Use of Donor Screening Tests to Test 
Donors of Human Cells, Tissues and 
Cellular and Tissue-Based Products 
for Infection with Treponema pallidum 
(Syphilis) 
_________________________________________________________________________ 
 
Guidance for Industry 
 
 
 
 
 
 
 
 
 
 
 
 
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/Guida
nces/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 
September 2015  Contains Nonbinding Recommendations 
 
 
Table of Contents 
 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
III.  RECOMMENDATIONS .................................................................................................. 3 
IV.    IMPLEMENTATION ...................................................................................................... 3 
V.  REFERENCE .................................................................................................................... 4 
 
 
 
i  Contains Nonbinding Recommendations 
 
Use of Donor Screening Tests to Test Donors of Human Cells, 
Tissues and Cellular and Tissue-Based Products for Infection with 
Treponema pallidum (Syphilis) 
__________________________________________________________________________ 
 
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 
 
We, FDA, are providing you, establishments that make donor eligibility determinations for 
donors of human cells, tissues and cellular and tissue-based products (HCT/P Establishments), 
with updated recommendations concerning donor testing for evidence of Treponema pallidum 
(T. pallidum) infection, the etiologic agent of syphilis.  As required under 21 CFR 1271.80(a) 
and (c) ( 1271.80(a) and (c)), you must test a donor specimen for evidence of the communicable 
disease agents specified in 21 CFR 1271.85, including T. pallidum, using appropriate FDA-
licensed, approved, or cleared donor screening tests, in accordance with the manufacturers 
instructions, unless an exception to this requirement applies under 21 CFR 1271.90.  This 
guidance clarifies that we do not consider cleared or approved diagnostic tests or pre-amendment 
devices (which have not been licensed, approved, or cleared) to be adequate for use in donor 
testing for T. pallidum infection under the criteria specified in  1271.80(c). 
 
This guidance applies to all HCT/P Establishments.  This guidance finalizes the draft guidance of 
the same title, dated October 2013.  This guidance supersedes the recommendations on 
compliance with the requirements for testing of HCT/P donors for T. pallidum infection under  
 1271.80(c), that are contained in the FDA guidance 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) (Ref. 1).  
 
FDAs guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidances describe 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. 
 
 
1  Contains Nonbinding Recommendations 
 
II.  BACKGROUND 
 
This guidance updates previous recommendations contained in the 2007 Donor Eligibility 
guidance concerning donor testing for evidence of infection with T. pallidum and clarifies the 
type of tests FDA considers appropriate to adequately and appropriately reduce the risk of 
transmission of T. pallidum.  We are providing this clarification to assist HCT/P Establishments 
in complying with the requirements under 21 CFR Part 1271, subpart C, for donor-eligibility 
determinations based on donor screening tests for T. pallidum.   
 
Under 21 CFR 1271.45(b), a donor-eligibility determination, based on donor screening and 
testing for relevant communicable disease agents and diseases, is required for all donors of cells 
or tissues used in HCT/Ps, except as provided under  1271.90.  To adequately and appropriately 
reduce the risk of transmission of relevant communicable diseases, and except as provided under  
 1271.90, you must test a specimen from the donor of cells or tissue, whether viable or 
nonviable, for evidence of infection due to relevant communicable disease agents, including T. 
pallidum (see  1271.85(a)(5)).  As stated previously in this guidance, under  1271.80(c), you 
must test for evidence of infection using appropriate FDA-licensed, approved, or cleared donor 
screening tests in accordance with the manufacturers instructions to adequately and 
appropriately reduce the risk of transmission of the disease agent. 
 
The 2007 Donor Eligibility guidance contains recommendations for complying with the 
requirements in 21 CFR Part 1271, subpart C, and applies to all HCT/Ps recovered on or after the 
effective date of the regulations, May 25, 2005.  In footnote 6 of the 2007 Donor Eligibility 
guidance, we stated, For purposes of this guidance, we consider FDA-cleared diagnostic 
serological tests to be adequate for use in donor screening for syphilis.  The 2007 Donor 
Eligibility guidance did not address the use of pre-amendments devices to meet the requirements 
of  1271.80(c), as applied to donor screening for syphilis.  The term pre-amendments device 
refers to a device legally marketed in the United States before May 28, 1976, when the Medical 
Device Amendments of 1976 (Pub. Law No. 94-295, 90 Stat. 539 (1976)) became effective.  A 
device can be a pre-amendments device if it has the same intended use as that marketed before 
May 28, 1976, has not been significantly changed or modified since then, and if a regulation 
requiring a premarket approval application for the device has not been issued by FDA.  Pre-
amendments devices meeting the above criteria are exempted from requirements for premarket 
submission and review requirements under the Medical Device Amendments of 1976.    
 
