CBER Current Considerations for Blood Donor Screening for West Nile Virus Pradip N. Akolkar, Ph.D. Maria Rios, Ph.D. DETTD, OBRR Blood Products Advisory Committee March 9, 2006

CBER Background Summer 1999 Summer 1999: First outbreak of WNV in the US August 2002 August 2002: The theoretical potential for transmission of WNV by blood transfusion was raised in a publication by CDC (Transfusion. August 2002, 42:1019) September 2002 September 2002: Transmission of WNV by transplantation was confirmed, followed by the confirmation of transmission by transfusion (MMWR 2002; 51(35):790) AABB sponsored meeting of decision makers, experts in the field from various Govt. agencies, blood and device industry

CBER Background….. November 2002 November 2002: FDA sponsored workshop aiming to support test development and facilitate communication between test manufacturers and users July 2003 July 2003: Nationwide screening of volunteer blood donations for WNV RNA using NAT implemented under approved INDs performed on mini-pools (MP-NAT) of 6 or 16 donations, depending on the assay

CBER Background….. November 2003 November 2003: Evaluation of MP-NAT sensitivity to detect low viremia by retrospective studies using ID-NAT Identification of ID-NAT-positive and MP- NAT-negative units 6 confirmed cases of WNV transmission by transfusion of MP-NAT-negative units Summer 2004 and 2005 Summer 2004 and 2005: Prospective testing by ID-NAT replaced MP-NAT in areas of high WNV activity during limited periods of time

CBER Benefits of WNV Screening YearUnits InterdictedNo. T.T. Cases Source: CDC update to AABB WNV Taskforce

CBER Status of WNV Assays FDA licensed first WNV NAT for volunteer blood donor screening (Procleix® WNV Assay on eSAS) in December

CBER Current Considerations on Assay Implementation We recognize that WNV RNA NAT for testing samples from volunteer blood donations for transfusion may involve the use of complex pooling and testing systems We are considering recommending that you implement a licensed NAT for WNV RNA within six months from the date of the publication of a Notice in the Federal Register announcing the availability of the Final guidance

CBER Current Testing Considerations 1.The implementation of licensed NAT for WNV RNA for screening volunteer donors of Whole Blood and blood components for transfusion will improve the safety of the nation’s blood supply 2.WNV screening by MP-NAT to be performed year-round with implementation of ID-NAT in specific geographical areas where WNV activity is high

CBER Current Testing Considerations (Cont.) 3.Switch from MP- to ID-NAT to be defined by triggers based on incidence rates. This would increase the sensitivity of WNV testing within the constraints of available technology and personnel 4.We need a dialogue with the blood establishments regarding the criteria to define the trigger to switch from MP-NAT to ID-NAT in geographical areas with high WNV activity, and the appropriate parameter to switch back from ID-NAT to MP-NAT

CBER Donor Deferral and Reentry Considerations 1.Diagnosed or suspected acute WNV illness or infection: Defer donor for 120 days following diagnosis or onset of illness 2.Presumptive viremia (WNV NAT-reactive): Defer donor for 120 days following date of NAT-reactive donation (June 2005 Guidance

CBER Donor Deferral and Reentry Considerations (Cont.) 3.Suspected WNV illness in a donor within 2 weeks after donation: Defer donor for 120 days following onset of illness 4.Donor who may have transmitted WNV infection: Defer donor for 120 days following date of donation 5. May reenter deferred donor after 120 days (June 2005,

CBER Donor Management Considerations 1.Reasonable attempts be made to notify deferred donors of test results 2.Additional testing -Alternate NAT and antibody testing may provide information for donor counseling purposes -Follow-up testing may provide further information on the course and outcome of infection

CBER Unit Management Considerations Discard units that are NAT-reactive Retrieve and quarantine in-date blood and blood components including unpooled recovered plasma, Source Plasma and Source Leukocytes from a donor who: - Was diagnosed with WNV infection or illness - Is presumptively viremic (WNV NAT-reactive) - May have transmitted WNV infection - Has an undiagnosed illness that represents likely infection with WNV (June 2005,

CBER Recipient Notification Considerations Blood establishments that receive information regarding diagnosis of WNV infection or illness may consider tracing records and notifying transfusion services regarding “relevant units” Transfusion services may then consider notifying treating physicians of prior recipients (June 2005,

CBER Labeling Considerations We are considering recommending: The container label and instruction circular that reflects the results of WNV NAT be consistent with the labeling for other infectious disease markers upon implementation of licensed NAT WNV reactive unit not 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