.. _.,,.hrr 
~ 
~ DEPARTl\\ENT Of HEALTH&. HUMAN SERVICES  Public Health Service 
Food and Drug Administration 
Bethesda, MD  ~20892 
December  2,  1987 
FROM:  Director;  Office of Biologics Research  and  Review 
Food  and  Drug  Administration 
SUBJECT:  Recommendations  for the Management  of Donors  and Unitsl 
that are  Initially Reactive  for Hepatitis B Surface Antigen  (HBsAg) 
TO:  All Reg_ist.ered  Blood  Establishments 
These  recommendations  set forth a  series of procedures  by  which  an  initially 
HBsAg  reactive donor  may  be  reevaluated by  a  blood  establishment,  providing 
that all other donor  suitability requirements  are met.  The  decision of 
whether an  initially reactive donor  is to be  reevaluated  is  left to the  blood 
establishment.  Furthermore,  a  blood  establishment may  adopt more  stringent 
procedures,  provided  they are. consistent with  these  recommendations.  At  each 
step in  this procedure,  the  performance  of each test and  the  interpretation of 
results  should  be  as  specified, in  the package  insert  for  that kit. 
I.  Test for HBsAg  ("Screening Test") 
Each donation shall  be  tested for HBsAg  by  an  FDA-licensed  test of 
third-generation  sensitivity (21  CFR  610.40).2 
a.  If the  initial  test result is non-reactive,  the donor may  be  accepted 
and  the  unit may  be  used  for  transfusion or further manufacturing. 
b.  If the  initial  test  result  is reactive,  the  sample  should be 
retested,  in duplicate. 
i.  If the  sample  is not repeatably reactive,  the donor may  be 
accepted  and  the unit may  be  used  for  transfusion or further 
manufacturing. 
ii.  If  the  sample  is  repeatably reactive  (i.e.,  if either or both of 
the duplicates are reactive),  the unit  should not be used  for 
transfusion or  further manufacturing,  except.  as  provided  in 
21  CFR  610.40(d).  For evaluation of  the donor,  the sample 
should  be  tested by  an  FDA-licensed  confirmatory 
(neutralization)  test for HBsAg.  See Section II. 
iii.  If repeac.testing  is inconclusive,  not  done  in duplicate, 
initially ~isinterpreted, etc.,  see Section V and  treat the 
unit as  reactive. 
!Throughout  these  recommendations,  "unit" has  t;>ee~ used as  if it were 
synonymous  With  an  entire donation.  However,  1t 1s  intended  to apply to 
all components  prepared  from  the  unit  in question. 
2Exceptions  to each donation being  tested for HBsAg  may  be  made  in the 
case of donations  from  "dedicated donors"  as described  in "Revised 
Guidelines  for  the Collection of Platelets,  Pheresis," January 1985.  2 
II.  Confirmatory Test for HBsAg 
a.  If the sample  is confirmed positive,  the donor  is permanently 
deferred. 
b.  If the sample  is not  neutralizable,  it should  be  tested for anti-HBc 
with an FDA-approved  test.  See Section  III. 
c.  If testing  is  inconclusive,  see Section V and  treat the  unit as 
reactive. 
III.  Test for Anti-HBc 
The  testing  referred  to  this Section is intended  to evaluate further 
i~ 
the  status of the donor.  If this  testing has  already been performed  in 
the course  of surrogate  testing  for  this donation,  those  results may  be 
used. 
a.  If the  initial test result is reactive,  the  test should be  repeated 
in duplicate with that kit. 
i.  If the  sample  is  repeatably reactive  (i.e.,  if either or both of 
the duplicates are reactive),  the donor  should be  permanently 
deferred. 
ii.  If the sample  is not  repeatably  reactive,  proceed as  in 
Section  III.b,  below. 
b.  If the  sample  is non-reactive,  the donor  need  not be  excluded  but 
should  be  put in a  status  that will  require  review (see Section 
IV)  at the  time  of  the subsequent donation,  after a minimum  of 
eight weeks. 
c.  If testing  is inconclusive,  not done  in duplicate,  initially 
misinterpreted,  etc.,  see Section V and  treat the unit as  reactive. 
