[Federal Register Volume 84, Number 74 (Wednesday, April 17, 2019)]
[Notices]
[Pages 16022-16023]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-07711]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2018-N-3758]


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Individual Patient 
Expanded Access Applications

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is announcing that a 
proposed collection of information has been submitted to the Office of 
Management and Budget (OMB) for review and clearance under the 
Paperwork Reduction Act of 1995.

DATES: Fax written comments on the collection of information by May 17, 
2019.

ADDRESSES: To ensure that comments on the information collection are 
received, OMB recommends that written comments be faxed to the Office 
of Information and Regulatory Affairs, OMB, Attn: FDA Desk Officer, 
Fax: 202-395-7285, or emailed to [email protected]. All 
comments should be identified with the OMB control number 0910-0814. 
Also include the FDA docket number found in brackets in the heading of 
this document.

FOR FURTHER INFORMATION CONTACT: JonnaLynn Capezzuto, Office of 
Operations, Food and Drug Administration, Three White Flint North, 10A-
12M, 11601 Landsdown St., North Bethesda, MD 20852, 301-796-3794, 
[email protected].

SUPPLEMENTARY INFORMATION: In compliance with 44 U.S.C. 3507, FDA has 
submitted the following proposed collection of information to OMB for 
review and clearance.

Guidance for Industry on Individual Patient Expanded Access 
Applications: Form FDA 3926

OMB Control Number 0910-0814--Extension

    This information collection supports Agency regulations, associated 
guidance, and Form FDA 3926 concerning individual patient expanded 
access. Individual patient expanded access allows an individual patient 
who has a serious or immediately life-threatening disease or condition 
and there is no comparable or satisfactory alternative therapy to 
diagnose, monitor, or treat the disease or condition, the use of an 
investigational new drug (IND) outside of a clinical investigation, or 
the use of an approved drug where availability is limited by a risk 
evaluation and mitigation strategy. When applicable criteria in Sec.  
312.305(a) (21 CFR 312.305(a)) (which apply to all types of expanded 
access) and the criteria in Sec.  312.310(a) (21 CFR 312.310(a)) (which 
apply specifically to individual patient expanded access, including for 
emergency use) are met, FDA may permit expanded access.
    Section 312.305(b) sets forth the submission requirements for all 
types of expanded access requests. To assist respondents with 
requirements in Sec.  312.305, we developed Form FDA 3926 (Individual 
Patient Expanded Access Investigational New Drug Application) and the 
guidance document entitled, ``Individual Patient Expanded Access 
Applications: Form FDA 3926,'' which are available at https://www.fda.gov/AboutFDA/ReportsManualsForms/Forms/default.htm and https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm432717.pdf, respectively.
    The physician may satisfy some of the submission requirements by 
referring to information in an existing IND, ordinarily the one held by 
the investigational drug's manufacturer, if the physician obtains 
permission from that IND holder. If permission is obtained, the 
physician should then provide to FDA a letter of authorization (LOA) 
from the existing IND holder that permits FDA to reference that IND.
    One of the requirements under Sec.  312.305(b)(2) is that a ``cover 
sheet'' must be included ``meeting the requirements of Sec.  
312.23(a).'' This provision applies to several types of submissions 
under part 312 (21 CFR part 312), ranging from commercial INDs under 
Sec.  312.23 that involve large groups of patients enrolled in clinical 
trials to requests from physicians to use an investigational drug for 
an individual patient. Sponsors currently use Form FDA 1571 for all 
types of IND submissions to meet the requirements in Sec.  312.23(a).
    Concerned that physicians requesting expanded access for an 
individual patient may encounter difficulty in completing Form FDA 1571 
and the associated documents because the form is not tailored to 
requests for individual patient expanded access, we developed Form FDA 
3926 to comply with the IND submission requirements in Sec. Sec.  
312.23, 312.305(b), and 312.310(b). Form FDA 3926 provides a 
streamlined means to request expanded access and is available for 
licensed physicians. FDA considers a completed Form FDA 3926 with the 
box in Field 10 checked and the form signed by the physician to be a 
request in accordance with Sec.  312.10 for a waiver of any additional 
requirements in part 312 for an IND submission, including additional 
information currently provided in Form FDA 1571 and Form FDA 1572 
(Statement of Investigator, which provides the identity and 
qualifications of the investigator conducting the clinical 
investigation).
    Under Sec.  312.310(d), in an emergency situation that requires the 
patient to be treated before a written submission can be made, the 
request to use the investigational drug for individual patient expanded 
access may be made by telephone (or other rapid means of communication) 
to the appropriate FDA review division. Authorization of the emergency 
use may be given by an FDA official over the telephone, provided the 
physician explains how the expanded access use will meet the 
requirements of Sec. Sec.  312.305 and 312.310 and agrees to submit an 
expanded access application within 15 working days of FDA's initial 
authorization of the expanded access use (Sec.  312.310(d)). The 
physician may choose to use Form FDA 3926 for the expanded access 
application.
    As explained in the instructions for Form FDA 3926 and discussed in 
the guidance document, the following information is submitted to FDA:
     Initials for the patient and date of submission.
     Type of submission (initial or followup submission).
     Clinical information, including indication, brief clinical 
history of the patient (age, gender, weight, allergies, diagnosis, 
prior therapy, response to prior therapy), and the reason for

