
[Federal Register Volume 80, Number 246 (Wednesday, December 23, 2015)]
[Notices]
[Pages 79913-79915]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-32250]



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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2015-D-1211]


Revised Recommendations for Reducing the Risk of Human 
Immunodeficiency Virus Transmission by Blood and Blood Products; 
Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a document entitled ``Revised Recommendations for 
Reducing the Risk of Human Immunodeficiency Virus Transmission by Blood 
and Blood Products; Guidance for Industry.'' The guidance document 
provides blood establishments that collect blood or blood components, 
including Source Plasma, with revised donor deferral recommendations 
for individuals at increased risk for transmitting human 
immunodeficiency virus (HIV) infection. The guidance document 
recommends corresponding revisions to donor educational materials, 
donor history questionnaires and accompanying materials, along with 
revisions to donor requalification, product management, and testing 
procedures. The guidance announced in this notice finalizes the draft 
guidance of the same title dated May 2015 and supersedes the memorandum 
to blood establishments entitled ``Revised Recommendations for the 
Prevention of Human Immunodeficiency Virus (HIV) Transmission by Blood 
and Blood Products'' dated April 23, 1992 (1992 blood memo). While this 
guidance represents FDA's current thinking on the subject, our 
recommendations may evolve over time as new scientific evidence becomes 
available.

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 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-1211 for ``Revised Recommendations for Reducing the Risk of 
Human Immunodeficiency Virus Transmission by Blood and Blood 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: Valerie A. Butler, 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, 
``Revised Recommendations for Reducing the Risk of Human 
Immunodeficiency Virus Transmission by Blood and Blood Products; 
Guidance for Industry.'' The emergence of Acquired Immune Deficiency 
Syndrome (AIDS) in the early 1980s and the recognition that it could be 
transmitted by blood and blood products had profound effects on the

