Put to the test: ensuring the safety of medical respiratory devices

Mike Ludlow, market development manager for E&L at Element Life Sciences shares how to ensure the safety of medical respiratory devices and the importance of the correct implementation of the ISO 18562 testing guidelines.

The recent recall of an estimated 5 million ventilators and BiPAP / CPAP sleep apnoea devices by Philips Respironics, due to the reported failure of a polyurethane foam sound insulating material, has highlighted how critical rigorous analytical testing can be in ensuring the safety of medical devices and componentry used in the provision of respiratory care or in the supply of substances directly to the respiratory tract.

The ISO 18562 international standard addresses the need to assess the major potential risks of solid particulate matter, volatile organic extractable compounds and condensate related leachable materials from medical respiratory devices on the patient’s breathing pathway.

This article describes the key considerations in the implementation of ISO 18562, including an overview of the testing requirements, the product device types and components which are impacted by the standard and a discussion around associated challenges including some recent case studies.

Biocompatibility evaluation

A number of recent global product recalls of medical breathing devices have highlighted the importance of the biocompatibility evaluation of breathing gas pathways in devices such as ventilators, breathing systems and respiratory monitors.

In July 2023, Dräger issued a worldwide voluntary recall for its Carina Sub-Acute Care Ventilator devices due to the presence of an acutely toxic and potentially carcinogenic contaminant in the device’s airpath. The contaminant, 1,3-Dichloropropan-2-ol, was derived from a polyurethane foam component used for sound insulation.

The FDA recall of more than 5 million Philips’ BiPAP and CPAP sleep apnoea devices in 2022 is reported to have cost the manufacturer an estimated $1.3 billion. The breakdown of another polyurethane foam component, used for sound proofing the devices, gave rise to particulate matter in the gas pathway which could potentially be delivered directly to the respiratory tract during patient treatment.

The ISO 18562 guidelines have been developed to ensure that respiratory devices and associated accessories used in primary care applications do not pose any undue health risks to patients. These types of devices are medical products designed to aid or regulate the breathing process. Manufacturers of this equipment utilise these standards to demonstrate compliance with regulatory requirements concerning biocompatibility.

The guidelines propose methodologies suitable for the assessment of the potential risks of device componentry that may come into contact with breathing gases and considers these risks in terms of patient toxicity, sensitisation, and irritation. 

The standard comprises of four sections which each address different aspects of the biocompatibility evaluation of respiratory devices and provides a framework for the risk assessment of these products. 

The proposed methodology is similar to the approach used for the chemical assessment of extractables and leachables from pharmaceutical drug container and delivery systems but, due to the specific mode of use of these types of devices, includes additional physical testing of particulate matter.

 a. Risk evaluation

The opening part of the standard outlines the overall risk management process to be used for the evaluation of respiratory products and defines the information required to complete the biocompatibility evaluation plan.

This plan includes an initial paper-based assessment of all existing data, identifies any information gaps, and confirms any requirements for additional data and testing, with the general goal of reducing the need for animal testing where possible. 

b. Particulate matter

Particulate matter can potentially impact on both respiratory health and on the cardiovascular system. The smaller the particle, the deeper into the lungs it can penetrate and the longer the body takes to eliminate it.

In order to ensure that the components in contact with the breathing gas pathway in respiratory devices do not release particulate matter that could pose a risk in terms of patient safety dry air is passed through the device and sampled using either gravimetric or particle counting techniques. The level of particulate matter is monitored and the minimum, maximum, and average particulate concentration are assessed and compared against defined threshold limits.

c. Volatile Organic Compounds (VOCs)

VOCs such as residual solvents which can be derived from the production process of plastic components present a high risk in terms of irritation of the mucous membranes, skin sensitisation and toxicity which can result in long term effects on the nervous system. It is therefore vital to confirm that these compounds are not present in the gas pathway of respiratory products.

Gas samples are collected through the device and analysed using gas chromatography-mass spectrometry (GC-MS) which provides a quantitative characterisation of the VOCs. These results are then converted to patient exposure levels and assessed, based on contact exposure, against defined thresholds of toxicological concern (TTCs).

d. Leachables in condensate

The final part of ISO 18562 applies to any devices which may form a condensate during clinical use. Potential leachables deriving from components within the breathing pathway include salts and metals and are characterised by performing a simulated use extraction study of the device, using a combination of inductively coupled plasma-mass spectrometry (ICP-MS) and gas chromatography-mass spectrometry (GC-MS) techniques to identify inorganic and organic leachable species respectively.

The results from the various test procedures are then assessed in terms of patient toxicity in order to complete the biocompatibility assessment for the device.

Summary

The ISO 18562 standard provides a comprehensive framework for ensuring the safety of gas pathway respiratory devices in terms of the risks associated with particulate matter, volatile organic compounds, and condensate leachables and the potential for any adverse impact on a patient’s health during the use of these devices.