81 FR 54811 - Use of Nucleic Acid Tests To Reduce the Risk of Transmission of Hepatitis B Virus From Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products; Guidance for Industry; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 81, Issue 159 (August 17, 2016)

Page Range		54811-54813
FR Document		2016-19588

The Food and Drug Administration (FDA or Agency) is announcing the availability of a document entitled ``Use of Nucleic Acid Tests to Reduce the Risk of Transmission of Hepatitis B Virus from Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products; Guidance for Industry.'' The guidance document provides establishments that make donor eligibility determinations for donors of human cells, tissues, and cellular and tissue-based products (HCT/Ps), with recommendations concerning the use of FDA-licensed nucleic acid tests (NAT) in donor testing for hepatitis B virus (HBV) deoxyribonucleic acid (DNA). The guidance finalizes the draft guidance of the same title dated January 2016 and supplements previous FDA recommendations to HCT/P establishments concerning donor testing for hepatitis B surface antigen (HBsAg) and total antibody to hepatitis B core antigen (anti-HBc), in the document entitled ``Guidance for Industry: Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps)'' dated August 2007 (2007 Donor Eligibility Guidance).

Federal Register, Volume 81 Issue 159 (Wednesday, August 17, 2016)

[Federal Register Volume 81, Number 159 (Wednesday, August 17, 2016)]
[Notices]
[Pages 54811-54813]
From the Federal Register Online [www.thefederalregister.org]
[FR Doc No: 2016-19588]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2015-D-5073]

Use of Nucleic Acid Tests To Reduce the Risk of Transmission of
Hepatitis B Virus From Donors of Human Cells, Tissues, and Cellular and
Tissue-Based Products; 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 document entitled ``Use of Nucleic Acid Tests to
Reduce the Risk of Transmission of Hepatitis B Virus from Donors of
Human Cells, Tissues, and Cellular and Tissue-Based Products; Guidance
for Industry.'' The guidance document provides establishments that make
donor eligibility determinations for donors of human cells, tissues,
and cellular and tissue-based products (HCT/Ps), with recommendations
concerning the use of FDA-licensed nucleic acid tests (NAT) in donor
testing for hepatitis B virus (HBV) deoxyribonucleic acid (DNA). The
guidance finalizes the draft guidance of the same title dated January
2016 and supplements previous FDA recommendations to HCT/P
establishments concerning donor testing for hepatitis B surface antigen
(HBsAg) and total antibody to hepatitis B core antigen (anti-HBc), in
the document entitled ``Guidance for Industry: Eligibility
Determination for Donors of Human Cells, Tissues, and Cellular and
Tissue-Based Products (HCT/Ps)'' dated August 2007 (2007 Donor
Eligibility Guidance).

DATES: Submit either electronic or written comments on Agency guidances
at any time.

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

[[Page 54812]]

