1. FDA Guidance for Industry: Use of Serological Tests to Reduce the Risk of Transmission of Trypanosoma cruzi Infection in Whole Blood and Blood Components Intended for Transfusion Presentation to BPAC Dec. 15, 2010 Robert Duncan, Ph.D.

2. Background FDA licensed the Ortho T. cruzi ELISA Test System, Dec. 2006, as a donor screening test for blood and tissue donors. A second test, the ABBOTT PRISM Chagas ChLIA was licensed Apr. 2010. The majority of blood centers voluntarily tested all donors for antibodies to T. cruzi at each donation with the licensed test in 2007, 2008 and part of 2009. Repeatedly reactive (RR) specimens were mostly retested with an unlicensed Radio Immune Precipitation Assay (RIPA) because no licensed supplemental test was available. 2

3. Background An FDA draft guidance recommending universal testing of blood and tissue donors was released on March 26, 2009. At the April 2009 BPAC meeting, –FDA presented several potential testing strategies for T. cruzi infection in blood donors and a risk analysis for selective testing strategies. –The epidemiology of Chagas disease in the U.S., the experience with blood donor testing for T. cruzi antibodies during the approximately 2 years since licensure and the experience with asking donors questions to assess their risk of Chagas disease were discussed. –The committee voted in favor of a selective testing strategy in which one negative test would qualify a donor for all future donations without further testing or the need to be asked questions regarding risk of a newly acquired infection. –The committee’s recommendation was contingent upon the continuation of studies to define the incidence of new T. cruzi infections in previously screened negative donors. Comments on the draft guidance document were reviewed and incorporated into the final guidance as well as consideration of the recommendation of BPAC Final Guidance was published on Dec. 6, 2010. 3

4. Guidance Recommendations : Blood Donor Testing and Management Blood establishments should: –Continue to ask the question on the Donor History Questionnaire, “Have you ever had Chagas disease” at every donation. –Test each donor one time for antibodies to T. cruzi Nonreactive donors may return to donate without further testing. Review establishments records to determine the testing history of each prospective donor. Recommended for allogeneic and autologous (when applicable) donors Contingent upon the outcome of studies of the risk of newly acquired T. cruzi infection

5. Guidance Recommendations : Blood Donor Testing and Management Blood establishments should: –Defer (indefinitely) and notify all donors repeatedly reactive by the licensed test –Counsel reactive donors to seek a physician’s advice, explain the significance of possible cross-reactivity. Additional medical diagnostic testing may provide useful information. –Allow reentry only once a supplemental test is licensed and reentry recommendation is published

6. Guidance Recommendations : Product Management Blood establishments should: –Index donations quarantine and destroy or label, “NOT FOR TRANSFUSION” all repeatedly reactive blood and blood components –Products from prior collections from a reactive donor retrieve, quarantine and destroy or label Lookback period: 10 years (indefinitely with electronic records) or, in a previously tested donor, 12 months prior to the most recent negative T. cruzi test result

7. Guidance Recommendations : Product Management (cont.) Blood establishments should: –Lookback (recipient tracing) When identifying a donor who is repeatedly reactive by a licensed test for T. cruzi antibodies, and for whom there is additional information indicating risk of T. cruzi infection, such as a positive test result on a licensed T. cruzi supplemental test, when such test is available. Until such a licensed supplemental test is available, geographical risk for exposure in an endemic area, or medical diagnostic testing of the donor may provide additional information Notify consignees to encourage notification of recipients’ physician of increased risk of T. cruzi infection.

8. Product Management (Continued) Recommendation for Autologous donations –Test when allogeneic use of these units is allowed or units are shipped to centers where allogeneic use is allowed [21 CFR 610.40(d)(1) through (3)]. –Reactive units may only be released for autologous use with approval of the donor’s physician. –Reactive units for autologous use must be labeled “Biohazard” (21 CFR 610.40)

9. Product Management (Continued) Blood establishments must: –Circular of Information update to include a statement like the following: “All blood has been collected from donors who have tested negative by a licensed test for antibodies to T. cruzi either on the current donation or at least one previous donation.” –Biological Product Deviation Report and Fatality report report any event that represents deviation from cGMP, regulations, standards or established specifications that may effect the product’s safety, purity or potency. Also, when a transfusion involving T. cruzi is confirmed to be fatal, you must notify FDA.

10. Product Management (Continued) Licensed Blood establishments adopting the recommendations contained in the guidance must report the following changes to the FDA: –Revisions of Donor History Questionnaire –Test Implementation –Revision to the Circular of Information