a) NAT testing must be able to detect all available repository p24-positive antibody-negative window period blood donation specimens detected since the start of p24 screening when those specimens are included in a plasma pool. (whether or not they remain p24-positive when diluted in the pool) or when tested individually.
Data showing that NAT testing can detect p24-positive samples in commercial plasma donor seroconversion panels when tested individually or with adequate sensitivity to address the dilution factor due to pooling (i.e., when those samples are diluted in a plasma pool).
c) Data from clinical trials comparing the relative frequencies of detection for antigen testing and NAT testing in prospective studies of Whole Blood and plasma populations. The number of p24-positive or NAT-positive window period units required would be established prior to such clinical trials by statistical evaluation and agreed to by FDA. This prospective data will include analysis of the NAT-positive rate for p24-positive antibody-positive as well as p24-positive antibody-negative specimens.
2. Data showing that NAT testing is able to detect all HIV variants (including HIV-1 group M subtypes A through G and group O) that would be detected by the licensed p24 antigen tests. This can be provided by testing well-characterized p24-positive antibody-positive samples from HIV-1 variants (10 of each HIV-1 group M subtype A-G). A combination of naturally-occurring human serum samples and cell culture fluids from HIV-1 variants spiked into normal plasma should be used to demonstrate the sensitivities of the p24 assay and the NAT test. FDA may work with industry to identify and collect such specimens and establish a validation panel.
3. Data from reproducibility studies of the NAT testing method in routine operational settings to demonstrate that even weakly reactive p24 antigen samples will be detected by the NAT test on multiple days
, instrument systems
, and product lots.
4. The NAT testing method must be licensed by FDA. (NAT testing under IND will not be allowed to replace p24 antigen testing).
5. A testing organization must submit an IND or amend an existing IND that outlines specific clinical trials to substantiate a claim of replacing HIV p24 antigen testing with NAT testing. Because of differences in NAT methods and INDs
, licensure of NAT testing with a substantiated claim for replacement of p24 antigen testing for a specific testing organization will form the basis for discontinuation of p24 antigen testing by that organization using the licensed NAT method. This approach will be adopted rather than an industry-wide withdrawal of p24 antigen testing recommendations by FDA.