Medtronic ENT Position paper on PVC and DEHP Plasticizer

MEDTRONIC ENT POSITION SUMMARY:
Sub-populations of patients have been identified which are considered to be at risk from exposure to PVC/DEHP.
Products known to contain PVC/DEHP have been compared with the Medtronic ENT product range, while considering their likely use amongst identified "at risk" sub-populations.

The analysis identifies the following Medtronic ENT products, which contain PVC/DEHP, and which are likely to be used with the identified sub-populations.

When considering DEHP exposure in patients from identified "at risk" sub-population, consideration should be made of the contribution to aggregate exposure if the above products are used.

Medtronic ENT Position paper on PVC and DEHP Plasticizer

BACKGROUND:
The use of PVC in medical applications has received sporadic attention over the years leaving a number of questions unresolved concerning the material and its use in medical devices.

This discussion is intended to document the position regarding the material and Medtronic ENT's products.

INTRODUCTION:
The material commonly known as PVC is a polymer of vinyl chloride. The raw material has intrinsic properties such as hardness and flexibility which can be modified by the addition of agents known as "plasticisers".
It has been reported that because the plasticisers used with PVC are not chemically bound to the polymer, they may leach out when in contact with certain media [1].

Some plasticisers, in particular DEHP¹ which is the most widely used, have been associated with a range of adverse effects in laboratory animals. However, the ability of DEHP to produce such effects in humans is controversial [2].

THE PVC/DEHP CONTROVERSY:
A thorough review of the world position concerning PVC/DEHP was reported by the Health & Consumer Protection Directorate-General of The European Commission, through The Scientific Committee on Medicinal Products and Medical Devices who issued a paper on 26 September 2002 entitled: "Opinion On Medical Devices Containing DEHP Plasticised PVC; Neonates and Other Groups Possibly at Risk from DEHP Toxicity"[3].

This paper concluded that:
	"On the basis of the evidence presented in this report, no Tolerable Intake Value for DEHP in medical devices can be recommended."
Significantly however, the discussion also states:
	"The contribution of DEHP-PVC to the delivery of health care should be taken into account in the consideration of the potential risks of adverse effects of DEHP in these patients."
The US FDA position has been publicized in the paper "Medical Devices Made With Polyvinylchloride (PVC) Using the Plasticizer di-(2-Ethylhexyl)phthalate (DEHP); Draft Guidance for Industry and FDA" dated September 6, 2002 [4]. This paper (issued for comment) states:
	" not all devices made with PVC contain DEHP. Further, FDA recognizes that many devices with PVC containing DEHP are not used in ways that result in significant human exposure to the chemical. Therefore, FDA is focusing attention on the small subset of medical devices where PVC containing DEHP may come in contact with the tissue of a sensitive patient population in a manner and for a period of time that may raise concerns about the aggregate exposure to DEHP. We believe that many devices used in Neonatal Intensive Care Units (NICUs) meet this criteria and should be a primary focus."
ADVAMED (previously HIMA – Health Industry Manufacturers Association) includes in its publication "Frequently Asked Questions regarding PVC and DEHP in Medical Devices" [5]:
	"For the majority of its applications, medical device manufacturers believe that PVC remains the most appropriate material available because of its unique properties and history of safe use. Any new alternative would lack the long history of tested, proven research that supports the safe and effective use of PVC in medical devices."
The publication also cites the Food and Drug Administration position as:
	"Since there is consumer concern, we will look at it again. But we would need to see a substantial amount of testing to make sure that we weren't moving from a product with good characteristics to one that we don't know very much about," 2
Eucomed, the European Medical Technology Industry cooperative body, has published a position paper [6] which concludes:
	" the many benefits of the continued use of plasticised PVC in medical products totally offset any perceived risks."
These and other publications on this subject are perhaps best summarized by the European opinion paper [3] which states:
	"These reviews generally conclude that there should be no concerns for the vast majority of adults in relation to toxicity following DEHP exposure. For children, the situation is different. On the basis of in vitro and in vivo toxicity studies, there are concerns for testicular toxicity, depressed fertility and reproductive developmental toxicity following oral exposure to PVC containing DEHP in children. In view of these concerns, the use of DEHP in soft toys has recently been forbidden in some areas (European Commission, 1999). However, there are no general concerns for either adults or children in relation to acute toxicity, irritation, sensitisation, mutagenicity or carcinogenicity"

TAKING A POSITION:
To evaluate a medical device position therefore, it is reasonable to consider both the product groups which use the material, and the patient groups possibly at risk.

