[Federal Register Volume 86, Number 92 (Friday, May 14, 2021)]
[Notices]
[Pages 26525-26526]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-10179]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2021-N-0347]


Evaluating the Clinical Pharmacology of Peptides; Establishment 
of a Public Docket; Request for Information and Comments

AGENCY: Food and Drug Administration, HHS.

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

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SUMMARY: The Food and Drug Administration (FDA or Agency) is 
establishing a public docket to collect comments on evaluating the 
clinical pharmacology of peptides. For the purpose of this request, FDA 
is specifically interested in comments regarding the characterization 
of the effects of hepatic impairment, drug-drug interactions, and 
immunogenicity on the pharmacokinetics of peptides, as well as the 
effects of peptides on cardiac electrophysiology. However, there may be 
other clinical pharmacology considerations concerning the development 
of peptides. Public comments will help FDA develop recommendations for 
the design and conduct of studies important to the safe and effective 
use of peptides and facilitate the regulatory assessment of such 
studies.

DATES: Although you can comment at any time, to ensure that the Agency 
considers your comment in our development of recommendations, submit 
either electronic or written information and comments by July 13, 2021.

ADDRESSES: You may submit comments and information 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-2021-N-0347 for ``Evaluating the Clinical Pharmacology of Peptides; 
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, 240-
402-7500.
     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.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, 240-402-7500.

FOR FURTHER INFORMATION CONTACT: Jagan Parepally, Office of Clinical 
Pharmacology, Center for Drug Evaluation and Research, Food and Drug 
Administration, 10903 New Hampshire Ave., Silver Spring, MD 20993-0002, 
301-796-1688.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA uses the term ``peptide'' to refer to polymers composed of 40 
or fewer amino acids.\1\ Peptides can be isolated

[[Page 26526]]

from whole animal tissue, or produced in vitro, synthetically or 
through recombinant expression, and often serve as signaling molecules 
for many physiologic functions that are regulated by endogenous 
proteins. Peptides can exhibit distinct combinations of characteristics 
regarding their chemistry, pharmacology, sites of action, 
pharmacokinetic disposition, and pharmacodynamics. Although FDA has 
been regulating peptides for decades, there is a growing appreciation 
for specific considerations for the design and conduct of clinical 
pharmacology studies to assess peptides, such as those designed to 
evaluate the effects of organ impairment or drug interactions. 
Currently, there are no FDA-published guidance documents on clinical 
pharmacology assessments that contain specific recommendations for 
peptides.\2\
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    \1\ FDA Proposed Rule ``Definition of the Term `Biological 
Product' '' (83 FR 63817 at 63821, December 12, 2018).
    \2\ There is an FDA draft guidance entitled ``ANDAs for Certain 
Highly Purified Synthetic Peptide Drug Products That Refer to Listed 
Drugs of rDNA Origin'' (October 2017) that is specific for ANDA 
applications for chemically synthetized peptides that refers to 
listed drugs of rDNA origin; available at https://www.fda.gov/media/107622/download.
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II. Request for Information and Comments

    Interested persons are invited to provide detailed information and 
comments on certain aspects of evaluating the clinical pharmacology of 
peptides. For all questions, organize any discussion by the type of 
peptide (e.g., isolated from animal source, or produced in vitro, 
synthetically or through recombinant expression) and route of 
administration. Please provide the rationale for your suggestions and 
include supporting data if available. FDA is particularly interested in 
responses to the following overarching questions:
    (1) Under what circumstances should the following assessments be 
warranted or not warranted for peptides?

(a) Evaluating pharmacokinetics-based drug-drug interactions (DDIs)
(b) Evaluating the pharmacokinetics in hepatic impairment
(c) Evaluating immunogenicity and its impact on pharmacokinetics, 
safety, and efficacy
(d) Evaluating QT prolongation

    (2) In circumstances where the assessments above are warranted, 
what types of assessments are suitable and why? What are the study 
design considerations (e.g., in vitro test systems, population, 
analytes, immunogenicity risk assessment, immunogenicity assay 
development and validation) for the types of assessments discussed in 
the following items? Please describe the rationale for any design 
considerations proposed.
    (a) For evaluating pharmacokinetics-based DDIs (e.g., in vitro 
studies, dedicated clinical studies, including cocktail studies, 
population pharmacokinetic analyses), please discuss the advantages, 
challenges, and limitations for these assessments.
    (b) For evaluating pharmacokinetics in hepatic impairment (e.g., 
dedicated clinical studies, population pharmacokinetic analyses), 
please discuss the advantages, challenges, and limitations for these 
assessments.
    (c) For evaluating immunogenicity and its impact on 
pharmacokinetics, safety, and efficacy (e.g., antibodies against the 
active ingredient peptide, peptide-related impurities, or endogenous 
counterpart, if present, neutralizing activity and antibody titers, 
cytokine measurements), please discuss the advantages, challenges, and 
limitations for these assessments.
    (d) For evaluating cardiac electrophysiology (e.g., hERG inhibition 
assay, thorough QT assessment) in nonclinical or clinical studies, 
please discuss the advantages, challenges, and limitations for these 
assessments.
    (3) Are there other clinical pharmacology considerations for 
peptides not covered in the questions above, such as use of 
pharmacodynamic biomarkers and/or pharmacokinetic assessments for dose 
selection? If yes, provide a description and rationale for any proposed 
considerations, as well as approaches, advantages, challenges, and 
limitations for the assessment.
    The public comments collected will help FDA develop recommendations 
for the design and conduct of clinical pharmacology studies important 
to the understanding of the safe and effective use of peptides and 
facilitate the regulatory assessment of such studies.

III. Electronic Access

    Persons with access to the internet may obtain relevant clinical 
pharmacology guidances at https://www.fda.gov/regulatory-information/search-fda-guidance-documents.

    Dated: May 7, 2021.
Lauren K. Roth,
Acting Principal Associate Commissioner for Policy.
[FR Doc. 2021-10179 Filed 5-13-21; 8:45 am]
BILLING CODE 4164-01-P