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 Department of Health and Human Services Food and Drug Administration 21 CFR Part 312
[Docket No. FDA-2015-D-0268]
 AGENCY: Food and Drug Administration, HHS.
 ACTION: Notice of draft guidance.
 SUMMARY: The Food and Drug Administration (FDA or the Agency) is announcing the availability of a draft guidance for industry entitled “Individual Patient Expanded Access Applications: Form FDA 3926.” The draft guidance provides for public comment and describes draft Form FDA 3926 (Individual Patient Expanded Access—Investigational New Drug Application (IND)), which, when finalized, FDA intends to make available for licensed physicians to use for expanded access requests for individual patient INDs. Individual patient expanded access allows for the use of an investigational drug outside of a clinical trial 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. When finalized, draft Form FDA 3926 is intended to provide a streamlined alternative for submitting an Investigational New Drug Application (IND) for use in cases of individual patient expanded access.
 DATES: February 10, 2015. Although you can comment on any guidance at any time (see 21 CFR 10.115(g)(5)), to ensure that the Agency considers your comment on this draft guidance before it begins work on the final version of the guidance, submit either electronic or written comments on the draft guidance by April 13, 2015. Submit either electronic or written comments concerning the collection of information proposed in the draft guidance by April 13, 2015.
 ADDRESSES: Submit written requests for single copies of the draft guidance to the Division of Drug Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10001 New Hampshire Ave., Hillandale Building, 4th Floor, Silver Spring, MD 20993, or to the Office of Communication, Outreach and Development, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, MD 20993-0002. Send one self-addressed adhesive label to assist that office in processing your requests. See the 
                        **SUPPLEMENTARY INFORMATION**
                         section for electronic access to the draft guidance document. Submit electronic comments on the draft guidance to 
                        *http://www.regulations.gov.*
                         Submit written comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
 FOR FURTHER INFORMATION CONTACT: Lori Bickel, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 6353, Silver Spring, MD 20993-0002, 301-796-0210; or Stephen Ripley, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-0002, 240-402-7911.


SUPPLEMENTARY INFORMATION:  I. Background FDA is announcing the availability of a draft guidance for industry entitled “Individual Patient Expanded Access Applications: Form FDA 3926.” The draft guidance provides draft Form FDA 3926 for public comment. When finalized, draft Form FDA 3926 will be available for licensed physicians to use for expanded access requests for individual patient INDs as an alternative to Form FDA 1571 (Investigation New Drug Application (IND)). On August 13, 2009, FDA published a final rule (74 FR 40900, August 13, 2009) to amend its IND regulations by removing the certain sections of part 312 (21 CFR part 312) on treatment use of investigational drugs and adding subpart I of part 312 on expanded access (part 312, subpart I). Subpart I describes the following categories of expanded access:
                    ( print page 7319) Expanded access for individual patients, including for emergency use;
                Expanded access for intermediate-size patient populations (smaller than those typical of a treatment IND or treatment protocol); and
                Expanded access through a treatment IND or treatment protocol (designed for use in larger patient populations). The final rule was, among other things, intended to increase awareness and knowledge of expanded access programs and the procedures for obtaining investigational drugs for treatment use for patients who have serious or immediately life-threatening diseases or conditions who lack therapeutic alternatives. The final rule was also intended to facilitate the availability, when appropriate, of investigational new drugs for treatment use, while protecting patient safety and avoiding interference with the development of investigational drugs for marketing under approved applications. The draft guidance is intended to address the submission of draft Form FDA 3926, when finalized, for a new individual patient expanded access IND by a licensed physician. For information on expanded access in general, including how to submit an expanded access protocol to an existing IND, see FDA's draft guidance for industry “Expanded Access to Investigational Drugs for Treatment Use—Qs and As” (available at 
                    *http://www.fda.gov/​Drugs/​GuidanceComplianceRegulatoryInformation/​Guidances/​default.htm*). FDA may permit expanded access to an investigational new drug for an individual patient when the applicable criteria in § 312.305(a), which pertains to all types of expanded access, and the criteria in § 312.310(a), which pertains to individual patient expanded access, including in an emergency, 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 manufacturer, if the physician obtains permission from that IND holder. If permission is obtained, the physician should then provide 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 expanded access uses. One of the requirements under § 312.305(b)(2) is that a “cover sheet” must be included “meeting the requirements of § 312.23(a).” This provision applies to several types of submissions under part 312, ranging from commercial INDs under § 312.23 involving large groups of patients enrolled in clinical trials to requests from licensed physicians to use an investigational drug for an individual patient. FDA is concerned that its goal of facilitating access to drugs for individual patient treatment use may have been complicated by difficulties experienced by physicians in submitting Form FDA 1571 (currently used by sponsors for all types of IND submissions) including associated documents, which is not tailored to requests for individual patient expanded access. In an effort to streamline the submission process for individual patient expanded access INDs, FDA intends to make draft Form FDA 3926 available, when finalized, for licensed physicians to request expanded access to an investigational drug outside of a clinical trial for an individual patient who has a serious or immediately life-threatening disease or condition and for whom there is no comparable or satisfactory alternative therapy to diagnose, monitor, or treat the disease or condition (
