1. r Diagnostics June 19, 2003 WNV FDA BPAC MeetingPCR NAT Blood Screening TaqScreen West Nile Virus Program - Roche Update James L. Gallarda, Ph.D. Roche Molecular Diagnostics

2. r Diagnostics June 19, 2003 WNV FDA BPAC MeetingPCR NAT Blood Screening Critical Milestones (Update from March BPAC) IND filed - April 21, 2003 –Approved to allow sites to begin as test of record Phase I –Training, Installation (5 sites - US and Canada) –Initiated studies (completed May, 2003) Unlinked studies focused on workflow, training Phase II –Training, Installation (completed June 14) –Safety and effectiveness in detecting WNV

3. r Diagnostics June 19, 2003 WNV FDA BPAC MeetingPCR NAT Blood Screening First Fully Automated System in North America - TaqScreen™ WNV COBAS AmpliPrep COBAS TaqMan Hamilton Pipettor

4. r Diagnostics June 19, 2003 WNV FDA BPAC MeetingPCR NAT Blood Screening Non-Clinical Performance Studies & Capacity Analysis

5. r Diagnostics June 19, 2003 WNV FDA BPAC MeetingPCR NAT Blood Screening Non-Clinical Performance Studies Clinical specificity - 400 random volunteer samples from WNV low- and high- prevalence areas Analytical specificity studies with non-WNV microorganisms Limit of detection studies with CDC WNV lysate Analytical sensitivity studies with IMPATH/BCP WNV Lineage 1 isolate Analytical sensitivity studies with BBI WNV Lineage 2 (QWN701) Isolate Reactivity to Japanese encephalitis serocomplex members

6. r Diagnostics June 19, 2003 WNV FDA BPAC MeetingPCR NAT Blood Screening Clinical specificity - 400 random volunteer samples from WNV low- and high- prevalence areas

7. r Diagnostics June 19, 2003 WNV FDA BPAC MeetingPCR NAT Blood Screening Analytical specificity studies with non-WNV microorganisms Human T-cell leukemia virus (HTLV I/II) Hepatitis B virus (HBV) Human immunodeficiency virus Type I (HIV-1) Hepatitis C virus (HCV) Cytomegalovirus (CMV) Hepatitis A virus (HAV) Adenovirus Herpes simplex virus (HSV) Human papilloma virus (HPV) Varicella virus Chlamydia trachomatis Proprionibacterium acnes Staphylococcus aureus Staphylococcus epidermidis Neisseria gonorrhoeae Candida albicans

8. r Diagnostics June 19, 2003 WNV FDA BPAC MeetingPCR NAT Blood Screening Analytical specificity studies with non-WNV microorganisms Each of the 125 samples positive for these microorganisms tested negative in the TaqScreen WNV assay - no false-positive test results were observed. All associated Armored Internal Controls were positive for each sample tested.

9. r Diagnostics June 19, 2003 WNV FDA BPAC MeetingPCR NAT Blood Screening Limit of detection studies with CDC WNV lysate Positive @ > 10 7 dilution

10. r Diagnostics June 19, 2003 WNV FDA BPAC MeetingPCR NAT Blood Screening Analytical sensitivity studies with IMPATH/BCP WNV Lineage 1 isolate* 95% LOD estimated to be < 5 copies/mL

11. r Diagnostics June 19, 2003 WNV FDA BPAC MeetingPCR NAT Blood Screening Analytical sensitivity studies with BBI WNV Lineage 2 (QWN701) Isolate* 95% LOD (PROBIT) = 7.41 copies/mL (95% CI: 4.78 – 16.13)

12. r Diagnostics June 19, 2003 WNV FDA BPAC MeetingPCR NAT Blood Screening Reactivity to Japanese Encephalitis serocomplex members Additional WNV isolate (ATCC VR-1267) St Louis encephalitis virus (ATCC VR-1265) Murray Valley encephalitis virus (ATCC VR- 77) All isolates detected

13. r Diagnostics June 19, 2003 WNV FDA BPAC MeetingPCR NAT Blood Screening Phase I Capacity Analysis (Gulf Coast Regional Blood Center) Start pooling 0630 hrs (average pooling time 19.5 minutes) First extractions on COBAS AmpliPrep begin 0649 hrs First amplifications begin 0900 hrs Total throughput with 2 FTE operating 2 systems = 1728 samples in 11 ½ hours Conservative extrapolation (one shift of 8 hours with “reporting” in the last 3 ½ hours) estimates ~500,000 samples per 2 FTE operating 2 system per year.

14. r Diagnostics June 19, 2003 WNV FDA BPAC MeetingPCR NAT Blood Screening Current Status & Issues All 11 US sites and 3 Canadian sites are installed and prepared for linked testing on or before July 1 Potential expansion to other sites Assisting public health lab diagnostic needs Dissemination of prevalence data through REDS USDA permit requirements to ship WNV panels Standardization of WNV panel Capital, training, and support costs are substantial to execute multi-site IND

15. r Diagnostics June 19, 2003 WNV FDA BPAC MeetingPCR NAT Blood Screening Roche Diagnostics - Commitment to West Nile Response Branchburg & Belleville, NJ Manufacturing & Quality IT/SAP Alameda, CA Legal/Licensing Research Roche Genetics Rotkreuz, SW Engineering Manufacturing Penzberg, GmbH Development Regulatory Marketing Pleasanton, CA Development Marketing Regulatory/Clinical Finance & Admin. Laval, Que, Canada Distribution Customer Support Regulatory Clinical Trial Support Indianapolis, IN Distribution Customer Support