PRODUCT GROUPS:
The FDA in a publication entitled "Safety Assessment of Di(2-ethylhexyl)phthalate (DEHP) Released from PVC Medical Devices" [2] identifies a list of products known to release DEHP. The list is: 

PATIENT GROUPS:
The "Health Canada Expert Advisory Panel On Dehp In Medical Devices" [7] identifies sub-populations with the highest concern for risks associated with DEHP exposure.
The report identifies the sub-populations as: 
5. The sub-populations to be considered at greatest risk should include the following: 
• Newborns including premature 
• Infants and young children 
• ECMO patients 
• Cardiopulmonary bypass patients 
• Exchange transfusion patients (infants and children) 
• Patients receiving certain IV therapies, particularly those on TPN and those receiving lipophilic drug formulations, etc.

  Sub-populations that should be considered to be at possible but presently undetermined risk include: 
• Trauma patients receiving multiple blood transfusions 
• Hemodialysis patients 
• Oxygen therapy patients 
• Children of breast-feeding (lactating) females 
• The fetus (i.e. pregnant women) 
• Pre-pubescent males

Medtronic ENT Position
Review of the "Products Known to Contain PVC" against the Medtronic ENT product range has identified the following:

The following table summarizes the review of this product range and consideration of the use of those products with the sub populations considered to be at risk.

MEDTRONIC ENT POSITION SUMMARY:
Sub-populations of patients have been identified which are considered to be at risk from exposure to PVC/DEHP.

Review of the list of products "known to contain PVC/DEHP" and the Medtronic ENT product range has identified such products likely to be used amongst the identified sub-populations.

CONCLUSION:
When considering DEHP exposure in patients from the identified sub-population, consideration should be made of the contribution to aggregate exposure if the above products are used.

BIBLIOGRAPHY:
[1] MDDI, September 2002,
"THERMOPLASTICS: Polyurethane Film as an Alternative to PVC and Latex MATERIAL CHOICES", 
located on Medical Device Link at: http://www.devicelink.com/mddi/archive/02/09/004a.html

[2] "Safety Assessment of Di(2-ethylhexyl)phthalate (DEHP) Released from PVC Medical Devices",
Center for Devices and Radiological Health, U.S. Food and Drug Administration, undated. Available from: http://www.fda.gov/cdrh/ost/dehp-pvc.pdf

[3] European Commission, Health & Consumer Protection Directorate-General Of The European Commission,
"Opinion On Medical Devices Containing DEHP Plasticised PVC; Neonates and Other Groups Possibly at Risk from DEHP Toxicity",
26 September 2002, Document: SANCO/SCMPMD/2002/0010 Final. Available from: http://europa.eu.int/comm/food/fs/sc/scmp/out43_en.pdf

[4] "Medical Devices Made With Polyvinylchloride (PVC) Using the Plasticizer di-(2-Ethylhexyl)phthalate (DEHP); Draft Guidance for Industry and FDA"
September 6, 2002, at: http://www.fda.gov/cdrh/ode/guidance/1407.html

[5] "Frequently Asked Questions regarding PVC and DEHP in Medicasl Devices": 
HIMA, April 1999, http://www.advamed.org/publicdocs/faq499.pdf

[6] "EUCOMED position on the use of phthalate plasticised PVC in medical products",
12 December 2000, at: http://www.medicalplast.com/upload/documents/document4.pdf

[7] "HEALTH CANADA EXPERT ADVISORY PANEL ON DEHP IN MEDICAL DEVICES: Final Report 2002 January 11" at: http://www.hc-sc.gc.ca/hpb-dgps/therapeut/zfiles/english/advcomm/eap/dehp/eap-dehp-final-report-2002-jan-11_e.pdf

Footnotes:
1 diethyl-hexyl phthalate
2 David Feigal, M.D., deputy director for medicine, FDA's Center for Biologics Evaluation and Research [as quoted in The Washington Post (February 22, 1999)]