Today’s complex global regulatory environment creates a challenging situation for many medical device manufacturers who are developing a strategy that meets the changing testing requirements. Partners with a pulse on evolving expectations can help proactively plan for new and upcoming standards. With the recent changes to ISO 10993 chapters, new approaches to preclinical safety testing should be considered.

WuXi AppTec Medical Device Testing has partnered with thousands of companies in its path towards approvals with regulatory bodies worldwide. Its experts are leading global standards committees and frequently communicate with regulators, and track and trend feedback, resulting in an extensive understanding of the latest and future requirements. From advising testing plans, and supporting responses and justifications requested during the review process, it has plenty to share regarding ISO 10993.

A device’s full story

Before the release of ISO 10993-1:2018, manufacturers were used to conducting a more standardised set of tests based on the nature and duration of device contact. With the 2018 revisions, the evaluation of a device’s biological safety experienced significant change. Physical and chemical device information was now the foundation for identifying device-specific risks and manufacturers needed to develop biological test strategies based on those risks.

Over time, the requirements for conducting chemistry testing have become more rigorous. As a result, regulators supported refining acceptable testing plans to include chemical characterisation. These analytically selective and sensitive methods began to prove their value as the industry shifted from a checklist approach to a more strategic biological safety testing method.

Establish consistency

The publication of ISO 10993-18:2020 created a ‘common language’ between two integral parts of the evaluation process and helped establish manufacturer expectations from laboratory partners. It also introduced the analytical evaluation threshold (AET), which converts a dose-based threshold used by toxicologists to a concentration-based threshold used by chemists.

The AET requires a partnership between the chemist and toxicologist who will perform the risk assessment. The industry continuously establishes more consistent and thorough evaluation procedures that better recognise each device’s chemical risks. Regulators are gradually implementing enhanced material identification expectations, so manufacturers must pay close attention and frequently assess their compliance with the latest requirements. “ISO 10993-18 revisions have been a major learning curve for any laboratory.

Laboratories who are underprepared or less engaged in the regulatory landscape can cause significant and unexpected delays for their clients,” says Sandi Schaible, senior director of analytical chemistry and regulatory toxicology at WuXi AppTec Medical Device Testing. Building out the capabilities to support such identification requires investing in time, technology and internal support. More than ever, chemists and toxicologists are working closer together, highlighting the value of integrated laboratories with notable regulatory involvement.

Change on the horizon

As the latest chemical characterisation methods reveal more materials, a growing amount of data challenges toxicologists to determine the steps for evaluating the remaining risks. Upcoming changes to ISO 10993-17 will help usher in a new era of streamlined toxicological risk assessments. Managing a range of products during this transition can be an arduous process, but it will benefit devices and patients in the long run. Companies heightening their strategies for gathering preclinical safety and regulatory compliance information will face many guidance updates, but they don’t have to do it alone.