Medical Device Link.

MATERIALS

In 1997, Stockholm County Council decided to phase out poly(vinyl chloride) (PVC) and phthalates from the health sector. To speed up the phase-out-process, in 2003 the Karolinska University Hospital in Stockholm entered into co-operation with the Stockholm County Council and the international Health Care Without Harm organisation. The hospital is the biggest hospital in Sweden and the only one in the world that is environmentally certified. In September 2005, it held a seminar to report on its efforts thus far. The seminar focussed on some of the companies that have developed PVC-free or phthalate-free products. Approximately 150 people attended, many of whom were purchasers and representatives of the Swedish environmental authorities as well as nurses and doctors.

The cost of PVC-free alternatives

The seminar allowed various suppliers a voice in the debate and an opportunity to inform attendees of the available alternatives to PVC and phthalates. For example, Mediplast (www.mediplast.com) talked about the variety of PVC-free tubes that it offers. Made from polyurethane and silicone, the tubes cost up to 10 times as much as those made from PVC, and they do not sell any of them. “We have the products, but no one is demanding them,” commented a company representative.

Fresenius Medical Care (www.fmc-ag.com) informed the audience that it has developed PVC- and phthalate-free dialysis kits for the home-care market. The kit is more expensive than the one containing PVC products and the representative for the company commented, “the market is screaming for alternatives, but no one is buying them.”

Gambro (www.gambro.com) has developed phthalate-free tubes for blood using adipate as the substitute plasticiser. The company has not, however, succeeded in developing an acceptable alternative to PVC in general. Because there are high demands on the tubes’ performance when they are used to transport blood, there are no serious alternatives for this application. This means that there are only alternatives for the plasticiser, not for the PVC material in general.

The head of the blood bank at the Karolinska University Hospital, Hans Gullikson, was among the speakers. He said that no alternatives for di(2-ethylhexyl) phthalate (DEHP) or PVC had been found for use in the blood-bag business. Karolinska has tried to use blood bags with citrate plasticisers; however, this has been abandoned because of problems with working with these products on a daily basis, including reports of swelling around the mouth and face, breathing difficulties and reddening of hands.

Demand for more data on alternatives

Following the supplier presentations, a representative from West Götaland Region Purchasing and Logistic Organisation, which is responsible for purchasing medical devices for hospitals in the area, stressed that from now on the hospitals will be putting pressure on the suppliers of PVC-free
and phthalate-free devices. She said that there is a lack of data on the alternatives and that her organisation will not accept this in the future.

Hospital results so far

The only changes implemented by the Karolinska University Hospital to date have been in connection with phthalates. According to the suppliers
at the seminar, some of them have changed from using phthalates to other plasticisers. It is important to note that this is not a movement away from PVC, but a movement towards using other plasticisers in PVC such as citrates and adipates.

Furthermore, the alternatives to PVC are, in general, too expensive for the Karolinska Hospital to buy. No hospital’s budget can sustain paying up to 10 times as much for a PVC-free product. Of course there are some applications, for example, neonatal and infusion devices, where alternatives have taken market share, but these markets are limited.

From the seminar, it is evident that hospitals want DEHP-free medical devices and this is particularly true in the neonatal field. However, with regard to the desire to phase out phthalates in general and phase out PVC, the picture is more varied.

There are two essential points to note. First, a representative of the Swedish Chemicals Inspectorate said at the seminar that there is no risk associated with the use of the phthalates diisononyl phthalate (DINP) and diisodecyl phthalate (DIDP). Second, it is worth noting that there was no explanation made at the seminar as to why PVC should be phased out.

Phthalates risk assessments

Because phthalates are so widely used, a number of studies have been made on their possible health and environmental effects. Five of the most used phthalates are currently subject to an individual and independent scientific risk assessment.¹

When these risk assessments are finalised, 86% of all phthalates produced will have been subject to risk assessments. The risk assessments are intended to verify whether the substances are causing an unintentional risk to human health and the environment and if so, to ensure that the necessary steps are taken to eliminate or control these risks.

The preliminary results, which can be viewed on the European Chemicals Bureau’s website: http://ecb.jrc.it indicate that some phthalates can be safely used under current regulation;² for others such as DEHP risk reduction strategies will be prepared.

Concern has been expressed over the use of DEHP in some types of medical devices. DEHP is classified as reproduction toxic because it has been seen in the reproductive systems of rodents after exposure to large quantities of the substance. The classification is, therefore, advising industrial users of DEHP, who employ it as a raw material, to avoid long periods of exposure.