IV.  Tests at the Time  of  the Subsequent Donation 
A minimum  of eight weeks  should  elapse between  the previous donation 
(i.e.,  that considered  in Sections  I-III) and  the one  considered  in this 
Section.  A sample  drawn  at the  time  of  this subsequent donation should 
be  initially tested and,  if reactive,  retested  in duplicate for HBsAg  and 
for anti-HBc as  in?icated in Sections  I  and  III,  respectively,  above. 
a.  If the  sample  drawn  at this time  is reactive for anti-HBc  (regardless 
of  the  result of the  test for HBsAg),  the donor  should be  permanently 
deferred and  thErUnit  should  not be  used.  3 
b.  If the  sample  drawn  at this time  is non-reactive  for anti-HBc  and  the 
initial test result  is non-reactive for HBsAg,  the donor may  be 
accepted  and  the unit may  be  used. 
c.  If the sample  drawn  at this  time  is non-reactive for anti-HBc  and  the 
initial test result is  reactive for HBsAg,  the sample  should be 
subjected to  the  testing algorithm which  begins  with  I.b,  above.3 
V.  If,  at any  point after an  initially reactive  for HBsAg  but before 
resul~ 
completion of  the  testing on a donation,  the quantity of material  from 
that donation becomes  insufficient for completion of the  testing,  the 
unit must  not be  used  and  the  testing algorithm which begins with  IV, 
above,  should be  used  in d~termining donor acceptability. 
The  recommendations  contained in this memorandum  may  be  implemented 
immediately.  Any  questions  concerning  the  recommendations  should  be 
addressed  to Dr.  Robin Biswas,  Division of Blood  and  Blood  Products,  at 
(301)  496-4288. 
~~ 
Elaine C.  Esber,  M.D. 
3If this testing leads  to point III.a.ii or III.b,  above,  i.e.,  if the 
sample  is repeatably  reactive for HBsAg  but  not neutralizable in the 
confirmatory test for HBsAg  and  non-reactive for anti-HBc,  the unit should 
not be  used  but the donor may  (at his/her own  discretion and  that of  the 
establishment)  return and  re-enter the  testing scheme  at point IV,  above. 
Such  returns may  be  repeated  (at the discretion of the donor  and  the 
establishffien~) until a  final  decision (i.e.,  that equivalent to IV.a  or 
IV.b)  can be  made  on  the basis of  the  testing algorithm.  (It is 
recommended  that,  for the  initial and  the second  donations,  the  tests for 
HBsAg  be  performed with one  type  of kit--e.g.,  mouse  monoclonal  EIA  from 
the same  manufacturer.  If the  results suggest that the samples  are 
repeatably  reactive  but no~ confirmed because of  interaction with animal 
antibody used  in this kit,  a  kit employing  antibody from  a different 
species may  be  used  tG test subsequen~ donations.)  December  2,  1987 
Flow  01art for Hepatitis B Testing 
(Numbering  of Steps Corresponds  to  that in Recommendations; 
-_  R = Reactive;  NR  =Non-reactive) 
I.  HBsAg  "Screening Test" 
~ 
I.a.  Result:  NR  I.b.  Result: R 
Use  unit  Retest X 2 
Retain Donor  ~ 
I.b.i.  Result:  2 NR  I.b.ii. Result:  2 R or 1 R,  1 NR 
Use  unit- "HBsAg  Repeatably Reactive" 
Retain Donor  Discard unit 
l 
II. HBsAg  Confirmatory Test 
_  (Neutralization) 
Confi~tneutralizable 
II.a.  Result:  l 
Positive  [Discard  unit]* 
[Discard  unit]* 
Defer Donor 
permanently 
III.  Test  for Anti-HBc** 
~ 
III.a.  Result:  R  III.b. Result:  NR 
[Discard  unitl*  [Discard  unit]* 
Retest X 2  "Flag,. Donor  record 
III.a.i. Result:  2 R or 1 R,  1 NR  III.a.i1.  Result:  2 NR 
nAnti-HBc  Repeatably Reactive"  [Discard uni tf 
[Discard  unit]*  "Flag" Dono~rd 
Defer Donor  permanently 
Review donor 
status at 
next.donation 
I 
' 
...v 
see next  page 
* 
Square brackets  indicate that this decision 
was  already made  at step  I.b.ii. 
**If this  testing has  already been performed  in the 
course of surrogate  testing for  this donation,  those 
results may  be  used.  December  2,  1987 
Flow  Chart  for Hepatitis B Testing,  continued 
(Numbe~ing of Steps  Corresponds  to  that  in Recommendations; 
R =Reactive;  NR  =Non-reactive) 
IV.  Tests at Time  of Subsequent Donation  (~ 8  weeks) 
Test for Anti-HBc 
Result:  R 
Retest X 2 
IV.a.  Result:  2 R or 1 R,  1 NR  Result:  2 NR 
"Anti-HBc Repeatably  Positive" 
~ 
Discard  unit 
Defer Donor  Permanently  Test for HBsAg 
~ 
IV. b.  Result:  NR  IV.c.  Result:  R 
Use  unit  Retest. X 2 
Re-enter Donor  ~ . 
Result:  2 NR~  Result:  ~R or 1 R,  1 NR 
Use  unit  "HBsAg  Repeatably Reactive 
Re-enter Donor  Discard unit 
Proceed  as  in 
Section  II of 
Recommendations 
(See  also footnote  3)