1. 1 Donor Deferral / Ineligibility for Time Spent in Saudi Arabia to Reduce Risk of vCJD Transmitted by Blood and Blood Products and by Human Cells, Tissues and Cellular and Tissue-Based Products (HCT/Ps) Pedro Piccardo Laboratory of Bacterial and TSE Agents DETTD, OBRR, CBER US FDA TSEAC 1 Aug 2011 - Piccardo

2. vCJD in individuals born in Saudi Arabia Case 1 Individual born 1986 raised in Saudi Arabia (SA) Short visits to UK (near the end of the UK dietary risk period) Age onset 23 yr Tonsil biopsy (Canada) PrP TSE positive - PRNP 129 MM Diagnosis: probable vCJD No history of surgery or blood transfusion Foodborne exposure to BSE agent likely in SA M.B.Coulthart et al. Prion2011, Montreal, Canada TSEAC 1 Aug 2011 - Piccardo

3. Case 2 Individual born 1983 raised in SA No history travel to UK - short visits to US - lived in US since 2005 Age at onset 22.8 yr Tonsil & brain biopsy (UCSF) PrPTSE positive - PRNP 129 MM Diagnosis: vCJD No history of blood transfusion Foodborne exposure to BSE agent likely in SA CDC Website. vCJD in the US in a patient from the Middle East (http://www.cdc.gov/ncidod/dvrd/vcjd/other/vcjd_112906.htm)http://www.cdc.gov/ncidod/dvrd/vcjd/other/vcjd_112906.htm TSEAC 1 Aug 2011 - Piccardo

4. Case 3 Individual born 1970 raised in SA Short visits to UK / France and 1 year in US Age at onset 32.5 yr Brain biopsy (Mayo Clinic, CWRU) PrPTSE positive - PRNP 129 MM Diagnosis: vCJD No history of blood transfusion Foodborne exposure to BSE agent likely in SA Belay ED. et al. cCJD, United States Emerg Infect Dis. 2005;11(9):1351-4 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1622 9761).http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1622 9761

5. 5 vCJD cases per estimated population 2011 Country vCJD cases a Estimated population 2011 b Crude rate c UK17562,688,0002.8 x 10 -6 Ireland24,671,0004.3 x 10 -7 France2465,103,0003.7 x 10 -7 Portugal210,760,0001.9 x 10 -7 Netherlands316,847,0001.8 x 10 -7 Spain546,755,0001.1 x 10 -7 Saudi Arabia326,132,0001.1 x 10 -7 Italy261,017,0003.3 x 10 -8 Japan1126,476,0007.9 x 10 -9 [a] Cases resident in UK  6 mo attributed to UK. [b] US Census Bureau estimates mid-2011 [c] Not corrected for population age distribution or efficiency of case recognition/reporting. Provided by D. Asher TSEAC 1 Aug 2011 - Piccardo

6. 6 - Based on current US policy the 3 SA-resident vCJD patients described previously would not have been deferred as donors. (Guidance for Industry – Revised Preventive Measures to Reduce the Possible Risk of Transmission of CJD and vCJD by Blood and Blood Products, May 2010) - FDA assumes that major risk of human exposure to BSE agent in SA was from live cattle and meat/products of UK origin (1980-1996). - Risk of Saudi population estimated less than that in UK: * 10% beef imported into SA from UK (1980-1996) Sanchez-Juan P, et al. Emerg Infect Dis. 2007;13:1166-9 * per capita beef consumption in SA about ¼ of UK http://www.fas.usda.gov/dlp/circular/2006/06-03lp/bpppcc.pdf TSEAC 1 Aug 2011 - Piccardo http://www.indexmundi.com/agriculture/?country=sa&commodity=beef-and-veal meat&graph=production

