In vitro and in vivo evaluation of leukoreduced red cell concentrates stored in non‐ DEHP storage bags

Background and Objectives Europe will ban di(2‐ethylhexyl) phthalate (DEHP), used in blood bags, after 1 July 2030. This two‐phase study assessed the in vitro quality and in vivo 24‐h post‐transfusion recovery (PTR) of whole blood–derived leukoreduced red cell concentrates (RCCs) collected and processed in 1,2‐cyclohexane dicarboxylic acid diisononyl ester (DINCH)‐plasticized sets and stored for 42 days in non‐DEHP Erythromate‐plasticized, a proprietary blend of DINCH and N ‐butyryl‐tri‐ n ‐hexyl citrate (BTHC), disposable sets. Materials and Methods In Phase 1, in vitro parameters of RCCs ( n = 32) stored in non‐DEHP sets containing phosphate‐adenine‐glucose‐guanosine‐saline‐mannitol (PAGGSM) were compared with those of RCCs stored in DEHP sets containing saline‐adenine‐glucose‐mannitol (SAGM) ( n = 24). These parameters were assessed against the European Directorate for the Quality of Medicines & Health Care (EDQM) criteria. In Phase 2, PTR of 42‐day autologous non‐DEHP RCCs was evaluated using biotin‐labelled methods in 24 healthy participants and compared against the EDQM and the US Food and Drug Administration (FDA) criteria. Results Phase 1 results showed that haemoglobin concentrations remained stable. Haemolysis in non‐DEHP/PAGGSM disposable sets was below the EDQM limit (<0.8%) with a 95% confidence limit (CL) of 0.25% on Day 42 and was significantly lower (0.22% ± 0.11%) compared to DEHP/SAGM (0.31% ± 0.14%). In Phase 2, PTR exceeded the 75% threshold set by the EDQM and FDA in all infusions (lower CL: 88.3%), with a mean of 93.3% ± 6.7%. Conclusion RCCs stored in non‐DEHP/PAGGSM disposable sets met the in vitro EDQM criteria for quality and in vivo EDQM and FDA criteria for transfusable RCCs, thereby providing a suitable alternative to current DEHP‐plasticized disposable sets. Trial Registration The clinical trial was registered at the World Health Organization—International Clinical Trials Registry Platform (ICTRP): NL‐OMON56734, registration date 30 April 2024.