
[Federal Register Volume 80, Number 242 (Thursday, December 17, 2015)]
[Notices]
[Pages 78743-78745]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-31690]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2015-D-4562]


Safety Assessment for Investigational New Drug Application Safety 
Reporting; Draft Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

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SUMMARY: The Food and Drug Administration (FDA, we, or Agency) is 
announcing the availability of a draft guidance for industry entitled 
``Safety Assessment for IND Safety Reporting.'' The draft guidance 
provides recommendations to sponsors on developing a systematic 
approach to investigational new drug application (IND) safety reporting 
for human drugs and biological products developed under an IND. This 
draft guidance is a follow-on to the guidance for industry and 
investigators entitled ``Safety Reporting Requirements for INDs and BA/
BE Studies'' that provides recommendations for how sponsors of INDs can 
identify and evaluate important safety information that must be 
submitted to FDA and all participating investigators, including a 
recommendation that sponsors develop a safety assessment committee.

DATES: 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draft guidance before it begins work on the final version of the 
guidance, submit either electronic or written comments on the draft 
guidance by February 16, 2016. Submit comments on the information 
collection issues under the Paperwork Reduction Act of 1995 by February 
16, 2016.

ADDRESSES: You may submit comments as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to http://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on http://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper 
submissions): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of 
Dockets Management, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2015-D-4562 for ``Safety Assessment for Investigational New Drug 
Application Safety Reporting; Draft Guidance for Industry; 
Availability.'' Received comments will be placed in the docket and, 
except for those submitted as ``Confidential Submissions,'' publicly 
viewable at http://www.regulations.gov or at the Division of Dockets 
Management between 9 a.m. and 4 p.m., Monday through Friday.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on http://www.regulations.gov. 
Submit both copies to the Division of Dockets Management. If you do not 
wish your name and contact information to be made publicly available, 
you can provide this information on the cover sheet and not in the body 
of your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to http://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Division of Dockets Management, 5630 Fishers 
Lane, Rm. 1061, Rockville, MD 20852.
    Submit comments on information collection issues to the Office of 
Management and Budget in the following ways:
     Fax to the Office of Information and Regulatory Affairs, 
OMB, Attn: FDA Desk Officer, FAX: 202-395-7285, or email to 
oira_submission@omb.eop.gov. All comments should be identified with the 
title ``Safety Assessment for IND Safety Reporting.''
    Submit written requests for single copies of the draft guidance to 
the Division of Drug Information, Center for Drug Evaluation and 
Research, Food

[[Page 78744]]

and Drug Administration, 10001 New Hampshire Ave., Hillingdale Bldg., 
4th Floor, Silver Spring, MD 20993-0002; or the Office of 
Communication, Outreach and Development, Center for Biologics 
Evaluation and Research, 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.

