1. Deferral of Blood and Plasma Donors for History of Transfusion in BSE Countries of Europe Alan E. Williams, Ph.D. Director, Division of Blood Applications Office of Blood Research and Review CBER, FDA TSE Advisory Committee February 8, 2005

2. Current FDA Recommendations: vCJD –Related Donor Deferral Guidance to Industry January, 2002 > 3 months residence/travel in U.K. 1980 - 1996 > 5 years residence/travel in Europe  For donors of Source Plasma this criterion applies only to France (5-10% consumption of UK beef) > 6 months on certain US military bases in Europe between 1980-1990 or 1980-1996 (up to 35% UK beef consumed) Transfusion in the U.K. 1980 – present Receipt of bovine insulin sourced in the U.K. after 1980

3. TSEAC October 14, 2004 Review of current FDA recommendations regarding vCJD-related donor eligibility No TSEAC recommendations for further FDA actions to protect the blood supply Discussion: –Predictive value of donor questions to exclude TSE risk –Feasibility of deferral for history of transfusion outside of the UK

4. Predictive value of the donor questionnaire Limited data. True validation of donor screening process is complex/expensive DH Task Force - Major progress to improve and streamline the donor questionnaire from a design and cognitive understanding standpoint

5. Estimates of false negative donor responses derived from post-donation research studies Anonymous REDS mail surveys post-donation demonstrated 2 – 3 % overall “deferrable risk” (0.1 – 0. 5% for individual behavioral risks; higher for less-well- defined exposures) JAMA 1997 277(12):967-972 Parallel findings from other similarly-designed studies (Canada, Hong Kong) Numerous studies based on post-donation interviews of test-positive donors show a high prevalence of deferrable risk

6. Post Donation Information (PDI) linked to Biological Product Deviation Reports Biological Product Deviation Reports (BPDR) –Reported to FDA only when implicated product was issued. (May substantially underestimate true incidence of actual deviations in some situations) –PDI – most common Biological Product Deviation Report (BPDR) –vCJD travel was most common PDI reported in FY ‘03

7. Post Donation Information (PDI) linked to Biological Product Deviation Reports Source of PDI* –Subsequent donation – 92% –Telephone call from donor – 4.2% –Third party (e.g., doctor, family member – 3.8% When deferral was known by donor* –Known at time of donation but not provided – 91.8% –Not known at time of donation – 8.1%

8. BPDRs for Blood and Plasma Donor Centers FYBPDRsPDIsPDIs due to vCJD Travel #%#% FY0123,36318,25678.12,87915.8 FY0232,16223,162723,96617.1 FY0338,99430,32177.88,36927.6 FY0436,23826,85474.16,42023.9

9. Summary – Predictive value of donor screening Estimates of the predictive value of donor screening are crude, however based upon available data, false negative self-report of donor eligibility may be in ~ 3-5% range of donors deferred on-site, and may be higher in relation to complex questions

10. Donor Deferrals for History of Transfusion Current FDA recommendation is deferral for transfusion in the U.K. (1980 – present) Recent developments: Probable vCJD transmissions by transfusion Prior donations by vCJD case in France Donor deferral for any previous transfusion –France – 1998 –The Netherlands – 2004 (est 8% donor loss)

11. Range of possible policy extensions Transfusion in France since 1980 Transfusion in any BSE country in Europe since 1980 Any transfusion since 1980

12. Estimated Donor Loss Related to History of Transfusion in UK and France Hx tx (UK - deferral already accomplished) 0.4 x 0.05 = 2/10,000 Hx Tx (France) 0.4 x 0.7 x 0.05 = 1.4/10,0000 (Source Plasma donor impact expected to be less due to younger age) Assumptions: – 5% prevalence of transfusion in US donors overall (REDS data) – >/= 5 yr travel/residence CONSERVATIVELY approximates lifetime transfusion exposure (4/10,000 donors have > 5 year UK exposure) –rate of tx among long term residents/travelers to Europe and UK = overall US donor prevalence –prevalence of travel to France = 0.7 x travel to UK

13. Estimated Donor Loss Related to Deferral for a History of Transfusion in Europe Hx Tx (any Europe, excl. UK) 0.7% x 0.05 = 3/10,000 (Source Plasma donor impact expected to be less due to younger age) Assumptions: – 5% prevalence of transfusion in US donors overall (REDS data) – >/= 5 yr travel/residence CONSERVATIVELY approximates lifetime transfusion exposure (7/10,000 donors reported > 5 year exposure in non-UK Europe) –rate of tx among long term residents/travelers to Europe = overall US donor prevalence

16. The Euroblood program Began in the early 1970’s At its peak represented one third of the New York area RBC supply and approximately 2.0 % of the total US RBC supply Over 200 New York Metropolitan-area hospitals supplied with Euroblood over the 30 year period of importation (est. >4 million components )

17. The Euroblood Program In the absence of a massive lookback effort, Euroblood recipients currently living in the US are largely untraceable. The Euroblood program ended in the months prior to the 10/31/02 implementation of FDA deferral recommendations (Phase II)

18. Questions for the Committee

19. Question 1. Based upon the available scientific information, does the committee recommend deferral of blood donors transfused since 1980 a. In France? b. In other BSE countries of Europe?

20. Question 2. Based upon the available scientific information, does the committee recommend deferral of Source Plasma donors transfused since 1980 a. In France? b. In other BSE countries of Europe?