FDA Recommendations for Donor Deferral (12/12/91)

Date:     December 12, 1991

From:     Acting Director, Center for Biologics Evaluation and
          Research

Subject:  Clarification of FDA Recommendations for Donor
          Deferral and Product Distribution Based on the Results
          of Syphilis Testing

  To:     All Registered Blood Establishments

Background

For at least 30 years, a screening test for syphilis has been
performed as part of routine laboratory testing on every unit of
blood or blood component for transfusion.  Most, if not all,
states have required reporting of reactive screening results to
the Department of Health, and confirmatory testing has usually
been done by health departments rather than blood centers.  Whole
blood and red blood cells with reactive screening results and
negative confirmatory results are usually discarded, although FDA
has stated that use is acceptable if units are labeled with both
the reactive screening test result of record and the negative
confirmatory test.  Source Plasma collected prior to receipt of
screening test results has been considered acceptable for further
manufacturing.  Donors whose blood or plasma tested reactive were
not in the past deferred for any specific time period, but were
often asked to provide evidence of treatment before donating
again.  

FDA regulations require that Source Plasma donors be tested for
syphilis on the day of first medical examination for
plasmapheresis and at least every four months thereafter.  The
regulations do not require the labeling of each unit with the
screening test results.  FDA has not recommended product
retrieval when repeat donors test reactive for syphilis because
transmission of syphilis has not been considered a health risk
for plasma derivatives.  For continued Source Plasma collection
from a donor who is known to have a reactive test for syphilis,
documentation of medical treatment is required (21 CFR
640.65)(2)(iv).  

In the memorandum to all blood establishments dated December 5,
1990, the Food and Drug Administration (FDA) recommended that
blood establishments defer potential blood and plasma donors who
provide positive responses to a question about having had or
having been treated for syphilis or gonorrhea during the
preceding 12 months.  Since publication of this recommendation, a
number of blood establishments have sought clarification as to
whether this additional donor suitability criterion has altered
the way in which tests for syphilis should be used as a basis for
donor deferral, removal of product from use channels, or
recipient tracing.  The purpose of this memorandum is to clarify
FDA's recommendations on the use of tests for syphilis in regard
to AIDS-related risk. 

Rationale for Change

Asking donor history questions concerning risk factors and
performing serological tests for markers of infectious diseases
are each important elements to better assure the safety of the
blood supply.  In recommending that donors who have a history of
diagnosis or treatment for syphilis or gonorrhea in the last 12
months be deferred, the FDA intended to broaden the donor
deferral criteria to exclude additional individuals who might be
at increased risk of HIV infection due to heterosexual
transmission.  Although recommendations for management of units
or donors based on the results of serological testing for
syphilis were not specifically addressed earlier, it cannot be
ignored that a confirmed positive screening test for syphilis is
in most cases evidence of recent or untreated syphilis and that
this information can supplement the use of donor history
questions in making deferral decisions. 

Donor Deferral Recommendation

To ensure a uniform approach to these issues, FDA is now making
an additional recommendation that may be implemented immediately. 
Concurrent with implementation, licensed establishments should
revise their standard operating procedures and submit a statement
to their license application file containing the information
indicated in the attached example.  This statement indicates that
a revised standard operating procedure consistent with the
following recommendation has been implemented:
 
     Donors who are found to have a reactive screening
     test for syphilis by the Automated Reagin Test (ART),
     the Rapid Plasma Reagin Test (RPR), the Venereal
     Disease Research Laboratory Slide Technique (VDRL),
     or other screening test, should be temporarily
     deferred pending the outcome of a confirmatory test
     such as the Fluorescent Treponemal Antibody
     Absorption Test (FTA).  Donors who are found to have
     a positive FTA (or other confirmatory test), or for
     whom no additional test result is available, should
     be deferred for 12 months.  (In the event that a
     history of therapy for syphilis in the last 12 months
     is established, the 12 month deferral period may be
     calculated from the established date of diagnosis.) 
     After 12 months, deferred donors may be requalified
     if they have a negative screening test.  For cases in
     which the positive serology was confirmed, evidence
     of adequate treatment for syphilis, documented by a
     letter from a physician or public health clinic,
     should also be obtained.

The following additional points of clarification are intended to
resolve confusion which may exist regarding current
recommendations:

1.   FDA is not recommending at this time that extant units of
     whole blood, blood components, and Source Plasma be removed
     from use channels if previously collected from donors who
     subsequently provide a history of syphilis or gonorrhea
     within the last 12 months, or who are found subsequently to
     have reactive or confirmed tests for syphilis and have no
     other disqualifying history or test results, nor is FDA
     recommending that the blood center notify hospitals for the
     purpose of tracing recipients of such products.

2.   For Source Plasma, current collection and labeling
     requirements related to the results of serologic tests are
     found in 21 CFR 640.65 and 21 CFR 640.70.  FDA is not
     recommending that the frequency of serological testing for
     syphilis for Source Plasma be altered (i.e., initially,
     then every four months) and Source Plasma collected before
     serologic test results are received may be used for further
     manufacturing.      

3.   For whole blood and blood components, otherwise suitable
     units may be released for transfusion if they were obtained
     from donors who tested reactive for syphilis by screening
     tests but had negative results of confirmatory testing by
     FTA or equivalent methods on the same collection.  For
     units to be released for transfusion, the confirmatory test
     should be performed on every donation for which there is a
     reactive screening test (i.e., prior negative confirmatory
     results are insufficient to qualify a collection with a
     reactive screening test).  Such units should be labeled as
     reactive by a screening test for syphilis and negative by
     FTA (or other confirmatory test).

4.   In cases of autologous donation of blood or components,
     collections with reactive screening tests which are either
     positive by FTA, or not further tested, may be used for
     transfusion provided that they bear both an "Autologous Use
     Only" label and a biohazard label.  A written report of the
     test results should be provided to the patient's physician
     before transfusion.  Guidance on proper labeling of
     autologous blood and components may be found in memoranda
     dated March 15, 1989 and February 12, 1990.  Biohazard
     labels are described in the current Guideline for the
     Uniform Labeling of Blood and Components.

     It should be noted that the recommendation on labeling of
     autologous blood and components reactive for syphilis
     differs from FDA recommendations issued on March 15, 1989,
     with respect to restrictions on the use of autologous blood
     which is positive for other infectious disease markers. 
     For release of autologous units found to be repeatedly
     reactive for anti-HIV or HBsAg, the physician's written
     request remains necessary.      

                            ____________________________
                            Gerald V. Quinnan, Jr., M.D.  
                            Acting Director, CBER

     _________________________________________________________

Gerald V. Quinnan, Jr., M.D.
Acting Director
Center for Biologics Evaluation and Research
Food and Drug Administration
8800 Rockville Pike
Bethesda, MD. 20892
ATTN: HFB 240

Dear Dr. Quinnan:

In response to your recent recommendations for revision of STS
positive donor deferral and product distribution procedures
affirm that: 

______    Our program is in complete compliance with FDA's
          recent recommendations included in the memorandum to
          all registered blood establishments dated Dec. 5,
          1990.

______    A revised standard operating procedure consistent
          with the recommendations has been implemented.

          Date implemented: __________________

          
Please add this information to the license file for facility:

     License No. ____________________________________

     Registration No. _______________________________

     Facility Name __________________________________

     Address ________________________________________

     ________________________________________________

 Responsible Person:Name _________________________

     Telephone No. _______________________________

     Date of response ____________________________

     Sincerely yours,

     _________________________________
     Signature