At the upcoming IME East in New York, NY, Thor S. Rollins, vice president and global market segment leader - medical device at Nelson Laboratories, will host the session “Big Changes to ISO 10993-1, What is Happening to the Main Biocompatibility Standard Now?” and discuss the latest updates to the standard as well as its possible future acceptance around the globe. To further dive into ISO 10993 before the session, MD+DI talked with Rollins about the history of the standard, specific testing during the process like an extractables study, and how Nelson can aid clients in understanding its intricacies.
As we talk about current proposed changes and updates to ISO 10993, a quick history lesson may be warranted. What did ISO 10993 look like when it was initially created for the biological evaluation of medical devices? What process was it replacing, if any?
Rollins: ISO 10993 is a set of standards that provides guidance on the biological evaluation of medical devices. It was first introduced in 1995 as a replacement for the outdated USP (United States Pharmacopeia) biological testing approach. The initial version of ISO 10993 included a checklist of tests that manufacturers had to perform to assess the safety of their devices, including cytotoxicity, sensitization, and irritation.
In 2018, ISO 10993 was updated to emphasize a risk-based approach rather than a checkbox approach. This shift aimed to allow manufacturers to focus on the endpoints of concern for their specific device and reduce unnecessary testing, which could lead to more efficient and cost-effective evaluations. It also put more emphasis in understanding the materials and processing impact either by research or through chemical analysis.
What changes were implemented in 2018?
Rollins: One major change was the introduction of a biological evaluation plan, which outlines the testing required for a specific device and the rationale for selecting specific tests. This approach allows manufacturers to tailor the evaluation to the specific device and endpoints of concern, rather than performing a fixed set of tests. Additionally, the updated standard included new guidance on how to perform and interpret biological endpoints, such as genotoxicity and carcinogenicity.
What was the industry’s reaction to these changes in 2018?
Rollins: Mixed, obviously the move to more efficient and cost-effective evaluations is a positive but with any move away from checkbox testing it requires more expertise and then agreeance with the regulatory bodies. This means more uncertainty and reliance on expertise.
Why was there a shift towards implementing a risk-based strategy for specific biological endpoints of concern compared to the previous checkbox testing approach?
Rollins: The shift towards a risk-based strategy was driven by the realization that many of the tests in the initial version of ISO 10993 were not relevant or necessary for certain devices. By focusing on the specific biological endpoints of concern, manufacturers could perform more targeted evaluations that better assess the safety of their devices.
How does one decide whether an extractables study is needed in the ISO 10993 process? Is it always needed?
Rollins: The need for extractables testing in the ISO 10993 process depends on the device's materials and how they may interact with the body. If a device contains materials that may leach out or interact with the body, an extractables study may be necessary to assess the potential risk to patients. However, not all devices require extractables testing, and this decision is made on a case-by-case basis. The main determination is on the length of contact with the body, short term contacting device, generally, do not require extractables evaluations, but long-term contacting devices generally do.
What updates to ISO 10993 are currently being proposed? Has there been industry pushback?
Rollins: Currently, ISO 10993 is undergoing many updates, with proposed changes expected to be published in late 2023. Some of the changes being considered include new guidance on how to perform in vitro assays and updates to the biological endpoints of concern. Also, a final draft of 10993-17 has been published and current work on 10993-1, -3, -5 and -18 are underway. There has been some industry pushback, particularly around the proposed updates to the carcinogenicity endpoint and aggressive solvent extractions for extractable studies.
How can Nelson aid in helping clients to have a better understanding of the ISO 10993 standard?
Rollins: Nelson Laboratories, a subsidiary of Sotera Health, is a leading provider of testing and consulting services for medical devices. We offer a range of services to help clients navigate the ISO 10993 standard, including biocompatibility testing (in vivo and in vitro), extractables and leachables testing, and toxicological risk assessments. We also offer training and consulting services to help clients understand and comply with the latest regulatory requirements and many of these training can be found free at our Sotera Academy.