7. 7 BSE exposure UK origin in SA markedly reduced >1996 - TSEAC/BPAC (Jan 2002) Dr. Peter Soul (UK-DEFRA) described extensive measures implemented by end 1996 in the UK to (i) stop the spread, amplification of the BSE agent (ii) prevent the contamination of the food supply http://www.fda.gov/ohrms/dockets/ac/cber02.htm Transcript 2002 page 159-97 - Commission of the European Communities Mar 1996 “UK shall not export to Member States or third countries” (i) Live bovine animals, (ii) Meat / products of bovine origin liable to enter animal feed or human food chain. TSEAC 1 Aug 2011 - Piccardo (http://www.neenar.com/europaenhancer/Enhancer.pl?ojref=CELEX:31996D0239:EN:HTML&ojpdf=OJ: L:1996:078:0047:0048:EN:PDF&format=).

8. 8 BSE exposure of UK origin in SA - SA authorities imposed restrictions on imports of bovine materials from BSE countries (Saudi Food and Drug Authority) TSEAC 1 Aug 2011 - Piccardo

9. 9 Based on crude rate estimates, we have no reason to think that the prevalence of vCJD in the population of SA is different from that in several Western European countries. TSEAC 1 Aug 2011 - Piccardo

10. 10 US Military Personnel in SA Acknowledging uncertainties, FDA assumes that a significant amount of beef consumed by military personnel after 1980 originated in UK and decreased after 1989. We cannot assume with confidence that the origin of beef consumed on US bases in SA differed significantly from that in European bases south of the Alps. (Information provided to FDA by the Armed Forces Service Blood Program Office, DoD) We therefore conclude that the possible risk of dietary exposure to the BSE agent by US military personnel in SA is similar to that on European bases south of the Alps TSEAC 1 Aug 2011 - Piccardo

11. 11 Donor loss At-risk groups affected under the proposed recommendation: - US Military Personnel - US Military Contractors - US Non-Military Contractors - Saudi Immigrants to USA Calculated blood donors lost 24,500 blood units lost 41,700 ( most likely scenario ) (H Yang, S Anderson – FDA, OBE, TSEAC 1 Aug 2011) National survey determined that ~ 11M persons donated blood in 2008 (US.DHHS 2009 National Blood Collection and Utilization Survey) TSEAC 1 Aug 2011 - Piccardo

12. Under current FDA recommendations 2 ( Saudi born- raised-living in North America ) of 5 vCJD cases diagnosed in North America ( 3 US, 2 Canada ) would not have been deferred as donors of blood, blood products and HCT/Ps. Three others - long term residents of UK- would have been deferred. (Guidance for Industry – Revised Preventive Measures to Reduce the Possible Risk of Transmission of CJD and vCJD by Blood and Blood Products, May 2010) Under the recommendations considered by FDA all 5 vCJD cases would have been deferred. TSEAC 1 Aug 2011 - Piccardo

13. Questions for TSEAC Question 1. Do available data support consideration by FDA to recommend deferring donors of blood and blood components, including Source Plasma, and to be ineligible donors of Human Cells, Tissues and Cellular and Tissue- Based products who a. spent six months or more cumulatively in Saudi Arabia as US military personnel from the beginning of 1980 through the end of 1996 or b. otherwise spent more than five years cumulatively in Saudi Arabia from the beginning of 1980 through the end of 1996? TSEAC 1 Aug 2011 - Piccardo

14. Questions for TSEAC Question 2. Please discuss the likely contribution of those recommendations to the safety of the products involved and the possible impact on supplies of blood, blood components, plasma derivatives and HCT/Ps. Question 3. Please comment on additional information that might better inform FDA’s consideration of the proposed or any further safety measures. TSEAC 1 Aug 2011 - Piccardo

15. 15 Acknowledgements Steven Anderson, OBE David Asher, OBRR Bryan Emery, DSAC - CBER Jay Epstein, OBRR Joseph Giglio, OBRR Melissa Greenwald, OCTGT Luisa Gregori, OBRR Ginette Michaud, OBRR Martin Ruta, OBRR Jennifer Scharpf, OBRR Alan Williams, OBRR Hong Yang, OBE TSEAC 1 Aug 2011 - Piccardo