management of donors and units that test hbv nat positive: current considerations july 21, 2005 bpac...
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![Page 1: Management of Donors and Units that Test HBV NAT Positive: Current Considerations July 21, 2005 BPAC Meeting Robin Biswas, M.D. FDA/CBER/OBRR/DETTD](https://reader035.vdocuments.mx/reader035/viewer/2022070411/56649f565503460f94c7af5d/html5/thumbnails/1.jpg)
Management of Donors and Units Management of Donors and Units that Test HBV NAT Positive: Current that Test HBV NAT Positive: Current
ConsiderationsConsiderationsJuly 21, 2005 BPAC MeetingJuly 21, 2005 BPAC Meeting
Robin Biswas, M.D.Robin Biswas, M.D.FDA/CBER/OBRR/DETTDFDA/CBER/OBRR/DETTD
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Issue
FDA seeks Committee advice on management of donors* and units, and on a proposed algorithm to permit reentry of some donors, when a donor tests positive for:
Hepatitis B Virus (HBV) DNA by a Nucleic Acid Test (NAT)------------------------------------ *Donors of Whole Blood and blood components for transfusion (WB) and
Source Plasma (SP) for manufacture into injectable plasma derivatives
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Background
FDA recently licensed an HBV NAT (COBAS AmpliScreen HBV Test) for WB & SP donations
Currently HBV NAT donor testing is optional
It could be recommended in the future
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Current Donor Testing for HBV
Consistent with current regulations and guidance documents:
Whole Blood/Components for transfusion is tested for - Hepatitis B surface antigen (HBsAg) - Antibody to hepatitis B core antigen (anti-HBc)
Source Plasma for further manufacture is tested for - HBsAg
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HBV Donor Testing Performed by Centers that Implement HBV NAT
Whole Blood/Components for transfusion:
HBsAg, anti-HBc, and HBV NAT Source Plasma for further manufacture:
HBsAg, and HBV NAT
Centers will need to make decisions regarding donor/unit management based on test result combinations
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HBV Testing for Centers that implement HBV NAT, contd.FDA’s current position:
If a unit tests HBV NAT negative: - Donor/unit management is c/w current FDA requirements and recommendations for HBsAg and anti-HBc. - Units that test NAT and serology negative used. If a unit tests HBV NAT positive: - Units that test NAT and /or serology positive not used. - Donor indefinitely deferred.
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HBV NAT and Donor Reentry
Proposal:
An algorithm can be developed to determine eligibility of donors who test HBV NAT positive, based on subsequent negative HBV NAT and serologic test results.
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Category HBV NAT HBsAg
Anti-HBc Donor and Unit
1 Positive Repeat Reactive/
neutralized
Non-Reactive Unit Not Used, Donor Permanently Deferred
2 Positive Repeat Reactive/
neutralized
Repeat Reactive
3 Positive Repeat Reactive/
Not neutralized
Repeat Reactive
4 Positive Non-Reactive Repeat Reactive
5 Positive Non-Reactive Non-Reactive Unit Not Used, Donor Indef Deferred, May be reentered
6 Positive Repeat Reactive/
Not neutralized
Non-Reactive
Whole Blood and Blood Components for TransfusionWhole Blood and Blood Components for Transfusion
(overview)(overview)
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Whole Blood and Blood Components for Transfusion,Whole Blood and Blood Components for Transfusion,
contd.contd.
Category HBV NAT HBsAg
Anti-HBcDonor and Unit
1 Positive Repeat Reactive/
Neutralized = Positive
Non-Reactive
Unit not used, Donor perma-nently
deferred
2 Positive Repeat Reactive/
Neutralized =
Positive
Repeat Reactive
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Whole Blood and Blood Components for Transfusion,Whole Blood and Blood Components for Transfusion,
contd.contd.
