[Federal Register Volume 81, Number 48 (Friday, March 11, 2016)]
[Notices]
[Pages 12908-12910]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-05491]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2015-D-0268]


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Guidance for Industry 
on Individual Patient Expanded Access Applications: Form FDA 3926

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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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 April 
11, 2016.

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-New and 
title ``Individual Patient Expanded Access Applications: Form FDA 
3926.'' Also include the FDA docket number found in brackets in the 
heading of this document.

FOR FURTHER INFORMATION CONTACT: FDA PRA Staff, Office of Operations, 
Food and Drug Administration, 8455 Colesville Rd., COLE-14526, Silver 
Spring, MD 20993-0002, [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--NEW

I. Background

    In the Federal Register of February 10, 2015 (80 FR 7318), FDA 
announced the availability of a draft guidance for industry entitled 
``Individual Patient Expanded Access Applications: Form FDA 3926.'' In 
the draft guidance, FDA provided draft Form FDA 3926 (Individual 
Patient Expanded Access--Investigational New Drug Application (IND)) at 
Appendix 1 and described this draft form, which FDA stated it intended 
to make available for licensed physicians to use for expanded access 
requests for individual patient INDs as an alternative to Form FDA 1571 
(Investigational New Drug Application (IND)).
    As described in the final guidance, Form FDA 3926 provides a 
streamlined means to request expanded access to an investigational drug 
outside of a clinical investigation, or to an approved drug where 
availability is limited by a risk evaluation and mitigation strategy 
(REMS), for 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. Form FDA 3926 may also be used for certain 
followup submissions to an individual patient expanded access IND.
    FDA may permit expanded access to an investigational new drug 
outside of a clinical investigation, or to an approved drug where 
availability is limited by a REMS, for an individual patient when the 
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. 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.
    Section 312.305(b) sets forth the submission requirements for all 
types of expanded access requests. 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 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. Form FDA 1571 is 
currently used by sponsors for all types of IND submissions to meet the 
requirements in Sec.  312.23(a). FDA intends to accept submission of a 
completed Form FDA 3926 to comply with the IND submission requirements 
in Sec. Sec.  312.23, 312.305(b), and 312.310(b). FDA intends to 
consider 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, the following 
information would be submitted to FDA by those using Form FDA 3926:
     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 12909]]

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. Alter na tively, 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 intends 
to accept Form FDA 3926 for certain followup/additional submissions, 
which include the following: Initial Written IND Safety Report (Sec.  
312.32(c)); Follow-up 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 February 10, 2015 (80 FR 7318), FDA 
published a 60-day notice requesting public comment on the proposed 
collection of information. Twelve comments were received. However, FDA 
received no comments concerning the accuracy of FDA's estimate of the 
burden of the proposed collection of information. FDA received several 
comments on ways to enhance the quality, utility, and clarity of FDA 
Form 3926 through, for example, the addition of instructions for 
completing the form and use of the form for certain followup 
submissions.
    (Comment 1) Five comments requested instructions, clarification, or 
directions concerning the use and submission of Form FDA 3926.
    (Response) FDA updated instructions based on information originally 
included in the draft guidance that will be provided in conjunction 
with final Form FDA 3926. Clarifying language on form fields has been 
added to the instructions and the guidance.
    (Comment 2) One comment asked for clarification regarding Field 1 
of Form FDA 3926 to indicate that the requesting physician should 
provide this information (not the patient).
    (Response) Clarification on Field 1 has been added to the form 
instructions to state that the patient need not initial the form. This 
is to indicate that the requesting physician should enter the patient's 
initials.
    (Comment 3) One comment stated that the information requested in 
Field 3 of draft Form FDA 3926 could become lengthy to complete and 
asked if a PDF could be attached to the form to provide this 
information.
    (Response) This information is now requested in Field 5. Field 5 
has been enlarged to accommodate more handwritten information. The 
space also has been updated to allow expansion when information is 
entered electronically in the fillable PDF. Clarifying language has 
been added to the form and instructions.
    (Comment 4) Three comments requested electronic submission 
capability to expedite applications.
    (Response) FDA is determining whether electronic submissions are 
feasible. FDA intends to provide additional information via its Web 
site should this become an option.
    (Comment 5) Several comments concerned the use of FDA Form 3926 for 
followup submissions. One comment suggested that FDA develop a new form 
for followup submissions (rather than requiring the use of Form FDA 
1571). Three comments asked that instructions be developed for ongoing 
patient reporting (i.e., followup submissions).
    (Response) FDA has revised the guidance, instructions, and Form FDA 
3926 so that the form may be used instead of Form FDA 1571 for certain 
followup submissions to an existing single patient expanded access IND. 
Form FDA 3926, the instructions, and the guidance identify the types of 
followup submissions that qualify and provide additional information on 
how to use Form FDA 3926 for such submissions.

II. Burden Estimate

    As discussed previously in this document, Form FDA 3926 will be 
available for licensed physicians to use as a streamlined means to 
request expanded access to an investigational drug outside of a 
clinical investigation, or to an approved drug where availability is 
limited by a REMS, for 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, and to submit certain followup reports. 
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, 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. Form FDA 1571 is currently used by sponsors for all 
types of IND submissions. However, FDA is concerned that physicians 
requesting expanded access for an individual patient may have 
encountered difficulty in completing Form FDA 1571 and the associated 
documents because the form is not tailored to requests for individual 
patient expanded access.
    The submission requirements for all types of expanded access 
requests for investigational drugs are provided under Sec.  312.305(b) 
of FDA's expanded access regulations. Additional submission 
requirements for individual

[[Page 12910]]

patient expanded access requests are provided under Sec.  312.310(b), 
and the requirements for requesting individual patient expanded access 
for emergency use are provided under Sec.  312.310(d). FDA currently 
has OMB approval under control number 0910-0014 for individual patient 
expanded access information collection under Sec. Sec.  312.305(b), 
312.310(b), and 312.310(d). The submission requirements concerning the 
use of Form FDA 3926 for certain followup reports are provided under 
Sec. Sec.  312.32(c), 312.32(d), 312.33, 312.310(c)(2), 312.30, 312.41, 
and 312.42(e).
    The estimates for ``number of respondents,'' ``number of responses 
per respondent,'' and ``total annual responses'' were obtained from the 
Center for Drug Evaluation and Research (CDER) reports and data 
management systems 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 provided by CDER and other Department of Health and 
Human Services personnel who are familiar with preparing and reviewing 
expanded access submissions by practicing physicians.
    Based on data for the number of submissions to FDA during 2011, 
2012, and 2013, we originally estimated that approximately 790 licensed 
physicians would use Form 3926 to submit 1.46 requests per physician 
(respondent) for individual patient expanded access, for a total of 
1,153 responses annually. In response to comments received, FDA 
clarifies in the final guidance and in the form instructions that 
licensed physicians may also use Form FDA 3926 for certain followup 
submissions. Based on data for the number of followup submissions 
during 2011, 2012, and 2013, FDA estimates that about 790 physicians 
will each use Form FDA 3926 to submit 1.57 followup submissions per 
physician, for approximately 1,241 followup 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. Under OMB control number 0910-0014, 
FDA currently has OMB approval of 17,592 hours for these submissions. 
The use of FDA Form 3926 will reduce the current burden by 15,797 
hours.
    FDA estimates the burden of this collection of information as 
follows:

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


    Dated: March 8, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-05491 Filed 3-10-16; 8:45 am]
 BILLING CODE 4164-01-P