                    *i.e.,*
                     for individual patient expanded access, including in emergencies). Draft Form FDA 3926 is shorter than Form FDA 1571 and requests the following information: (1) Patient's initials and date of submission; (2) clinical information; (3) treatment information; (4) LOA from the investigational drug's manufacturer, if applicable; (5) physician's qualifications; (6) physician's contact information and the physician's IND number, which is not the same as the manufacturer's IND number, (if the number is known); (7) request for authorization to use draft Form FDA 3926, when finalized, for individual patient expanded access applications instead of Form FDA 1571; and (8) certification statement and physician's signature. Draft Form FDA 3926 is provided in the draft guidance for public comment as Appendix 1. As discussed in the draft guidance, FDA intends to accept submission of draft Form FDA 3926, when finalized, to comply with the IND submission requirements in §§ 312.23, 312.305(b), and 312.310(b). To the extent that information required under part 312 is not contained in draft Form FDA 3926, FDA intends to consider the submission of that form, when finalized, with the box in item 7 checked and the form signed by the physician, to constitute a request under § 312.10 to waive any other applicable application requirements, including additional information included in Form FDA 1571 and Form FDA 1572 (Statement of Investigator, providing the identity and qualifications of the investigator conducting the clinical investigation). 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, and authorization of the emergency use may be given by the FDA official over the telephone, provided the physician explains how the expanded access use will meet the requirements of §§ 312.305 and 312.310 and agrees to submit an expanded access submission within 15 working days of FDA's initial authorization of the expanded access use (§ 312.310(d)). The draft guidance is being issued consistent with FDA's good guidance practices regulation (21 CFR 10.115). The draft guidance, when finalized, will represent the Agency's current thinking on the use of draft Form FDA 3926, when finalized, by licensed physicians for individual patient expanded access applications. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. An alternative approach may be used if such approach satisfies the requirements of the applicable statutes and regulations. II. Paperwork Reduction Act of 1995 The draft guidance contains information collection provisions that are subject to review by the Office of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). The title, description, and respondent description of the information collection are given under this section with an estimate of the annual reporting burden. Included in the estimate is the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. We invite comments on these topics: (1) Whether the proposed collection of information is necessary for the proper performance of FDA's functions, including whether the information will have practical utility; (2) the accuracy of FDA's estimate of the burden of the proposed collection of information, including the validity of the methodology and assumptions used; (3) ways to enhance the quality, utility, and clarity of the information to be collected; and (4) ways to minimize the burden of the collection of information on respondents, including through the use of automated collection techniques, 
                    ( print page 7320)
                    when appropriate, and other forms of information technology. *Title:*
                     Draft Guidance on Individual Patient Expanded Access Applications: Form FDA 3926. *Description:*
                     The draft guidance provides for public comment and describes draft Form FDA 3926. When finalized, draft Form FDA 3926 will be available for licensed physicians to request the use of an investigational drug outside of a clinical trial 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 (
                    *i.e.,*
                     for individual patient expanded access). FDA regulations (§ 312.305(b)(2)) require that a cover sheet meeting the requirements of § 312.23(a) (currently Form FDA 1571) be submitted for all expanded access requests. As explained in the draft guidance, the following information would be submitted to FDA by those using draft Form FDA 3926 when it is finalized: Patient's initials and date of submission.
                Clinical information, including indication, brief clinical history of the patient (age, gender, weight, allergies, diagnosis, prior therapy, response to prior therapy), and the rationale for requesting the proposed treatment, including an explanation of why the patient lacks other therapeutic options.
                Treatment information, including the investigational drug's name and manufacturer and the treatment plan. The plan should include the planned dose, route of administration, planned duration of treatment, monitoring procedures, and planned modifications to the treatment plan in the event of toxicity.