FOR FURTHER INFORMATION CONTACT: Dianne Paraoan, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 3326, Silver Spring, MD 20993-0002, 301-
796-2500; 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 ``Safety Assessment for IND Safety Reporting.'' The draft 
guidance provides recommendations to sponsors on developing a 
systematic approach to IND safety reporting for human drugs and 
biological products developed under an IND. The draft guidance is a 
follow-on to the guidance for industry and investigators entitled 
``Safety Reporting Requirements for INDs and BA/BE Studies.'' \1\ It 
provides recommendations for how sponsors of INDs can identify and 
evaluate important safety information that must be submitted to FDA and 
all participating investigators under the IND safety reporting 
regulations at Sec.  312.32 (21 CFR 312.32). The draft guidance 
provides recommendations on the following: (1) The composition and role 
of a safety assessment committee, (2) aggregate analyses for comparison 
of adverse event rates across treatment groups, (3) planned unblinding 
of safety data, (4) reporting thresholds for IND safety reporting, and 
(5) the development of a safety surveillance plan.
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    \1\ The guidance is available on the Internet at http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm (under Guidances [Drugs]).
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    The IND safety reporting requirements for human drugs and 
biological products are found at Sec.  312.32, and the guidance for 
industry and investigators entitled ``Safety Reporting Requirements for 
INDs and BA/BE Studies'' describes and provides recommendations for 
complying with these requirements. During the evaluation of comments to 
the draft guidance for industry and investigators entitled ``Safety 
Reporting Requirements for INDs and BA/BE Studies'' (Docket No. FDA-
2010-D-0482) and at meetings with stakeholders, FDA identified the need 
for additional guidance on IND safety reporting topics for IND studies.
    It is critical for sponsors to detect and report, as early as 
possible, serious and unexpected suspected adverse reactions and 
clinically important increased rates of previously recognized serious 
adverse reactions (Sec.  312.32(c)(1)(i) and (iv)). Early detection of 
such occurrences will enable sponsors to carry out their obligation to 
monitor the progress of the investigation (21 CFR 312.56(a)) and, when 
necessary, to take steps to protect subjects to allow an 
investigational drug to be safely developed despite potential risks. 
Early detection also allows sponsors to report meaningful safety 
information to FDA and all participating investigators in an IND safety 
report as soon as possible.
    Timely reporting of meaningful safety information allows FDA to 
consider whether any changes in study conduct should be made beyond 
those initiated by the sponsor and allows investigators to make any 
needed changes to protect subjects. For these reasons, the draft 
guidance provides recommendations intended to help sponsors meet their 
obligations under Sec.  312.32. We recommend that sponsors develop a 
safety assessment committee and a safety surveillance plan as key 
elements of a systematic approach to safety surveillance. A safety 
assessment committee would be a group of individuals chosen by the 
sponsor to review safety information in a development program and 
tasked with making a recommendation to the sponsor regarding whether 
the safety information must be reported in an IND safety report. A 
safety surveillance plan should describe processes and procedures for 
assessing serious adverse events and other important safety 
information.
    This 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 current thinking of FDA on safety 
assessment for IND safety reporting. It does not establish any rights 
for any person and is not binding on FDA or the public. You can use an 
alternative approach if it satisfies the requirements of the applicable 
statutes and regulations.

II. Paperwork Reduction Act of 1995

    Under the Paperwork Reduction Act of 1995 (the PRA) (44 U.S.C. 
3501-3520), Federal Agencies must obtain approval from the Office of 
Management and Budget (OMB) for each collection of information that 
they conduct or sponsor. ``Collection of information'' is defined in 44 
U.S.C. 3502(3) and 5 CFR 1320.3(c) and includes Agency requests or 
requirements that members of the public submit reports, keep records, 
or provide information to a third party. Section 3506(c)(2)(A) of the 
PRA (44 U.S.C. 3506(c)(2)(A)) requires Federal Agencies to provide a 
60-day notice in the Federal Register for each proposed collection of 
information before submitting the collection to OMB for approval. To 
comply with this requirement, FDA is publishing this notice of the 
proposed collection of information set forth in this document.
    With respect to the collection of information associated with this 
draft guidance, FDA invites comments on the following topics: (1) 
Whether the proposed information collected is necessary for the proper 
performance of FDA's functions, including whether the information will 
have practical utility; (2) the accuracy of FDA's estimated burden of 
the proposed information collected, including the validity of the 
methodology and assumptions used; (3) ways to enhance the quality, 
utility, and clarity of the information collected; and (4) ways to 
minimize the burden of information collected on the respondents, 
including through the use of automated collection techniques, when 
appropriate, and other forms of information technology.
    Title: Safety Assessment for IND Safety Reporting.
    Description of Respondents: The respondents to this collection of 
information are sponsors that conduct IND studies.
    Burden Estimate: The draft guidance provides recommendations to 
sponsors on developing a systematic approach to IND safety reporting 
for human drugs and biological products developed under an IND. The 
draft guidance also provides recommendations on the following: (1) The 
composition and role of a safety assessment committee, (2) aggregate 
analyses for comparison of adverse event rates across treatment groups, 
(3) planned unblinding of safety data, (4) reporting thresholds for IND 
safety reporting, and (5) the development of a safety surveillance 
plan.

