[Federal Register Volume 88, Number 107 (Monday, June 5, 2023)]
[Notices]
[Pages 36588-36589]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-11900]



[[Page 36588]]

-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2020-D-1480]


Drug-Drug Interaction Assessment for Therapeutic Proteins; 
Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a final guidance for industry entitled ``Drug-Drug 
Interaction Assessment for Therapeutic Proteins.'' With the continued 
market growth and increased clinical use of therapeutic proteins, it is 
important to understand the nature of and the potential for drug-drug 
interactions (DDIs) with these products. The purpose of this guidance 
is to help sponsors of investigational new drug applications (INDs) and 
applicants of biologics license applications (BLAs) determine the need 
for DDI studies for a therapeutic protein by providing a systematic, 
risk-based approach. This guidance finalizes the draft guidance of the 
same title issued on August 10, 2020.

DATES: The announcement of the guidance is published in the Federal 
Register on June 5, 2023.

ADDRESSES: You may submit either electronic or written comments on 
Agency guidances 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-2020-D-1480 for ``Drug-Drug Interaction Assessment for Therapeutic 
Proteins.'' 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.
    You may submit comments on any guidance at any time (see 21 CFR 
10.115(g)(5)).
    Submit written requests for single copies of this 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 guidance document.

FOR FURTHER INFORMATION CONTACT: Elimika Pfuma Fletcher, Center for 
Drug Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 2162, Silver Spring, MD 20993, 301-796-
3473; or Diane Maloney, Center for Biologics Evaluation and Research, 
Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 
7301, Silver Spring, MD 20993-0002, 240-402-8113.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``Drug-Drug Interaction Assessment for Therapeutic Proteins.'' 
With the continued market growth and increased clinical use of 
therapeutic proteins, it is important to understand the nature of and 
the potential for DDIs with these products. This guidance supplements 
the final FDA guidances for industry entitled ``In Vitro Drug 
Interaction Studies--Cytochrome P450 Enzyme- and Transporter-Mediated 
Drug Interactions'' and ``Clinical Drug Interaction Studies--Cytochrome 
P450 Enzyme- and Transporter-Mediated Drug Interactions'' (January 
2020) by providing recommendations for a systematic, risk-based 
approach to determining the need for DDI studies for therapeutic 
proteins. This guidance discusses considerations for assessing DDIs for 
therapeutic proteins, including situations where determining the DDI 
potential of a therapeutic protein is warranted. The guidance also 
discusses various types of DDI assessments,

[[Page 36589]]

considerations for study design, and recommendations for labeling.
    This guidance finalizes the draft guidance entitled ``Drug-Drug 
Interaction Assessment for Therapeutic Proteins'' issued on August 10, 
2020 (85 FR 48259). FDA considered comments received on the draft 
guidance as the guidance was finalized. Changes from the draft to the 
final guidance include: (1) clarifying that FDA review divisions should 
be consulted related to novel modalities, and that limitations exist in 
knowledge related to effect of therapeutic proteins on transporters; 
(2) including more literature references; (3) limiting the text related 
to antibody-drug conjugates (ADCs) because a draft guidance on clinical 
pharmacology considerations for ADCs has been published; and (4) 
including language about potential use of various modeling approaches 
on a case by case basis. In addition, editorial changes were made to 
improve clarity.
    This guidance is being issued consistent with FDA's good guidance 
practices regulation (21 CFR 10.115). The guidance represents the 
current thinking of FDA on ``Drug-Drug Interaction Assessment for 
Therapeutic Proteins.'' 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 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 the submission of investigational new drug 
applications in 21 CFR part 312 have been approved under OMB control 
number 0910-0014. The collections of information for the submission of 
new drug applications in 21 CFR part 314 have been approved under OMB 
control number 0910-0001. The collections of information for the 
submission of biologics license applications in 21 CFR part 601 have 
been approved under OMB control 0910-0338. The collections of 
information pertaining to the submission of prescription drug labeling 
under 21 CFR 201.56 and 201.57 have been approved under OMB control 
number 0910-0572.

III. Electronic Access

    Persons with access to the internet may obtain the draft guidance 
at https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs, https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances, https://www.fda.gov/regulatory-information/search-fda-guidance-documents, or https://www.regulations.gov.

    Dated: May 31, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-11900 Filed 6-2-23; 8:45 am]
BILLING CODE 4164-01-P