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Maria Rios, Ph.D. CBER/FDA Blood Products Advisory Committee May 1st, 2008

2007 WNV Epidemiology & FDA’s Recommendations on the Use of NAT to Reduce the Risk of Transmission of WNV in Whole Blood and Blood Components for Transfusion and Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) . Maria Rios, Ph.D. CBER/FDA

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Maria Rios, Ph.D. CBER/FDA Blood Products Advisory Committee May 1st, 2008

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  1. 2007 WNV Epidemiology& FDA’s Recommendations on the Use of NAT to Reduce the Risk of Transmission of WNV in Whole Blood and Blood Components for Transfusion and Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) Maria Rios, Ph.D. CBER/FDA Blood Products Advisory Committee May 1st, 2008

  2. Update on the 2007 season Human cases Animal cases including sentinel chickens Mosquito pools Geographical distribution Draft Guidance on Blood Donor Screening for Infection with WNV Screening test platform MP-NAT ID-NAT Additional Testing Donor Counseling Outline

  3. 2007 Human cases in 43 states 43 states 47 states, DC & PR Activity in 47 states, DC & PR WNV Update for 2007 • CDC: 3,623 human cases: • 1,213 (33%) WNV ND • 2,347 (65%) WNF (milder) • 63 (2%) unspecified with a total of 124 deaths • USGS and/or State Dept report as WNV positive: • 3,628 animal cases • 8,625 mosquito pools

  4. WNV in the U.S. Human cases from 1999 to 2007

  5. April 2008 4 Human cases TN (1 in Jan), AZ (1 Mar), MS (2 Mar, Apr) 1 horse (AL) 12 Dead Birds CA (11), SC (1) 10 Mosquito Pools CA (9), FL (1) 4 Sentinel Chickens FL (2), CA (2) WNV Activity in the US • WNV infection is • Notifiable to the CDC • Endemic (peak spring/fall) • Since 2002 yearly: >1,000 WNV ND ≥ 100 fatalities • Since 2005, onset of WNV clinical cases have been reported to the CDC from Jan to Dec

  6. WNV Blood Screening in the U.S. • From 2003 to 2007 resulted in: • Interdiction of ~2,600 WNV NAT-reactive units • Prevention of ~2,600 to 7,800 potential transmissions by transfusion Transmission by Transfusion *All seronegative for WNV; + Lack of f/up, sample, recipient loss ‡ Negative in MP-NAT and positive on ID-NAT (low viremia)

  7. Test individually each specimen included in the pool NAT R MP-NAT ID-NAT R NAT NR Unit (s) discard; Donor deferred for 120 days Additional tests performed for counseling purposes ID-NAT NR If suitable: Released for transfusion Ab to WNV Note: Ab cross-reactivity among Flaviviruses Repeat NAT using same or alternate NAT assay of ≥ sensitivity PPV 98% Sensitivity 98% Current Testing Algorithm

  8. Absent Present Rep ID-NAT R Rep ID-NAT NR Positive False Positive or TN ≤ 10% of IR Rep NAT NR TP on Ab Positive 2% TP on Follow up Algorithm for Additional Testing of Index Donation Specimen Prior to Donor Counseling ID-NAT Reactive Repeat NAT using same or alternate NAT assay of ≥ sensitivity Ab to WNV

  9. 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 (1 in 2004 and 2 in 2006)

  10. Issues Regarding Testing In April 2007, the following considerations were presented to the BPAC • 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 • whether blood establishments should define and validate criteria to trigger ID-NAT and to revert back to MP-NAT

  11. 2007 ARC studies on suitability of ID-NAT implementation criteria (SL Stramer, 2008) Results showed that ID-NAT was required to detect: • 148/540 (27%) in 2003-2004 • 44/154 (29%) in 2005 • 76/212 (36%) in 2006 (in some cases early implementation based on 2 ID-PVD) • 65/147 (44%) 2007 • ARC evaluated criteria for ID-NAT implementation

  12. ID-NAT Detected 42 Confirmed WNV Positive Donations in Validation Studies (SL Stramer, 2008) Trigger criteria 1 PVD** 2 PVD 2 PVD & 1:1000 Yield 5 (12%) 42* (100%) 31 (74%) 11 26 Incremental Yield 6.2-fold increase (88%) 8.4-fold increase 37 *Presumed viremic donor defined as ID-NAT with S/CO ≥ 17 or repeat reactive ID-NAT **12 /42 (29%) were IgG only (18%) (100%) Yield minus IgG (FP?) 30 20 (67%) 5 Incremental Yield 15 10 4-fold increase 25 (83%) 6-fold increase • New data show that the previous criteria for ID-NAT implementation are inadequate

  13. Draft WNV NAT Guidance for Industry Draft Guidance published on April 28, 2008 for comment purposes only 90-day comment period closing in July 27, 2008

  14. Recommendations on Testing • Screen for WNV should be performed year-round using a licensed NAT on donor samples of whole blood and blood components intended for transfusion. • Either MP-NAT or ID-NAT may be used for WNV screening. • ID-NAT should replace MP-NAT during high WNV activity in your region (using a previously defined geographic area).

  15. Screening Algorithm for Blood Donations Using a licensed MP-NAT for WNV Using a licensed ID-NAT for WNV MP-NAT reactive MP-NAT non-reactive ID-NAT non-reactive ID-NAT non-reactive unit (s) Test each specimen in the pool by ID-NAT If suitable, release unit for transfusion If suitable, release unit(s) for transfusion ID-NAT reactive unit (s) Discard unit (s). Defer donor (s) for 120 days. Retrieve in-date products from prior collections dating back 120 days. Initiate WNV ID-NAT for that region

  16. Algorithm for ID-NAT Implementation Test each specimen in the pool by ID-NAT MP-NAT reactive Initiate ID-NAT for all collections from that region in 24 hours ONE ID-NAT reactive unit Discard unit (s); Defer donor (s); Retrieve in-date products If >24 hours of collection: consider performing retrospective ID-NAT testing of retention samples from collections within that time period If blood establishments wish to revert back to MP-NAT, they may do so when the high WNV activity in the defined geographic area has subsided (e.g., minimum of 7 days has passed without a single WNV ID-NAT reactive donation)

  17. Additional Testing Algorithm ID-NAT reactive unit (s) Perform additional testing on index donation specimen as follows: 1. Repeat ID-NATusing the same assay or an alternate NAT* of ≥ sensitivity 2. Test for WNV-antibodies (WNV-Ab) using a cleared Ab assay ID-NAT reactive & WNV-Ab either Pos or Neg ID-NAT non-reactive & WNV-Ab Positiveª ID-NAT non-reactive & WNV-Ab Negative Notify of deferral & counsel the donor as inconclusive for WNV infection. Encourage donor return after 30 days for follow-up testing by ID-NAT and WNV-Ab. Notify of deferral & counsel the donor as testing Positive for WNV infection • * If NAT for all JE viruses used, we encourage WNV discriminatory prior to counseling • ª Cross-reactivity among different Flaviviruses.

  18. Recommendations Regarding Labeling • Container label and instruction circular to reflect results of WNV NAT, consistent with labeling for other infectious disease markers “A Licensed Nucleic Acid Test (NAT) for West Nile Virus (WNV) RNA has been performed and found to be non-reactive.” • 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

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