DEHP Regulations Impact Cord Blood Storage

Studies have shown that once cord blood stem cells are cryogenically preserved, they will remain viable for clinical use for decades^1,2. Cord blood banks are a legacy resource. In the case of family banks, cord blood that was stored at the birth of a child may be used later when that child has become an adult³. In the case of public cord blood banks, inventory collected from genetically diverse donors can be used to transplant patients from underserved groups decades later, and this potential is enhanced by the development of cell expansion protocols^4-6.

Nonetheless, recent shifts in the regulatory landscape affecting cell therapy manufacturing can have a significant impact on the ability to deliver cord blood therapies internationally. One of the biggest concerns is the introduction of environmental legislation prohibiting the use of DEHP in blood collection and storage bags.

DEHP is an acronym for Di(2-ethylhexyl) phthalate. It is a plasticizer, which is a class of chemicals that are added to plastic products to make them more flexible. Phthalates like DEHP have been used in blood bags and other medical devices for over 50 years; DEHP in particular has superior performance at protecting red blood cells⁷. However, a growing body of evidence has raised concerns about the use of DEHP and other phthalates in medical devices. There are two problems. The first problem is that DEHP is what bioengineers call a “leachable”; small quantities of DEHP leach into any fluid held in the plastic container under normal operating conditions⁸. The second, and more serious, problem is that studies have shown that DEHP has many toxic properties. Exposure to DEHP can cause disruption to reproduction, neonatal development, endocrine function, and poses carcinogenic risk^9,10. Environmental exposure to DEHP has been increasing around the world, but the long-term impact of DEHP exposure in humans, and the role of exposure during medical treatment, is still under study¹¹.

Figure 1: Blood bags participating in a quality study conducted by Canadian Blood Services⁷.

The European Union (EU) has issued a ban on DEHP in medical devices that will take effect in 2030. The momentum behind this ban has been building for some time. The active legislation is a 2006 EU law called REACH (EC No 1907/2006: regulation concerning the Registration, Evaluation, Authorization, and restriction of CHemicals)^12,13. This law governs the production and use of chemicals that impact human health and the environment. REACH has classified DEHP as a substance of very high concern (SVHC) since 2011¹³. Starting in 2019, the EU began restricting DEHP in all plasticized materials, but medical devices were placed in an exempted category (Annex XIV) which gave them until 27 May 2025 to phase out DEHP^13,14. Finally, in 2023 EU Regulation No. 2023/2482 amended REACH to extend the sunset date for DEHP in medical devices by five years, until 1 July 2030¹⁵. Medical device manufacturers who feel they must continue using DEHP in their products beyond the sunset date are required to submit an application for authorization no later than 1 January 2029¹⁵.

The EU ban on DEHP and other phthalates is a regional law that has a global impact on the practice of medicine^16-18.

We live in a time when the practice of medicine is globally interconnected; medical devices and therapies often must cross borders in order to reach patients. Any disruption in the supply chain of manufacturing therapies or delivering therapies will impact patient outcomes. In medical fields such as hematopoietic stem cell transplantation and cellular therapy, cross-border cooperation is crucial. A patient in one country may depend on a life-saving therapy that is derived from a cord blood unit that was cryopreserved years earlier in a biobank located in another country⁴.

Figure 2: World Marrow Donor Association (WMDA) data on the exchange of cord blood units between continents during 2023

For biobanks in general and cord blood banks specifically, the REACH legislation poses challenges both going forward and looking backward. Going forward, the first challenge is that blood banks and biobanks that are based within the EU have until 2030 to identify and validate acceptable alternatives to DEHP and other banned phthalates for the manufacture of blood bags and associated medical devices like IV tubing, etc. Secondly, the EU regulations will impose constraints on manufacturers in other countries that want to ship products into the EU. Looking backward, biobanks must obtain exemptions to authorize the release of specimens from their pre-existing inventory of cryopreserved cell therapies that are held in bags containing DEHP. It is not feasible to repackage these cryopreserved specimens in new containers. The life-saving potential of these cell therapies should override the DEHP exposure risks posed by their containers. To give an example, evidence-based findings indicate that the survival benefits of medical interventions in the neonatal intensive care unit (NICU) outweigh the neurological risks associated with DEHP exposure in very low birth weight infants¹⁹.

