# Presentation: 847501

## Topic 1: FDA Draft Guidance “Revised Preventive Measures to Reduce the Possible Risk of Transmission of CJD and vCJD by Blood and Blood Products”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 1980-1996; 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 366:999-1000, 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- into FDA draft guidance 8/27/01
- (_[http://www.fda.gov/cber/gdlns/cjdvcjd.htm](http://www.fda.gov/cber/gdlns/cjdvcjd.htm)_)
-  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## FDA Draft Guidance: Donor Deferrals Phase IImplementation 5/31/02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, 1980- 1996**
**2.  France **_**>**_** 5 years, 1980- present**
**3.  U.S. military base, **_**>**_** 6 months 1980- 1990**
**N. of Alps; 1980- 1996 S. of Alps **
**4.  Recipients of transfusion in U.K.**

## U.K. Donor Deferral 1980- 1996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 2001****	****	**
**http://www.defra.gov.uk/animalh/bse/index.html**

## Cases of BSE by year of report - U.K. Through

**Cases of BSE by year of report - U.K. Through**
**June 30, 2001 - The Declining Epidemic and Effectiveness U.K. Measures**
**Year****	****BSE cases****	**
- (a) 	442	 (all cases prior to becoming notifiable)
- 1988	2469
- 1989	7137
- 1990	14,181
- 1991	25,032
- 1992	36,682
- 1993	34,370
- 1994	23,945
- 1995	14,302
- 1996	8,016
- 1997	4,312
- 1998	3,179
- 1999	2,274
- 2000	1354
- 2001*	311
**Total****	****178,006****	****	**
- From “BSE in Great Britain:  A Progress Report,”  DEFRA June 2001
- http://www.defra.gov.uk/animalh/bse/index.html

## 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 1980 - 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 national 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%)**