The in vivo and in vitro quality of RBCs stored for 42 days in ADDITIVE SOLUTION FORMULA 3 (AS-3) storage solution has been assessed in three clinical studies.

In Vivo Recovery of Autologous Radiolabeled RBC 

A single-arm, multicenter, in vivo study was conducted to assess the recovery of radiolabeled RBCs 24 hours post infusion. Acceptability of in vivo recovery was determined using established FDA-CBER acceptance criteria. Double collection RBCs (dRBC) were collected using the Trima Accel system and stored in ADDITIVE SOLUTION FORMULA 3 (AS-3) solution for 42 days, then radiolabeled with 51Chromium, and transfused back to the original subject. Table 2 summarizes the in vivo recovery data. Of the 27 units transfused, 26 had > 75% RBC recovery.

FDA-CBER Criteria for Acceptable Recovery: Radiolabeled RBC recoveries should average at least 75%, with a standard deviation of at most 9%. In addition, the 95% one-sided lower confidence limit for the population proportion of successes should be > 70%, with success being defined as an individual red blood cell in vivo recovery of at least 75%. No more than 3 out of 24 data points may have less than 75% radiolabeled red cell recovery at 24 hours post infusion.

The primary outcome was met for RBCs collected on the Trima Accel system and stored in ADDITIVE SOLUTION FORMULA 3 (AS-3) storage solution.

In Vitro RBC Quality Studies

The in vitro quality of RBCs collected in single RBC collection (sRBC) and dRBC procedures using the Trima Accel system was assessed after 42 days of storage in ADDITIVE SOLUTION FORMULA 3 (AS-3) solution in a multicenter, paired study. In vitro quality was determined using established FDA-CBER acceptance criteria. The quality of RBCs stored in ADDITIVE SOLUTION FORMULA 3 (AS-3) solution (test) was compared to RBCs stored in plasma (control). Table summarizes the in vitro RBC quality data for collection on the Trima Accel system and storage in ADDITIVE SOLUTION FORMULA 3 (AS-3) solution.

FDA-CBER Criteria for Acceptable Day 42 Hemolysis: Zero failures (hemolysis ≥ 1% after 42-day storage) out of 60 test units that were not excluded from analysis by the Extreme Studentized Deviate test with α=0.05, which satisfies the binomial distribution testing requirement that, with 95% probability and a one-sided 95% lower confidence limit, the post-storage hemolysis was less than 1% per unit.

There were 0/68 sRBC test units and 0/70 dRBC test units with Day 42 hemolysis ≥ 1%. No donors were excluded as hemolysis was < 1% for all test units. Therefore, the primary objective was met for RBCs stored in ADDITIVE SOLUTION FORMULA 3 (AS-3).

The in vitro quality of sRBC and dRBC units collected using the Trima Accel system was assessed after 42 days of storage in AS-3 solution in a multicenter study. The quality of RBCs was compared between sRBC and dRBC units, and between units A and B of the dRBC collection. Table summarizes the in vitro RBC quality data for collection using the Trima Accel system and storage in ADDITIVE SOLUTION FORMULA 3 (AS-3).

The primary outcome of this study was to demonstrate RBC collection, storage, and viability in vitro.

The sRBC and dRBC units collected were comparable. The hematocrits, blood gasses, ATP, potassium, total hemoglobin, and osmotic fragility were within acceptable ranges following storage. Two statistically significant differences were identified between the A and B units in the dRBC collection at Day 42 (sodium and plasma free hemoglobin), but these differences were not clinically significant. There was no difference between dRBC units in hemolysis following storage in ADDITIVE SOLUTION FORMULA 3 (AS-3). A statistically significant difference was identified in the osmotic fragility of RBCs stored in ADDITIVE SOLUTION FORMULA 3 (AS-3) following sRBC collection or dRBC collection at Day 42, but the difference was not clinically significant. All the RBC units collected averaged less than 1% hemolysis on Day 42. These results are consistent with US and European guidelines for hemolysis on transfusion. ATP recovery was greater than 70% of all units, which is predictive of good in vivo viability, and potassium levels on Day 42 average less than 50 mEq/L indicating good RBC membrane stability over the storage period.