# Presentation: 795724

## Issues Related to Implementation of Blood Donor Screening for Infection with West Nile Virus (WNV)

- Maria Rios, Ph.D.
- CBER/FDA
- Blood Products Advisory Committee
- April 27, 2007

- Issues Related to Implementation of Blood Donor Screening for Infection with West Nile Virus (WNV)

## WNV Test Implementation 

- 	FDA seeks comments from the Committee on issues related to implementation of donor screening with NAT for WNV RNA
- Regarding:
- Screening
- Additional Testing
- Donor Counseling

## WNV Infection in the U.S. 

- Identified as a threat to the blood supply in 2002
- Nationwide blood screening under IND in 2003 and that resulted in:
-    > 2,000 units interdicted due to WNV NAT reactivity
-    Prevention of 2,000 to 6,000 transmissions by transfusion

## WNV Infection in the U.S. 

- 	Based on estimation of: *1 in 150 to **1 in 350 infections are neuroinvasive, there have been ~1.5 to 3.5 Million infections
- Epidemics re-occurred every year since 1999
- 23,967 human cases of disease have been reported to the CDC

## Status of WNV Assays

- Dec 2005: FDA licensed the first WNV NAT for volunteer blood donor screening (Procleix® WNV Assay)
- Mar 2007: FDA licensed the first fully automated NAT for volunteer blood donor screening (Procleix® WNV Assay on Procleix® TIGRIS System)
- Other WNV NAT for donor screening are currently under IND

## Onset of Human WNV Disease,

- United States 1999-2005*

***Reported as of 2/14/2006**

***Reported as of 2/14/2006**

**Notes:**
The human WNV season was quite short in 1999; however, it steadily lengthened over the following years, and reached the longest duration yet in 2005, spanning almost the entire year, from Jan. 2 to Dec. 16.

## Issues Regarding Testing

- WNV is endemic in the US (peak spring to fall) and is a reportable disease to the CDC
- 	Since 2002:
- > 1,000 WNV neuroinvasive cases / year
- ≥ 100 documented WNV fatalities / year
- We are considering whether blood establishments should screen for WNV by  MP-NAT year-round

## Issues Regarding Testing

- 2003: 6 cases of TT-WNV after MP-NAT
- MP-NAT detects 75% of WNV infected units (25% undetected)
- 2004: ID-NAT used in high WNV activity regions
- ID-NAT implementation criteria: 1 in 1000 donations reactive or 2 MP-NAT positives in a week, whichever comes first
- Since selective ID-NAT: Three (3) confirmed cases of WNV transmission by transfusion

## Issues Regarding Testing

- We are considering whether blood establishments should implement ID-NAT in areas with high WNV activity
- Uniform criteria to initiate ID-NAT is desirable
- Fully automated NAT system licensed
- Paucity of data to define uniform criteria
- AABB voluntary recommendation: Bulletin #07-02
- We are considering whether blood establishments should define and validate criteria to trigger ID-NAT and to revert back to MP-NAT

## Current Testing Algorithm

##  Issues Regarding Additional Testing 

- We are considering whether blood establishments should:
- Retest IR donations by ID-NAT using:
- 			 screening assay
- 				or
- 			 an alternate NAT of equal sensitivity
- Test ID-NAT IR donations for Ab to WNV
- Note: antibody cross-reactivity among Flaviviruses

## Issues Regarding Additional Testing 

- 	If a NAT screening assay is specific for Flaviviruses but is not discriminatory for WNV:
- We are considering whether blood establishments should perform a WNV-specific discriminatory assay to determine WNV infection

## Additional Testing Algorithm

##  Issues Regarding Donor Counseling

- We are considering whether it is appropriate for:
- IR specimens not to be regarded as *False Positive* based solely on negative test results obtained on additional testing in the index donation
- A donor to be considered *True Positive* based on RR by NAT or WNV Ab positive

- Note: If NAT assay does not discriminate WNV from other viruses of the JE serogroup, it is not appropriate to consider *True Positive for WNV*

## Issues Regarding Donor Counseling

- Due to the potential for *False Negative* results, it is desirable to inform donors with IR ID-NAT about a possible infection with WNV
- Donors with IR ID-NAT may be counseled and invited for follow-up testing (ID-NAT and antibody) at least 30 days post IR donation
- IR ID-NAT donations may not be released for transfusion and donors be deferred for 120 days

## Issues Regarding Labeling

- We are considering whether it is appropriate for:
- Container label and instruction circular to reflect results of WNV NAT, consistent with labeling for other infectious disease markers
- WNV reactive unit not to be shipped or used except as provided in FDA approved programs and/or research or autologous use only, and such units be labeled with appropriate warnings

##  		Issues Regarding:
			Donor Deferral and Reentry
			Product Retrieval
			Recipient Notification
	We are considering maintaining the recommendations as stated in the June 2005 Guidance: WWW.fda.gov/cber/gdlns/wnvguid.htm

- 			Donor Deferral and Reentry
- 			Product Retrieval
- 			Recipient Notification
- 	We are considering maintaining the recommendations as stated in the June 2005 Guidance: WWW.fda.gov/cber/gdlns/wnvguid.htm

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