[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
[[Page 14860]]
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]
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