Document ID: FDA-2021-D-1041-0001
Agency: fda
Document Type: Notice
Title: Immunogenicity Information in Human Prescription Therapeutic Protein and Select Drug Product Labeling Content and Format; Draft Guidance for Industry; Availability
Posted Date: 2022-02-04T05:00Z

[Federal Register Volume 87, Number 24 (Friday, February 4, 2022)]
[Notices]
[Pages 6574-6575]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-02348]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2021-D-1041]

Immunogenicity Information in Human Prescription Therapeutic 
Protein and Select Drug Product Labeling--Content and Format; Draft 
Guidance for Industry; Availability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 the Agency) is 
announcing the availability of a draft guidance for industry entitled 
``Immunogenicity Information in Human Prescription Therapeutic Protein 
and Select Drug Product Labeling--Content and Format.'' This draft 
guidance provides recommendations for incorporating clinically relevant 
immunogenicity information into the labeling of products having 
immunogenicity assessments. Appropriate inclusion and consistent 
placement of immunogenicity information in the Prescribing Information 
helps to make clinically relevant information accessible to the health 
care practitioner and promotes the safe and effective use of 
prescription drug and biological products. When finalized, the 
recommendations in this guidance will supersede the immunogenicity 
labeling-specific recommendations in the guidances for industry 
entitled ``Labeling for Biosimilar Products'' and ``Clinical 
Pharmacology Section of Labeling for Human Prescription Drug and 
Biological Products--Content and Format.''

DATES: Submit either electronic or written comments on the draft 
guidance by April 5, 2022 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 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:
     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-D-1041 for ``Immunogenicity Information in Human Prescription 
Therapeutic Protein and Select Drug Product Labeling--Content and 
Format.'' 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 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 the 
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: Eric Brodsky, Center for Drug 
Evaluation and Research, Food and Drug

[[Page 6575]]

Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 6485, Silver 
Spring, MD 20993, 301-796-0855; 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 ``Immunogenicity Information in Human Prescription Therapeutic 
Protein and Select Drug Product Labeling--Content and Format.''
    Evaluation of a therapeutic protein product's and certain select 
drug products' immunogenicity (e.g., risk of developing anti-drug 
antibodies, including neutralizing antibodies) and its potential 
clinical impact generally plays an important role in the assessment of 
the product's safety and effectiveness for each proposed indication. 
Because some, but not all, anti-drug antibodies have been associated 
with safety concerns or loss of effectiveness, FDA believes that 
presenting immunogenicity information in a consistent manner would 
enable health care practitioners to more easily differentiate products 
associated with anti-drug antibodies having clinical effect(s) from 
products with anti-drug antibodies that do not have a clinically 
meaningful effect on pharmacokinetics, pharmacodynamics, safety, or 
effectiveness.
    This draft guidance recommends the use of a dedicated 
Immunogenicity subsection (subsection 12.6) under the CLINICAL 
PHARMACOLOGY section. Information and statements to include in this 
subsection (e.g., data on anti-drug antibody incidence, clinical 
pharmacologic effects of anti-drug antibodies) are described in the 
draft guidance, along with recommended content to include in other 
sections of the labeling (e.g., summary of anti-drug antibody-
associated effects on safety and/or effectiveness in the WARNINGS AND 
PRECAUTIONS, ADVERSE REACTIONS, and/or CLINICAL STUDIES sections, as 
applicable). The labeling recommendations are based on: (1) Adequacy of 
the methodology for detection of anti-drug antibodies, (2) sufficiency 
of available data to draw clinical conclusions, and (3) whether the 
anti-drug antibodies have clinically significant effect(s). In addition 
to recommendations on presentation of known immunogenicity information, 
this draft guidance also provides recommendations for consistently 
stating when such information is unknown, if appropriate. The draft 
guidance also provides procedural information, including 
recommendations for updating immunogenicity information in the 
Prescribing Information of applicable approved products.
    When finalized, this guidance will supersede the immunogenicity 
labeling-specific recommendations from the guidance for industry 
entitled ``Clinical Pharmacology Section of Labeling for Human 
Prescription Drug and Biological Products--Content and Format'' 
(available at https://www.fda.gov/media/74346/download). When 
finalized, this guidance will also supersede the recommendations in 
section IV.C.3., ADVERSE REACTIONS, Immunogenicity, of the guidance for 
industry entitled ``Labeling for Biosimilar Products'' (available at 
https://www.fda.gov/media/96894/download), including the statement 
``Immunogenicity information for therapeutic protein products is 
usually placed in a subsection in the ADVERSE REACTIONS section 
entitled Immunogenicity'' and statements recommended for inclusion as 
the first paragraph in the ADVERSE REACTIONS subsection that precedes 
the immunogenicity data. FDA has verified the website addresses as of 
the date this document publishes in the Federal Register, but websites 
are subject to change over time.
    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 
``Immunogenicity Information in Human Prescription Therapeutic Protein 
and Select Drug Product Labeling--Content and Format.'' 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 new 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 in 21 CFR part 314 have been approved under OMB control 
number 0910-0001. The collections of information in 21 CFR part 600 
have been approved under OMB control number 0910-0308. The collections 
of information in 21 CFR part 601 have been approved under OMB control 
number 0910-0338. The collections of information in 21 CFR 201.56 and 
201.57 have been approved under OMB control number 0910-0572. The 
collections of information related to pharmacology data have been 
approved under OMB control number 0910-0014. The collections of 
information submitting biologics license applications under section 
351(k) of the Public Health Service Act have been approved under OMB 
control number 0910-0719.

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/regulatory-information/search-fda-guidance-documents, https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances, or https://www.regulations.gov.

    Dated: January 28, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-02348 Filed 2-3-22; 8:45 am]
BILLING CODE 4164-01-P