1. 1 Verax Biomedical Platelet PGD ® Test

2. 2 Verax Biomedical Platelet PGD ® Test Results in approximately 30 minutes Designed for use with LR or non-LR: RDPs, Pooled RDPs & SDPs 2 to 3 minutes attended labor per test Analytical sensitivity ~ 10 3 – 10 4 CFU/mL 510(k) lots produced, prepared to enter clinical trials

3. 3 Medical Advisory Board James AuBuchon, M.D. Dartmouth-Hitchcock Medical Center Leslie Silberstein, M.D. Harvard School of Medicine Ira Shulman, M.D. University of Southern California Roslyn Yomtovian, M.D. Case Western Reserve University Mark Brecher, M.D. University of North Carolina

4. 4 Patented PGD ® technology Detects conserved antigens on bacteria Expressed on surface of bacteria > 200,000 copies per cell Therapeutic antibody targets Antigen detection via immunoassay LPS on all Gram-negative LTA on all Gram-positive Pan Genera Detection

5. 5 Labeling by LTA conjugate antibodies Gram positive Sandwich Immunoassay LTA capture antibodies GP bacterial capture Labeling by LPS conjugate antibodies Gram negative Sandwich Immunoassay LPS capture antibodies GN bacterial capture PGD Immunoassay Format – two tests run simultaneously

6. 6 1 Add 8 drops of Reagent to 500uL Platelet Sample - Solution Turns Green A. Spin for 5 Minutes & Decant Verax Biomedical Platelet PGD ® Test procedure Add 8 drops of Reagent 2 B.C. Add 4 drops of Reagent Solution Turns yellow 3 GPGN CC GPGN CC GPGN CC Transfer to well and Wait for results Negative Positive Invalid Interpret results CentrifugationResuspensionReading - or - and Resuspend Pellet Solution Turns BLUE

7. 7 Unused test cartridge Test Results and Interpretation

8. 8 Valid non-reactive result Test Results and Interpretation

9. 9 Valid reactive result Test Results and Interpretation

10. 10 Invalid result Test Results and Interpretation

11. 11 May be too few bacteria to sample Results in False Negatives Clinical sensitivity Sampling early in life limits Pre-Storage Testing Not all units “bloom” within 24 hours Culture sample @ 24 hours High Titer False Negatives Current early sampling techniques risk false negatives

12. 12 Breakthrough cases – False Negatives associated with current testing Reported by CDC at January 2005 DHHS Blood Safety & Availability Meeting: FATALITY - Culture false negative FATALITY - pH false negative 74 year old patient with leukemia receiving a routine platelet transfusion. Received a 5 unit irradiated platelet pool tested normal by pH (>6.4). Pool contaminated with Staph aureus. Patient died after a 21 day hospital stay. 79 year old coronary-artery bypass patient transfused apheresis unit that tested negative for bacteria by BacT Alert on a 24 hour sample. Unit contaminated with Staphylococcus lugdunensis. Patient died 27 hours later. Original BacT culture still negative after 10 days. Premature newborn received two doses from an apheresis platelet unit. Unit tested negative by 24 hour sample plate culture and normal pH (7.3). Unit contaminated with Serratia marcescens. Child died 27 hours later. Second culture on original sample also negative.

13. 13 Testing near time of transfusion offers a potential benefit maximizes clinical sensitivity Testing close to transfusion Testing at Release Simple pre-transfusion test Avoid call-backs Reduce false negatives Run our test at time of issue Minimizes False Negatives & Their Titer

14. 14 This approach is the one most likely to demonstrate equivalence for QC purposes: Considerations for the establishment of a regulatory pathway for rapid tests for bacterial contamination…. - Allows for the differing analytical sensitivities of the two methods Kinetic studies for QC claim equivalence - Allows for the widely differing time of sampling for culture methods and rapid tests intended to be used near the time of release

15. 15 We must be careful in establishing a priori analytical sensitivity targets now for tests intended for use near the time of transfusion: Considerations for the establishment of a regulatory pathway for rapid tests for bacterial contamination…. - Time of testing is likely to be a more significant driver of clinical performance than analytical sensitivity - The more important question is: how many contaminated units do we avoid transfusing? – best answered with populations studies Analytical sensitivity targets

16. 16 Residual Risk of Testing With a Rapid Test With a Sensitivity of: Species Causing 98% + of Contamination Staph Bacillus Strep E coli Klebsiella Salmonella Pseudomonas Serratia Enterobacter Enterococcus Corynebacter Proteus 60% 15% 10% 5% 3% 1% + Time Required To Grow One Log 8.3 Hours 3.6 Hours 5.5 Hours 5.3 Hours 8.5 Hours 7.9 Hours 12.8 Hours 4.4 Hours 12.3 Hours 12.8 Hours + Distribution Of Platelet Transfusions Day 2 12% Day 3 29% Day 4 26% Day 5 33% = Assuming: 1:2,000 Underlying Incidence Rate & Testing Within 4 Hours of Transfusion Calculated Impact of Analytical Sensitivity Testing Close to Transfusion 1 : 6,225 1 : 8,220 1 : 11,899 1 : 18,333 1 : 31,052 1 : 67,957 1 : 188,311 1 : 662,268 1 : 2,494,651 1 : 5,038 10 9 CFU/mL 10 8 CFU/mL 10 7 CFU/mL 10 6 CFU/mL 10 5 CFU/mL 10 4 CFU/mL 10 3 CFU/mL 10 2 CFU/mL 10 1 CFU/mL 10 10 CFU/mL

17. 17 Calculated Impact of Analytical Sensitivity Testing Close to Transfusion Approximates 1:10,000 FDA Hurdle for Culture Release Indication Residual Risk Of Contamination 1 in 6,225 1 in 8,220 1 in 11,899 1 in 18,333 1 in 31,052 1 in 67,957 1 in 188,311 1 in 662,268 1 in 2,494,651 1 in 5,038 Average Sensitivity Level of Test 10 9 CFU/mL 10 8 CFU/mL 10 7 CFU/mL 10 6 CFU/mL 10 5 CFU/mL 10 4 CFU/mL 10 3 CFU/mL 10 2 CFU/mL 10 1 CFU/mL 10 10 CFU/mL Typical Platelet PGD ® Analytical Sensitivity

18. 18 Given the need for tests with release indications, we are concerned that FDA’s proposal may not be the least burdensome route to a release test: Considerations for the establishment of a regulatory pathway for rapid tests for bacterial contamination…. - a 450,000 unit post market surveillance data set, plus - an additional 100,000 unit post market study comparing with culture @ outdate (how is this possible when units have been transfused?) Three tiers of data required for a release test indication - a post market study of unknown size testing culture positives, plus - the requirement for a QC equivalence claim, plus

19. 19 For example: Considerations for the establishment of a regulatory pathway for rapid tests for bacterial contamination…. - this pathway would likely delay a release indication by 3 to 4 years Three tiers of data required for a release test indication - this pathway would take longer to answer the question of the actual clinical sensitivity of the method than simply performing a classic virus screening trial - the 3 post market data sets would appear to gather overlapping data - some data (culture confirmation at outdate for rapid test-negatives) could not be obtained as the platelets would have been transfused

20. 20 We recommend that FDA consider a streamlined, two-step regulatory strategy for a release claim: - Step 1: 510(k) for Quality Control - Step 2: Screening for release (well-controlled, structured trial comparing to culture at time of transfusion on 50,000 to 100,000 units) Three tiers of data required for a release test indication Considerations for the establishment of a regulatory pathway for rapid tests for bacterial contamination…. - Supplemented by ongoing post market surveillance of observed incidence data from end-users