Regulatory expectations are always evolving to enhance medical device safety, and the publication of ISO 1099318:2020 (part 18) demonstrates the importance of staying up to date on the regulatory landscape. Understanding what part 18 means for device material identification expectations and chemical characterization studies is crucial for a successful submission and, ultimately, a product’s overall life cycle. Furthermore, a firm grasp on the requirements can influence how manufacturers approach timelines and budgets, saving them time and money down the road.

The updated guidance may have a more significant effect on testing plans than anticipated. For example, the recent regulation changes regarding biological evaluations might mean retesting for manufacturers aiming to collect medical device material data. Reviewing previous chemical characterization testing may reveal that chemical characterization testing, as recent as late 2019, is already outdated.

Adhering to part 18 will require new reporting expectations, process changes, and planning for limited laboratory availability and the potential for increased costs. To satisfy intensified standards for chemical characterization, investing in thoroughly performed extractable studies and identification reporting is critical to proving device safety and gaining approval to enter the market.

Submission Expectations

Regulators are more sophisticated in their technical expertise than ever and are continuously refining their submission reviews because of it. Companies must prepare for evolving interpretations of guidance, which can vary between regulatory bodies. Depending on which regulatory body a manufacturer is submitting their device to, the testing parameters companies provide to their laboratory may differ, as well as budgets and timelines.

Part 18 challenges laboratories to approach biological evaluations more intentionally. Greater compound identification levels are now formally documented expectations, and the ISO hopes to gear laboratories toward an exhaustive, customized approach to study design. For example, laboratories should use three replicates in chemical characterization for a thorough evaluation. Also, determining the identification threshold is a collaborative process that considers the device’s contact type and exposure duration. While these specific examples are more widely enforced, governing bodies have a varied application of other changes.

U.S. FDA. The U.S. Food and Drug Administration’s (FDA) interpretation of part 18 is still evolving, after ISO 10993-18 published in January 2020, the FDA communicated expectations through various presentations at staple industry events. Formal documentation from the FDA has yet to be released. While the FDA states that in the transition period it will accept testing that complies with the previous standard until July 10, 2022, it’s best to get ahead as responses from regulators may prove otherwise and manufacturers should prepare their project timelines accordingly. 1

The FDA is currently probing deeper during the submission review process and asking for more technical evidence supporting chemical characterization. Manufacturers must have documented justifications for everything from solvent choice, extraction techniques, sample preparation, and more to clarify the decision-making process and achieve a successful submission. It’s essential to recognize the work and attention to detail these expectations add to the testing process. Not only does it require more time in the testing lab, but also additional resources. Companies should consider these factors early on to avoid unexpected delays or unanticipated costs.

EU MDR. In the EU, the Medical Device Regulation (MDR) accepts updates to part 18 as “state-of-the-art” and holds companies pursuing approval to the expectations outlined in the guidance. While official harmonization will take time, notified bodies will look to see whether testing followed part 18 processes. If not, repercussions could lead to significant delays and submission challenges.

One of the significant installments from part 18 is the analytical evaluation threshold (AET), which sets more stringent requirements for labs during testing.2 The AET established a level of consistency to the chemistry process and laboratories without sufficient equipment and expertise may struggle to identify compounds or provide detailed information discerning the compounds’ chemical structure for the toxicological risk assessment.

The consistency in expectations for the chemistry process prompts the need for thorough justifications in laboratory reporting. If those justifications are lacking, plan for an increase in requests for additional information from governing bodies. The potential for an influx of requests means it’s smart to add padding to timelines, which can already last far longer than what companies typically plan for. Depending on when companies performed chemistry testing — responding to these requests could mean further testing is necessary.

Sidestep Industry Challenges

Manufacturers are now able to have a more robust and comprehensive understanding of their medical device’s makeup with the changes upheld by part 18. For companies in the testing stage, selecting a quality partner well-versed in recent guideline updates may cost more on the front end but can mitigate the risk of delays or further testing later on. Allowing laboratories the appropriate investigation time in this stage is critical to achieving thoughtful, scientifically sound justifications and recommendations.

Set Up for Success. Backlogs have become unavoidable in every stage of the development process, and the testing phase is not immune. Various delays have laboratories’ capacity filling quickly. Considering the rigor required of analysts to deliver results and the impact this has on their remaining availability, communicating projects with ample lead time is the best way to secure a spot.

Dodge Delays. Shipping and supply chains are still recovering from the unexpected challenges from the last year. Companies must be proactive about getting test articles to testing sites on time. Laboratories also need to stock their supplies in anticipation of shortages. Distributors have faced issues keeping products available at the levels demanded by the market. With unpredictable material scarcity and other production roadblocks, keeping a backstock can limit the impact of these situations.

Support Further Assessment. Companies must ensure that chemistry testing supports toxicological risk assessments (TRA) with precise and accurate information. Testing laboratories should identify and quantify materials according to standards; otherwise, subsequent stages of the biological evaluation will be unable to deliver accurate device analysis. For chemistry experts to refine unknown materials, a clear understanding of the composition, production and any sterilization methods used supports the ability to narrow in on a chemical structure.

The chemistry process needs to be more precise than ever to identify and quantify medical device chemical constituents. Preparing samples takes more attention to detail for consistent replicates. Longer run times on instrumentation are essential to gather data. Also, data processing needs time to account for a greater number of identifications from increased sensitivity. Even reviewing the final report is a tedious, time-consuming process. Ensuring justifications at every point in the process supports the final submission. It helps experts in later testing stages to understand the solvents used, extraction methods, surrogate standards referenced and the preparation method.

Thinking Long-Term Changes

Companies have overcome countless difficulties in the past year, which challenged standard processes across the board. While settling into new routines, take the time to understand which adjustments should stay or go. Investing time, energy, and budget into learning about the importance of extensive chemical characterization will have long-term benefits.

With a dynamic industry landscape, medical device manufacturers are becoming increasingly nimble during the development and approval process. Establish consistent engagement with regulators and industry experts to understand in detail what future enhancements to the biocompatibility testing process will look like, as additional guidance publishes.

Lean into the learning curve of ISO 10993-18:2020 and the impacts on chemistry testing. Surprises can feel inevitable following recent events around the world, and while many — even regulators — still work to catch up, remember that short-sighted decisions can be the most costly.


  1. ISO 10993-18, Second edition 2020-01, Biological evaluation of medical devices – Part 18: Chemical characterization of medical device materials within a risk management process.”
  2. S. Schaible, “Preparing for MDR? Don’t Overlook the Analytical Evaluation Threshold,” Medical Design Briefs, February 2020, Vol. 10, No. 2, pp 20–24.

This article was written by Sandi Schaible, Senior Director of Analytical Chemistry and Regulatory Toxicology at WuXi Medical Device Testing, St. Paul, MN. She specializes in extractables and leachables studies. Schaible is a U.S. delegate and international delegate for ISO 10993 part 18 in chemical characterization and a U.S. delegate for ISO 10993 part 13 and the particulates committee (TIR 42). For more information, visit here .