A transfusion-transmitted malaria meeting has been held by the U.S. Food and Drug Administration’s (FDA) Blood Products Advisory Committee (BPAC) to weigh, “proposed strategies to reduce the risk of transfusion-transmitted malaria (TTM) by testing blood donations from donors at risk of malaria exposure.” The transfusion-transmitted malaria meeting discussions focused on:
- the agency’s proposed strategies for selectively testing blood donations from donors at risk for malaria using an FDA-licensed nucleic acid test (NAT):
- Strategy 1A: Selective testing for history of malaria, history of prior residence in malaria-endemic country, history of travel to a malaria-endemic area;
- Strategy 1B: One-time testing of all donors and selective testing for history of malaria and history of travel to a malaria-endemic area; [and]
- FDA’s proposal that blood establishments should implement time-limited NAT screening of all donations collected in area(s) of the U.S. when a single case of local mosquito-borne malaria is reported by public health authorities.”
The FDA BPAC transfusion-transmitted malaria meeting featured experts from the Centers for Disease Control and Prevention (CDC), FDA’s Center for Biologics Evaluation and Research’s (CBER) Office of Blood Research and Review (OBRR), the OBRR Division of Emerging and Transfusion Transmitted Diseases (DETTD), and Roche Diagnostics Solutions presenting on topics that included the surveillance and epidemiology of malaria; local malaria outbreaks in the U.S.; transfusion-transmitted malaria in the U.S.; the scientific rationale regarding FDA’s proposed measures to mitigate TTM risk in the U.S; donor characteristics and clinical presentation of TTM; the potential impact of malaria risk deferrals on donor availability; NAT to screen blood donors for malaria risk; molecular testing for of asymptomatic Plasmodium infections; describing FDA’s regulatory framework for blood safety against TTM; and discussing the pro and cons of the proposed selective testing strategies.
During the public hearing portion of the FDA BPAC transfusion-transmitted malaria meeting, America’s Blood Centers (ABC) Chief Medical Officer Jed Gorlin, MD, MBA addressed the committee explaining that, “ABC recommends delaying publication of a draft guidance on malaria testing, until real world modeling studies help determine the clinical sensitivity of available tests in specific donor populations. Virtually all U.S. cases of transfusion-transmitted malaria in the last two decades were from asymptomatic donors originally from endemic countries. Those individuals are known to have relatively low levels of parasitemia relative to symptomatic cases, so we have concerns whether the assay sensitivity is sufficient. While clinical studies may not be feasible, we recommend waiting for completion of modeling studies demonstrating adequate clinical sensitivity, as well as the approval of more than one test prior to issuing guidance.”
Dr. Gorlin also stated that, “we [agree] with FDA that universal testing at this time would be quite cost-ineffective…ABC recommends that FDA maintain allowing the current deferral options given the fact that [only] been 13 cases in the last 21 years in over 200,000,000 donations. We recommend they allow current deferral options while also allowing for a selective testing strategy to qualify a donation after returning to the U.S. following a short incubation period for individuals who traveled to an endemic country but who were not prior residents of a malaria-endemic country.” He concluded by noting that, “given the recent cases of autochthonous malaria in Florida and other states at our southern borders, ABC supports the potential for testing strategy for donations in regions with local, mosquito-borne malaria transmission, but recommends having a higher minimum threshold than a single case for triggering testing determined through the recommended modeling studies.”
During the committee discussion portion of the FDA BPAC transfusion-transmitted malaria meeting, the FDA addressed concerns it received in public comments about the performance of the Roche cobas® Malaria NAT. The agency approved a biologics license application (BLA) from Roche for the malaria test in March but the test is not commercially available yet. CBER explained that from the data presented, the arguments being used in public comments calling into question its sensitivity, “are flawed. From the data that we have, we believe the test would be sensitive and has proven sensitive [in cases of TTM] where the donor was called back and performed less sensitive PCR tests that were still positive. For those reasons, although admittedly it is indirect, we believe there is more evidence to support that the test will work to detect asymptomatic parasitemia than it won’t work.”
Additionally at the FDA BPAC transfusion-transmitted malaria meeting, babesia was not seen as a good example or comparable to malaria. Another potential limitation of Strategy 1B was identified with the three-month interval following travel to an endemic area and asymptomatic donors, while residents of an endemic area are being tested at every donation. It was acknowledged that three-months might not be the correct interval for consideration for testing following re-exposure to a malaria-endemic area. However, it was stated by CBER that, Strategy 1B, “picks up more of what we know is causing the cases of TTM to make it through.” It was also noted that, while additional modeling is beneficial, it could prove challenging with such low malaria numbers in the U.S.
The committee also discussed a single case of malaria being the trigger for implementation of time-limited NAT screening of all donations collected in areas where public health authorities report mosquito-borne malaria. Multiple committee members identified the challenges with the single-case trigger. A suggestion was made that rather than a specific trigger, FDA instead has the discretion to decide on local screening in consultation with CDC and local jurisdictions. Also, a question was raised regarding how long time-limited NAT would continue.
CBER officials thanked the committee for their discussion, the presenters and those individuals who made public comments for their participation at the FDA BPAC transfusion-transmitted malaria . The agency will review the feedback received as they work on the next steps. A recording of the meeting is available. ABC previously submitted written comments to the FDA ahead of the BPAC meeting that “strongly recommended” that the agency delay publishing draft guidance until modeling studies are finished and additional malaria testing assays are approved and available. “Prior to publication of a draft guidance on malaria testing, real world modeling studies should be performed to determine the sensitivity of available tests, including studies performed in malaria-endemic locations and including data on semi-immune donor populations.” The comments specified that, “there is currently only one malaria test approved for screening of the blood supply. As FDA knows, this raises concerns about the blood supply’s reliance on a single test. Without an alternative, supply chain challenges could cripple the blood supply.”