David Utermöhle explains how regulatory pressure and BASF's Hexamoll DINCH are paving the way forward in the medical devices sector for the substitution of DEHP.
The use of PVC in medical devices has been a success story; its flexibility, chemical stability and affordability making it the most viable polymer for a variety of medical applications. However, while it has been safely in use in medical devices for over half a century, innovative developments in plasticising PVC in other industry segments have not yet found traction in medical applications.
DEHP is still the most commonly used plasticiser to soften rigid PVC, despite its identification as a reproductive toxicant in test animals more than 20 years ago. In the EU, DEHP is restricted in toys and childcare articles, cosmetics, body care products, and plastics that come into contact with food. It is listed as a substance of very high concern (SVHC) in annex XIV of the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) regulation. Concerning human health risks, the use of DEHP in medical devices is exempted from authorisation. However, the European Chemicals Agency (ECHA) has recently updated the SVHC status and included DEHP on the candidate list, due to concern about the serious effects it may have on mammals. If DEHP is listed as an SVHC due to its effects on the environment, medical devices will fall into the scope of REACH.
Many national authorities are already aware that the hazardous potential of DEHP reaches critical levels in highly exposed patients, such as in repeated treatments of haemodialysis, massive blood infusions into trauma patients and the high cumulative exposure in neonatal intensive care units. Studies have shown that DEHP exposure to neonates is potentially in excess of levels known to cause adverse health effects that were detected in relevant animal studies. Areas affected include the reproductive system, lungs, heart and liver.
In 2001, the US FDA was one of the first authorities to evaluate those risk groups, and France was the first European country to take action upon it. The use of tubes containing DEHP in paediatrics, neonatology and maternity has been banned in the country since 1 July 2015. In the course of this development, it can be expected that other countries will soon follow to regulate DEHP for more critical treatments - and in the long term, potentially for all medical devices. Additionally, the European Directorate for the Quality of Medicines and Healthcare (EDQM) flagged DEHP in the European Pharmacopoeia for replacement. DEHP use has consequently been declining, resulting in a market shift toward other plasticisers.
In 1998, BASF developed the non-phthalate plasticiser Hexamoll® DINCH®, specifically for close-human-contact applications. Thanks to its toxicological profile and low migration rate, the plasticiser is suitable for a range of sensitive applications. The exhaustive set of regulatory studies regarding physico-chemical, ecotoxicological and toxicological properties have shown that the plasticiser is qualified for its sensitive uses. The validity of these studies is reflected in the approval of third-party authorities worldwide. In Europe, medical devices made of Hexamoll DINCH are compliant with Medical Device Directive 93/42/ECC, which requires that devices must be safe for their intended use.
R M David's 2015 study investigating the safety of Hexamoll DINCH on the intravenous route indicates no substance-related systemic toxicity. For applications under high scrutiny such as blood treatments, studies have shown that Hexamoll DINCH is an effective substitute for DEHP, as it is capable of stabilising red blood cells, and storing platelets and fresh frozen plasma. Because of these outstanding properties and its excellent toxicological profile, Hexamoll DINCH has been used in blood applications for many years, and was awarded the SolVin Award in 2013. Many other medical devices containing the non-phthalate plasticiser, such as enteral nutrition sets, tubings and gloves, are already available and are readily marketed as DEHP-free.
To account for the general growth of non-phthalate plasticisers, and to ensure the highest supplier reliability, BASF built a second plant for the use of Hexamoll DINCH in 2014, thereby doubling production capacity to 200,000t a year. Recent evaluations by the Swedish Chemicals Agency and the Danish Ministry of Environment concluded that Hexamoll DINCH is one of the most promising alternative plasticisers for medical applications.