E B—Anti-HBc Chart 3 10/2004 Anti-HBc Testing Background uCan an algorithm be validated to reenter deferred donors who are falsely anti-HBc reactive? uIf so, what would be the yield of reentry? uUnanimous support from BPAC (Oct 21, 2004) for validation of a reentry algorithm –Test a follow up sample by: Highly sensitive HBV DNA assay (
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E0304148B—Anti-HBc Chart 1 10/2004 Anti-HBc Testing and Donor Reentry Results of a Pilot Study Susan L. Stramer, Ph.D. Susan L. Stramer, Ph.D. American Red Cross American Red Cross Blood Products Advisory Committee Blood Products Advisory Committee Meeting Meeting Nov 4, 2005 (update from Oct 21, 2004 Nov 4, 2005 (update from Oct 21, 2004 meeting) meeting) In collaboration with: In collaboration with: National Genetics Institute and Abbott Laboratories National Genetics Institute and Abbott Laboratories
Transcript
E0304148B—Anti-HBc Chart 1 10/2004
Anti-HBc Testing and Donor ReentryResults of a Pilot Study
Nov 4, 2005 (update from Oct 21, 2004 meeting)Nov 4, 2005 (update from Oct 21, 2004 meeting)
In collaboration with:In collaboration with:
National Genetics Institute and Abbott LaboratoriesNational Genetics Institute and Abbott Laboratories
E0304148B—Anti-HBc Chart 2 10/2004
Anti-HBc TestingBackground
Historical/present RR rates range from 0.4%-1.6%Historical/present RR rates range from 0.4%-1.6%– False positivity highFalse positivity high
• 25-87% reported25-87% reported• dependent on specificity of test useddependent on specificity of test used
No confirmatory/supplemental testsNo confirmatory/supplemental tests– 1X anti-HBc RR may donate again; impact of RR notification1X anti-HBc RR may donate again; impact of RR notification– 2X anti-HBc RR deferred2X anti-HBc RR deferred
Historical number of deferred donors who lack other Historical number of deferred donors who lack other deferral codes deferral codes – > 200,000 April 1991-Dec 2003> 200,000 April 1991-Dec 2003– > 500,000 nationwide since Feb 1987> 500,000 nationwide since Feb 1987
E0304148B—Anti-HBc Chart 3 10/2004
Anti-HBc TestingBackground
Can an algorithm be validated to reenter deferred Can an algorithm be validated to reenter deferred donors who are falsely anti-HBc reactive?donors who are falsely anti-HBc reactive?
If so, what would be the yield of reentry?If so, what would be the yield of reentry? Unanimous support from BPAC (Oct 21, 2004) Unanimous support from BPAC (Oct 21, 2004)
for validation of a reentry algorithmfor validation of a reentry algorithm– Test a follow up sample by:Test a follow up sample by:
• Highly sensitive HBV DNA assay (Highly sensitive HBV DNA assay (<<10 copies/mL)10 copies/mL)• ““Alternate” anti-HBc assay having improved Alternate” anti-HBc assay having improved
specificityspecificity• (and HBsAg)(and HBsAg)• Above tests must be negative Above tests must be negative
E0304148B—Anti-HBc Chart 4 10/2004
Anti-HBc TestingProject Yield Based on Current 2X Reactive Algorithm
3.9 million donors (6.5 million donations) from 2000 3.9 million donors (6.5 million donations) from 2000 studiedstudied– 0.64% anti-HBc overall repeat reactive rate0.64% anti-HBc overall repeat reactive rate
• 1.37% from FT/0.24% from RPT donors 1.37% from FT/0.24% from RPT donors 75% 1X anti-HBc reactive donors became 2X on 75% 1X anti-HBc reactive donors became 2X on
next donation (plus another 13% over next 3 years)next donation (plus another 13% over next 3 years)– 88% FT and 38% RPT88% FT and 38% RPT
Anti-HBc reentry algorithms projected to have higher Anti-HBc reentry algorithms projected to have higher yields if a “different” test is introduced; i.e., blood yields if a “different” test is introduced; i.e., blood system converts to a different methodsystem converts to a different method
E0304148B—Anti-HBc Chart 5 10/2004
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Mean RR by NTL (FY2006)NTL Percent N NTL Percent N NTL Percent N
Reactive Rates for Anti-HBc (Ortho)through July 2005
Mean RR = 0.39 Total N = 1,142,470Mean IR = 0.54
DET 0.28 289,547 CHA 0.42 227,840 PHL 0.41 241,895STL 0.32 216,655 POR 0.57 166,533
3000 anti-HBc RR 3000 anti-HBc RR unlinkedunlinked donations selected in 2001 for donations selected in 2001 for further testing by NAT (HBV PCR at NGI)further testing by NAT (HBV PCR at NGI)– Surplus NAT samples in PPTs (limit contamination)Surplus NAT samples in PPTs (limit contamination)– Criterion for inclusion was nonreactive by all other test Criterion for inclusion was nonreactive by all other test
methodsmethods– No preselection of 1X versus 2X anti-HBc RRsNo preselection of 1X versus 2X anti-HBc RRs
• 3000 chosen to allow a large enough sample size to 3000 chosen to allow a large enough sample size to include significant numbers of 2X RR donorsinclude significant numbers of 2X RR donors– 23.6% of ARC donors over a comparable time 23.6% of ARC donors over a comparable time