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U.S. blood system. Although initially identified in men who have sex 
with men (MSM) and associated with male-to-male sexual contact, AIDS 
was soon noted to be potentially transmitted by transfusion of blood 
products, and by infusion of clotting factor concentrates in 
individuals with hemophilia. Beginning in 1983, FDA issued 
recommendations for providing donors with educational material on risk 
factors for AIDS and for deferring donors at increased risk for AIDS in 
an effort to prevent transmission of the agent responsible for AIDS 
(later understood to be caused by HIV) by blood and blood products. MSM 
(originally identified as gay or bisexual men) were deferred due to the 
strong clustering of AIDS illness among MSM and the subsequent 
discovery of high rates of HIV infection in that population. FDA's 
recommendation for deferral of MSM was modified over time to improve 
its clarity and to promote compliance, including a shift of focus from 
a deferral based on group identification to a deferral based on 
specific behavior (male sex with another male).
    Since September 1985, FDA has recommended that blood establishments 
indefinitely defer male donors who have had sex with another male, even 
one time, since 1977. On April 23, 1992, FDA issued the 1992 blood 
memo, which consolidated its recommendations regarding the deferral of 
donors at risk of HIV, including the deferral for MSM, as well as 
deferral recommendations for other persons with behaviors associated 
with high rates of HIV exposure, namely commercial sex workers, those 
who inject non-prescription drugs, and certain other individuals with 
HIV risk factors.
    The use of donor educational material, specific deferral questions, 
and advances in HIV donor testing have reduced the risk of HIV 
transmission from blood transfusion from about 1 in 2500 transfusions 
prior to HIV testing to a current estimated residual risk of about 1 in 
1.47 million transfusions. Since the implementation in 1985 of donor 
testing for antibodies to HIV, FDA and the U.S. Department of Health 
and Human Services (HHS) have held a number of public meetings, 
including public scientific workshops and meetings of the Blood 
Products Advisory Committee and the HHS Advisory Committee on Blood 
Safety and Availability (ACBSA) to further review evidence and discuss 
FDA's blood donor deferral policies to reduce the risk of transmission 
of HIV by blood and blood products. Consistent with recommendations of 
the ACBSA in June 2010, studies that might support a policy change were 
carried out by the Public Health Service in 2011 to 2014. A 
recommendation for a policy change to the blood donor deferral period 
for MSM from indefinite deferral to 1 year since the last sexual 
contact was announced by the Commissioner of Food and Drugs in December 
2014. This guidance implements that recommended policy change.
    In addition, the guidance provides donor deferral recommendations 
for other individuals at increased risk for transmitting HIV infection, 
including commercial sex workers, non-prescription injection drug 
users, women who have sex with MSM, and certain other individuals with 
other risk factors. The guidance provides revised recommendations for 
donor educational materials, donor history questionnaires and 
accompanying materials, as well as for donor requalification and 
product management procedures.
    In the Federal Register of May 15, 2015 (80 FR 27973), FDA 
announced the availability of the draft guidance of the same title 
dated May 2015. FDA received over 700 comments on the draft guidance 
and those comments were carefully considered as the guidance was 
finalized. Comments were received from a variety of organizations, 
including patient advocacy groups representing users of blood products; 
lesbian, gay, bisexual and transgender advocacy groups; medical and 
professional societies; academic institutions; human rights 
organizations; local governments; members of Congress; and, the blood 
industry. Comments were also received from hundreds of individual 
commenters.
    Approximately one-half of the comments opposed FDA's time-based 
deferral policy for MSM and considered the proposed policy to be 
discriminatory and lacking a scientific rationale. Many of these 
comments recommended that FDA adopt an individual risk assessment based 
approach, regardless of an individual's sexual orientation or gender 
identity. Other comments supported a time-based deferral policy shorter 
than 1year, or no deferral period at all, because of advances in blood 
donor testing technologies that permit earlier detection of new HIV 
infections. Comments requested that FDA commit to reexamining its 
deferral policies as new technologies, such as pathogen reduction 
technology are implemented and data regarding compliance with the 
revised policies become available.
    Most of the remaining comments advocated for the continuation of 
the indefinite deferral policy for MSM and expressed concern regarding 
the safety of the blood should the revised policy for MSM donors be 
adopted. Opponents of the proposed change commented on the HIV 
incidence and prevalence rates among MSM; the potential failure of HIV 
tests to capture window-period infections; the risk of emerging 
pathogens for which testing does not exist; and, the potential for 
decreased compliance rates with the new deferral policy. Other comments 
argued that FDA should not compromise public health and the safety of 
the blood supply to satisfy special interest groups.
    A smaller number of comments, including those from certain patient 
advocacy organizations, supported the proposed 1-year deferral policy 
for MSM predicated on the establishment of a transfusion-transmitted 
infectious disease monitoring system to enhance safety monitoring and 
allow rapid responses to emerging threats to the blood supply. Further, 
similar comments advocated for an evaluation of the effectiveness of 
the donor educational materials and donor history questionnaires prior 
to the implementation of new donor deferral policies.
    Finally, comments received from the blood industry were generally 
supportive of the revised MSM donor deferral policy. However, some 
comments noted that manufacturers of plasma for further manufacturing 
use (i.e., to make injectable products), including Source Plasma, 
collected in the United States and intended for further manufacturing 
use in other countries, may need to retain an indefinite deferral 
policy for MSM to comply with the indefinite deferral policies 
established in other countries. Industry commenters also requested 
revisions to certain other donor deferral criteria for HIV risk and 
disagreed with FDA's proposal to include the signs and symptoms 
associated with HIV infection in the donor educational materials. 
Comments requested clarification regarding the eligibility of donors 
with false-positive HIV tests and on recommendations for product 
retrieval and notification of consignees of distributed blood 
components collected from a donor who should have been deferred for HIV 
risk factors. Some comments were also supportive of the additional 
guidance provided by FDA regarding transgender donors.
    Finally numerous commenters requested FDA to clarify the 
recommendation for deferral of women who have had sex with MSM.
    FDA carefully considered all of the comments received in response 
to the draft guidance and the available scientific data, including the 
results of

