[Federal Register Volume 83, Number 67 (Friday, April 6, 2018)]
[Notices]
[Pages 14859-14861]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-07028]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2018-N-0791]


Exposure-Response Analysis in Drug Development and Regulatory 
Decision Making; Establishment of a Public Docket; Request for Comments

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice; establishment of a public docket; request for comments.

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SUMMARY: The Prescription Drug User Fee Act of 2017 (PDUFA VI), part of 
the FDA Reauthorization Act of 2017 (FDARA, highlights the goal of 
advancing model-informed drug development (MIDD). Exposure-response 
analysis is a MIDD strategy that has been used in drug development and 
regulatory decision making. The Food and Drug Administration (FDA or 
Agency) is opening a docket to receive public comments on experience 
leveraging exposure-response analysis since publishing the guidance for 
industry (GFI) entitled ``Exposure-Response Relationships--Study 
Design, Data Analysis, and Regulatory Applications,'' which was 
announced in the Federal Register on May 6, 2003. Specifically, the 
Agency wants to identify areas of scientific policy that may need 
further clarity or elaboration, as well as any obstacles that prevent 
use of exposure-response analyses in drug development and regulatory 
review.

DATES: To ensure that the Agency considers your input, submit either 
electronic or written comments by July 5, 2018.

ADDRESSES: You may submit comments as follows. Electronic comments must 
be submitted on or before July 5, 2018. Comments received by mail/hand 
delivery/courier (for written/paper submissions) will be considered 
timely if they are postmarked or the delivery date service acceptance 
receipt is on or before that date:

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

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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-2018-N-0791 for ``Exposure-Response Analysis in Drug Development 
and Regulatory Decision Making; Request for Comments.'' 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 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.gpo.gov/fdsys/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.

FOR FURTHER INFORMATION CONTACT: Kevin Krudys, Office of Clinical 
Pharmacology, Center for Drug Evaluation and Research, Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 3110, Silver 
Spring, MD 20993-0002, 301-796-3859, [email protected].

SUPPLEMENTARY INFORMATION: 

I. Background

    On May 6, 2003, FDA issued a GFI entitled ``Exposure-Response 
Relationships--Study Design, Data Analysis, and Regulatory 
Applications'' (available at https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM072109.pdf) (68 FR 
24004). This guidance provides recommendations for sponsors of 
investigational new drugs (INDs) and applicants submitting new drug 
applications (NDAs) or biologics license applications (BLAs) on the use 
of exposure-response analyses in the development of drugs, including 
therapeutic biologics. Since then, FDA and drug developers have gained 
a wealth of experience performing exposure-response analyses and 
leveraging the results to influence drug development and inform 
regulatory review. Additionally, obstacles that limit the routine 
application and acceptance of exposure-response analyses to address key 
drug development and regulatory decisions have since been identified. 
Given that PDUFA VI goals highlight advancing MIDD, FDA wants to 
capture the public's experience to inform future efforts on providing 
additional clarity, new insights, and updated recommendations for 
employing exposure-response analyses in drug development. To achieve 
these ends, FDA is opening the docket ``Exposure-Response Analysis in 
Drug Development and Regulatory Decision Making: Request for Comments'' 
to give interested parties an opportunity to identify areas of 
scientific policy that may need further clarity or elaboration, as well 
as any obstacles preventing use of exposure-response analyses in drug 
development and regulatory review.

II. Additional Issues for Consideration: Request for Information and 
Comments

    Interested persons are invited to provide detailed information and 
comments on the use of exposure-response analysis in drug development 
and regulatory review. FDA is particularly interested in responses to 
the following questions:
    1. In general, are there any aspects of the 2003 GFI entitled 
``Exposure-Response Relationships--Study Design, Data Analysis, and 
Regulatory Applications'' that merit further elaboration? Additionally, 
are there any new topic areas that should be addressed?
    2. What are best practices for conducting exposure-response 
analysis that can be generally applied across development programs and 
regulatory submissions? Input on best practices can include any of the 
following topic areas:
     Planning and design (e.g., data considerations, assumption 
setting);
     Analytical approaches (e.g., exposure and response 
metrics, choice and inclusion of predictors, methods for addressing 
confounding factors);
     Model evaluation and qualification (e.g., goodness-of-fit, 
assessment of model risk, impact on regulatory decisions); and
     Communication of results and impact on subsequent drug 
development or regulatory decisions.
    3. What attributes of an exposure-response analysis are critical to 
effectively inform a drug development or regulatory decision? 
Additionally, what are the main obstacles preventing widespread 
acceptance of exposure-response analyses?
    4. During which stages of drug development would it be most 
productive to interact with the FDA regarding exposure-response 
analysis planning? What type of feedback would be useful to inform 
exposure-response analyses and to reduce uncertainty in regulatory 
acceptance?
    FDA will consider all information and comments submitted.

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III. Electronic Access

    Persons with access to the internet may obtain the 2003 GFI 
entitled ``Exposure-Response Relationships--Study Design, Data 
Analysis, and Regulatory Applications'' at either https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM072109.pdf or https://www.fda.gov/Drugs/GuidancecomplianceRegulatoryInformation/Guidances/default.htm.

    Dated: April 2, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-07028 Filed 4-5-18; 8:45 am]
 BILLING CODE 4164-01-P