REGULATORY UPDATE: BPAC Considering Blood Donor Testing for Malaria

The Food and Drug Administration’s Blood Products Advisory Committee (BPAC) met in open session May 9 for a series of presentations related to transfusion transmission of malaria (TTM) and to consider proposed strategies to reduce the risk of TTM through blood donor testing.

The meeting began with opening remarks by Anne Eder MD, PhD, director, Office of Blood Research and Review (OBRR), Center for Biologics Evaluation and Research (CBER), followed by a series of presentations to help inform the committee’s discussion. First, Seymour Williams, MD, MPH, from CDC’s Division of Parasitic Diseases and Malaria (DPDM) Malaria Branch, provided an overview of ongoing malaria surveillance activities, epidemiology, prevention efforts and clinical care in the United States. He also described the 2023 outbreak of local malaria transmission that included 10 cases in four U.S. states, noting that while the U.S. has eliminated endemic malaria, the country remains at risk for sporadic mosquito outbreaks.

The program continued with a presentation by Sanjai Kumar, PhD, FASTMH, chief of the Laboratory of Emerging Pathogens in OBRR’s Division of Emerging and Transfusion Transmitted Diseases, on the transfusion transmission of malaria. In his presentation, Kumar noted that while the current donor deferral recommendations – which include deferral of donors with a history of malaria or those who have traveled or lived in endemic countries – are effective, they fail to identify and defer all blood donors with asymptomatic Plasmodium infections. This results in infrequent but continued cases of TTM and the loss of an estimated 50,000-160,000 of otherwise healthy donors who are not actually infected with Plasmodium parasite. These donors are less likely to return to donate, he noted.

The meeting continued with a presentation on the first FDA-licensed test to screen blood donors in the U.S. for malaria, Roche’s Cobas malaria test. In this presentation, Susan Galel, MD, senior director of medical affairs, blood screening, Roche Molecular Systems, provided an overview of the test’s workflow and analytical sensitivity. She also described a study conducted in a malaria-endemic region of Nigeria to detect asymptomatic infections and an investigation into sample testing of TTM cases in Canada, Europe and the United States. In those cases, PCR testing was able to detect malaria in all but two cases. Galel noted that the Cobas malaria test is approximately 1,000-fold more sensitive than the PCR assays used in these cases.

In the final presentation before the public comment period, OBRR’s Jennifer Scharpf, MPH, provided an overview of FDA’s policy considerations for testing blood donations for malaria. Two proposed selective testing strategies were presented for discussion:

• Strategy 1A: Selective test blood donations from donors at risk for malaria exposure, as determined solely by donor questioning. This would include donors who have had a history of malaria, those who have traveled to a malaria-endemic country within three months of donation, or those who have ever lived in a malaria-endemic country.
• Strategy 1B: Test all donors at least one time and then selectively test blood donations from donors at risk for malaria exposure, as determined by donor questioning. This would include donors who have had a history of malaria or those who have traveled to a malaria-endemic area within the three months preceding their donation.
  

Additionally, FDA asked the committee to consider the implementation of time-limited NAT screening of all donations in a geographic collection area, defined by zip code, when a single case of local mosquito-borne malaria is reported by public health officials.

During the public comment period, Ralph Vassallo, MD, FACP, incoming chair of AABB’s Transfusion Transmitted Diseases Committee, presented a joint statement on behalf of AABB, America’s Blood Centers and the American Red Cross. The statement noted that the blood community strongly supports FDA’s consideration of multiple, flexible strategies to reduce the risk of TTM to meet the unique operational and budgetary challenges of blood collectors. Vassallo thanked FDA for its steps to remove unnecessary donor deferrals and increase donor diversity and recommended continuing with the current deferral process while also allowing for a testing strategy for individuals with travel to malaria-endemic countries. The statement also emphasized the blood community’s support for a modelling study prior to the release of any draft guidance.

While members of BPAC weighed the pros and cons of both options, most  seemed to favor option 1A, with some nothing that the testing policy could maintain the safety of the blood supply while increasing its diversity. Others noted that both options are an improvement over the current policy, which defers many donors who may otherwise be eligible.

In response to FDA’s proposed time-sensitive NAT screening following local malaria transmission, some committee members voiced concern that a threshold of a single case of locally transmitted malaria reported by public health may be too low to trigger widespread NAT testing of all donors. Others spoke in favor of this proposal, emphasizing that as climate change accelerates, the risk of local malaria transmission may increase.

AABB will update members as new information becomes available. Those with questions may contact regulatory@aabb.org.