Plastic is a popular medical device material. In fact, it is estimated that nearly one-third of all medical devices are made with polyvinyl chloride, or PVC. Of devices made with PVC, the most frequently used
DEHP is an example of a phthalate, a man-made chemical used to soften plastics and make them pliable. It is the most commonly used plasticizer because it is cost-effective, malleable and useful in the production of medical devices. It is possible you have been exposed to DEHP. Common medical devices that contain phthalates include blood and
intravenous bags and tubing, umbilical artery catheters and tubes used in cardiopulmonary bypass, hemodialysis and extracorporeal membrane oxygenation. Although phthalates have been in use since 1955, in the past several years they have garnered international headlines and caused much debate. This column will illustrate the political evolution of phthalate regulation.
The use and effectiveness of phthalates as plasticizers is widely accepted; however, the safety of phthalates is not. Those opposed to the use of phthalates argue that the incineration of PVC products produces dioxin, a known carcinogen, and that DEHP has adverse effects on humans. Other phthalates have been cited as having reproductive toxicity. The “Safety Assessment of DEHP Released from PVC Medical Devices” conducted by the U.S. Food and Drug Administration concluded that DEHP is toxic in animals, but not necessarily in humans.1
Those who favor the use of phthalates contend the benefits of phthalates (use as a plasticizer, cost, etc.) outweigh possible risks. This does not mean DEHP and other phthalates are without risk. Unanswered questions about risk almost certainly raise more questions, such as continued use of the material and the future of phthalate regulation. Answering those questions will likely trigger debate and controversy.
The Political Evolution of Phthalate Regulation
In September 2004, a member of the German Green party and member of the Environment Committee, said, “The Greens/EFA in the European Parliament call on the European Commission to build on this prohibition [phthalates] and to immediately present a phase-out of soft PVC products, in particular for medical devices, for which alternatives are available.”2 The counter to this argument is the safety of alternative materials and their comparable clinical use is no more conclusive than data on phthalates. The European Commission enlisted the Scientific Committee of Emerging and Newly Identified Health Risks to evaluate alternatives in 2007, and it too derived the same conclusion. Since then, the debate has continued, and the opposing sides’ positions are as stark in contrast as they ever were. Medical device regulatory authorities have responded with new labeling requirements for medical devices that contain certain phthalates.
2007/47/EC: Phthalate Labeling
Directive 2007/47/EC amends MDD 93/ 42/EEC and has been explored in other issues of this column. One impact it will have on the medical device industry affects devices made with certain phthalates. In an excerpt from Annex I, section 7.5 of the European Union’s Medical Device Directive as amended by 2007/47/EC, a new requirement states: “If parts of a device (or a device itself) intended to administer and/ or remove medicines, body liquids or other substances to or from the body, or devices intended for transport and storage of such body fluids or substances, contain phthalates which are classified as carcinogenic, mutagenic or toxic to reproduction, of category 1 or 2, in accordance with Annex I to Directive 67/548/EEC, these devices must be labeled on the device itself and/or on the packaging for each unit or, where appropriate, on the sales packaging as a device containing phthalates.”3
How Will This New Requirement Be Met?
The European Committee for Standardization, or CEN, is the committee charged with developing harmonized European standards that meet requirements delineated in the MDD, as amended by 2007/47/EC. The European Commission enlisted a committee, CEN/CLC/TC 3, to develop a European standard to meet the new phthalate labeling requirement and to issue specific guidelines on labeling medical devices containing phthalates. Called prEN 15986, this European standard is in the approval stage and has an availability date set for January 2012.
The near two-year gap between the 2010 implementation of 2007/47/EC, and the issuance of the CEN European standard (presumably not until January 2012) has created confusion for manufacturers of phthalate-containing devices because no guidance exists. With the aim of establishing a harmonized symbol in the interim, the European medical technology industry association Eucomed has proposed a set of symbols to meet the 2007/ 47/EC requirement. Further, Eucomed hopes that prEN 15986 will emulate its recommended template when CEN issues the official European standard. The proposed symbols display the label “PHT” to note the presence of a phthalate inside a round-edged triangle. The specific phthalate nomenclature is listed either on the side or below the PHT and triangular symbol. Examples of Eucomed-proposed symbols indicating the presence of DEHP are:
Phthalate Debate Continues
Proposed phthalate regulation has certainly navigated various courses. From requests for the prohibition of the use of phthalates in medical devices to unspecified labeling requirements, the journey of phthalate legislation has experienced vicissitudes. What will prove interesting is the extent to which labeling requirements will affect the use of phthalates in device manufacturing. Will the addition of symbols denoting phthalate presence deter device buyers or spark awareness in consumer and health provider bases? Or will the new requirements have no effect on phthalate presence in continued production?
And what will come of the debate? Will the new requirements bring solace to the controversy, or will the bilateral positions further diverge? The issue is ongoing and one to continue to follow.
References
1. “Safety Assessment of Di(2-ethylhexyl)phthalate (DEHP) Released from PVC Medical Devices.” Rep. U.S. Food and Drug Administration, September 2001. Web. Oct. 7, 2009. www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM080457.pdf.
2. “Ban of Toxic Softeners in PVC Toys Extended: The Beginning of the End for soft PVC.” The Greens | European Free Alliance in the European Parliament. Sept. 29, 2004. Web. Oct. 7, 2009. http://greens- efa.org/cms/pressreleases/dok/101/101003.ban_of_toxic_softeners_in_pvc_toys_exten@en.htm.
3. “Directive 2007/47/EC of the European Parliament and of the Council.” Official Journal of the European Union (2007). Sept. 21, 2007. Web. Oct. 7, 2009 http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2007:247:0021:0055:EN:PDF.
4. “Labeling of Medical Devices Containing Phthalates.” Eucomed Medical Technology, July 7, 2009. Web. Oct. 8, 2009. www.eucomed.org/~/media/1A6C01F8F41545AB81E449A71CA2A850.ashx.