Companies Charge Ahead with DEHP-Free Devices

The push for medical devices free of di(2-ethylhexyl) phthalate (DEHP) isn’t a new phenomenon. However, medical device manufacturers and their myriad suppliers recently have been trying to get out in front of recently passed or imminent regulatory requirements calling for DEHP-free materials for healthcare applications.

Patients undergoing medical procedures such as IV therapy, enteral and parenteral nutrition support, blood transfusion, hemodialysis and peritoneal dialysis, cardiopulmonary bypass and extracorporeal membrane oxygenation can be exposed to DEHP, a compound used as a plasticizer for polyvinyl chloride (PVC) medical devices. Because PVC is hard and brittle at room temperature, a softener typically is added to increase the flexibility of many products, such as tubes and IV bags. In most medical devices, the softener is DEHP.

DEHP has been shown to produce a wide range of adverse effects in experimental animals, notably liver toxicity and testicular atrophy. Although the toxic and carcinogenic effects of DEHP have been well established in experimental animals, the ability of this compound to produce adverse effects in humans remains controversial. As a result, the ability of DEHP and other phthalate esters to produce adverse effects in humans has been a topic of active discussion and debate in the scientific and regulatory communities.

Since patients undergoing medical procedures can be exposed to DEHP, U.S. Food and Drug Administration’s Center for Devices and Radiological Health (CDRH) and similar agencies abroad have to provide risk managers with information necessary for informed regulatory decision-making regarding the safety of DEHP released from PVC medical devices.

According to the European Commission Scientific Committee on Health and Environmental Risks (SCHER), exposure to DEHP may exceed the tolerable daily intake in some specific population groups, in particular people exposed through medical procedures such as kidney dialysis. The American Academy of Pediatrics has advocated not to use medical devices that can leach DEHP into patients and, instead, to resort to DEHP-free alternatives.

More than 10 years ago, in July 2002, the FDA issued a Public Health Notification on DEHP, noting: “We recommend considering such alternatives when these high-risk procedures are to be performed on male neonates, pregnant women who are carrying male fetuses, and peripubertal males,” adding that the alternatives were to look for non-DEHP exposure solutions. Even a documentary by the Canadian Broadcasting Company titled “The Disappearing Male” highlighted concerns about sexual development in male fetal development, miscarriage (as DEHP is an androgen antagonist [e.g., any substance capable of inhibiting the biological effects of androgens, which cause masculinization] found in PVC plastic products, many cosmetics and fragrances, and numerous other consumer products), and as a cause of dramatically lower sperm counts in men.

More recently, the FDA doesn’t recommend that caregivers avoid performing high-risk procedures simply because DEHP could pose a health risk.

“Forgoing a necessary procedure is far riskier,” according to recommendation letter written by researchers at CDRH this summer. “However, you can take some precautions. For some procedures, you can use PVC devices that don’t contain DEHP or use devices made from other materials, such as ethylene vinyl acetate, silicone, polyethylene, or polyurethane. If you must use devices with DEHP, you can minimize exposure by using the freshest possible blood products stored at the lowest possible temperature or by using heparin-coated ECMO (extracorporeal membrane oxygenation) circuits.”

The alternatives most strongly recommended by the FDA are for high-risk procedures on male infants, peripubertal boys, and pregnant women carrying a male fetus. For other patients, the decision to use alternatives should be based on the medical advantages, drawbacks, and availability of substitute materials, according to the FDA.

A number of companies at this year’s Medica/Compamed medical product trade fair in Dusseldorf, Germany, were highlighting products that offered alternatives to traditional options containing DEHP.

Vancive Medical Technologies, formerly Avery Dennison Medical Solutions, was touting its DEHP-free products, including InteliShield Barrier Film, to manufacturers of temporary-adherent medical devices who are concerned about potential DEHP requirements.

“With the introduction of DEHP-free InteliShield barrier film for ostomy applications, we are anticipating a growing demand for plasticizer-free medical devices,” said Kevin Jones, global segment market manager for Chicago, Ill.-based Vancive Medical Technologies. “That need gained even greater urgency when fresh concerns arose in the European Union over use of the plasticizer DEHP in medical products.”

Following a study asserting that blood bags containing DEHP posed a significant health risk, the European Commission recently requested an updated opinion from its Scientific Committee on New and Emerging Health Risks. The committee was asked to review and reevaluate safety concerns related to the use of DEHP in PVC plasticized medical devices. It was also asked to identify possible alternatives to DEHP that could reduce potential risks. The completed review is expected by March.

“In light of the European Commission’s action, medical device manufacturers are well advised to conduct an internal review of their product offerings,” Jones added. “Manufacturers will want to make sure they are ahead of the curve and prepared for any eventuality. They should have options on hand that will allow them to adapt to new regulatory requirements that could be forthcoming.”

Vancive officials noted that they support their clients with technical assistance and materials that anticipate possible rules on DEHP use. For example, the company’s InteliShield film is designed with a combination of plastics that are devoid of PVC and plasticizers including DEHP, but provides the strength, softness and flexibility required for the ostomy market. Ostomy bags fabricated from the film have passed or exceeded the demanding industry standard requirements for that application, officials said.

Saint-Gobain Performance Plastics’ healthcare division, a supplier of medical device components, was another company at Compamed that highlighted its proactive approached to DEHP-free materials. Company officials said they would discontinue manufacturing medical-grade tubing with DEHP by June 2013. Saint-Gobain has been offering replacement products that are non-DEHP.

“We are committed to staying one step ahead of evolving regulations in the healthcare industry,” Aaron Updegrove, marketing manager for Saint-Gobain’s Healthcare Markets Business, said earlier this year following the company’s announcement about discontinuing DEHP use. “This is an integral part of our medical strategy that aligns with a corporate-wide initiative to remove DEHP from all of our products. Over the next 12 months, we’ll be working closely with our customers to coordinate a smooth transition to a non-DEHP plasticized solution, ensuring compliance well in advance of a REACH deadline.”

REACH is a European Union regulation concerning the Registration, Evaluation, Authorization and restriction of CHemicals. REACH took effect in 2007 and establishes European-wide uniform legal standards. It replaces the former evaluation of existing substances and the notification of new chemical substances. It has implications for producers, importers, formulators, distributors and users of chemicals, as well as those producing and/or importing articles. The next deadline for companies is in 2013.

More than 18 months ago, Saint-Gobain introduced its Tygon ND, which provides tubing options that use a non-DEHP plasticizer.

“Over the next 12 months, we’ll be working with our customers to help them transition,” Updegrove told Medical Product Outsourcing during Compamed. “It’s a move we’ve made across all our product lines, not just healthcare. But particularly in healthcare, we know that our clients need a lot of lead-time for testing and validation. So, we’re getting started as early as possible and working with our partners to ensure they have time for proper testing.