Revised Recommendations for 
Determining Eligibility of Donors of 
Human Cells, Tissues, and Cellular and 
Tissue-Based Products Who Have 
Received Human-Derived Clotting Factor 
Concentrates 
 
 
Guidance for Industry 
 
This guidance is for immediate implementation. 
 
FDA is issuing this guidance for immediate implementation in accordance with  
21 CFR 10.115(g)(2) without initially seeking prior comment because the Agency has 
determined that prior public participation is not appropriate. 
 
FDA invites comments on this guidance.  Submit one set of either electronic or written 
comments on this guidance at any time.  Submit electronic comments 
to http://www.regulations.gov.  Submit written comments to the Division of Dockets 
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, 
Rockville, MD 20852.  You should identify all comments with the docket number listed in the 
notice of availability that publishes in the Federal Register.  FDA will review any comments we 
receive and revise the guidance when appropriate. 
 
Additional copies of this guidance are available from the Office of Communication, Outreach 
and Development (OCOD), 10903 New Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, 
MD 20993-0002, or by calling 1-800-835-4709 or 240-402-8010, or email ocod@fda.hhs.gov, or 
from the Internet 
at http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Gui
dances/default.htm. 
 
For questions on the content of this guidance, contact OCOD at the phone numbers or email 
address listed above. 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Biologics Evaluation and Research 
November 2016  Contains Nonbinding Recommendations 
 
Table of Contents 
 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 1 
III.  RECOMMENDATIONS .................................................................................................. 2 
IV.  IMPLEMENTATION ...................................................................................................... 3 
V.  REFERENCES .................................................................................................................. 4 
i  Contains Nonbinding Recommendations 
 
Revised Recommendations for Determining Eligibility of Donors of 
Human Cells, Tissues, and Cellular and Tissue-Based Products Who 
Have Received Human-Derived Clotting Factor Concentrates 
 
 
Guidance for Industry 
 
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or 
Agency) on this topic.  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.  To discuss an alternative approach, contact the FDA staff 
responsible for this guidance as listed on the title page. 
 
 
I.  INTRODUCTION 
 
This guidance provides you, establishments that make donor eligibility (DE) determinations for 
donors of human cells, tissues, and cellular and tissue-based products (HCT/Ps), with 
information on infectious-disease risks related to receipt of FDA licensed human-derived clotting 
factor concentrates (HDCFCs).  This guidance explains that FDA no longer considers FDA 
licensed HDCFCs as a risk factor for Human immunodeficiency virus (HIV), Hepatitis B virus 
(HBV), or Hepatitis C virus (HCV).  As such, receipt of FDA licensed HDCFCs, or sex with a 
person who has received FDA licensed HDCFCs, should not be considered a risk factor when 
determining eligibility of a donor of HCT/Ps.  This guidance supplements the recommendations 
regarding HDCFCs that are contained in the guidance entitled Eligibility Determination for 
Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps); Guidance 
for Industry dated August 2007 (August 2007 Guidance).   
 
FDAs guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidances describe the FDAs current thinking on a topic and should be 
viewed only as recommendations, unless specific regulatory or statutory requirements are cited.  
The use of the word should in FDAs guidances means that something is suggested or 
recommended, but not required. 
 
 
II.  BACKGROUND 
 
The manufacture of HDCFCs requires pooling of plasma from a large number of donors.  From 
the 1970s through the early 1980s, there were numerous reported cases of HIV, HBV, and/or 
HCV transmissions by pooled plasma products such as HDCFCs (Refs. 1, 2).  Methods for viral 
inactivation using solvent-detergent treatments were developed in 1985 and shown to be very 
effective against enveloped viruses, including HIV, HBV, and HCV (Refs. 3, 4, 5, 6).  These 
viral inactivation methods, which are currently being used by manufacturers, have led to 
1  Contains Nonbinding Recommendations 
 
substantial improvements in the safety of HDCFCs.  In addition, the licensure of new infectious-
disease testing technologies, such as nucleic acid tests (NATs), has improved HDCFC safety 
(Refs. 7, 8).  
 
In the August 2007 Guidance, FDA explained that HCT/P donors who have received HDCFCs, 
or who have had sex with a recipient of HDCFCs, should be considered ineligible to donate cells 
or tissues, in accordance with 21 CFR 1271.75(d), due to a risk of HIV, HBV, and HCV (Ref. 9).  
However, since publication of the August 2007 Guidance, it has become evident that the 
significant advances in viral inactivation technologies, pathogen reduction technologies, 
enhanced donor screening requirements, and improved testing technologies were effective in 
increasing HDCFC safety, as no transmissions of HIV, HBV, or HCV by an FDA licensed 
HDCFC have been documented in the past 25 years1 (Refs. 1, 2, 3, 10). 
 