Ban because of suspicion

The European Commission has placed DEHP on its list of hormone-disrupting substances (one of 66). Chemical substances are classified as such if they have shown a hormone disrupting effect in at least one animal test, as has DEHP. The effects in question are poor sperm quality and congenital deformity of the sexual organs. There is no proof that DEHP is harmful to human health; however, most people agree that there is a need for further studies because the consequences can be serious. Thus, it is solely due to suspicion that the Danish environmental authorities, for example, want to limit the use of DEHP in medical devices and that many environmental organisations around the world want its total ban.

Study on humans encouraging

The concerns about certain phthalates are solely based on animal studies. To examine whether there is any risk to humans with exposure to DEHP, a research team at the George Washington School of Medicine and Health Studies, USA, (www.gwumc.edu/smhs/) studied whether there is evidence of harm to humans, who as infants had relatively heavy exposure to DEHP.³ The subjects had received treatment that involved the use of DEHP-plasticised PVC blood bags and DEHP-plasticised PVC tubing. Each underwent a comprehensive physical examination. All had normal values for the thyroid gland, kidneys and liver and the sexual hormone function was in line with typical levels at puberty. The scientists concluded that their results indicated that adults who as premature babies had been exposed to considerable quantities of DEHP show no signs of harm to physical growth or sexual maturity.

EU says look at experience

The European Commission’s Scientific Committee on Medicinal Products and Medical Devices has also looked closer into the applications of DEHP in medical devices. In September 2002, the Committee published an “Opinion on Medical Devices Containing DEHP plasticised PVC.”⁴ This concluded that, when speaking specifically about medical devices, it is important that the positive properties and long experience with DEHP-containing devices is taken into consideration when analysing the potential risks of the material.

The Committee’s Opinion refers to a number of animal studies performed on mice and rats that show that large doses of DEHP can be harmful to rodents’ organs; the organs most affected are liver, kidneys and testicles. The Committee emphasises, however, that similar studies in monkeys do not show any proof of negative influence even after heavy DEHP exposure. Its statement concludes that, “In view of the lack of full analysis of all risks associated with potential alternative materials, at this moment no specific recommendations can be made to limit the use of DEHP in any particular patient group. Nevertheless it is strongly proposed that detailed studies are performed and further data collected in order to monitor this situation.”

Latest initiatives

On 4 October 2005, a recently formed European Commission working group, the Scientific Committee on Emerging and Newly Identified Health Risks, agreed to undertake an action plan for DEHP in medical devices. The Committee is to

• provide a statement on the DEHP issue based on the previously mentioned opinion by the Scientific Committee on Medicinal Products and Medical Devices published in 2002
• provide a statement of its attitude to the knowledge about the quality and safeness of the alternatives that are currently available
• prepare guidelines for labelling in special circumstances
• examine whether there is any possibility of reducing exposure to DEHP in medical devices under the current legislation.

Dr David Cadogan, Director of the European plasticisers organisation, ECPI, has said that the Scientific Committee on Emerging and Newly Identified Health Risks is expected to finalise its opinion on DEHP in medical devices within the first six months of 2006. He was speaking at the Plasticisers 2006 Conference, held in January 2006 in Brussels, Belgium, organised by European Plastics News. Dr Cadogan also said that medical device companies are expected to move away from using DEHP in PVC-based medical devices, although this will take some time: “This sector is conservative and reluctant to change from DEHP, which has given no adverse effects in patients.” He commented that it should not be a technical problem to shift away from DEHP, because there are many PVC plasticisers that can easily do the job.

Data needed to overturn history

It is not only price that is decisive in any deselection of phthalate-plasticised PVC. Hospital purchasers and health authorities have now begun to question whether the alternatives available in the market are preferable to phthalate-plasticised PVC. The time has passed when suppliers can sell products solely on the basis that they do not contain PVC and phthalates. The purchasers are now requesting environmental and health data for the alternatives and the health authorities are refusing to recommend alternatives until they have a sufficient basis of data. After all, it requires an extremely strong argument to overturn 50 years of good experiences with phthalate-plasticised PVC.

Ole Grøndahl Hansen, is General Manager at the PVC Information Council Denmark, Nørre Voldgade 48, DK-1358 Copenhagen, Denmark, tel. +45 3330 8630, e-mail: ogh@pvc.dk www.pvc.dk.