[Federal Register Volume 84, Number 22 (Friday, February 1, 2019)]
[Notices]
[Pages 1163-1164]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-00666]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2009-D-0539]


Immunogenicity Testing of Therapeutic Protein Products--
Developing and Validating Assays for Anti-Drug Antibody Detection; 
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 final guidance for industry entitled 
``Immunogenicity Testing of Therapeutic Protein Products--Developing 
and Validating Assays for Anti-Drug Antibody Detection.'' This guidance 
provides recommendations to facilitate industry's development and 
validation of assays for assessment of the immunogenicity of 
therapeutic protein products during clinical trials. The guidance 
applies to assays for the detection of anti-drug antibodies (ADAs) and 
may also apply to some peptides, oligonucleotides, and combination 
products on a case-by-case basis. The guidance includes recommendations 
regarding the development and validation of screening assays, 
confirmatory assays, titration assays, and neutralization assays. This 
guidance finalizes the revised draft guidance for industry entitled 
``Assay Development and Validation for Immunogenicity Testing of 
Therapeutic Protein Products'' issued in April 2016 and includes a 
revised title.

DATES: The announcement of the guidance is published in the Federal 
Register on February 1, 2019.

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-2009-D-0539 for ``Immunogenicity Testing of Therapeutic Protein 
Products--Developing and Validating Assays for Anti-Drug Antibody 
Detection.'' 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.
    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; 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 guidance document.

[[Page 1164]]


FOR FURTHER INFORMATION CONTACT: Ebla Ali-Ibrahim, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 6302, Silver Spring, MD 20993, 301-796-
3691; 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 guidance for industry 
entitled ``Immunogenicity Testing of Therapeutic Protein Products--
Developing and Validating Assays for Anti-Drug Antibody Detection.'' 
This guidance finalizes the revised draft guidance for industry 
entitled ``Assay Development and Validation for Immunogenicity Testing 
of Therapeutic Protein Products'' issued in April 2016. Changes made to 
the guidance took into consideration comments received. In addition to 
editorial changes primarily for clarification, this guidance includes 
updated information on titration and confirmatory assays and an 
additional discussion of immunogenicity risk assessment.
    Immune responses to therapeutic protein products have the potential 
to affect product pharmacokinetics, pharmacodynamics, safety, and 
efficacy. The clinical effects of patient immune responses are highly 
variable, ranging from no measurable effect to extremely harmful. 
Detection and analysis of ADA formation is a helpful tool in 
understanding potential patient immune responses. Information on immune 
responses observed during clinical trials, particularly the incidence 
of ADA induction or any implications of ADA responses affecting 
pharmacokinetics, pharmacodynamics, safety, and efficacy, is crucial 
for any therapeutic protein product development program. Accordingly, 
such information, if applicable, should be included in the prescribing 
information as a subsection of the ADVERSE REACTIONS section entitled 
``Immunogenicity.''
    In general, results from assays for detection of ADA facilitate 
understanding of the immunogenicity, pharmacokinetics, 
pharmacodynamics, safety, and efficacy of therapeutic protein products. 
However, the detection of ADA is dependent on key operating parameters 
of the assays (for example, sensitivity, specificity), which vary 
between assays. Therefore, the development of valid, sensitive, 
specific, and selective assays to measure ADA responses is a key aspect 
of therapeutic protein product development.
    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 ``Immunogenicity Testing of Therapeutic 
Protein Products--Developing and Validating Assays for Anti-Drug 
Antibody Detection.'' 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. This guidance is not subject to Executive Order 12866.

II. Paperwork Reduction Act of 1995

    This guidance refers to previously approved collections of 
information found in FDA regulations. These collections of information 
are subject to review by the Office of Management and Budget (OMB) 
under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). The 
collections of information in 21 CFR part 201 have 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; the 
collections of information in 21 CFR part 312 have been approved under 
OMB control number 0910-0014; 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 58 have been approved under 
OMB control number 0910-0119; and the collections of information in 21 
CFR part 601 have been approved under OMB control number 0910-0338.

III. Electronic Access

    Persons with access to the internet may obtain the guidance at 
https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, or 
https://www.regulations.gov.

    Dated: January 16, 2019.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2019-00666 Filed 1-31-19; 8:45 am]
 BILLING CODE 4164-01-P