[[Page 16023]]

requesting the proposed treatment, including an explanation of why the 
patient lacks other therapeutic options.
     Treatment information, including the investigational 
drug's name and the name of the entity supplying the drug (generally 
the manufacturer), the applicable FDA review division (if known), and 
the treatment plan. This should include the planned dose, route and 
schedule of administration, planned duration of treatment, monitoring 
procedures, and planned modifications to the treatment plan in the 
event of toxicity.
     LOA, generally obtained from the entity that is the 
sponsor of the IND (e.g., commercial sponsor/drug manufacturer) being 
referenced, if applicable.
     Physician's qualification statement. An appropriate 
statement includes medical school attended, year of graduation, medical 
specialty, State medical license number, current employment, and job 
title. Alternatively, the relevant portion of the physician's 
curriculum vitae may be attached.
     Physician's contact information, including name, physical 
address, email address, telephone number, facsimile number, and 
physician's IND number, if previously issued by FDA.
     Contents of submission (for followup/additional 
submissions), including the type of submission being made. FDA accepts 
Form FDA 3926 for certain followup/additional submissions, which 
include the following: Initial written IND safety report (Sec.  
312.32(c)); followup to a written IND safety report (Sec.  312.32(d)); 
annual report (Sec.  312.33); summary of expanded access use (treatment 
completed) (Sec.  312.310(c)(2)); change in treatment plan (Sec.  
312.30); general correspondence or response to FDA request for 
information (Sec.  312.41); and response to clinical hold (Sec.  
312.42(e)).
     Request for authorization to use Form FDA 3926 for 
individual patient expanded access application.
     Signature of the physician certifying that treatment will 
not begin until 30 days after FDA receives the completed application 
and all required material unless the submitting physician receives 
earlier notification from FDA that the treatment may proceed. The 
physician agrees not to begin or continue clinical investigations 
covered by the IND if those studies are placed on clinical hold. The 
physician also certifies that informed consent will be obtained in 
compliance with Federal requirements (including FDA's regulations in 21 
CFR part 50) and that an institutional review board (IRB) that complies 
with all Federal requirements (including FDA's regulations in 21 CFR 
part 56) will be responsible for initial and continuing review and 
approval of the expanded access use. The physician also acknowledges 
that in the case of an emergency request, treatment may begin without 
prior IRB approval, provided the IRB is notified of the emergency 
treatment within 5 working days of treatment. The physician agrees to 
conduct the investigation in accordance with all other applicable 
regulatory requirements.
    In the Federal Register of November 7, 2018 (83 FR 55723), FDA 
published a 60-day notice requesting public comment on the proposed 
collection of information. No comments were received.
    FDA estimates the burden of this collection of information as 
follows:

                                                     Table 1--Estimated Annual Reporting Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                         Number of
 Guidance on individual patient expanded access  applications: Form     Number of      responses per     Total annual    Average burden    Total hours
                              FDA 3926                                 respondents       respondent       responses       per response
--------------------------------------------------------------------------------------------------------------------------------------------------------
Expanded access submission elements included in Form FDA 3926......             790             3.03            2,394   0.75 (45 mins.)           1,795
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.

    Based on a review of the information collection, we are retaining 
the currently approved burden estimate. The estimates for ``number of 
respondents,'' ``number of responses per respondent,'' and ``total 
annual responses'' were obtained from reports and data management 
systems from the Center for Drug Evaluation and Research (CDER) and 
from other sources familiar with the number of submissions received for 
individual patient expanded access use under part 312. The estimates 
for ``average burden per response'' were based on information CDER 
provided and personnel of the U.S. Department of Health and Human 
Services familiar with preparing and reviewing expanded access 
submissions by practicing physicians.
    Based on data from the Document Archiving, Reporting, and 
Regulatory Tracking System for the number of submissions to FDA using 
FDA Form 3926 during fiscal years 2015, 2016, and 2017, we estimate 
that approximately 790 licensed physicians would use FDA Form 3926 to 
submit 1.46 requests per physician (respondent) for individual patient 
expanded access, for a total of 1,153 responses annually. Based on 
these estimates, FDA calculates the total annual responses to be 2,394 
(1,153 requests for individual patient expanded access and 1,241 
followup submissions) by 790 physicians for an average of 3.03 
responses per respondent. FDA estimates the average burden per response 
to be 45 minutes (0.75 hour). Based on this estimate, FDA calculates 
the total burden to be 1,795 hours.

    Dated: April 11, 2019.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2019-07711 Filed 4-16-19; 8:45 am]
 BILLING CODE 4164-01-P


