
[Federal Register Volume 81, Number 79 (Monday, April 25, 2016)]
[Notices]
[Pages 24106-24107]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-09449]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

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


Assay Development and Validation for Immunogenicity Testing of 
Therapeutic Protein Products; Revised Draft Guidance for Industry; 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the availability of a revised draft guidance for industry entitled 
``Assay Development and Validation for Immunogenicity Testing of 
Therapeutic Protein Products.'' This guidance provides recommendations 
to facilitate industry's development and validation of immune assays 
for assessment of the immunogenicity of therapeutic protein products 
during clinical trials. The guidance for assay development and 
validation provided in this document applies to assays for detection of 
anti-drug antibodies (ADA). This document includes guidance regarding 
the development and validation of screening assays, confirmatory 
assays, titering assays, and neutralization assays. This guidance 
revises the draft guidance for industry entitled ``Assay Development 
for Immunogenicity Testing of Therapeutic Proteins'' issued in December 
2009. This revised draft guidance includes new information on titering 
and confirmatory assays.

DATES: Although you can comment on any guidance at any time (see 21 CFR 
10.115(g)(5)), to ensure that the Agency considers your comment on this 
revised draft guidance before it begins work on the final version of 
the guidance, submit either electronic or written comments on the 
revised draft guidance by June 24, 2016.

ADDRESSES: You may submit comments as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to http://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 http://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): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of 
Dockets Management, 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 ``Assay Development and Validation for 
Immunogenicity Testing of Therapeutic Protein Products; Revised Draft 
Guidance for Industry; Availability.'' Received comments will be placed 
in the docket and, except for those submitted as ``Confidential 
Submissions,'' publicly viewable at http://www.regulations.gov or at 
the Division of Dockets Management 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 http://www.regulations.gov. 
Submit both copies to the Division of Dockets Management. If you do not 
wish your name and contact information to be

[[Page 24107]]

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: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to http://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 Division of Dockets Management, 5630 Fishers 
Lane, Rm. 1061, Rockville, MD 20852.
    Submit written requests for single copies of the revised 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; or the Office of the Center Director, Guidance 
and Policy Development, Center for Devices and Radiological Health, 
Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 66, Rm. 
5431, 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 revised 
draft guidance document.

FOR FURTHER INFORMATION CONTACT: Ebla Ali Ibrahim, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 6308, Silver Spring, MD 20993, 301-796-
0281; 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; or Peter Hudson, 
Center for Devices and Radiological Health, Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 66, Rm. G434 (HFZ-410), 
Silver Spring, MD, 20993-0002, 301-796-6440.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a revised draft guidance for 
industry entitled ``Assay Development and Validation for Immunogenicity 
Testing of Therapeutic Protein Products.'' Patient immune responses to 
therapeutic protein products have the potential to affect product 
safety and efficacy. The clinical effects of patient immune responses 
are highly variable, ranging from no effect at all to extreme harmful 
effects to patient health. 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 and the implications of ADA 
responses for drug safety and efficacy, is crucial for any therapeutic 
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, assays for detection of ADA facilitate understanding of 
the immunogenicity, safety, and efficacy of therapeutic protein 
products. However, the detection of ADA is dependent on key operating 
parameters of the assays (e.g., 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 revises the draft guidance for industry entitled 
``Assay Development for Immunogenicity Testing of Therapeutic 
Proteins'' issued in December 2009. The information in the draft 
guidance has been reorganized for clarity, and the revised draft 
guidance includes new information on titering and confirmatory assays.
    This revised draft guidance is being issued consistent with FDA's 
good guidance practices regulation (21 CFR 10.115). The revised draft 
guidance, when finalized, will represent the current thinking of FDA on 
assay development and validation for immunogenicity testing of 
therapeutic protein products. 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

    This revised draft guidance refers to previously approved 
collections of information that 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 
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 numbers 0910-0001 and 0910-0230; 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 numbers 0910-0338 and 0910-0719.

III. Electronic Access

    Persons with access to the Internet may obtain the document at 
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, or http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, or 
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/default.htm, or http://www.regulations.gov.

    Dated: April 19, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-09449 Filed 4-22-16; 8:45 am]
BILLING CODE 4164-01-P


