In January 2020, the International Organization for Standardization (ISO) released their updated guidance ISO 10993 Biological evaluation of medical devices—Part 18: Chemical characterization of medical device materials within a risk management process. This update provides ongoing clarity into worldwide expectations for medical device biocompatibility assessment, though the document is still a dense 74 pages.
It may be a challenging or confusing read for companies and individuals relatively new to the regulatory aspects of this industry, but fortunately EKG Labs is here to help! With our extensive years of experience in analytical evaluation of medical devices, under the technical expertise of Dr. Allen Kesselring and Katie Grayson, we understand the ever-changing needs of medical device biocompatibility. We pride ourselves on the technical “consulting” and risk assessment assistance we build in to every conversation with our clients, right from the point of first contact.
Below we provide a brief overview of the updates in this guidance, but we encourage you to reach out to us at 810-354-5229 for further conversation. You can also read a general overview of ISO 10993 on our website.
What does this document mean for my medical device testing?
This document continues an encouraging industry emphasis on only performing the minimum appropriate testing (biological or chemical) necessary to establish that a medical device presents an acceptable health risk. A thorough biocompatibility risk assessment likely includes both chemical characterization and biological testing, though in this revised guidance, ISO states “in vitro tests should be favored as far as possible”. While chemical characterization is not a unilateral substitute for biological testing, ISO now states that the combination of chemical characterization and toxicological risk assessment “if appropriately conducted, can be used in lieu of certain biological tests”. This is fantastic news because chemical testing is generally less complex, more cost-effective, more robust, and less time-consuming than biological testing. This shifting preference toward chemical characterization was also emphasized in ISO 10993-1:2018, about which EKG Labs has written more extensively.
Some of the most helpful new portions of ISO 10993-18:2020 include:
- An expanded glossary.
- Revised chemical characterization process flowcharts.
- Explanations of exhaustive extractions, exaggerated extractions, simulated use extractions (including accelerated), and leachable testing.
- Specific guidance for the determination of extraction parameters for typical medical devices—based on device type, contact, and duration of exposure. This is the most comprehensive document yet, with many helpful tables and charts.
- Annex A “General principles of chemical characterization” is an extensive explanation of the purposes and directives of chemical characterization.
- Annex D “Principles of sample extraction” provides thorough descriptions of, and considerations for, each type of extraction.
- Annex E “Calculation and application of the analytical evaluation threshold” describes, with examples, the calculation of AETs. These are crucial values used in chemical characterization to determine the significance, analytically and toxicologically, of any data generated.
ISO 10993 Testing at EKG Labs
At EKG Labs we specialize in chemical characterization of medical device materials to provide ISO 10993 biocompatibility data for regulatory filings. Our team has years of experience working with diverse pharmaceutical products and a variety of medical device materials including polymers, metals, ceramics, and composites. In addition to these raw materials, we understand how to characterize ancillary chemicals associated with device production such as plasticizers, fillers, additives, cleaning agents, and release agents. We are prepared to flag any materials which need further toxicological evaluation.
EKG is particularly proud of our extractables/leachables program. Our extractables and leachables program is constructed around ISO 10993-12 (sample preparation) and ISO 10993-18 (characterization). We routinely carry out exhaustive extractions (assessed by gravimetric analysis), exaggerated extractions, simulated-use extractions, accelerated aging studies, and leachable studies—all per ISO 10993 guidance. Extraction solutions are typically evaluated, depending on solvent utilized, by LC-MS, GC-MS, and ICP-MS. The end report of an extractable study will list all compounds found and their in-sample concentrations. You can access EKG case studies here.
EKG Labs further supports medical device and combination drug device analysis by offering regulatory consulting services to help you navigate the complex FDA regulatory process.
About EKG Labs
EKG Labs is an analytical service provider for the pharmaceutical and medical device industries, operating out of Innovative Technology Enterprises (ITE) at the University of Missouri, St. Louis (UMSL). Our analytical services support product development, regulatory filings, and analytical chemistry investigations.
To find out more about ISO 10993 biocompatibility risk assessments and chemical characterization testing, contact EKG Labs at 810-354-5229.