[[Page 78745]]

A. Proposed Reporting Burden Estimates for Developing and Submitting a 
Safety Surveillance Plan

    This draft guidance proposes the following new collections of 
information for reporting:
    Developing and Submitting a Safety Surveillance Plan: The draft 
guidance recommends that a sponsor develop a safety surveillance plan 
that describes processes and procedures for assessing serious adverse 
events and other safety information. The draft guidance describes seven 
elements that should be included in a safety surveillance plan and 
recommends that the sponsor submit a portion of the safety surveillance 
plan to the IND. Specifically, the sponsor should submit the list of 
anticipated serious adverse events and previously recognized serious 
adverse reactions and guiding principles for periodic aggregate safety 
reviews.
    Based on information available to FDA, including burden estimates 
for collections of information approved under OMB control numbers 0910-
0014 [covers Sec.  312.23 (21 CFR 312.23) (IND content), portions of 
Sec.  312.32 (IND safety reports), and Sec.  312.66 (21 CFR 312.66) 
(investigator reporting to institutional review board)] and 0910-0733 
(development of a comprehensive monitoring plan), we estimate that 
approximately 88 sponsors will develop approximately 111 safety 
surveillance plans in accordance with the draft guidance and that the 
burden for each plan will be approximately 120 to 240 hours. This 
burden estimate includes the time sponsors will need to prepare safety 
surveillance plan amendments when appropriate. The average burden per 
response is estimated as a range to account for respondents that will 
make changes to a pre-existing premarket safety system and those that 
will develop a new premarket safety system. The average of this range 
(180 hours) was used to calculate the total hours estimated in table 1 
of this document (a total of 19,980 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
             Safety assessment for IND safety reporting                 Number of      responses per     Total annual   Average  burden    Total hours
                                                                       respondents       respondent       responses      per  response
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Develop and submit a safety surveillance plan......................              88             1.26              111              180           19,980
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.

B. Proposed Recordkeeping Burden Estimates for Maintaining a Safety 
Surveillance Plan

    This draft guidance proposes the following new collections of 
information for recordkeeping:
    The draft guidance recommends that a sponsor maintain the safety 
surveillance plan.
    Based on information available to FDA, we estimate that 
approximately 88 sponsors will maintain approximately 3 records in 
accordance with the draft guidance and that the average burden per 
recordkeeping is 6 hours (a total of 1,584 hours).
    FDA estimates the burden of this collection of information as 
follows:

                                                   Table 2--Estimated Annual Recordkeeping Burden \1\
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                                                                                         Number of                      Average  burden
             Safety assessment for IND safety reporting                 Number of       records per      Total annual         per          Total hours
                                                                      recordkeepers     recordkeeper       records       recordkeeping
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Maintain a safety surveillance plan................................              88                3              264                6            1,584
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.

    The draft guidance also refers to previously approved collections 
of information found in FDA regulations that have been approved under 
the OMB control numbers that follow.
     OMB control number 0910-0014 covers Sec.  312.23 (IND 
content), portions of Sec.  312.32 (IND safety reports), and Sec.  
312.66 (investigator reporting to institutional review board).
     OMB control number 0910-0116 covers 21 CFR 606.170(b) 
(adverse reaction file).
     OMB control number 0910-0230 covers 21 CFR 310.305 and 
314.80 (postmarketing reporting of adverse drug experiences).
     OMB control number 0910-0308 covers 21 CFR 600.80 
(postmarketing reporting of adverse experiences).
     OMB control number 0910-0672 covers more recent provisions 
of Sec.  312.32 that are not already approved under OMB control number 
0910-0014 (for example, reporting to FDA in an IND safety report any 
clinically important increase in the rate of occurrence of serious 
suspected adverse reactions over that listed in the protocol or the 
investigator brochure).

III. Electronic Access

    Persons with access to the Internet may obtain the document at 
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, or 
http://www.regulations.gov.

    Dated: December 11, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-31690 Filed 12-16-15; 8:45 am]
 BILLING CODE 4164-01-P


