81 FR 24106 - Assay Development and Validation for Immunogenicity Testing of Therapeutic Protein Products; Revised Draft Guidance for Industry; Availability
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration Federal Register Volume 81, Issue 79 (April 25, 2016)
Food and Drug Administration
Federal Register Volume 81, Issue 79 (April 25, 2016)
| Page Range | 24106-24107 | |
| FR Document | 2016-09449 |
[Federal Register Volume 81, Number 79 (Monday, April 25, 2016)] [Notices] [Pages 24106-24107] From the Federal Register Online [www.thefederalregister.org] [FR Doc No: 2016-09449] ----------------------------------------------------------------------- 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FDA-2009-D-0539] Assay Development and Validation for Immunogenicity Testing of Therapeutic Protein Products; Revised Draft Guidance for Industry; Availability AGENCY: Food and Drug Administration, HHS.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. ----------------------------------------------------------------------- SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing the availability of a revised draft guidance for industry entitled ``Assay Development and Validation for Immunogenicity Testing of Therapeutic Protein Products.''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 This guidance revises the draft guidance for industry entitled ``Assay Development for Immunogenicity Testing of Therapeutic Proteins'' issued in December 2009. This revised draft guidance includes new information on titering and confirmatory assays.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on any guidance at any time (see 21 CFR 10.115(g)(5)), to ensure that the Agency considers your comment on this revised draft guidance before it begins work on the final version of the guidance, submit either electronic or written comments on the revised draft guidance by June 24, 2016.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
![24106 Federal Register / Vol. 81, No. 79 / Monday, April 25, 2016 / Notices
DATES: The award will be issued for the DEPARTMENT OF HEALTH AND such as medical information, your or
project period to run concurrently with HUMAN SERVICES anyone else’s Social Security number, or
the existing grantee’s budget period of confidential business information, such
September 30, 2015 through September Food and Drug Administration as a manufacturing process. Please note
29, 2016. [Docket No. FDA–2009–D–0539] that if you include your name, contact
information, or other information that
FOR FURTHER INFORMATION CONTACT: identifies you in the body of your
Assay Development and Validation for
Aiesha Gurley, Office of Elder Justice Immunogenicity Testing of Therapeutic comments, that information will be
and Adult Protective Services, Protein Products; Revised Draft posted on http://www.regulations.gov.
Administration on Aging, Guidance for Industry; Availability • If you want to submit a comment
Administration for Community Living, with confidential information that you
330 C Street SW., Washington, DC AGENCY: Food and Drug Administration, do not wish to be made available to the
20024. Telephone: 202–795–7358; HHS. public, submit the comment as a
Email: aiesha.gurley@acl.hhs.gov. ACTION: Notice of availability. written/paper submission and in the
manner detailed (see ‘‘Written/Paper
SUPPLEMENTARY INFORMATION: The ACL SUMMARY: The Food and Drug
Submissions’’ and ‘‘Instructions’’).
National Center on Elder Abuse serves Administration (FDA or Agency) is
as a national resource center dedicated announcing the availability of a revised Written/Paper Submissions
to the prevention of elder mistreatment. draft guidance for industry entitled Submit written/paper submissions as
The NCEA disseminates elder abuse ‘‘Assay Development and Validation for follows:
information to professionals and the Immunogenicity Testing of Therapeutic • Mail/Hand delivery/Courier (for
Protein Products.’’ This guidance written/paper submissions): Division of
public, and provides technical
provides recommendations to facilitate Dockets Management (HFA–305), Food
assistance and training to states and to
industry’s development and validation and Drug Administration, 5630 Fishers
community-based organizations. NCEA of immune assays for assessment of the
is unique because it operates as a multi- Lane, Rm. 1061, Rockville, MD 20852.
immunogenicity of therapeutic protein • For written/paper comments
disciplinary consortium of equal products during clinical trials. The submitted to the Division of Dockets
partners with expertise in elder abuse, guidance for assay development and Management, FDA will post your
neglect, and exploitation. They serve as validation provided in this document comment, as well as any attachments,
a national clearinghouse of information applies to assays for detection of anti- except for information submitted,
for elder rights advocates, law drug antibodies (ADA). This document marked and identified, as confidential,
enforcement, legal professionals, public includes guidance regarding the if submitted as detailed in
policy leaders, researchers, and others development and validation of ‘‘Instructions.’’
