patient should contact if further 
1330  information is needed.  The available compensation and medical treatments may vary depending 
1331  on the medical circumstances of the patient or the policies of the institution.   
1332   
1333  Examples:  
1334   
1335    If this treatment results in an injury, [INSTITUTION] will provide you with medical care. 
1336   
1337    Cost for care related to treatment-related injuries will be billed in the ordinary manner to 
1338  you or your insurance company. 
1339   
  34  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
1340  10.  Who may see, use, or share your health information? 
1341    
1342  Provide information about the confidentiality policy of the clinic/hospital/sponsor OR include the 
1343  list of your policies.  Include a statement that the data from this investigational treatment will be 
1344  shared with FDA and note the possibility that FDA may inspect the records related to the 
1345  investigational treatment.  
1346   
1347  Examples: 
1348   
1349    If you receive this investigational drug, certain information about your treatment may be 
1350  shared with the following entities, but every effort will be made to keep your identity 
1351  private:  
1352    
1353    The manufacturer of the drug 
1354    The Food and Drug Administration  
1355    The institutional review board 
1356   
1357    In addition, the following people/institutions may have access to your identity and 
1358  information about your use of the investigational drug: 
1359   
1360    Your insurance company or health benefits program 
1361    The clinic staff directly involved in your medical care  
1362   
1363    If you stop treatment, information that was already collected may still be shared with 
1364  FDA.  
1365   
1366    If the result of this treatment is published, your personal identifying information will not 
1367  be used. 
1368   
1369    Although it is unlikely to happen, there is a possibility that your personal information will 
1370  be disclosed accidentally.     
1371   
1372  11.  What other important information do you need to know? 
1373   
1374  Provide a list of other important information not covered in the sections above. 
1375   
1376  Examples:  
1377   
1378    During your treatment, if we learn any new information about the risks or benefits of the 
1379  investigational drug Y, Dr. Z will let you know.  
1380   
1381    You will not receive any payment as compensation to take the investigational drug Y. 
1382   
1383    You may review our web-based, interactive educational program for patients with your 
1384  disease at the following link: [insert URL link]. 
  35  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
1385    Whom should I contact? 
1386   
1387  Provide consolidated contact information, as appropriate.  If the contact information changes at 
1388  any time, provide the new contact information to the patient. 
1389   
1390  Examples: 
1391   
Name  Contact information  For questions about... 
(Name of the doctor/clinical  (Phone number, email,  (Provide a consolidated list of 
staff/board/IRB/advocate,  or address, etc., as  issues for which a patient may 
etc.)  appropriate)  have questions) 
Name of the staff  Phone:    Treatment, including any injury 
from the treatment  
E-mail: 
  Emergency contact 
Address: 
information, including 24-hour 
contact information, if 
appropriate 
Name of the staff/board/IRB  Phone:    Administrative concerns (e.g., 
patient rights, billing) 
E-mail: 
Address: 
1392    
1393   
1394  12.  Permission Signatures 
1395   
1396  Include the list of signatories who should provide consent for the treatment.  Provide instructions 
1397  for the assent process, if you have any specific policies.  
1398   
1399  Examples: 
1400   
1401  Your signature below provides your consent to take part in this investigational treatment. 
1402   
1403     
1404  Name of patient 
1405   
1406         
1407  Signature of patient                 Date              Time 
1408   
1409     
1410  Name of legally authorized representative (if needed) 
1411   
  36  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
1412         
1413  Signature of legally authorized representative (if needed)  Date              Time 
1414   
1415     
1416  Legally authorized representatives relationship to patient (if needed) 
1417   
1418  Add any other signatures, following your institutional policy. 
  37