Recommendations for in vitro evaluation of blood components collected, prepared and stored in non‐DEHP medical devices

Abstract

Background and Objectives: DEHP, di(2-ethylhexyl) phthalate, is the most common member of the class of ortho-phthalates, which are used as plasticizers. The Medical Device Regulation has restricted the use of phthalates in medical devices. Also DEHP has been added to the Annex XIV of REACH, "Registration, Evaluation, Authorisation and Restriction of Chemicals" due to its endocrine disrupting properties to the environment. As such, the sunset date for commercialisation of DEHP-containing blood bags is May 27 th 2025. There are major concerns in meeting this deadline as these systems have not yet been fully validated and/or CE-marked. Also, since DEHP is known to affect red cell quality during storage, it is imperative to transit to non-DEHP without affecting blood product quality. Here, EBA members aim to establish common grounds on the evaluation and assessment of blood components collected, prepared and stored in non-DEHP devices.

Towards standardized human platelet lysate production in Europe: An initiative of the European Blood Alliance

“…As a result, some DEHP might be present in the final hPL product depending on the amount of plasma. At the time of writing, DEHP is still allowed for manufacturing blood collection sets, but this will change in 2025 as per the EU Medical Device Regulation [54]. From then on, DEHP is only allowed to be used in medical devices below a concentration of 0.1% (wt/wt).…”

Evaluation of platelets componentized with the Reveos Automated Blood Processing System and stored for 7 days at room temperature in a non‐Di(2‐ethylhexyl) phthalate (DEHP) platelet pooling set

“…11 Studies have shown that DEHP, among other ortho phthalates, can leach out of the plastic and into the blood. 12 To protect the safety and well-being of patients, the European legislation has been implemented to ban the use of four phthalates, including DEHP, in medical devices including blood product bags/bag systems through amendments to the European Chemicals Agency (ECHA) Annex XIV of REACH. More specifically, as per the Commission Regulation 2023/2482, the sunset date of July 1, 2030 is applicable for DEHP-containing medical devices within scope of Regulations (EU) 2017/745 and (EU) 2017/746, which includes blood bag systems.…”

“…13 Materials devoid of DEHP or other harmful phthalates are now in various stages of development using alternative plasticizers (including 1,2-cyclohexane dicarboxylic acid diisononyl ester [DINCH], di(2-ethylhexyl) adipate [DEHA], and di(2ethylhexyl) terephthalate [DEHT]) to ensure the highest level of safety for blood transfusions. 12 The objective of this study was to evaluate the in vitro platelet quality and functionality of PCs produced using the Reveos system and pooled into a transfusable dose using the IMUGARD Platelet Pooling Set, using DEHP-free blood collection sets. Furthermore, we compared PCs produced from WB componentized from fresh and overnight-stored WB.…”

“…However, DEHP has also been classified as a reproductive toxicant and endocrine disruptor in animal models 11 . Studies have shown that DEHP, among other ortho phthalates, can leach out of the plastic and into the blood 12 . To protect the safety and well‐being of patients, the European legislation has been implemented to ban the use of four phthalates, including DEHP, in medical devices including blood product bags/bag systems through amendments to the European Chemicals Agency (ECHA) Annex XIV of REACH.…”

“…More specifically, as per the Commission Regulation 2023/2482, the sunset date of July 1, 2030 is applicable for DEHP‐containing medical devices within scope of Regulations (EU) 2017/745 and (EU) 2017/746, which includes blood bag systems 13 . Materials devoid of DEHP or other harmful phthalates are now in various stages of development using alternative plasticizers (including 1,2‐cyclohexane dicarboxylic acid diisononyl ester [DINCH], di(2‐ethylhexyl) adipate [DEHA], and di(2‐ethylhexyl) terephthalate [DEHT]) to ensure the highest level of safety for blood transfusions 12 …”