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recent studies conducted by the Public Health Service and revised the 
guidance accordingly. FDA considered several options to address the 
comments in response to the revised MSM donor deferral policy. Because 
evidence indicates that the indefinite deferral policy for MSM may have 
become less effective over time, FDA has determined that a change in 
policy is warranted at this time. Data on the limitations of nucleic 
acid tests to identify antibody negative window period HIV infections 
suggests that donor testing alone, absent any deferral for MSM, would 
result in an unacceptable increased risk of transfusion-transmitted 
HIV. Similarly, pretesting at risk donors with a rapid HIV test prior 
to donation would be logistically challenging and would not necessarily 
identify newly HIV-infected individuals. While individual donor 
assessment for risk has been implemented in a few countries, the 
implementation of this strategy in the United States would present 
significant practical challenges and currently there is no validated 
and accepted individual risk assessment tool or questionnaire. 
Therefore, FDA concluded a time-based deferral for history of male-male 
sex is the most appropriate policy to maintain the safety of the U.S. 
blood supply. Scientific data regarding the effectiveness of a 1-year 
deferral in Australia, a country with similar HIV epidemiology to the 
United States, supports FDA's policy change to the blood donor deferral 
period for MSM from indefinite deferral to 1 year since the last sexual 
contact. Scientifically robust data are not available for time-based 
deferrals of less than 1 year. FDA also concluded that scientific data 
are not currently available that would support revisions to the 
indefinite deferral policy for commercial sex workers or intravenous 
drug users.
    In response to comments, FDA made the following changes when 
finalizing the guidance: (1) Amended the recommendations regarding the 
inclusion of signs and symptoms associated with HIV in the donor 
educational materials; (2) revised the recommendation for the deferral 
of female donors who have had sex with MSM; (3) stated that FDA no 
longer recommends deferral for individuals who have had sex with an 
individual with hemophilia or related clotting deficiencies requiring 
treatment with clotting factor concentrates; and (4) revised the 
recommendations regarding product retrieval and consignee notification 
of distributed blood products collected from a donor who should have 
been deferred for HIV risk factors. In addition, FDA made the following 
changes to clarify certain recommendations in the guidance, which are 
consistent with current policy: (1) Clarified that donors who have been 
determined to have a false-positive HIV test may be reentered according 
to a requalification method found acceptable to FDA; (2) noted that 
recipients of allogeneic blood transfusions (i.e., not autologous 
transfusions), should be temporarily deferred; (3) provided reference 
to an FDA guidance on the collection of blood components from donors at 
risk of HIV infection; and (4) clarified the deferral by the 
responsible physician of a blood establishment of any donor if the 
donation could affect the health of the donor or the safety of the 
blood component. Additionally, the background section has been expanded 
to summarize FDA's evaluation of the available policy options under the 
available evidence relevant to the MSM deferral policy. Minor editorial 
changes have also been made to the guidance.
    FDA remains committed to exploring options and engaging in public 
discussions regarding enhancements to donor and public education 
regarding safe blood donors and evaluating the effectiveness of the 
donor history questionnaire. Further, with the implementation of a 
transfusion transmitted infectious disease monitoring system, FDA will 
be able to monitor donor risk factors and the safety of the blood 
supply, as well as investigate and refine blood safety measures in the 
future. FDA's recommendations may evolve over time as new scientific 
data become available on strategies to maintain or improve blood 
safety.
    The guidance announced in this notice finalizes the draft guidance 
dated May 2015 and supersedes the 1992 blood memo.
    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 recommendations for reducing the risk of HIV 
transmission by blood and blood 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

    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. 3501-3520). The 
collections of information in 21 CFR 601.12 have been approved under 
OMB control number 0910-0338; the collections of information in 21 CFR 
606.171 have been approved under OMB control number 0910-0458; and the 
collections of information in 21 CFR 610.46, 630.6, 640.3 and 640.63 
have been approved under OMB control number 0910-0116.

III. 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: December 17, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-32250 Filed 12-22-15; 8:45 am]
BILLING CODE 4164-01-P