Category HBV NAT HBsAg
Anti-HBcDonor and Unit
3 Positive Repeat Reactive/
Not Neutralized
Repeat Reactive
Unit not used, Donor perma-nently
Deferred
4 Positive Non-Reactive Repeat Reactive
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Whole Blood and Blood Components for Transfusion,Whole Blood and Blood Components for Transfusion,
contd.contd.
Category HBV NAT HBsAg
Anti-HBcDonor and Unit
5 Positive Non Reactive Non Reactive
Unit Not Used, Donor
Indefinitely
Deferred, Possible Reentry
6 Positive Repeat Reactive/
Not neutralized
Non Reactive
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Source Plasma for Further Manufacture into Plasma Derivatives
Category HBV NAT HBsAg Donor and Unit
1 Positive Repeat Reactive/
Neutralized = Positive
Unit not used, Donor Permanently Deferred
2 Positive
Non Reactive Unit not used, Donor Indefinitely Deferred,
Possible reentry
3 Positive Repeat Reactive/
Not Neutralized
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Donor Reevaluation for Possible Reentry
During clinical trials of Roche’s COBAS AmpliScreen HBV NAT under IND,
- seroconversion studies showed that the maximum period of time that HBV DNA preceded HBsAg detection was 143 days.
- donor follow-up studies showed that the maximum period of time that HBV DNA preceded HBsAg detection was 17 days, and anti-HBc detection was 48 days .
Additional data will be presented.
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Donor Reevaluation for Possible Reentry, contd.
Therefore, FDA is considering recommending a minimum 6-month waiting period after a positive HBV NAT result with negative serology results prior to retesting, to ensure that, if a true infection exists, seroconversion to HBsAg and/or anti-HBc occurs
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Donor Reevaluation for Possible Reentry, contd.
A sample (not a donation) is collected at least 6 months after the index donation
For Whole Blood/Components for transfusion donors, sample tested for HBsAg, anti-HBc, HBV DNA by individual sample NAT
For Source Plasma donors, sample tested for HBsAg and HBV DNA by individual sample NAT
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Donor Reevaluation > 6 Months After Index Donation
Category HBV DNA by Individual Sample NAT
HBsAg and/or
Anti-HBc
Donor
a Positive Any test result Permanently Deferred
b Negative
Non reactive Eligible for reentry
Further evaluation, as described in FDA
recommendations
c Negative Repeat reactive
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Donor Testing Before the End of 6-Month Waiting Period
May be performed for notification or medical reasons If positive NAT obtained, donor should be permanently
deferred, irrespective of serology results Negative/non-reactive results may be used for
counseling Only negative individual NAT and negative serologic
test(s), collected at least 6 months after the index
donation, qualifies the donor for reentry
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Donor Reevaluation for Possible Reentry, contd.
A sample (not a donation) is collected at least 6 months after the index donation
For Whole Blood/Components for transfusion donors, sample tested for HBsAg, anti-HBc, HBV DNA by individual sample NAT
For Source Plasma donors, sample tested for HBsAg and HBV DNA by individual sample NAT
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Questions for the Committee
1. Based on the scientific data, does the Committee agree with FDA’s proposal that
a) A donor of Whole Blood and blood components for transfusion, who tests HBV NAT positive, anti-HBc non-reactive and HBsAg non-reactive or HBsAg repeatedly reactive /not confirmed by neutralization, may be reentered, if after a minimum period of 6 months a sample from the donor tests negative for HBV DNA by individual sample NAT, non-reactive for anti-HBc and non-reactive for HBsAg , ….
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Questions for the Committee, contd.
1. Based on the scientific data, does the Committee agree with FDA’s proposal that
b) A donor of Source Plasma for further manufacture into plasma derivatives, who tests HBV NAT positive and HBsAg non-reactive or HBsAg repeatedly reactive /not confirmed by neutralization, may be reentered, if after a minimum period of 6 months a sample from the donor tests negative for HBV DNA by individual sample NAT and non-reactive for HBsAg?
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Questions for the Committee, contd.
2. Please discuss any alternative approaches FDA should consider.