Topic 1: FDA Draft Guidance “Revised Preventive Measures to Reduce the Possible Risk of Transmission of CJD and vCJD by Blood and Blood Products” Dorothy Scott, M.D. Office of Blood Research and Review FDA October 25, 2001

Previous Guidance- Deferrals vCJD, CJD Risk factors for classical CJD (Family history, growth hormone injections, dura mater transplant BSE exposure risk: travel/residence in U.K. > 6 months ; injection bovine insulin (U.K. source)

Post 1999 Guidance Increasing rate of vCJD epidemic in United Kingdom Increased BSE epidemic detected in Europe (more countries, more cattle) Sheep transfusion transmission BSE (Lancet 366: , 2000) Continued scientific uncertainty - vCJD transmitted by blood ?

TSEAC 6/28/2001 Considered increased donor deferral for vCJD risk (BSE exposure) Weighed risk of shortage blood and need for precautionary measures –long incubation period limits epidemiological studies although if transmission possible, deferrals have current importance –experimental studies on infectivity of vCJD blood limited to date – blood shortage possible if large donor deferrals recommended

TSEAC 6/28/2001 Opinions and votes by TSEAC incorporated into FDA draft guidance 8/27/01 ( New donor deferrals decrease risk (based upon exposure to BSE) 91%; 5% donor loss anticipated (based on REDS survey data) - Phased implementation - Pilot studies for more stringent deferrals - Blood vs. Plasma (European donor deferral) - Blood supply monitoring

FDA Draft Guidance: Donor Deferrals Phase I Implementation 5/31/02 1. U.K. > 3 months, France > 5 years, present 3. U.S. military base, > 6 months N. of Alps; S. of Alps 4. Recipients of transfusion in U.K.

U.K. Donor Deferral Food Chain Controls U.K. implemented measures to prevent entry BSE into human food chain by 1996 – SRM ban (brain, spinal cord, intestines, etc.) – ban on mechanically recovered meat from vertebral columns – over-30-months scheme From “BSE in Great Britain: A Progress Report,” DEFRA June

Cases of BSE by year of report - U.K. Through June 30, The Declining Epidemic and Effectiveness U.K. Measures YearBSE cases (a) 442 (all cases prior to becoming notifiable) , , , , , , , , , , *311 Total178,006 From “BSE in Great Britain: A Progress Report,” DEFRA June

Non-European BSE First case documented September 2001in Japan - Confirmed in U.K. - USDA import ban announced 9/2001 MBM from U.K. shipped to many non-European countries, now also at risk for BSE - Need to assimilate current deferrals - Future consideration additional deferrals - Emphasizes importance food chain controls

FDA Draft Guidance: Donor Deferrals Phase II Implementation 10/31/02 Deferral Blood donors who have lived in Europe > 5 years present Donors of Source Plasma for plasma derivatives remain eligible

Source Plasma Model TSE agents partitioned/removed during plasma fractionation European risk of vCJD low (small BSE epidemic relative to U.K.) Magnitude of risk reduction achieved by fractionation at a minimum, 2 logs greater than that achievable by donor deferral Effects on nationwide/worldwide plasma supplies uncertain, but potentially severe

Source Plasma Source vs. recovered plasma- differentiated to prevent potential errors in use of deferred non-plasma components Recommendation will be reevaluated in light of additional epidemiologic evidence, transmission studies, and advances in validation of removal TSE agents by manufacturing

Effects of New Donor Deferrals Upon Supply of Blood/blood components FDA- recommended deferrals: 5% of donors deferred (REDS study) – greater proportion in coastal cities – 35% of NYBC supply affected (Euroblood + U.S. deferrals) Industry-proposed deferrals (3 months U.K.; 6 months Europe): 3% donors deferred (industry study); 9 % donors deferred (REDS study)

TSEAC Proposal Concerning Implementation of New Donor Deferrals, that “a n ational recruitment campaign and a system to monitor adequate blood supply,” be instituted

Current Efforts to Attenuate Effect of New Donor Deferrals on Blood Supply Phased-in deferrals, particularly European deferral (least risk - least BSE exposure) Recommending Pilot studies for more stringent deferrals – pilot program - donor recruitment, evaluation donor loss, endpoints for pilot –monitor recruitment efforts, fluctuations in hospital demand

Current Efforts to Attenuate Effect of New Donor Deferrals on Blood Supply National monitoring of blood supply, demand in place Encouragement of donor recruitment Encouraged cooperation among blood providers to supply in case of regional shortages

Draft Guidance - Future Collection and evaluation comments to the docket (period extended through October 28, 2001) Issuance of final guidance, with revisions Monitoring of blood supply as recommendations effected Continued assessment blood and plasma risk/benefit of donor deferrals

TSEAC-Recommended Donor Deferrals – Risk Reduction Current Risk reduced 72 % (Total Risk Reduced 91%)