West Nile Virus (WNV) and Donors of Human Cells, Tissues and Cellular and Tissue-Based Products (HCT/Ps) Melissa A. Greenwald, MD Division of Human Tissues Office of Cellular, Tissue and Gene Therapies Blood Products Advisory Committee 1-2 May 2008

Background CBER has been considering WNV and HCT/P donor screening and testing since the WORKSHOP ON DEVELOPMENT OF DONOR SCREENING ASSAYS FOR WEST NILE VIRUS held November 4-5, 2002 At that time the “new” 21 CFR Part 1271 HCT/P regulations were not yet in effect—therefore WNV not yet a relevant communicable disease agent or disease

WNV is now a Relevant Communicable Disease Agent or Disease (RCDAD) Proposed WNV as a relevant communicable disease agent or disease (RCDAD) in the Guidance for Industry (DRAFT)—Eligibility Determination for Donors of HCT/Ps (May 2004) WNV became an RCDAD as of the implementation date of the Guidance for Industry (final)—Eligibility Determination for Donors of HCT/Ps (published February 2007; Implementation date August 2007)

RCDADs—diseases for which all HCT/P donors are currently screened and/or tested Human immunodeficiency virus (HIV), types 1 and 2; Hepatitis B virus (HBV); Hepatitis C virus (HCV); Human transmissible spongiform encephalopathy (TSE), including Creutzfeldt-Jakob disease (CJD); and Treponema pallidum (syphilis) RCDADs are Relevant Communicable Disease Agents or Diseases

“New” RCDADs As of August 2007, the following are considered RCDADs for all HCT/Ps, as explained in the final Donor Eligibility guidance: West Nile Virus Sepsis Vaccinia (the virus used in smallpox vaccine)

HCT/P Donor Screening and WNV: Current Recommendations As part of donor screening, establishments are required to review relevant medical records for risk factors for RCDADs For WNV: 15. Persons who have had a medical diagnosis or suspicion of WNV infection (based on symptoms and/or laboratory results, or confirmed WNV viremia) you should defer for 120 days following diagnosis or onset of illness, whichever is later.15. Persons who have had a medical diagnosis or suspicion of WNV infection (based on symptoms and/or laboratory results, or confirmed WNV viremia) you should defer for 120 days following diagnosis or onset of illness, whichever is later. 16. Persons who have tested positive or reactive for WNV infection using an FDA-licensed or investigational WNV NAT donor screening test in the preceding 120 days.16. Persons who have tested positive or reactive for WNV infection using an FDA-licensed or investigational WNV NAT donor screening test in the preceding 120 days.

HCT/P Donor Screening and WNV: Current Recommendations As part of donor screening, establishments are required to review relevant medical records for clinical evidence of RCDADs For WNV: WNV infection: Because signs and symptoms of WNV can be nonspecific, you should consider the following clinical evidence in light of other information obtained about the donor in making a donor eligibility determination. (cont)WNV infection: Because signs and symptoms of WNV can be nonspecific, you should consider the following clinical evidence in light of other information obtained about the donor in making a donor eligibility determination. (cont)

HCT/P Donor Screening and WNV: Current Recommendations Mild symptoms might include fever, headache, body aches, or eye pain; –mild symptoms might also occasionally be accompanied by a skin rash on the trunk of the body; or o swollen lymph glands. Severe illness might include encephalitis, meningitis, meningoencephalitis, and acute flaccid paralysis; –signs and symptoms of severe illness might include headache, high fever, neck stiffness, stupor, disorientation, coma, tremors, convulsions, and muscle weakness or paralysis.

HCT/P Donor Screening and WNV: Current Recommendations In both the draft and final donor eligibility guidance, the following was stated: –We may recommend routine use of appropriate licensed donor screening test(s) to detect acute infections with WNV using NAT. There are two NAT donor screening tests licensed for testing both living and cadaveric HCT/P donors

Donor Testing and WNV: Draft Guidance Recommendations In this draft guidance, we are recommending year-round testing by ID- NAT for all donors of HCT/Ps As always, publication of draft guidance allows for the opportunity for public comment prior to publication of any final guidance recommendations

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