1. Blood Center Experience with Double Red Cell Collections by Apheresis: Adverse Events and Impact on Capacity Brian Custer, Hany Kamel, Marj Bravo Peter Tomasulo Blood Systems, Inc. FDA Blood Products Advisory Committee August 2011 1

2. Blood Systems 2010: Red Cells Collected – 1.1 Million, Platelets Collected –160,000 Donor Panels Tested – 4.2 Million 2

3. Allogeneic Donations Phlebotomy Time (min) Loss of Consciousness N% Mean (95% CI) LOC events LOC Rate/10000 Latest Onset (min) WB944,01875.4 8.7 (8.70-8.72) 2,36425252 2RBC178,80314.3 31.8 (31.73-31.86) 130733 2RBC and WB Phlebotomy Time and LOC rates in Allogeneic Donations BSI data, Allogeneic Donations, April 2009 to September 2010 3

4. Methods Study period: January 1 – December 31, 2007 Reactions studied: – moderate and severe vasovagal reactions (combined into a single category) Statistical analysis: – Logistic regression analyses that compared 2-RBC to WB donors. We report risks of AR using a diverse set of predictors based on an adjusted logistic regression model constructed using manual stepwise deletion. Kamel et al. Adverse Reactions in Whole Blood and Automated 2-unit Red Cell Donations among 2RBC- eligible allogeneic male donors: a multivariate analysis. 4

5. Results – Experience, Age, Blood Volume and Collection Method Kamel et al. Adverse Reactions in Whole Blood and Automated 2-unit Red Cell Donations among 2RBC- eligible allogeneic male donors: a multivariate analysis. 5

6. Adverse Event Rate / Procedure Type Custer et al. Associations between Collection Procedure Type and Donor Adverse Events. 6

7. Comparison of Vasovagal Reactions Across Time Course of Automated and WB Donations 7

8. BSI data, Allogeneic Donations, April 2009 to September 2010 8

9. BSI data, April 2009 to September 2010 9

10. By Period: Summary of Adjusted Odds Ratios Across Time Course of Blood Odds Ratios and Confidence Intervals

11. Bravo et al. Vasovagal Reaction, Outside Medical Care and Injury Rates During/After Whole Blood and Automated Collections. 11

12. THE LOC REACTIONS WHICH OCCUR WITH 2 RBC DONATIONS OCCUR EARLIER THERE ARE FEWER LOC REACTIONS AND FALLS PER DONATION WITH 2 RBC DONATIONS THAN WITH WHOLE BLOOD DONATIONS. 12

13. Custer et al. Donor adverse events: needle related injuries and vasovagal reactions are strongly associated. 13

14. RESULTS Factors associated with NRI (with VVR as a factor) Odds Ratios and 95% Confidence Intervals Custer et al. Donor adverse events: needle related injuries and vasovagal reactions are strongly associated. 14

15. RESULTS Factors associated with VVR (with NRI as a factor) Odds Ratios and 95% Confidence Intervals Custer et al. Donor adverse events: needle related injuries and vasovagal reactions are strongly associated. 15

16. VVR rate is higher for WB than for 2RBC or PP collections NRI rate is higher for 2RBC and PP collections Risk factors for VVR and NRI are not the same LOC and NRI are strongly associated VVR are influenced by NRI, EBV, age, donor history, donor race and procedure type NRI are influenced by VVR, donor weight and procedure type More likely that NRI  VVR than VVR  NRI Custer et al. Associations between Collection Procedure Type and Donor Adverse Events. 16

17. Collection Capacity DayMonTueWedThuFriSatSunMonTueWedThuFriSatSunMon Aph RBC 49116139145 1101012328219875137512114 WB207200426882629200314076722191932496956317419414236333655 Donors256212028272774214815176822314960698936392433114746353769 Units2852195292328732246160469224029809100416454444315076373840 17

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19. Presentations EBV & Hgb Criteria Male % Male Female % Female Total % Total EBV <4000ml & Hgb <13.5 g/dL 42,4669329,48065371,94637 EBV ≥4000ml & Hgb ≥13.5 g/dL 451,59091178,36035629,95062 No EBV or Hgb3,60012,80316,4031 Total497,656100510,6431001,008,299100 Estimated blood volume (EBV) and hemoglobin (Hgb) criteria among presenting donors BSI data, February 2010 to February 2011 19

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22. Apheresis in a Disaster: Electric Power Electric power needed to pump gasoline and diesel fuel Not all BSI collection locations have generators Not all generators can power apheresis devices – Most generators dedicated to refrigerators and computers Bus mobiles have generators WB throughput more rapid – capacity loading Apheresis may be reserved for platelets 22

23. Summary Fewer VVR, more NRI from 2 RBC apheresis Possibly fewer injuries per procedure with 2 RBC Reserve capacity is significant Red cell apheresis has little benefit in “routine” emergencies May help more in widespread prolonged disasters affecting donor availability (in which platelet apheresis would also be important) Apheresis requires power 23

24. 12-month BSI donor loss and possible donor gain with criteria modification (February 2010 to February 2011) DONOR LOSS (due to deferrals) POSSIBLE DONOR GAIN Current Criteria In a year N (%) Modified Acceptance criteria In a year In a week In a day Donor presentations 1008299 (100%) 193903878 Tattoo, 12 months 9625 (.95%) 6 months (NAT screening) 4813 (0.48%) 9319 Other risk of exposure to blood and body fluids*: 12 months 3296 (0.33%) 6 months (NAT screening) 1648 (0.16%) 326 Traveled to Malarial Area: 12 months 7488 (0.74%) Accept travelers to Mexico: (~60% of malarial travel deferrals) 4493 (0.45%) 8617 Not eligible due to: Hemoglobin of 11- 12.4g/dL 55721 (5.5%) Eligible if Hb =11-12.4 g/dl (Criteria for autologous donors) 55721 (5.5%) 1072214 Total Deferrals 76123 (7.5%) Total Gain 66672 (6.6%) 1283 (6.6) 256 (6.6%) * e.g., jail>72 hrs, blood transfusion, ear/body piercing, needle stick, etc. 24

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