working to ensure that all older screening assays, confirmatory assays, Instructions: All submissions received
Americans will live with dignity, titering assays, and neutralization must include the Docket No. FDA–
integrity, independence, and without assays. This guidance revises the draft 2009–D–0539 for ‘‘Assay Development
abuse, neglect, and exploitation. guidance for industry entitled ‘‘Assay and Validation for Immunogenicity
Additional funds are needed to Development for Immunogenicity Testing of Therapeutic Protein Products;
leverage the resource center’s funding Testing of Therapeutic Proteins’’ issued Revised Draft Guidance for Industry;
in December 2009. This revised draft Availability.’’ Received comments will
for elder abuse awareness through social
guidance includes new information on be placed in the docket and, except for
media and creating state leadership
titering and confirmatory assays. those submitted as ‘‘Confidential
networks through targeted campaigns
DATES: Although you can comment on Submissions,’’ publicly viewable at
that will assist states in spreading
any guidance at any time (see 21 CFR http://www.regulations.gov or at the
awareness. This supplementary funding Division of Dockets Management
10.115(g)(5)), to ensure that the Agency
would be provided for the approved between 9 a.m. and 4 p.m., Monday
considers your comment on this revised
period. draft guidance before it begins work on through Friday.
This program is authorized under the final version of the guidance, submit • Confidential Submissions—To
Title II of the Older Americans Act either electronic or written comments submit a comment with confidential
Section 202(d)(2) which establishes the on the revised draft guidance by June information that you do not wish to be
requirements for the National Center for 24, 2016. made publicly available, submit your
Elder Abuse. ADDRESSES: You may submit comments comments only as a written/paper
as follows: submission. You should submit two
Dated: April 19, 2016.
copies total. One copy will include the
Kathy Greenlee, Electronic Submissions information you claim to be confidential
Administrator and Assistant Secretary for Submit electronic comments in the with a heading or cover note that states
Aging. following way: ‘‘THIS DOCUMENT CONTAINS
[FR Doc. 2016–09560 Filed 4–22–16; 8:45 am] • Federal eRulemaking Portal: http:// CONFIDENTIAL INFORMATION.’’ The
BILLING CODE 4154–01–P www.regulations.gov. Follow the Agency will review this copy, including
instructions for submitting comments. the claimed confidential information, in
Comments submitted electronically, its consideration of comments. The
asabaliauskas on DSK3SPTVN1PROD with NOTICES
including attachments, to http:// second copy, which will have the
www.regulations.gov will be posted to claimed confidential information
the docket unchanged. Because your redacted/blacked out, will be available
comment will be made public, you are for public viewing and posted on
solely responsible for ensuring that your http://www.regulations.gov. Submit
comment does not include any both copies to the Division of Dockets
confidential information that you or a Management. If you do not wish your
third party may not wish to be posted, name and contact information to be
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![Federal Register / Vol. 81, No. 79 / Monday, April 25, 2016 / Notices 24107
made publicly available, you can SUPPLEMENTARY INFORMATION: II. Paperwork Reduction Act of 1995
provide this information on the cover This revised draft guidance refers to
sheet and not in the body of your I. Background
previously approved collections of
comments and you must identify this FDA is announcing the availability of information that are subject to review by
information as ‘‘confidential.’’ Any a revised draft guidance for industry the Office of Management and Budget
information marked as ‘‘confidential’’ entitled ‘‘Assay Development and (OMB) under the Paperwork Reduction
will not be disclosed except in Validation for Immunogenicity Testing Act of 1995 (44 U.S.C. 3501–3520). The
accordance with 21 CFR 10.20 and other of Therapeutic Protein Products.’’ collections of information in 21 CFR
applicable disclosure law. For more Patient immune responses to part 312 have been approved under
information about FDA’s posting of therapeutic protein products have the OMB control number 0910–0014; the
comments to public dockets, see 80 FR potential to affect product safety and collections of information in 21 CFR
56469, September 18, 2015, or access part 314 have been approved under
efficacy. The clinical effects of patient
the information at: http://www.fda.gov/ OMB control numbers 0910–0001 and
immune responses are highly variable,
regulatoryinformation/dockets/ 0910–0230; the collections of
ranging from no effect at all to extreme
default.htm. information in 21 CFR part 58 have been
Docket: For access to the docket to harmful effects to patient health.
Detection and analysis of ADA approved under OMB control number
read background documents or the 0910–0119; and the collections of
electronic and written/paper comments formation is a helpful tool in
understanding potential patient immune information in 21 CFR part 601 have
received, go to http:// been approved under OMB control
www.regulations.gov and insert the responses. Information on immune
responses observed during clinical numbers 0910–0338 and 0910–0719.
