Notice2022-02604
Clinical Pharmacology Considerations for Antibody-Drug Conjugates; Draft Guidance for Industry; Availability
Primary source
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Published
February 8, 2022
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled "Clinical Pharmacology Considerations for Antibody-Drug Conjugates," which provides recommendations for the development of antibody-drug conjugates (ADCs). Specifically, this guidance addresses the FDA's current thinking regarding clinical pharmacology considerations and recommendations for ADC development programs, including bioanalytical methods, dose selection and adjustment, dose- and exposure-response analysis, intrinsic factors, QTc assessments, immunogenicity, and drug- drug interactions (DDIs). Currently, there are no FDA guidances outlining the clinical pharmacology considerations for antibody-drug conjugates. This draft guidance is not final nor is it in effect at this time.
Full Text
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<title>Federal Register, Volume 87 Issue 26 (Tuesday, February 8, 2022)</title>
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[Federal Register Volume 87, Number 26 (Tuesday, February 8, 2022)]
[Notices]
[Pages 7184-7186]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2022-02604]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2021-D-1051]
Clinical Pharmacology Considerations for Antibody-Drug
Conjugates; Draft Guidance for Industry; Availability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the availability of a draft guidance for industry entitled ``Clinical
Pharmacology Considerations for Antibody-Drug Conjugates,'' which
provides recommendations for the development of antibody-drug
conjugates (ADCs). Specifically, this guidance addresses the FDA's
current thinking regarding clinical pharmacology considerations and
recommendations for ADC development programs, including bioanalytical
methods, dose selection and adjustment, dose- and exposure-response
analysis, intrinsic factors, QTc assessments, immunogenicity, and drug-
drug interactions (DDIs). Currently, there are
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no FDA guidances outlining the clinical pharmacology considerations for
antibody-drug conjugates. This draft guidance is not final nor is it in
effect at this time.
DATES: Submit either electronic or written comments on the draft
guidance by May 9, 2022 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:
<bullet> Federal eRulemaking Portal: <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to <a href="https://www.regulations.gov">https://www.regulations.gov</a>
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 <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
<bullet> 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:
<bullet> 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.
<bullet> 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-D-1051 for ``Clinical Pharmacology Considerations for
Antibody-Drug Conjugates.'' Received comments will be placed in the
docket and, except for those submitted as ``Confidential Submissions,''
publicly viewable at <a href="https://www.regulations.gov">https://www.regulations.gov</a> or at the Dockets
Management Staff between 9 a.m. and 4 p.m., Monday through Friday, 240-
402-7500.
<bullet> 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 <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
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: <a href="https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf">https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf</a>.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to <a href="https://www.regulations.gov">https://www.regulations.gov</a> 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.
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; or to
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: Kimberly Maxfield, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Silver Spring, MD 209903, 301-348-1978,
<a href="/cdn-cgi/l/email-protection#7c3715111e190e100552311d041a151910183c1a181d5214140f521b130a"><span class="__cf_email__" data-cfemail="7b301216191e09170255361a031d121e171f3b1d1f1a55131308551c140d">[email protected]</span></a>; 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 ``Clinical Pharmacology Considerations for Antibody-Drug
Conjugates.'' An ADC is a type of therapeutic biologic product that is
composed of a small-molecule moiety and an antibody moiety conjugated
together by a chemical linker. An antibody or antibody fragment carrier
is selected or engineered against a specific antigen of interest
present on the target, which is ideally unique to the disease state
being treated (e.g., a tumor-specific antigen). In general, when the
antibody or antibody fragment binds to its target antigen, the ADC is
internalized through physiological mechanisms (e.g., endocytosis), at
which point the small-molecule drug or payload moiety is released
either upon exposure to the low pH of the lysosome or by degradation of
the antibody/linker by lysosomal enzymes. The released small-molecule
drug then exerts its effect in the targeted cell (e.g., the cells
expressing the specific antigen of interest) while, ideally, minimizing
the effect on healthy cells (e.g., cells that do not express the
specific antigen of interest).
ADCs combine the selectivity of an antibody or antibody fragment
with the potency of a small molecule. Therefore, development of ADCs
requires careful consideration of the differences between the clinical
pharmacology of the antibody or antibody fragment and the small
molecule. This draft guidance addresses FDA's current thinking
regarding clinical pharmacology considerations and recommendations for
ADC development programs, including bioanalytical methods, dose
selection and adjustment, dose- and exposure-response analysis,
intrinsic factors, QTc assessments, immunogenicity, and DDIs. Although
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this draft guidance is primarily based on FDA's experience with ADCs
for oncology indications, the principles discussed in this guidance are
also generally applicable to the development of ADCs for other
indications.
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 ``Clinical
Pharmacology Considerations for Antibody-Drug Conjugates.'' 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
While this draft guidance contains no collection of information, it
does refer to previously approved FDA collections of information.
Therefore, clearance by the Office of Management and Budget (OMB) under
the Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3521) is not
required for this guidance. The previously approved collections of
information are subject to review by OMB under the PRA. The collections
of information for submissions of investigational new drug
applications, new drug applications, and biologic license applications
in 21 CFR parts 312, 314, and 601 have been approved under OMB control
numbers 0910-0014, 0910-0001, and 0910-0338, respectively. In addition,
the submission of prescription drug labeling under 21 CFR 201.56 and
201.57 has been approved under OMB control number 0910-0572. The
collections of information in 21 CFR part 211 have been approved under
OMB control number 0910-0139; and the collections of information
regarding good laboratory practice in 21 CFR part 58 have been approved
under OMB control number 0910-0119.
III. Electronic Access
Persons with access to the internet may obtain the draft guidance
at <a href="https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs">https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs</a>, <a href="https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances">https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances</a>, <a href="https://www.fda.gov/regulatory-information/search-fda-guidance-documents">https://www.fda.gov/regulatory-information/search-fda-guidance-documents</a>, or <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Dated: February 1, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-02604 Filed 2-7-22; 8:45 am]
BILLING CODE 4164-01-P
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