1 Development of an Anti-HIV 1+2 Assay for use on a Random Access System B Boyer, S Edwards, JM Glover: Ortho-Clinical Diagnostics, Rochester NY This assay is currently pending FDA approval. This is not a solicitation for sale but a scientific exchange of information for study.

2 Description of the test/protocol Clinical Performance Result Algorithm Intellicheck ® Summary/Conclusion Development of an Anti-HIV 1+2 Assay for use on a Random Access System

3 Test for the in vitro qualitative detection of antibodies to Human Immunodeficiency Virus types 1 and/or 2 (anti ‑ HIV 1 and anti ‑ HIV 2) in human serum and plasma (heparin, EDTA or citrate) using the VITROS ® ECi/ECiQ Immunodiagnostic System. The Vitros ® Anti-HIV 1+2 Assay* * Pending FDA approval

4 Architecture HIV 1 Env 13 - gp 120 and gp 41 region. HIV-1 Env 10 - gp41 region which extends beyond the C- terminus of Env 13. HIV-1 p24 - full length core protein of HIV-1. HIV-2 Env AL - contains a region from gp 36 of HIV-2.

5 Protocol 80  l sample 20  l assay reagent Incubate 29 minutes 20 seconds at 37°C Wash 100  l conjugate reagent Incubate 8 minutes at 37°C Wash 200  l signal reagent Read

6 Calibration and QC A single calibrator is run in duplicate once every 28 days 3 QC controls are available. –Negative, HIV 1, HIV 2 –Recommendation is that these controls are run in singleton: once every 24 hours of testing after calibration after certain service events

7 Performance: US Clinical Trials PopulationPositive Percent Agreement Negative Percent Agreement High Risk (U.S.)100% (54/54) 99.81% (2117/2121) High Risk (Ivory Coast) 100% (26/26) 98.92% (457/462) HIV Positive (U.S.) 100% (1121/1121) HIV Positive (International) 99.48% (193/194) HIV-2 Positive (Ivory Coast) 100% (208/208) Pregnant (High Risk–U.S.) 100% (5/5) 99.59% (243/244) High Risk Populations

8 Performance: US Clinical Trials (continued) PopulationPositive Percent Agreement Negative Percent Agreement Pregnant (Low Risk–U.S.) 100% (1/1) 100% (296/296) Labor and Delivery (Low Risk–U.S.) 97.96% (48/49) Insurance Applicants (Low Risk–U.S.) 100% (5/5) 99.80% (992/994) Pediatric (Low Risk–U.S.) 100% (99/99) Pediatric HIV Positive (U.S.) 100% (40/40) Total (High and low risk populations) 99.94% (1653/1654) 99.70% (4252/4265) Low Risk Populations

9 Performance: US Clinical Trials (continued) Borderline Range

10 Performance: Seroconversion * Pending FDA approval Panel IDLicensed Assay Vitros ® Assay* Difference days to HIV reactivity: Licensed assay minus Vitros ® Assay* -+-+ PRB PRB PRB PRB PRB PRB Seroconversion panels tested with a licensed assay and the Vitros ® Assay*. 14 panels converted at the same sample. 6 panels showed differential conversion between assays. Days to Evidence of HIV Infection

11 HIV 1 Genotype Detection 100% Sensitivity with all genotypes tested – including O

12 Performance: Precision Within occasion CV = 1.9% Day to day CV = 2.9% Total CV = 3.5%

13 Result Algorithm No further testing required. “Negative” An initial singleton result of <0.90 s/c indicates a non- reactive Sample that is “Negative” for Anti-HIV 1+2 If 2 of 3 results < 1.00 S/C, the Sample is “Negative” for Anti- HIV 1+2 If 2 of 3 results >/= 1.00 S/C, the Sample is “Reactive” for Anti- HIV 1+2 Retest in Duplicate An initial result of >/= 0.90 and < 1.00 s/c (“Retest?”) indicates a sample that requires duplicate repeat testing for Anti-HIV 1+2 No repeat testing required: Perform Supplemental Testing as Appropriate An initial singleton result of >/= 1.00 s/c indicates a sample that is “Reactive” for Anti-HIV 1+2

14 –Integrated Process Control Series of technologies that perform, monitor, verify and document diagnostic checks throughout sample and assay processing and reporting results Sample and Result Integrity Verification –Traceability with real-time operator notifications and documentation for exceptions Mistake proofing diagnostic systems

15 Patented Pressure Level-Sensing Technology Bubble, Clot, Viscosity, Short Sample, Thin Layer Fluid detection Normal Aspiration Abnormal Aspirate bubble detected Positive pressure detects Negative pressure aspirates Pressure profile detects anomalies Intellicheck Example: Sample Integrity Verification

16 Summary ParameterPerformance Clinical Performance Positive Percent Agreement 99.94% (1653/1654) Negative Percent Agreement 99.70% (4252/4265) Excellent separation of positive and negative populations PrecisionTotal precision of 3.5% in PMA studies GenotypesAll genotypes detected SeroconversionEarly detection of seroconversions Sample typeValidated for serum and plasma with normal, high risk and pediatric populations. Resolution Algorithm Singleton testing for both negative and positive samples. Repeat testing only for borderline samples. Calibration and controls Calibration only required once every 28 days Controls run once every 24 hours of testing SystemControl of a random access system with the security of Intellicheck ®