were 2X anti-HBc RRwere 2X anti-HBc RR– Approx 708 of 3000 were 2X anti-HBc RRApprox 708 of 3000 were 2X anti-HBc RR
E0304148B—Anti-HBc Chart 8 10/2004
Anti-HBc RR Donation PCR Testing (NGI)Pilot Study
Samples tested individually by HBV DNA Samples tested individually by HBV DNA – UltraQual 8-rxn, 0.2-mL inputUltraQual 8-rxn, 0.2-mL input– Reactivity in any of 8 tests = PositiveReactivity in any of 8 tests = Positive– Sensitivity 9 IU/mLSensitivity 9 IU/mL
– 11 < 100 copies/mL11 < 100 copies/mL• Average of 1.7 per 8 reactions reactiveAverage of 1.7 per 8 reactions reactive
– 8 with viral loads of 100-500 copies/mL; 287.5 mean8 with viral loads of 100-500 copies/mL; 287.5 mean• Average of 4.75 per 8 reactions reactiveAverage of 4.75 per 8 reactions reactive
E0304148B—Anti-HBc Chart 9 10/2004
HBV DNA in “anti-HBc-only” units
Sample dates 1991-95 2001 2002-03
No. tested 395 3,000 3,956
No. DNA-pos 4 19 14
Rate: Calc’ted Direct Direct
per HBc-pos 0.24% 0.63% 0.35%
per tx unit 1:49,000 1:37,000 1:54,000
Viral Load (copies/mL)
all < 100 68% < 100 93% MP- NAT (-)
Parameter REDS ARC Roche
E0304148B—Anti-HBc Chart 10 10/2004
Anti-HBc RR Donation PCR Testing (NGI)Pilot Study
3000 samples tested by Abbott PRISM anti-HBcore 3000 samples tested by Abbott PRISM anti-HBcore using licensed lotsusing licensed lots– Study initiated following qualification of PPTs on Study initiated following qualification of PPTs on
the PRISM and availability of “licensed” lotsthe PRISM and availability of “licensed” lots– Assumption is that 19 HBV DNA positives would Assumption is that 19 HBV DNA positives would
would represent “eligible donors” for reentrywould represent “eligible donors” for reentry• Testing completedTesting completed
– Anti-HBc reactives investigated for anti-HBc IgM Anti-HBc reactives investigated for anti-HBc IgM anti-HBs as samples volume allowsanti-HBs as samples volume allows• Study ongoingStudy ongoing
Summary and Conclusions Preliminary data indicate feasibility of anti-HBc Preliminary data indicate feasibility of anti-HBc
reentry algorithmreentry algorithm– All 19 HBV DNA-positive samples detected as reactive All 19 HBV DNA-positive samples detected as reactive
by Abbott PRISM anti-HBcore ChLIAby Abbott PRISM anti-HBcore ChLIA– All 19 strongly anti-HBc reactive All 19 strongly anti-HBc reactive
• Mean S/CO = 0.14 (range 0.02-0.49)Mean S/CO = 0.14 (range 0.02-0.49) Yield of reentry dependent on prior assayYield of reentry dependent on prior assay
– 25% for Ortho => Ortho (1X=>2X) 25% for Ortho => Ortho (1X=>2X) – 21% for Ortho => PRISM (pilot study)21% for Ortho => PRISM (pilot study)– 40% for Ortho => PRISM (Hema-Quebec)40% for Ortho => PRISM (Hema-Quebec)– ?? for Corzyme (prior Abbott) => PRISM?? for Corzyme (prior Abbott) => PRISM
E0304148B—Anti-HBc Chart 14 10/2004
Subsequent Studies Approx 5000 deferred donors (2X, with anti-HBc as only Approx 5000 deferred donors (2X, with anti-HBc as only
deferral criterion and HBV DNA negative) from Oct 04-Sept deferral criterion and HBV DNA negative) from Oct 04-Sept 05 invited to provide follow-up sample under NGI’s HBV 05 invited to provide follow-up sample under NGI’s HBV IND IND – Testing: HBV DNA (NGI; 5 copy/mL sens), HBsAg, anti-HBc Testing: HBV DNA (NGI; 5 copy/mL sens), HBsAg, anti-HBc
(Ortho; (Ortho; PRISM pendingPRISM pending), anti-HBs ), anti-HBs • Study will convert to Roche’s IND using FDA proposed Study will convert to Roche’s IND using FDA proposed
anti-HBc reentry algorithmanti-HBc reentry algorithm– Licensed PRISM anti-HBcore and HBsAg; nonreactives Licensed PRISM anti-HBcore and HBsAg; nonreactives
tested by investigational Roche HBV DNA protocoltested by investigational Roche HBV DNA protocol– 10% eligible donors have provided a follow up sample 10% eligible donors have provided a follow up sample
• 66% “past” HBV infection; leaves 44% for reentry66% “past” HBV infection; leaves 44% for reentry• Yield dependent on PRISM anti-HBcore reactivity, but due Yield dependent on PRISM anti-HBcore reactivity, but due
to low participation rate, maximum is 4.4%to low participation rate, maximum is 4.4%
E0304148B—Anti-HBc Chart 15 10/2004
PRISM HBcore Testing (N= 3776)
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S/CO Values
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Non-Reactive Reactive
Reactive = 2994 (79%) Nonreactive = 782 (21%)
HBV DNA Positives
N % of 3776 % of RxReactive 2994 79.29% Repeat Reactives 2989 79.16% Initial Reactive Only (rpt QNS) 5 0.13% 0.17%
S/CO Min (1st retest) 0.99 S/CO Max 0.01 S/CO Mean 0.23
N % of 3776 % of NRxNon-Reactive 782 20.71% Non-Reactive 771 19.42% Initial Reactive (rpt nonreactive)