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-2015-D-5073 for ``Use of Nucleic Acid Tests to Reduce the Risk of
Transmission of Hepatitis B Virus from Donors of Human Cells, Tissues,
and Cellular and Tissue-Based Products; Guidance for Industry.''
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 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 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: Angela Moy, 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 ``Use of
Nucleic Acid Tests to Reduce the Risk of Transmission of Hepatitis B
Virus from Donors of Human Cells, Tissues, and Cellular and Tissue-
Based Products; Guidance for Industry.'' The guidance provides
establishments that make donor eligibility determinations for donors of
HCT/Ps, with recommendations concerning the use of FDA-licensed NAT in
donor testing for HBV DNA. FDA considers the use of FDA-licensed HBV
NAT in testing HCT/P donors to be necessary to adequately and
appropriately reduce the risk of transmission of HBV. The FDA-licensed
HBV NAT can detect evidence of the viral infection at an earlier stage
than the HBsAg and total anti-HBc tests. Therefore, FDA recommends the
use of FDA-licensed HBV NAT for testing donors of HCT/Ps for evidence
of infection with HBV.
HBV is a major global public health concern and has been
transmitted by blood transfusions and tissue transplantation. Available
literature has indicated possible transmissions of HBV by hematopoietic
stem cells and blood with HBV NAT positive/hepatitis B surface antibody
(anti-HBs) positive/HBsAg negative blood, irrespective of anti-HBc test
results. In blood donors, adding the HBV NAT testing for HBV reduces
the residual risk of transmission of HBV infection beyond that which
can be achieved by screening donors using only HBsAg and total anti-HBc
tests. In addition, it can detect breakthrough infections in previously
vaccinated individuals who are exposed to the virus, and HBV mutants
appear to be more likely detected by HBV NAT than by HBsAg assays.
In the United States, there are currently FDA-licensed HBV NAT
assays intended to screen blood samples from donors of whole blood and
blood components, other living donors (individual organ donors when
specimens are obtained while the donor's heart is still beating), and
blood specimens from cadaveric (non-heart-beating) donors. Some of
these are multiplex assays that can simultaneously detect HIV, HCV, and
HBV in a single blood specimen, thus improving the feasibility of
routine NAT testing for HBV. By analogy to the experience in the blood
donor setting, it is reasonable to expect that the residual risk of
transmission of HBV infection would be reduced by adding HBV NAT to the
testing strategy for HCT/P donors. HBV NAT's potential utility in
further reducing risk of HBV transmission by transplantation is mainly
restricted to the early HBsAg-negative phase of infection. In summary,
the available scientific data and the availability of FDA-licensed
assays support a recommendation that all HCT/P donors should be tested
using an FDA-licensed HBV NAT.
In the Federal Register of January 8, 2016 (81 FR 937), FDA
announced the

[[Page 54813]]

availability of the draft guidance of the same title dated January
2016. FDA received a few comments on the draft guidance and those
comments were considered as the guidance was finalized. The guidance
announced in this notice finalizes the draft guidance of the same title
dated January 2016 and supplements previous FDA recommendations to HCT/
P establishments concerning donor testing for HBsAg and total antibody
to anti-HBc, in the 2007 Donor Eligibility Guidance.
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 the ``Use of Nucleic Acid Tests to Reduce
the Risk of Transmission of Hepatitis B Virus from Donors of Human
Cells, Tissues, and Cellular and Tissue-Based 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. Electronic Access

Persons with access to the Internet may obtain the guidance at
either http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm or http://www.regulations.gov.

Dated: August 11, 2016.
Jeremy Sharp,
Deputy Commissioner for Policy, Planning, Legislation, and Analysis.
[FR Doc. 2016-19588 Filed 8-16-16; 8:45 am]
BILLING CODE 4164-01-P

Federal Register / Vol. 81, No. 159 / Wednesday, August 17, 2016 / Notices 54811

TABLE 3—ESTIMATED ONE-TIME REPORTING BURDEN 1
Number of Average
Number of Total one-time
Information collection activity responses per burden per Total hours
respondents responses
respondent response

Initial VQIP application ......................................................... 100 1 100 80 8,000
Initial VQIP application w/additional information ................. 100 1 100 100 10,000

Total .............................................................................. ........................ ........................ ........................ ........................ 18,000
1 There are no capital or operating and maintenance costs associated with the collection of information.

The guidance will inform food program. For the purpose of this (80 hours/importer × 100 importers) and
importers of application procedures for analysis, we assume that 50 percent of 100 importers will spend 10,000 hours
VQIP. We estimate that up to 200 all applications received will require (100 hours/importer × 100 importers) to
qualified importers will be accepted in additional information and it would submit their initial VQIP applications
the first year of VQIP. We estimate that take an additional 20 person-hours by for a total one-time reporting burden of
it will take 80 person-hours to compile the importer to provide that 18,000 hours (see table 3).
all the relevant information and information. Therefore, we estimate that
complete the application for the VQIP 100 importers will spend 8,000 hours

TABLE 4—ESTIMATED ANNUAL REPORTING BURDEN 1
Number of Average
Number of Total annual
Information collection activity responses per burden per Total hours
responses responses
respondent response

Subsequent year VQIP application ...................................... 200 1 200 20 4,000
Request to reinstate participation ........................................ 2 1 2 10 20

Total .............................................................................. ........................ ........................ ........................ ........................ 4,020
1 There are no capital or operating and maintenance costs associated with the collection of information.

