Manager, Clinical Development Terumo BCT, Inc., Lakewood, CO Lakewood, Colorado, United States
Background/Case Studies: European Union regulations will prohibit di(2-ethylhexyl) phthalate (DEHP) in medical devices on 01 July 2030, necessitating research of alternative plasticizers. This study evaluated whether platelets collected using The Trima Accel™ Automated Blood Collection System (Terumo BCT, Inc., Lakewood, CO) into investigational non-DEHP disposable sets meet European Directorate for the Quality of Medicines and Healthcare (EDQM) and United States Food and Drug Administration (FDA) standards for transfusable products.
Study
Design/Methods: A randomized, crossover study was conducted using paired concurrent apheresis platelet/plasma collections into DEHP and non-DEHP sets (order randomized) occurring 28 to 42 days apart. Platelets were stored in 100% plasma and tested on Days 1, 5 and 7 (where Day 0 was the collection day). Platelet quality parameters from the non-DEHP sets were compared to EDQM and FDA criteria and to paired DEHP set values for equivalence within a 20% margin. The FDA criteria used 95% confidence/95% reliability for all parameters except yield, which used a 95% confidence/75% reliability. The EDQM criteria used 95% confidence/90% reliability for all parameters.
Results/Findings: A total of 46 participants were enrolled to achieve 33 evaluable product pairs. Platelet parameters are summarized in Table 1. Platelet collection in non-DEHP sets met the FDA criteria for Day 1 total residual white blood cell (rWBC) content in platelets (< 5×106), Day 1 platelet yield (≥3.0×1011), and Days 1, 5 and 7 pH (≥6.2). Platelet collection in non-DEHP sets met the EDQM criteria for Day 1 for total rWBC content (< 1×106), Day 1 platelet yield (≥2×1011), and Days 1, 5 and 7 pH ( >6.4). Using a one-sided 95% confidence interval (CI) for non-inferiority, the following parameters were within a 20% margin: Day 1 total rWBC content in platelets and Days 1, 5 and 7 for P-selectin (membrane-bound), extent of shape change (ESC), hypotonic shock response (HSR), and platelet morphology. Using two-sided 90% CIs for equivalence, Day 1 platelet volume and yield were both within a 20% limit. Day 1 residual red blood cell (rRBC) content in platelets had an upper 95% CI of 1.52×109/L (p=0.29) and, thus, did not meet the 20% margin for non-inferiority. However, this result was considered clinically inconsequential in regard to absolute RBC content, and the observed value remained well below the maximum recommended by AABB. No serious adverse events or unanticipated adverse device effects were reported.
Conclusions: Apheresis platelets collected and stored in non-DEHP disposable sets met FDA and EDQM quality standards, with no safety concerns. These findings support their use as acceptable alternatives to marketed disposable sets that expose donors and collected platelets to DEHP mainly from the collection circuit.
