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Ludwig R. Frontier Ramos MD MSc MBA DHSc
Scientific Marketing and Medical Manager for Macopharma, Atlanta, GA. 
Associate Researcher, Bioethics Faculty, Universidad Anáhuac México

Globalization not only brought the world the advantage of universal access to knowledge but also presents the challenge that information consumption presents a speed that can suffocate human capacity. It is for this reason that the consequences of decisions that occur in one place often impact the rest of the world. In this case, the European approach with the millennium goals and a demanding population regarding the environment brings a serious revolution in the world of plasticizers, which although it has been affecting the world of waste for years, is already preparing to infer in medical devices and the direct use of phthalates as an ingredient for the exploitation of polyvinyl chloride (PVC) in the medical industry. Globalization is evident when multinationals' strategic changes test the flexibility in global supply chains and become important for the protection of global innovations (1).

Healthcare providers worldwide must be concerned about the quality of care, and this includes the availability of care. There is a moral obligation to build supply strategies to meet healthcare objectives, and globalization brought with it new currents of thought such as bioethics and global health to respond to this need. The values of nationalism, individualism, and protectionism can threaten a health system that is not informed or prepared for what is happening in interdependent manufacturing and supply chains. However, cosmopolitanism tends to overlap and become a philosophical challenge for local politics (2).

So when the European Union (EU) ban in 2018 added Di(2-ethylhexyl) phthalate (DEHP) to their REACH (Registration, Evaluation, Authorization, and Restriction of Chemical) Authorization list, it issued its control regulation and elimination from the health registry of products containing phthalates, including DEHP, which is used in most blood bags and a substance to which protective properties are conferred against red blood cell storage injury, which is why the industry is on alert for the creation of alternatives that do not sacrifice the benefits of DEHP but that stop the possible harmful side effects.

Although the direct health effect of DEHP exposure is controversial, it has been classified as a toxic and endocrinologically disruptive substance. However, in addition to the effects at the level of sexual hormones and metabolism regulators, some plasticizers are deleterious to the environment, so environmental and health issues are of concern with the use of plasticizers. There is a list of alternative phthalates and plasticizers expected to be safer than DEHP, but medical devices replacing DEHP require time and are not widely available to date. The European Pharmacopoeia has listed since 2016 the following plasticizers as replacements for DEHP: Diisononyl cyclohexane-1,2-dicarboxylate (DINCH), Bis(2-ethylhexyl) terephthalate  (BTHC), Trioctyl trimellitate  (TOTM) (TETHM) and Di(2-ethylhexyl) terephthalate (also known as Dioctyl terephthalate) (DEHT) (DOTP/DEHTP). The deadline for the plasticizer transition in Europe has been postponed on several occasions due to the need to not affect the supply of blood banks and cellular therapies. Currently, DEHP cannot be used in medical devices starting July 1, 2030, unless manufacturers apply for authorization before January 1, 2029 (3) (4) (5).

If the EU is the one region with this prohibition, likewise the availability of DEHP and products that comply with international standards such as European ones are forced to validate products with other alternative phthalates. Furthermore, this globalist wave promotes regulatory concerns about materials. It would be rational to expect that this regulation will begin to be discussed in other geographic regions.

In early 2024 in the United States, Assemblywoman Lori D. Wilson's Bill submitted a proposal to eliminate DEHP in certain medical equipment, California Assembly Bill 2300 (AB 2300), and passed the Assembly floor with a bipartisan vote of 58 to 1. The original proposal mandated that beginning January 1, 2026, a person or entity shall not manufacture, sell, or distribute into commerce in the State of California intravenous solution containers made with intentionally added DEHP. This would make blood banking and cell therapy supplies, including blood fractionation bags, which currently contain DEHP, illegal in California and the timing that this law proposed is stricter than the original date in the EU which has already been postponed due to the difficulty that these changes create. California has previously legislated the elimination of DEHP in cosmetics, toys and childcare items. Despite having majority support for the elimination of DEHP in IV bags and tubing generally, a change already made by many manufacturers, a coalition of industry stakeholders was forced to promote a modification, as Amended on May 20, 2024, to postpone the original 2026 ban to begin January 1, 2030, and also an amendment  to exclude human blood collection and storage bags, apheresis and cell therapy blood kits and bags, including integral tubing from bill AB 2300 based on Title 21 of the Code of Federal Regulations (6).

The surveillance of laws affecting the good state of the health care system is a moral duty of the scientific community. Both Kantian ethics and utilitarians support the surveillance of manufacturing laws that would impact medical devices as an important step to safeguard the continuity of care and the categorical imperative of universality of the benefits of appropriate health care. In addition, virtue ethics may add that it is the right thing to do. The CA Bill AB 2300 is a successful example of duty and the moral action of being attentive to local political news that is frequently ignored by the popular focus that the federal government of the United States occupies, but it is local legislators who make decisions that can directly affect and immediately modify local operations. In the case of California, and due to the language used in the legislation, without the clause that excludes cell therapy kits, the state of California would have been short of supplies in record time. In California, it should not be surprising that there are other initiatives, which is why societies of professional health providers such as the International Society for Cell & Gene Therapy must ensure the quality of health services in their community (7).

References

1. Cuervo‐Cazurra Á, Doz Y, Gaur A. Skepticism of globalization and global strategy: Increasing regulations and countervailing strategies. Global Strategy Journal. 2020 Feb;10(1):3-1. https://doi.org/10.1002/gsj.1374
2. Audi, R. Nationalism, Patriotism, and Cosmopolitanism in an Age of Globalization. J Ethics 13, 365–381 (2009). https://doi.org/10.1007/s10892-009-9068-9
3. Labow RS, Card RT, Rock G. The effect of the plasticizer di (2-ethylhexyl) phthalate on red cell deformability. Blood. 1987 Jul 1;70(1):319-23. https://doi.org/10.1182/blood.V70.1.319.319
4. Wang Y, Qian H. Phthalates and their impacts on human health. InHealthcare 2021 May (Vol. 9, No. 5, p. 603). Multidisciplinary Digital Publishing Institute. https://doi.org/10.3390/healthcare9050603
5. European Directorate for the Quality of Medicines & HealthCare (EDQM). Press Release - The Ph. Eur. revised its general chapters on plasticised PVC materials. January 2018 [Internet]. [Place of publication unknown]: EDQM; 2018 [cited 2024 May 26]. Available from: https://www.edqm.eu/en/-/the-ph.-eur.-revised-its-general-chapters-on-plasticised-pvc-materials
6. California Legislature. Assembly Bill 2300, AB-2300. An act to amend Section 1203.4 of the Penal Code, relating to criminal procedure. 2023 [cited 2024 May 26]. Available from: https://legiscan.com/CA/bill/AB2300/2023
7. Dale S. Utilitarianism in crisis. Voices in Bioethics. 2020 May 8;6. https://doi.org/10.7916/vib.v6i.6082