1. Supplemental Testing of Donors for HIV and HCV September 18, 2003 BPAC Meeting Robin Biswas, M.D. Indira Hewlett, Ph.D. FDA/CBER/OBRR/DETTD

2. Supplemental Testing of Donors for HIV and HCV u Discussion of the utility of various supplemental testing strategies to CONFIRM A REPEATEDLY REACTIVE ENZYME IMMUNOASSAY (EIA) SCREENING TEST RESULT for - HIV using Western Blot, Nucleic Acid Tests, second EIA, and for - HCV using RIBA, Nucleic Acid Tests, high signal-to-cutoff ratio in screening EIA

3. Reason for Discussing HIV and HCV Supplemental Testing of Donors u 1998 MMWR recommended that, in the clinical laboratory, diagnostic setting, an anti-HCV reactive screening test result be verified by a more specific supplemental test, e.g., RIBA. u 2003 MMWR repeats and emphasizes the desirability of performing supplemental testing on screen reactives. It offers an option for reporting positive test results using high signal-to- cutoff ratios in the screening test, in the clinical laboratory, diagnostic setting.

4. Current Testing of Blood Donations for Antibodies to HIV and HCV, contd. EIA Screening Test Non-reactive (NR) Initially reactive (IR) Initially reactive (IR) Use unit, retain donor Use unit, retain donor Test sample in duplicate Both duplicates NR Use unit, retain donor Next slide

5. Current Testing of Blood Donations for Antibodies to HIV and HCV, contd. Test sample in duplicate Both duplicates NR Use unit, retain donor duplicates test reactive Either or both duplicates test reactive Unit is repeatedly reactive (RR), Unit not used, defer donor Donor evaluated by more testing using supplemental assays

6. Current Testing of Blood Donations for Antibodies to HIV and HCV, contd. u Supplemental testing on EIA screening test RRs - for anti-HCV use RIBA - for anti-HIV use Western Blot or IFA followed by anti-HIV 2, if indeterminate results are obtained

7. Supplemental Testing of Donors/Donations u Each screening test reactive donation must be tested by a supplemental test if approved for such use, 21 CRF 610.40 u Donors must be notified of deferral; an attempt must be made to obtain supplemental test results prior to donor notification, 21 CFR 630.6

8. Supplemental Testing of Donors/Donations, contd. u Alternative donor testing algorithms, not using supplemental tests, would conflict with regulations u Confirmation by “orthogonal testing” (testing using a different technique) advantageous over statistical validation methods, e.g., 2 nd EIA, high EIA s/co ratio

9. Why Perform Supplemental Testing on Donors? u 1) Providing deferred donors with accurate information about their disease status and deferral helps ensure a healthy donor population. - This impacts directly on blood safety in preventing communicable disease transmission.

10. Why Perform Supplemental Testing on Donors? contd. u 2) Information from supplemental testing can be used to evaluate donor for possible reentry into donor pool. - Requalification of donors contributes to donor availability

11. Testing in Different Settings u Donor Setting: selected, low risk population tested outside the health care environment u Medical Diagnostic Setting: higher risk populations, medical “index of suspicion,” doctor-patient relationship permits additional considerations -rapid HIV testing at point of care; inability to perform delayed confirmatory testing

12. Discussion Objectives Discuss: u The scientific merit and public health benefit of supplemental testing in a blood donor setting. u Relative performance of supplemental testing strategies for HIV and HCV: - HIV: Western Blot, NAT, 2 nd EIA - HCV: RIBA, NAT, high s/co in the screening EIA

13. Questions for the Committee u 1. Please comment on the relative performance of: (i) RIBA versus HCV NAT (ii) RIBA versus signal-to-cutoff ratio in the screening test for anti-HCV to confirm/validate a reactive screening test result in the blood donor testing setting.

14. Questions for the Committee u 2. Please comment on the relative performance of: (i) Western Blot versus HIV NAT (ii) Western Blot versus a second EIA for anti-HIV to confirm/validate a reactive screening test result in the blood donor testing setting.