A Joint Statement Presented Before the Food and Drug Administration's Blood Products Advisory Committee
31 July 2014
Reentry of Blood Donors Deferred on the Basis of Screening Test Results for Antibodies to Trypanosoma cruzi
Louis M. Katz, MD, chair, AABB Transfusion Transmitted Diseases Committee
We are pleased to have this opportunity to provide comment to the FDA on the reentry of donors with unconfirmed reactivity on donor screening tests for T. cruzi, and for the flexibility the agency has shown by providing the BPAC with multiple algorithms for consideration, although we believe that only option 4 is realistic based on both sensitivity and logistics.
Our organizations support the use of alternative reentry scenario 4. Donors with repeat reactivity on a screening test and a negative licensed confirmatory test at index (or a negative research RIPA at index or untested with a supplemental assay) are retested at an interval of several months after the index donation using both licensed screening tests. If nonreactive on both, they may be reentered into the eligible donor pool. Scenario 4 has optimal sensitivity based on the use of two screening tests containing both parasite-derived lysate antigens and recombinant antigens configured in automated assays using an objective interpretation. This scenario is accessible to most testing labs in the US (vs the ESA which is not and which poses logistical challenges based on testing a follow-up sample within the time frame specified in the product insert).
The FDA has classified as “less safe” two donors who were screened repeat reactive and ESA negative at index. These donors were negative on both screening tests when the index samples were retested, and again demonstrated no reactivity by both screening tests at follow-up, but had borderline reactivity with the ESA, a subjective assay. There is no evidence that such donors are infected or infectious. Such components, negative on screening tests, are transfused daily in the US, based on clinical specificity studies summarized in Tables II and III of the licensed ESA package insert; no transmissions have ever been documented from such units. Based on published lookback studies in the United States summarized by Dr. Susan Stramer, transmission rates are less than 1 percent, even from confirmed-positive donors. Further, fewer than 10 percent of confirmed-positive donors have detectable parasitemia when examined by hemoculture.
The agency’s preferred algorithm requires the use of the licensed ESA, in addition to both screening tests, on a follow-up sample, regardless of negative ESA results at index. This assumes that there are cases in which screening reactivity at index will disappear at follow-up, but supplemental reactivity will be preserved or enhanced. The rationale for the use of the ESA following two negative screening tests at follow-up appears to be based on the FDA’s assertion that “the relative analytical sensitivity of the ABBOTT ESA Chagas assay was shown to be greater than that of the two licensed screening tests”. Although this is stated in the FDA issues summary, we can find no data to support that statement. It appears the assertion is based on the results obtained from dilution series of highly reactive sera that are not characteristic of the donor samples of interest in this discussion. It also has been discussed at this and prior BPAC meetings that no recent seroconverting US blood donor has yet to be documented. Along these lines, donors with an indeterminate ESA or prior indeterminate RIPA result should not be discarded as potentially infected, if follow-up data demonstrate otherwise. These donors should not be permanently deferred but should have an opportunity to be re-entered based on testing of subsequent samples.
AABB is an international, not-for-profit association representing individuals and institutions involved in the field of transfusion medicine and cellular therapies. The association is committed to improving health by developing and delivering standards, accreditation and educational programs that focus on optimizing patient and donor care and safety. AABB membership consists of nearly 2,000 institutions and 8,000 individuals, including physicians, nurses, scientists, researchers, administrators, medical technologists and other health care providers. AABB members are located in more than 80 countries.
Founded in 1962, America's Blood Centers is North America's largest network of community-based, independent blood programs. The network operates more than 600 blood donor centers providing over half of the U.S., and a quarter of the Canadian blood supply. These blood centers serve more than 150 million people and provide blood products and services to more than 3,500 hospitals and healthcare facilities across North America. America's Blood Centers' U.S. members are licensed and regulated by the U.S. Food and Drug Administration. Canadian members are regulated by Health Canada.
The American Red Cross shelters, feeds and provides emotional support to victims of disasters; supplies about 40 percent of the nation's blood; teaches skills that save lives; provides international humanitarian aid; and supports military members and their families. The Red Cross is a not-for-profit organization that depends on volunteers and the generosity of the American public to perform its mission. About 5.6 million units of whole blood are collected from roughly 3.3 million Red Cross volunteer donors, separated into 8 million transfusable blood products and supplied to approximately 2,700 hospitals and transfusion centers across the country for patients in need.