Implications of the US Food and Drug Administration draft guidance for mitigating septic reactions from platelet transfusions

In March 2016, the US Food and Drug Administration (FDA) issued the second draft guidance entitled “Bacterial Risk Control Strategies for Blood Collection Establishments and Transfusion Services to Enhance the Safety and Availability of Platelets for Transfusion.”1 This draft guideline addresses the residual risk of bacterial contamination of platelet products, which may result in septic transfusion reactions. Among blood products, platelet products are most frequently associated with septic transfusion reactions, as they are stored at room temperature. Since 2004, multiple steps have been implemented to decrease the risk of contamination. These include skin cleansing, diversion pouch, and bacterial screening. These steps have decreased the rate of septic reactions from a reported range of 10 to 400 to 7 to 25 per 1 000 000, and the rate of fatal septic reactions from a reported range of 2 to 63 to 2 to12 per 1 000 000 apheresis platelet products transfused.2 Thus, the overall risk has decreased by approximately two thirds. In the last couple of years, additional steps to decrease risk of septic reactions have been FDA approved, including pathogen-reduction technologies (PRT) and point-of-issue (POI) (also known as point-of-release) testing capabilities. At the New York Blood Center (NYBC), the residual risk as reported from hospitals is septic reaction rate of 1 per 250 065.3 Recent data using prospective testing report 20 per 51 400 (1/2570) platelet products contaminated resulting in 4 per 51 400 (1/12 800) reactions (1 being fatal [1/51 400]).4 PRT decreases most bacteria load by >4 logs. Hemovigilance data have not reported septic transfusion cases with pathogen-reduced (PR) platelets.5 Prospective screening of apheresis platelets using the Pan Genera Detection (PGD) test (Verax Biomedical, Marlborough, MA), a POI test, demonstrated a residual bacterial contamination risk of 1 per 2302 (75% detected with PGD) apheresis platelets. The PGD has a false positive rate of 0.51% and a false negative rate of 1 in 9206.6 The FDA-reported fatality rates due to bacteria contamination of platelets (both pooled and apheresis) range from 1 to 4 per year from 2011 to 2015 in ∼2.1 million annual platelets transfused.7,8 Staphylococcus aureus was the contaminant in the majority of contaminated apheresis platelets. The FDA draft guidance asks for implementation of PRT, POI testing, or a second bacterial culture, or to shorten the shelf life of the platelet product from 5 to 3 days. Each of these methods has considerable logistical and clinical issues. In June 2016, during the open comment period, the NYBC, as well as other blood centers, including AABB (formerly known as the American Association of Blood Banks) and ABC (America’s Blood Centers), expressed their opinions regarding the impact of implementing the draft guidance as written (https://www.regulations.gov/docket?D=FDA-2014-D-1814). We have recently submitted additional comments and have urged the FDA to reopen the comment period to encourage a broader community to remark. Options for meeting these new guidelines based upon days from collection are shown in Table 1. Once the guidance is finalized, there is a proposed 1-year implementation date. Table 1. Platelet product shelf-life and draft guidance options