management of donors and units that test hbv nat positive: current considerations july 21, 2005 bpac...

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

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

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

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

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

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.

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.

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)

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

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

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

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

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.

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

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

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

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

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

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 , ….

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?

Questions for the Committee, contd.

2. Please discuss any alternative approaches FDA should consider.