The guidance states that each VQIP Dated: August 12, 2016. for donors of human cells, tissues, and
participant will submit to FDA a notice Jeremy Sharp, cellular and tissue-based products
of intent to participate in VQIP on an Deputy Commissioner for Policy, Planning, (HCT/Ps), with recommendations
annual basis. We expect that each of the Legislation, and Analysis. concerning the use of FDA-licensed
expected 200 importers in VQIP would [FR Doc. 2016–19643 Filed 8–16–16; 8:45 am] nucleic acid tests (NAT) in donor testing
apply in the subsequent year to BILLING CODE 4164–01–P for hepatitis B virus (HBV)
participate in VQIP. We expect that an deoxyribonucleic acid (DNA). The
application to participate in VQIP in a guidance finalizes the draft guidance of
subsequent year will take significantly DEPARTMENT OF HEALTH AND the same title dated January 2016 and
less time to prepare than the initial HUMAN SERVICES supplements previous FDA
application. We use 25 percent of the recommendations to HCT/P
amount of effort to prepare and submit Food and Drug Administration establishments concerning donor testing
the initial application for acceptance in [Docket No. FDA–2015–D–5073] for hepatitis B surface antigen (HBsAg)
VQIP. Therefore, it is expected that, on and total antibody to hepatitis B core
average, each VQIP importer will spend Use of Nucleic Acid Tests To Reduce antigen (anti-HBc), in the document
20 hours to complete and submit a VQIP the Risk of Transmission of Hepatitis entitled ‘‘Guidance for Industry:
application for each subsequent year. B Virus From Donors of Human Cells, Eligibility Determination for Donors of
The annual burden of completing a Tissues, and Cellular and Tissue- Human Cells, Tissues, and Cellular and
subsequent year application to Based Products; Guidance for Tissue-Based Products (HCT/Ps)’’ dated
participate in VQIP status by 200 Industry; Availability August 2007 (2007 Donor Eligibility
importers is estimated at 4,000 hours AGENCY: Food and Drug Administration, Guidance).
(200 applications × 20 hours/ HHS. DATES: Submit either electronic or
application) (see table 4). written comments on Agency guidances
ACTION: Notice of availability.
Finally, we have added to the VQIP at any time.
estimated annual reporting burden an SUMMARY: The Food and Drug ADDRESSES: You may submit comments
estimate of the burden associated with Administration (FDA or Agency) is as follows:
importers’ requests to reinstate announcing the availability of a
participation in VQIP after their document entitled ‘‘Use of Nucleic Acid Electronic Submissions
mstockstill on DSK3G9T082PROD with NOTICES

participation is revoked. We believe Tests to Reduce the Risk of Submit electronic comments in the
most participants will not need to use Transmission of Hepatitis B Virus from following way:
this provision, and we have included an Donors of Human Cells, Tissues, and • Federal eRulemaking Portal: http://
estimate that reflects this. Upon Cellular and Tissue-Based Products; www.regulations.gov. Follow the
implementation of the VQIP, we will Guidance for Industry.’’ The guidance instructions for submitting comments.
reevaluate our estimate for future OMB document provides establishments that Comments submitted electronically,
submission and revise it accordingly. make donor eligibility determinations including attachments, to

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Document Created: 2018-02-09 11:35:22
Document Modified: 2018-02-09 11:35:22

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		Submit either electronic or written comments on Agency guidances at any time.
Contact		Angela Moy, 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.
FR Citation		81 FR 54811

81 FR 54811 - Use of Nucleic Acid Tests To Reduce the Risk of Transmission of Hepatitis B Virus From Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products; Guidance for Industry; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICESFood and Drug Administration

Federal Register Volume 81, Issue 159 (August 17, 2016)

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration