On 10 September 2015, the Medicines and Healthcare Products Regulatory Agency (“MHRA”) published guidance in relation to medical devices which contain polyvinyl chloride (“PVC”) plastic with Di(2-ethylhexyl) phthalate (hereafter “DEHP phthalates”). The MHRA guidance would appear to be inspired by the publication of a report issued on 25 June 2015 by the European Commission which provides detailed discussion on the issue of DEHP phthalates in medical devices.
The MHRA guidance confirms that the use of medical devices which contain plastic with DEHP phthalates is permitted in circumstances where the applicable EU legal requirements have been met and where an appropriate benefit-risk assessment has been performed by the manufacturer.
Related safety issues
A list of commonly used DEHP-plasticised PVC medical devices are provided in the MHRA guidance. The MHRA guidance also outlines possible safety issues that could arise in relation to medical devices which contain DEHP phthalates. As an example, health and safety issues have been raised in connection with the leaching potential of DEPH phthalate into solutions, such as the blood or nutrition formulas. The administration of certain doses of DEHP phthalate has also been attributed to birth defects and infertility in animals.
European Commission Report concerning DEHP Phthalates
On 25 June 2015, the Scientific Committee on Emerging and Newly-Identified Health Risks (commonly referred to as, the “SCENIHR”) from the European Commission adopted an updatedreport in relation to “The safety of medical devices containing DEHP plasticized PVC or other plasticizers on neonates and other groups possibly at risk”. It concludes that sufficient evidence has not been adduced to suggest that medical devices which comprise DEHP phthalates constitute an unacceptable public health risk to patients.
The SCHENIHR report also provides that the potential for replacement of DEHP in medical devices should be considered against their efficiency in the concerned treatment, as well as the toxicological profile and leaching properties of the alternative materials. Substances that are available as alternatives to DEHP include butyl trihexyl citrate in blood bags and non-PVC materials such as enteral feeding bags made of ethyl vinyl acetate. According to the report, available evidence suggests that DEHP results in the most severe reproductive toxicity in animal studies when compared to alternative plasticizers such as di(2-ethylhexyl) adipate (DEHA) and di-iso-nonyl phthalate (DINP). Greater insight into the toxicological profile of alternatives to DEHP is provided in the report. The lack of data on their potential release from medical devices and consequent human exposure, however, precludes an appropriate risk assessment from being performed. As a result, the Committee emphasize that “the risk and benefit should be carefully evaluated for each individual medical device and each medical procedure in which the alternative needs to be used”.
Recommendations from the MHRA
The MHRA recognises that medical devices which incorporate plastic with DEHP may offer clinical benefit. Members of the medical device industry are encouraged to take into account the recommendations provided by the SCENIHR and also to use alternative materials to DEHP in medical devices where this is possible.
The MHRA holds the opinion that “no additional regulatory measures are necessary when phasing out the use of DEHP in medical devices”. Manufacturers are, however, expected to comply with the applicable provisions in the Medical Devices Directive which require that materials presenting a hazard are replaced as soon as alternatives with a more positive risk-to-benefit balance are available. Overall, the MHRA appears to consider that the DEHP “may still be essential in some medical devices in critical circumstances”.
Applicable legal obligations for manufacturers
In the European Union, a medical device cannot be used or marketed unless a CE mark has been validly affixed to it, in accordance with the provisions of the applicable EU legislation.
The MHRA developed guidance makes clear that medical device manufacturers are expected to ensure that the risk of exposure to DEHP is balanced against the anticipated benefits to the patient. Manufacturers must reduce or eliminate this risk where possible. Furthermore, the guidance reminds manufacturers that medical devices which contain DEHP phthalates must also bear the appropriate labelling. This requirement is provided in the Essential Requirements laid down in Annex 1 to the Medical Devices Directive. It is stated that any part of a medical device which contain phthalates “must be labelled on the device itself and/or on the packaging for each unit or, where appropriate, on the sales packaging as a device containing phthalates”.