[Federal Register Volume 85, Number 47 (Tuesday, March 10, 2020)]
[Notices]
[Pages 13903-13905]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-04877]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2019-N-6084]


Type 2 Diabetes Mellitus: Evaluating the Safety of New Drugs for 
Improving Glycemic Control; Draft Guidance for Industry; Availability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 or Agency) is announcing 
the availability of a draft guidance for industry entitled ``Type 2 
Diabetes Mellitus: Evaluating the Safety of New Drugs for Improving 
Glycemic Control.'' This draft guidance replaces the guidance for 
industry entitled ``Diabetes Mellitus--Evaluating Cardiovascular Risk 
in New Antidiabetic Therapies to Treat Type 2 Diabetes'' and the draft 
guidance for industry ``Diabetes Mellitus: Developing Drugs and 
Therapeutic Biologics for Treatment and Prevention,'' both of which are 
being withdrawn. This draft guidance outlines the Agency's current 
recommendations on the evaluation of safety for new drugs and biologics 
to improve glycemic control in patients with type 2 diabetes. 
Publication of this guidance is intended to provide clarity on the 
expectations for the development of drugs and biologics to improve 
glycemic control and to serve as a focus for commentary and feedback.

DATES: Submit either electronic or written comments on the draft 
guidance by June 8, 2020 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 
version of the guidance.

ADDRESSES: You may submit comments on any guidance at any time as 
follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://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 https://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): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, 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-2019-N-6084 for ``Type 2 Diabetes Mellitus: Evaluating the Safety 
of New Drugs for Improving Glycemic Control.'' Received comments will 
be placed in the docket and, except for those submitted as 
``Confidential Submissions,'' publicly viewable at https://www.regulations.gov or at the Dockets Management Staff 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

[[Page 13904]]

https://www.regulations.gov. Submit both copies to the Dockets 
Management Staff. 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: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://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 Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.
    You may submit comments on any guidance at any time (see 21 CFR 
10.115(g)(5)).
    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 20993-0002. 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: Silvana Borges, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, Rm. 3200, Silver Spring, MD 20993-0002, 301-
796-0963.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Type 2 Diabetes Mellitus: Evaluating the Safety of New Drugs 
for Improving Glycemic Control.'' This draft guidance replaces the 
guidance for industry entitled ``Diabetes Mellitus--Evaluating 
Cardiovascular Risk in New Antidiabetic Therapies to Treat Type 2 
Diabetes,'' published in December 2008, and the draft guidance for 
industry ``Diabetes Mellitus: Developing Drugs and Therapeutic 
Biologics for Treatment and Prevention,'' published in February 2008, 
both of which are being withdrawn.
    In response to questions and concerns about increased 
cardiovascular risk with certain antidiabetic therapies, FDA convened 
an advisory committee meeting in July 2008 to discuss the role of 
cardiovascular risk assessments for the safety evaluation of drugs and 
biologics developed for the treatment of type 2 diabetes. Based, in 
part, on comments expressed at that meeting, the Agency issued a 
guidance for industry in December 2008 outlining recommendations on the 
evaluation of cardiovascular risk for new antidiabetic therapies. That 
guidance stated that developers should demonstrate that new 
antidiabetic drugs and biologics would not result in an unacceptable 
increase in cardiovascular risk.
    Since that time, FDA has reviewed the results of several 
cardiovascular outcome trials (CVOTs) conducted to meet the December 
2008 guidance recommendations. None of the CVOTs to date have 
identified an increased risk of ischemic cardiovascular events; some of 
the CVOTs have instead demonstrated a reduced risk for cardiovascular 
events. In light of the CVOT results, FDA is revisiting the 
recommendations of the December 2008 guidance and is now proposing an 
updated approach to evaluating the safety of new drugs and biologics to 
improve glycemic control. In addition, FDA is withdrawing the February 
2008 guidance because its recommendations for safety assessment have 
become outdated.
    FDA is establishing this docket to solicit input from stakeholders 
on all aspects of these issues, including comments on specific 
questions posed in section II, Additional Issues for Consideration.
    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 ``Type 2 
Diabetes Mellitus: Evaluating the Safety of New Drugs for Improving 
Glycemic Control.'' 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. Additional Issues for Consideration

    FDA is soliciting comments from stakeholders regarding the issues 
described in this notice and the draft guidance. In addition to any 
other aspects of the guidance that stakeholders may care to comment 
upon, FDA is interested in answers to the following questions/topics in 
particular:

A. Size of Population and Exposure to the Investigational Drug/Biologic

    1. Is it more important to emphasize the number of patients exposed 
or the amount of exposure (i.e., number of patient-years)? Or should 
there be expectations set for both parameters?
    2. What would constitute a minimally acceptable database (either in 
number of patients, number of patient-years, or both) in terms of 
exposure to investigational drug/biologic at time of filing of the 
marketing application?

B. Demographic Characteristics of the Population

    1. What are the important comorbid conditions to include?
    2. What would be a minimally acceptable number of patients or 
number of patient-years to include for each important comorbid 
condition?

C. Necessary Safety Evaluations

    1. Are there specific safety concerns for patients with type 2 
diabetes that should be rigorously evaluated?
    2. If there are specific safety concerns that should be rigorously 
evaluated, how should that assessment be conducted?
    3. Is the adjudication of adverse events related to a specific 
safety concern a necessary part of the safety assessment? If so, should 
it be conducted by an independent, blinded adjudication committee or 
would other means of adjudication be adequate?

III. Paperwork Reduction Act of 1995

    This draft guidance refers to previously approved FDA collections 
of information. These collections of information are subject to review 
by the Office of Management and Budget (OMB) under the Paperwork 
Reduction Act of 1995 (44 U.S.C. 3501-3521). The collection of 
information in 21 CFR part 312 has been approved under OMB control 
number 0910-0014; the collection of information in 21 CFR part 314 has 
been approved under OMB control number 0910-0001; and the collection of 
information for clinical trial data monitoring committees has been 
approved under OMB control number 0910-0581.

IV. Electronic Access

    Persons with access to the internet may obtain the draft guidance 
at either https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs or https://www.regulations.gov.


[[Page 13905]]


    Dated: March 5, 2020.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2020-04877 Filed 3-9-20; 8:45 am]
BILLING CODE 4164-01-P