In the document entitled Revised Recommendations for Reducing the Risk of Human 
Immunodeficiency Virus Transmission by Blood and Blood Products; Guidance for Industry 
dated December 2015, FDA explains that, given the enhanced safety measures now used in the 
manufacture of clotting factor concentrates, FDA does not consider the receipt of FDA licensed 
clotting factor concentrates or sex with a person who has received clotting factor concentrates to 
be a risk factor for HIV or hepatitis (Ref. 11).  Accordingly, FDA no longer recommends 
deferral for donors of blood and blood products who have had sex with an individual with 
hemophilia or related clotting factor deficiencies requiring treatment with clotting factor 
concentrates.  Further, FDA has not recommended a deferral for the receipt of other FDA 
licensed plasma-derivatives because of HIV or hepatitis risks (Ref. 11). 
 
 
III.  RECOMMENDATIONS 
 
For the purpose of determining eligibility of a donor as required under 21 CFR 1271.45, FDA no 
longer considers the receipt of clotting factor concentrates, or sex with a person who has received 
clotting factor concentrates, to be a risk factor for HIV, HBV, or HCV.  As such, HCT/P donors 
should not be considered ineligible due to the following conditions, and screening for these 
conditions is no longer necessary: 
 
1.  Persons with hemophilia or other related clotting disorders who have received 
HDCFCs at any time; 
2.  Persons who received clotting factors once to treat an acute bleeding event at any 
time; or 
3.  Persons who have had sex at any time with either of the persons described above. 
 
These recommendations supersede the recommendations listed in section IV.E.3. of the August 
2007 Guidance. 
 
 
                                                 
1 FDA licensed clotting factor concentrates are manufactured using viral inactivation technologies. 
 
2  Contains Nonbinding Recommendations 
 
IV.  IMPLEMENTATION 
 
This guidance is being issued for immediate implementation.  However, in accordance with  
21 CFR 1271.47, establishments must revise their relevant procedures prior to implementing 
changes.  Therefore, the recommendations apply to all HCT/Ps that an establishment recovers 
after it has revised its relevant procedures to reflect the contents of this guidance document. 
 
 
3  Contains Nonbinding Recommendations 
 
V.  REFERENCES  
 
1.  Franchini, M and Mannucci, PM, Past, present and future of hemophilia: a narrative review. 
Orphanet J Rare Dis, 2012. 7:24. 
 
2.  Stramer, SL, Dodd, RY, and Subgroup, AT-TDEID, Transfusion-transmitted emerging 
infectious diseases: 30 years of challenges and progress. Transfusion, 2013. 53(10 Pt 
2):2375-83. 
 
3.  Tabor, E, The epidemiology of virus transmission by plasma derivatives: clinical studies 
verifying the lack of transmission of hepatitis B and C viruses and HIV type 1. Transfusion, 
1999. 39(11-12):1160-8. 
 
4.  Solheim, BG, Pathogen reduction of blood components. Transfus Apher Sci, 2008. 39(1):75-
82. 
 
5.  Dichtelmuller, HO, Biesert, L, Fabbrizzi, F, Gajardo, R, Groner, A, von Hoegen, I, Jorquera, 
JI, Kempf, C, Kreil, TR, Pifat, D, Osheroff, W, and Poelsler, G, Robustness of 
solvent/detergent treatment of plasma derivatives: a data collection from Plasma Protein 
Therapeutics Association member companies. Transfusion, 2009. 49(9):1931-43. 
 
6.  Burnouf, T, Safety aspects in the manufacturing of plasma-derived coagulation factor 
concentrates. Biologicals, 1992. 20(2):91-100. 
 
7.  Hourfar, MK, Jork, C, Schottstedt, V, Weber-Schehl, M, Brixner, V, Busch, MP, 
Geusendam, G, Gubbe, K, Mahnhardt, C, Mayr-Wohlfart, U, Pichl, L, Roth, WK, Schmidt, 
M, Seifried, E, Wright, DJ, and German Red Cross, NATSG, Experience of German Red 
Cross blood donor services with nucleic acid testing: results of screening more than 30 
million blood donations for human immunodeficiency virus-1, hepatitis C virus, and hepatitis 
B virus. Transfusion, 2008. 48(8):1558-66. 
 
8.  Burnouf, T and Radosevich, M, Reducing the risk of infection from plasma products: specific 
preventative strategies. Blood Rev, 2000. 14(2):94-110. 
 
9.  Food and Drug Administration, Eligibility Determination for Donors of Human Cells, 
Tissues, and Cellular and Tissue-Based Product; Guidance for Industry, August 
2007. http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulat
oryInformation/Guidances/Tissue/UCM091345.pdf 
 
10. Centers for Disease Control and Prevention, Blood safety monitoring among persons with 
bleeding disorders--United States, May 1998-June 2002. MMWR Morb Mortal Wkly Rep, 
2003. 51(51-52):1152-4. 
4  Contains Nonbinding Recommendations 
 
 
11. Food and Drug Administration, Revised Recommendations for Reducing the Risk of Human 
Immunodeficiency Virus Transmission by Blood and Blood Products; Guidance for Industry, 
December 
2015. http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulat
oryInformation/Guidances/Blood/UCM446580.pdf  
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