The keyword “biobank” is not referenced anywhere within the consolidated corpus of the REACH legislation currently in force, despite its length spanning several hundred pages and its history extending back to 2006¹³.

Meanwhile, the DEHP ban in the EU has inspired a surge of recent laws banning DEHP in individual US states. A thorough review of this legislative patchwork was published in July 2025 by Frontier & Van’t Hof¹⁸. California set the precedent, with a law enacted in 2024 that originally proposed to ban DEHP in all medical devices after 1 January 2026^17,18. Fortunately, stakeholders were able to convince the legislature that this deadline was unrealistic, and the final law set the sunset date to 1 January 2030. The final California law also has an amendment which excludes human blood collection and storage bags, and apheresis and cell therapy blood kits and bags, including integral tubing^17,18. Subsequently, a few more states have proposed bans on DEHP (see Table 1 of Frontier & Van’t Hof)¹⁸. To date, the enacted state laws have all followed California’s precedent and created carve outs for blood banking¹⁸. None of the state laws acknowledge the existence of biobanking. It would be a mistake to be over-confident that US state laws will always follow well-established medical precedents. Politicians in some states have recently decided to write their own state-level cell therapy regulations, with results that are not always rational^20,21.

The medical community is under increasing threat from well-meaning politicians who enact laws that are strictly forward-looking, and who seem to have no awareness that life-saving therapies also rely on reaching backward to retrieve cryopreserved specimens in biobanks. It is imperative that stakeholders in biobanking join forces and make their voices heard in the corridors where these regulations are debated and enacted. Biobanks need to prepare and submit applications to the competent EU authorities, before the deadline of 1 January 2029, to request REACH exemptions for archived therapies that are cryopreserved in bags containing DEHP.

The call to action for the cord blood community is to assemble a task force, representing multiple banks, that will prepare an application requesting REACH exemptions for cryopreserved cord blood units.

References

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2. Liedtke S, Többen S, Gressmann H, Meyer A, Verde PE, Gluckman E, Kogler G. Long-Term Stability of Cord Blood Units After 29 Years of Cryopreservation: Follow-Up Data From the José Carreras Cord Blood Bank. Stem Cells Translational Medicine. 2024; 13(1):30-42.
3. Verter F. Cured by his own cord blood 19 years later. Parent's Guide to Cord Blood Foundation Newsletter. Published 2023-10
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12. European Chemicals Agency. Understanding REACH. Legislation.
13. Consolidated text: Regulation (EC) No 1907/2006 of the European Parliament and of the Council of 18 December 2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), establishing a European Chemicals Agency, amending Directive 1999/45/EC and repealing Council Regulation (EEC) No 793/93 and Commission Regulation (EC) No 1488/94 as well as Council Directive 76/769/EEC and Commission Directives 91/155/EEC, 93/67/EEC, 93/105/EC and 2000/21/EC (Text with EEA relevance). EUR-Lex. Last updated 2025-04-02 [2019]
14. European Chemicals Agency. Endocrine disrupting properties to be added for four phthalates in the Authorisation List. News. Published 2019-07-10
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17. Frontier LR. The Moral Duty to Protect the Supply of Quality Health Care. ISCT Telegraft. Published 2024-08-15
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19. Stroustrup A, Bragg JB, Andra SA, Curtin PC, Spear EA, Sison DB, Just AC, Arora M, Gennings C. Neonatal intensive care unit phthalate exposure and preterm infant neurobehavioral performance. PLoS ONE 2018; 13(3):e0193835.
20. Verter F. Utah attempts to legalize placenta cell therapy. Parent's Guide to Cord Blood Foundation Newsletter Published 2024-04
21. Verter F. Florida Stem Cell Law Flaunts the FDA. Parent's Guide to Cord Blood Foundation Newsletter Published 2025-06