When the 2007 Donor Eligibility guidance was issued, few screening tests for evidence of T. 
pallidum infection in donors were licensed, cleared, or approved.  HCT/P Establishments 
expressed concern that the adoption of platform based donor screening tests would be overly 
burdensome during the early implementation of Part 1271.  After considering these issues, and as 
an interim measure pending greater availability of and access to these tests, we advised in the 
2007 Donor Eligibility guidance that we would consider all cleared serological diagnostic tests 
for evidence of T. pallidum infection to be adequate for donor screening purposes.  We are now 
updating the recommendation provided in the 2007 Donor Eligibility guidance regarding use of 
2  Contains Nonbinding Recommendations 
 
all cleared serological diagnostic tests to test for T. pallidum1.  In this guidance, we also are 
clarifying the status of pre-amendments devices used to test for T. pallidum.  Since the 2007 
Donor Eligibility guidance issued, several donor screening tests have been cleared.  We believe 
that the technology for donor screening tests has evolved such that FDA-licensed, approved, or 
cleared test systems with an indication for use in donor screening to test for evidence of T. 
pallidum infection are now widely available, and that laboratories now are proficient in their 
ability to utilize such systems.  The wide availability of this testing technology and widespread 
testing laboratory proficiency with these systems no longer support a policy for the use of 
diagnostic syphilis tests for use as a donor screening test.  We now clarify that, as of the 
implementation date of this guidance, we do not intend to exercise enforcement discretion related 
to the use of such tests as donor screening tests. 
 
 
III.  RECOMMENDATIONS  
 
This guidance updates prior recommendations and clarifies that:  
 
1.  We no longer intend to exercise enforcement discretion with respect to the use of 
diagnostic tests for evidence of infection with T. pallidum for use as HCT/P donor 
screening tests.  Rather, we intend to enforce the requirements provided under  
 1271.80(c) that establishments must use appropriate FDA-licensed, approved, or 
cleared donor screening tests in accordance with the manufacturers instructions to 
adequately and appropriately reduce the risk of transmission of disease agents such as T. 
pallidum. 
2.  Pre-amendments devices are not acceptable for use as a donor screening test for evidence 
of infection with T. pallidum.   
3.  This guidance applies to all HCT/Ps recovered after the implementation date of this 
guidance. 
 
You must, under  1271.85(a), test all donors of HCT/Ps for evidence of infection due to 
relevant communicable diseases including syphilis, except as provided under  1271.90(a).  You 
must test using appropriate FDA-licensed, approved, or cleared donor screening tests, in 
accordance with the manufacturers instructions, to adequately and appropriately reduce the risk 
of transmission of the disease agent ( 1271.80(c)).  Current FDA-licensed, approved or cleared 
donor screening tests are listed on the FDAs website at 
http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/TissueSafety/ucm095440.htm.  
 
 
IV.  IMPLEMENTATION 
 
We recommend that you implement the recommendations in this guidance as soon as feasible, 
but not later than 6 months after issuance of this guidance. 
                                                 
1 FDA provides additional discussion of syphilis assays, including information about nontreponemal and treponemal 
assays, in section VI.A of FDAs Guidance for Industry: Eligibility Determination for Donors of Human Cells, 
Tissues, and Cellular and Tissue-Based Products (HCT/Ps), dated August 2007 (Ref. 1). 
3  Contains Nonbinding Recommendations 
 
V.  REFERENCE 
 
1.  FDA Guidance for Industry: Eligibility Determination for Donors of Human Cells, Tissues, 
and Cellular and Tissue-Based Products (HCT/Ps), August 2007.  
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/G
uidances/Tissue/default.htm.  
 
4