Speaker Interview with Marco Costante

Ahead of the 2025 Extractables & Leachables Europe conference, we spoke to Marco Costante, Leader – Human Health Environmental & Human Toxicology at knoell Germany. Our interview provides a sneak peek of what you can expect from the event...

What do you think are the biggest hurdles for manufacturers trying to transition from the “old” 10993-1 version to this new revision?
The new ISO 10993-1 revision puts a much stronger emphasis on risk management. It’s been nearly two decades since the checklist approach was removed from the standard, with this new revision even more emphasis will be added to the risk management process.

This new version shifts the focus to the impact on humans and not to cells or test animals and the toxicology behind. It really forces manufacturers and safety assessors to go through the exercise of risk evaluation, taking into account the current state of the art in toxicology and biological safety assessments.

For example: if a device is used every day for 1 hour, you should consider that exposure as equivalent to a full day of use. And if the device is used for more than 30 days, it must be treated as a long-term use device — because from a toxicological perspective, you are delivering a daily dose that could have cumulative effects over time.

Another significant hurdle will be considering reasonably foreseeable misuse. This will require a combination of robust risk analysis and strong post-market surveillance processes.

Finally, there is the challenge of evaluating risk across the entire device lifecycle. Every medical device is unique, and the standard is not intended to provide step-by-step guidance but setting a framework. Exchange is ongoing within ISO/TC 194 to set up guidance documents complementing the standard. This will take time.

knoell provides regulatory consulting across global markets. How do you see regional regulatory authorities around the world perceiving or adopting the new standard differently?
It’s still early to say definitively, but I believe this revision — being science-driven — will eventually gain broad consensus worldwide.

That said, there are concerns, that this revision could increase the regulatory burden in an already complex and costly area. And yes, it probably will — because it pushes manufacturers to use scientific reasoning rather than simply ticking boxes.

Will the new standard result in significantly improved patient safety?
In most cases, probably not — and I actually hope not, because it would mean most devices are already safe. But there are certainly some cases where compliance with the new requirements will be challenging — and where the additional rigor will ultimately benefit patients' safety.

At knoell, our role as scientists working in a regulatory context is to keep patient safety at the forefront while remaining pragmatic. We aim to guide our clients through compliance without adding unnecessary burden.

How do you see the role of extractables and leachables testing evolving under the new ISO 10993-1 revision?
E&L are essential tools for assessing the biological safety of medical devices. Their role will not fundamentally change with the new revision, because they remain the foundation for determining whether or not there is a potential risk to the patient.

What will change is the expectation for substance identification and the way data are interpreted. Particular attention will need to be given to cases such as bioaccumulative substances. For example, even if a device is used only once for 10 minutes, the presence of a bioaccumulative compound could shift its categorization to “long term use,” since the substance may persist in the body and trigger toxicological responses over time. 

This means that fir for purpose scientific approaches and deeper expertise are needed — not just analytical chemistry, but also toxicology and risk assessment working hand in hand. The ultimate goal remains the same: to ensure that decisions are scientifically sound and that patient safety is always preserved.