                LOA obtained from the investigational drug's manufacturer and attached to draft Form FDA 3926, if applicable.
                Physician's qualification statement that specifies the medical school attended, year of graduation, medical specialty, state medical license number, current employment, and job title. Alternatively, the first few pages of the physician's curriculum vitae may be attached, provided they include the information described previously.
                Physician's contact information, including the physical address, email address, telephone number, facsimile number, and physician's IND number, if known.
                Request for authorization to use Form FDA 3926, when finalized, for the initial submission of individual patient expanded access applications instead of Form FDA 1571.
                Signature of the physician certifying that treatment will not begin until 30 days after FDA receives the application, unless the submitting physician receives earlier notification from FDA that the treatment may proceed; that the physician will obtain informed consent, consistent with Federal requirements; that an institutional review board (IRB) that complies with the Federal IRB requirements will be responsible for initial and continuing review and approval of the treatment use; and that in the case of an emergency request, treatment may begin without prior IRB approval, provided that the IRB is notified of the emergency treatment within 5 working days of treatment. Section 312.305(b)(2) of FDA's expanded access regulations sets forth the submission requirements for all types of expanded access requests for investigational drugs. Section 312.310(b) contains additional submission requirements for individual patient expanded access requests, and § 312.310(d) contains the requirements for requesting individual patient expanded access for emergency use. FDA currently has OMB approval under control number 0910-0014 for individual patient expanded access information collection under §§ 312.305(b), 312.310(b), and 312.310(d). As shown in Table 1, based on data for the number of these responses to FDA during 2011, 2012, and 2013, we estimate that we will receive approximately 593 requests annually for individual patient expanded access use from approximately 393 licensed physicians and will receive approximately 560 requests annually for individual patient expanded access emergency use from approximately 397 licensed physicians. The current OMB approval also estimates that it takes each licensed physician approximately 8 hours to request each individual patient expanded access use and approximately 16 hours to request each individual patient expanded access for emergency use. These estimates are based on the use of Form FDA 1571. When a finalized Form FDA 3926 is submitted instead of current Form FDA 1571, we estimate that the burden time will be 45 minutes, resulting in a burden reduction of 7 hours and 15 minutes for each individual patient expanded access request and a burden reduction of 15 hours and 15 minutes for each individual patient expanded access for emergency use request. That estimate is based on information provided by Department of Health and Human Services (DHHS) personnel who are familiar with preparing and reviewing expanded access submissions by practicing physicians. As shown in Table 1, we estimate a total of approximately 864.75 hours annually for requesting individual patient expanded access use and individual patient expanded access emergency use using draft Form FDA 3926, when finalized. This is a reduction of 16,727.25 hours from what was approved under OMB control number 0910-0014 for these submissions. The total estimated reporting burden for the draft guidance is as follows: Table 1—Estimated Annual Reporting Burden
[Reduces currently approved burden of 17,592 hours under 0910-0014 by 16,727.25 hours] 1
Draft guidance on individual patient expanded 
                             access applications; Form FDA 3926
Number of 
                             respondents
Number of 
                             responses per  
                             respondent
Total annual 
                             responses
Average 
                             burden per  
                             response  
                             (minutes)
Total hoursExpanded access submission for treatment of an individual patient, including submission of draft Form FDA 3926, when finalized, instead of Form FDA 1571
790
1.46
1,153
45
864.751
                         There are no capital costs or operating and maintenance costs associated with this collection of information.
 
 
 III. Comments Interested persons may submit either electronic comments regarding this document to 
                    *http://www.regulations.gov*
                     or written comments to the Division of Dockets Management (see 
                    **ADDRESSES**
                    ). It is only necessary to send one set of comments. Identify comments with the docket number found in brackets in the heading of this document. Received comments may be seen in the Division of Dockets Management between 9 a.m. and 4 p.m., Monday through Friday, and will be posted to the docket at 
                    *http://www.regulations.gov.* IV. Electronic Access Persons with access to the Internet may obtain the document at 
                    *http://www.fda.gov/​Drugs/​GuidanceComplianceRegulatoryInformation/​Guidances/​default.htm;*
                     or 
                    *http://www.fda.gov/​BiologicsBloodVaccines/​GuidanceComplianceRegulatoryInformation/​Guidances/​default.htm;*
                     or 
                    *http://www.regulations.gov.* Dated: February 3, 2015. Leslie Kux, Associate Commissioner for Policy.


[FR Doc. 2015-02561 Filed 2-9-15; 8:45 am] BILLING CODE 4164-01-P