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 fresh frozen plasma (FFP) and plasma frozen within 24 hours after phlebotomy held at room temperature (RT) up to 24 hours after phlebotomy (PF24RT24) collected using the The Trima Accel™ Automated Blood Collection System (Terumo BCT, Inc., Lakewood, CO) with 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: For FFP assessment, a randomized, crossover study was conducted using paired concurrent apheresis platelet/FFP collections into DEHP and non-DEHP sets (order randomized) occurring 28 to 42 days apart. FFP was stored (-20˚C) for 30+ days. FFP measures from the non-DEHP disposable sets were compared to EDQM criteria and to paired DEHP disposable set measures for equivalence within 20% (recommended by FDA). For PF24RT24 assessment, plasma was collected using a non-DEHP set, then split into the following bags for RT hold and frozen storage: 1) DEHP bag (non-aged), 2) non-DEHP bag (non-aged), and 3) non-DEHP bag (2 year accelerated aged). Post-thaw outcome measures were compared across groups.
Results/Findings: For the FFP assessment, 46 participants were enrolled to obtain 33 evaluable products. A summary of FFP parameters is reported (Table 1). FFP measures met the EDQM criteria for plasma collection volume error (±10%), residual leukocytes (< 1×106), residual red blood cells (< 6.0×109/L), and residual platelets (< 50×109/L) at Day 0 and Factor VIII levels (≥70 IU/100 mL and ≥70% retention) after frozen storage (Day 30+). Although there are no specific FDA standards around plasma, the parameters were equivalent within 20% between non-DEHP and DEHP disposable set collections at Day 0 and after frozen storage (Day 30+) for the following: prothrombin time, activated partial thromboplastin time, Factors V, VIII, IX, XI, protein S (activity), protein C (activity), von Willebrand Factor (antigen and activity), prothrombin fragment 1+2, and complement activation. For the PF24RT24 assessment, 43 participants yielded 31 evaluable products. All quality parameters met equivalency after frozen storage when non-DEHP (non-aged) disposable set collections were compared to DEHP (non-aged) disposable set collections and when non-DEHP (aged) were compared to non-DEHP (non-aged) disposable set collections. No serious adverse events or unanticipated adverse device effects were reported.
Conclusions: Apheresis plasma, FFP and PF24RT24, 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 DEHP disposable sets.
