Document ID: FDA-1999-D-0081-0051
Agency: fda
Document Type: Notice
Title: Testing of Retroviral Vector-Based Human Gene Therapy Products for
Replication Competent Retrovirus During Product Manufacture and
Patient Follow-up; Guidance for Industry; Availability
Posted Date: 2020-01-30T05:00Z

[Federal Register Volume 85, Number 20 (Thursday, January 30, 2020)]
[Notices]
[Pages 5448-5450]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-01700]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-1999-D-0081]

Testing of Retroviral Vector-Based Human Gene Therapy Products 
for Replication Competent Retrovirus During Product Manufacture and 
Patient Follow-up; 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 entitled ``Testing of Retroviral 
Vector-Based Human Gene Therapy Products for Replication Competent 
Retrovirus During Product Manufacture and Patient Follow-up; Guidance 
for Industry.'' The guidance provides

[[Page 5449]]

sponsors of retroviral vector-based human gene therapy products 
recommendations regarding the testing for replication competent 
retrovirus (RCR) during the manufacture of retroviral vector-based gene 
therapy products, and during follow-up monitoring of patients who have 
received retroviral vector-based gene therapy products. Recommendations 
include the identification and amount of material to be tested, and 
general testing methods. In addition, recommendations are provided on 
monitoring patients for evidence of retroviral infection after 
administration of retroviral vector-based gene therapy products. The 
guidance supersedes the document entitled ``Guidance for Industry: 
Supplemental Guidance on Testing for Replication Competent Retrovirus 
in Retroviral Vector Based Gene Therapy Products and During Follow-up 
of Patients in Clinical Trials Using Retroviral Vectors,'' dated 
November 2006. The guidance announced in this notice finalizes the 
draft guidance of the same title dated July 2018.

DATES: The announcement of the guidance is published in the Federal 
Register on January 30, 2020.

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-1999-D-0081 for ``Testing of Retroviral Vector-Based Human Gene 
Therapy Products for Replication Competent Retrovirus During Product 
Manufacture and Patient Follow-up; Guidance for Industry.'' 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.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.
    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 guidance to the 
Office of Communication, Outreach and Development, Center for Biologics 
Evaluation and Research (CBER), 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 the office in processing 
your requests. The guidance may also be obtained by mail by calling 
CBER at 1-800-835-4709 or 240-402-8010. See the SUPPLEMENTARY 
INFORMATION section for electronic access to the guidance document.

FOR FURTHER INFORMATION CONTACT: Melissa Segal, 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 document entitled ``Testing 
of Retroviral Vector-Based Human Gene Therapy Products for Replication 
Competent Retrovirus During Product Manufacture and Patient Follow-up; 
Guidance for Industry.'' The guidance provides sponsors of retroviral 
vector-based human gene therapy products recommendations regarding the 
testing for RCR during the manufacture of retroviral vector-based gene 
therapy products, and during follow-up monitoring of patients who have 
received retroviral vector-based gene therapy products. Recommendations 
are also provided for RCR testing during manufacture, including 
identification and amount of material to be tested, and general testing 
methods. In addition, recommendations are provided on monitoring 
patients for evidence of retroviral infection after administration of 
retroviral vector-based gene therapy products. The guidance supersedes 
the document entitled ``Guidance for Industry: Supplemental Guidance on 
Testing for Replication Competent Retrovirus in Retroviral Vector Based 
Gene Therapy Products and During Follow-up of Patients in Clinical 
Trials Using Retroviral Vectors'' dated November 2006. The guidance 
also supplements two other final guidance

[[Page 5450]]

documents, entitled ``Long Term Follow-Up After Administration of Human 
Gene Therapy Products; Guidance for Industry'' and ``Chemistry, 
Manufacturing, and Control Information for Human Gene Therapy 
Investigational New Drug Applications; Guidance for Industry,'' 
announced elsewhere in this issue of the Federal Register.
    In the Federal Register of July 12, 2018 (83 FR 32309), FDA 
announced the availability of the draft guidance of the same title 
dated July 2018. FDA received several comments on the draft guidance 
and those comments were considered as the guidance was finalized. In 
addition, editorial changes were made to improve clarity. The guidance 
announced in this notice finalizes the draft guidance dated July 2018.
    This guidance is being issued consistent with FDA's good guidance 
practices regulation (21 CFR 10.115). The guidance represents FDA's 
current thinking on testing of retroviral vector-based human gene 
therapy products for replication competent retrovirus during product 
manufacture and patient follow-up. 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

    The 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. 3501-3521). The 
collections of information in 21 CFR part 312 have been approved under 
OMB control number 0910-0014; 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 
either https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances or 
https://www.regulations.gov.

    Dated: January 27, 2020.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2020-01700 Filed 1-29-20; 8:45 am]
BILLING CODE 4164-01-P