April 28, 2008
Dear Dr Vostal and Ms Erdman:
We are sending this note on behalf of the AABB ad hoc task force organized by Lou Katz, MD, to propose an alternate post-market study design to permit transfusion of Trima® and AmicusTM platelets up to 7 days after collection. The design proposed in brief outline below is the result of many teleconferences and an all day face-to-face meeting.
We initially focused the redesign efforts around the inclusion of a point of issue bacterial test, as had been discussed among the FDA, Fenwal, and Gambro BCT earlier this year. We have moved away from this as a requirement due to our opinion that the incremental safety of the proposal and the low incidence and severity of septic transfusion reactions (STRs) from day 6 and 7 transfusions in the original PASSPORT surveillance study supports the clinical safety of the new proposal for 7-day platelets. The significant logistical problems of secondary culture for surveillance (hospital testing, communicating with the donor center, and relabeling, for example) and the problem of large numbers, because of the ever diminishing rate of expected positives, led to approaches that were felt by the task force as well as blood banks and hospitals to be either undoable or to require unacceptable burdens in cost and time.
We have developed 7-day platelet preparation and release criteria that will provide an improved safety profile to the patient over that of the original approach. Additional safety is conferred by doubling the sample volume in each of the culture bottles for the day 1 release test, requiring diversion of an initial bolus of blood, and requiring implementation of best practice for venipuncture site preparation. The post marketing surveillance of the enhanced 7-day platelet methods will determine the rate of STRs as a function of the age of the platelet products at transfusion with a focus on the rate at day-5 vs. days-6 and 7. We propose also adding labeling information about the bacterial-related risks of transfusion as a function of product age and the availability of tests that may reduce these risks. Finally, we propose an independent expert panel for adjudication and review of reported STRs and ongoing safety monitoring.
We would like to discuss the study proposal with the agency at your earliest convenience and are providing this proposal at this time to inform you of the progress and direction of the redesign task force prior to the BPAC meeting on May 1st.
Bob Schuyler, PhD, Gambro BCT and Peyton S Metzel, PhD, Fenwal, Inc.
for the AABB task force:
Richard Benjamin, MD, PhD, ARC
Mark Brecher, MD, UNC
Allene Carr-Greer, MT (ASCP)SBB, AABB
Larry Dumont, PhD, Dartmouth–Hitchcock Medical Center
Jaime Houghton, MS, MT (ASCP) Fenwal, Inc
Lou Katz, MD, Mississippi Valley Regional Blood Center
Becky Lippincott, BS, Gambro BCT
Peter Tomasulo, MD, BSI
Proposed 7-day Platelet Release Plan with Post-Market Surveillance Study for Reinitiation of 7-Day Platelet Availability
The proposal is similar to the current 7-day release test requirement detailed in the Trima and Amicus instructions for use and operators manuals, and the PASSPORT Surveillance Protocol, with the following modifications/additions/similarities:
1. Place in labeling the results of the PASSPORT surveillance and statements that testing cannot guarantee sterility, that risk of bacterial contamination increases with age, and that there are products available for secondary bacterial testing later in storage or at issue. [addition]
2. Increase release test sample volume to 8-10 mL/bottle for both the aerobic and anaerobic bottles. [modification]
3. Sample at 24-36 hours, culture for a minimum of 24 hours prior to transfusion. [modification]
4. Require adequate diversion of initial blood bolus in accordance with AABB Standards. [addition]
5. Require implementation of acceptable venipuncture site preparation in accordance with AABB Standards. [addition]
6. Label for 7-day expiration. [same]
7. Inform recipient hospitals of initial positives and reculture, if available, per AABB and industry standards. [same]
8. Post marketing surveillance will be passive reporting of transfusion reactions to blood center, as in the current PASSPORT study. (Perhaps enhanced at a later date after the rollout of the AABB Hemovigilance reporting network) [same]
9. Implement an enhanced process whereby a Blood Center follows up with transfusing physician and gathers specific information concerning suspected STR. [modification]
10. Data will be reported to an independent Panel of Experts for adjudication according to specific criteria. [addition]
11. Panel of Experts will also serve a data safety and monitoring role. [addition]
12. Blood centers will obtain, possibly from a subset of hospitals supplied, the date of issue for transfusion of specific products. [addition]
13. Using data from #12, blood center determines age of product at issue. [addition]
14. Estimates will be made of the rate of STRs as a function of product age. [addition]
No active clinical or culture surveillance to be done, i.e. no analog to Current PASSPORT Surveillance Protocol