Author: James Morrison
The ISO 18562 series of standards for Biocompatibility evaluation of breathing gas pathways in healthcare applications was initially published in 2017. These standards evaluate the safety of substances added to the inlet air by the medical device. Since the series was written, it has been put to good use in a number of jurisdictions, although with varying degrees of recognition.
As I’ve observed in a previous article, regulatory acceptance is an important aspect for a Standard. Whilst it’s true that (ISO) standards are not supposed to be written for regulatory purposes, it’s pretty important that standards find a high degree, if not universal, acceptance. A Standard isn’t really “standard” until or unless it is very broadly accepted.
So now, after about five years of use, it’s being revised. Actually, the initial revision proposal was submitted by the USA, for just ISO 18562-4, a couple of years ago – but circumstances often intervene in standardisation.
As work on the revision of Part 4 has progressed, it’s become clear that it will also spill over into the revision of the other three parts of the series. The following is a brief description of how the revisions are going, and some of the underlying rationale.
Part 4: Tests for leachables in condensate is being technically revised. This particularly includes a requirement to determine the volume of condensate that can reach the patient. In the first edition, this volume of condensate was set at a standard value, informed by the experts’ understanding of clinical practice and its implications. With time and experience, the relevance of the standard value has been shown to be less than ideal. Thus, the volume will in future need to be determined.
It is likely that the volume will need to be determined experimentally, in the first instance. Subsequent evaluations (of the same device) may rest on scientific rationale. This may present a challenge to manufacturers, but if so, it’s probably an overdue challenge. Condensate exposure is something probably already included in the device risk management file.
Along with the condensate, volume comes a requirement to calculate the resulting dose of leachables to the patient. In the same way the ISO 10993-1 is a worked example of the risk management principles of ISO 14971, the ISO 18562 series is a worked example of the principles of ISO 10993, as applied to breathing gas pathway devices. And that means that the ISO 18562 series is all about toxicological risk assessment.
That this is so should surprise no one who has used the documents. From the outset of the initial drafting process, through publication and now into revision, the key consideration has always been the actual dose-to-patient; I am again reminded of the statement from Paracelsus, the Father of Toxicology, “Only the dose makes the poison.”
As most observers and participants in the medical device industry will be aware, biological evaluation of devices is increasingly dependent on (and engaged with) toxicological risk assessment. This is a field that has existed for a fair while but is still very much a work-in-progress for its application to medical devices. It was first presented to the users of the ISO 10993 series in Part 17:2002 Establishment of allowable limits for leachable substances. When the comprehensive and long-running revision of Part 17 is completed, I anticipate the title will become: Toxicological risk assessment of medical device chemical constituents.
To be fair, to call the revision of ISO 10993-17 “comprehensive” is to understate the efforts of the ISO Working Group substantially. The process is not simply updating the standard to reflect the state of the art. It is actually breaking new ground, developing new concepts and tools, and driving consensus between myriad stakeholders. Considerable advances are being made.
Fortunately for ISO 18562 series, some of the experts participating in the revisions are also involved with ISO 10993-17. Much of the value developed for Part 17 will find its way (promptly) into the parts of ISO 18562.
Part 1: Evaluation and testing within a risk management process is also being technically revised. This will include clarifying the appropriate breathing gas volumes for use in the risk analysis. It turns out that breathing, particularly the quantification thereof, is a whole lot more complicated than most of us realise. Probably due to our autonomic reflexes, which allow/make us breathe without conscious engagement, we don’t appear to think about breathing much or appropriately.
Quantification of breathing is a multi-dimensional problem, where factors include: age, height, weight, activity state, pathology, etc. There are also many ways of measuring breathing: rate, tidal volume, daily volume. All of these contribute to the understanding of dose-to-patient, which is normally expressed as mg/kg body weight/d.
It is likely that there will be a new table of nominal body weights and breathing volumes to allow for adjustments for different patient groups.
Part 2: Tests for emissions of particulate matter is likely just to have an editorial revision. This should not be seen as less worthy of attention. (Technical revision also includes editorial revision.) This will include the addition of some informative annexes which map the standard clauses to relevant regulatory requirements. Manufacturers operating to the European MDR are likely to find these quite valuable. There will also be some clarification of the terms and definitions used in the document. Clearly, even minor changes to definitions can have major impacts.
Part 3: Tests for emissions of volatile organic compounds (VOCs) will become Tests for emissions of volatile organic substances, as the result of editorial revision. This makes the application a little broader, without changing the technical intent. VOCs has a fairly strict definition, so making the subject “substances” removes the limitation.
As the revision process continues, there will doubtless be other changes to these standards. But on the whole, the trajectory looks promising. The revised series will be an improved four parts, with better recognition, better process and better rationale. This also paves the way for future additional parts, to cover other aspects of breathing gas pathway biocompatibility. All good things take time!
Manufacturers may find managing device safety, applying standards and complying with regulations and guidance, to be a challenge. Brandwood CKC experts are always available to assist in all levels of medical device safety and compliance. Please reach out to us for guidance and assistance in this matter.
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