docket number, found in brackets in the
heading of this document, into the trials, particularly the incidence of ADA III. Electronic Access
‘‘Search’’ box and follow the prompts induction and the implications of ADA
Persons with access to the Internet
and/or go to the Division of Dockets responses for drug safety and efficacy, is
may obtain the document at http://
Management, 5630 Fishers Lane, Rm. crucial for any therapeutic product
www.fda.gov/Drugs/
1061, Rockville, MD 20852. development program. Accordingly,
GuidanceCompliance
Submit written requests for single such information, if applicable, should
RegulatoryInformation/Guidances/
copies of the revised draft guidance to be included in the prescribing
default.htm, or http://www.fda.gov/
the Division of Drug Information, Center information as a subsection of the BiologicsBloodVaccines/
for Drug Evaluation and Research, Food ADVERSE REACTIONS section entitled GuidanceCompliance
and Drug Administration, 10001 New ‘‘Immunogenicity.’’ RegulatoryInformation/Guidances/
Hampshire Ave., Hillandale Building, In general, assays for detection of default.htm, or http://www.fda.gov/
4th Floor, Silver Spring, MD 20993– ADA facilitate understanding of the MedicalDevices/DeviceRegulationand
0002; or the Office of Communication, immunogenicity, safety, and efficacy of Guidance/GuidanceDocuments/
Outreach, and Development, Center for therapeutic protein products. However, default.htm, or http://
Biologics Evaluation and Research, the detection of ADA is dependent on www.regulations.gov.
Food and Drug Administration, 10903 key operating parameters of the assays
New Hampshire Ave., Bldg. 71, Rm. Dated: April 19, 2016.
(e.g., sensitivity, specificity), which vary Leslie Kux,
3128, Silver Spring, MD 20993–0002; or between assays. Therefore, the
the Office of the Center Director, Associate Commissioner for Policy.
development of valid, sensitive,
Guidance and Policy Development, [FR Doc. 2016–09449 Filed 4–22–16; 8:45 am]
specific, and selective assays to measure
Center for Devices and Radiological BILLING CODE 4164–01–P
ADA responses is a key aspect of
Health, Food and Drug Administration,
therapeutic protein product
10903 New Hampshire Ave., Bldg. 66,
development. DEPARTMENT OF HEALTH AND
Rm. 5431, Silver Spring, MD 20993–
0002. Send one self-addressed adhesive This guidance revises the draft HUMAN SERVICES
label to assist that office in processing guidance for industry entitled ‘‘Assay
your requests. See the SUPPLEMENTARY Development for Immunogenicity Food and Drug Administration
INFORMATION section for electronic Testing of Therapeutic Proteins’’ issued [Docket No. FDA–2015–P–3299]
access to the revised draft guidance in December 2009. The information in
document. the draft guidance has been reorganized Determination That THALITONE
for clarity, and the revised draft (Chlorthalidone USP) Tablets, 15
FOR FURTHER INFORMATION CONTACT: Ebla
guidance includes new information on Milligrams, Were Not Withdrawn From
Ali Ibrahim, Center for Drug Evaluation
titering and confirmatory assays. Sale for Reasons of Safety or
and Research, Food and Drug
Administration, 10903 New Hampshire This revised draft guidance is being Effectiveness
Ave., Bldg. 51, Rm. 6308, Silver Spring, issued consistent with FDA’s good AGENCY: Food and Drug Administration,
MD 20993, 301–796–0281; or Stephen guidance practices regulation (21 CFR HHS.
Ripley, Center for Biologics Evaluation 10.115). The revised draft guidance, ACTION: Notice.
and Research, Food and Drug when finalized, will represent the
Administration, 10903 New Hampshire current thinking of FDA on assay SUMMARY: The Food and Drug
asabaliauskas on DSK3SPTVN1PROD with NOTICES
Ave., Bldg. 71, Rm. 7301, Silver Spring, development and validation for Administration (FDA or Agency) has
MD 20993–0002, 240–402–7911; or immunogenicity testing of therapeutic determined that THALITONE
Peter Hudson, Center for Devices and protein products. It does not establish (chlorthalidone USP) tablets, 15
Radiological Health, Food and Drug any rights for any person and is not milligrams (mg), were not withdrawn
Administration, 10903 New Hampshire binding on FDA or the public. You can from sale for reasons of safety or
Ave., Bldg. 66, Rm. G434 (HFZ–410), use an alternative approach if it satisfies effectiveness. This determination will
Silver Spring, MD, 20993–0002, 301– the requirements of the applicable allow FDA to approve abbreviated new
796–6440. statutes and regulations. drug applications (ANDAs) for
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Document Created: 2016-04-23 01:38:50
Document Modified: 2016-04-23 01:38:50
| Category | Regulatory Information | |
| Collection | Federal Register | |
| sudoc Class | AE 2.7: GS 4.107: AE 2.106: | |
| Publisher | Office of the Federal Register, National Archives and Records Administration | |
| Section | Notices | |
| Action | Notice of availability. | |
| 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. | |
| 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. | |
| FR Citation | 81 FR 24106 |
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