Computer modeling accelerates improvements in implantable devices

The development and regulatory approval of cardiovascular implants is a complex process which is both time-consuming and expensive. ‘SIMCor’, an EU-funded project led by Charité, will see researchers develop computer-based models which aim to speed up this development and improve product quality. The use of in silico modeling will drastically reduce - and in some cases replace - the need for animal testing.

Cardiovascular medical devices such as stents, pacemakers and micropumps undergo a lengthy development process. Numerous testing stages must be completed before implants can be authorized for first-in-human testing. Implants may, for instance, be mounted in machines which test their mechanical strength, after which they will undergo multiple stages of animal-based testing. All of this is time-consuming, expensive, and not really up to 21st century standards.
This view is certainly shared by Prof. Dr. Titus Kühne, Director of Charité’s Institute for Imaging Science and Computational Modeling in Cardiovascular Medicine (ICM). Working alongside his interdisciplinary team, whose members represent the fields of computer science, mathematics, physics and engineering, the pediatric cardiologist is developing ‘in silico models’. This involves the use of intelligent computer algorithms to simulate what had previously been possible only in vivo (i.e., using a living organism), such as the implantation of a pacemaker into a beating heart.

SIMCor – an EU-funded collaboration led by Charité
It is thanks to the ICM’s expertise that Charité’s SIMCor (In-silico testing and validation of cardiovascular implantable devices) project was able to secure funding under the Horizon 2020 program in the fall of 2020. Funded by the European Union and involving twelve additional partners from eight countries, this collaboration will receive a total of € 7.2 million over three years. The aim of the project is to create a computer-based platform for the development, testing, validation, and regulatory approval of cardiovascular implants which will serve as a guide for research and industry, and even the relevant regulatory authorities. Titus Kühne is responsible for the project’s coordination.
Explaining the aims of the project, he says: “Ultimately, the aim is to improve the quality and safety of cardiovascular implants. Another aim is to speed up development and reduce costs in order to create socioeconomic added value.”

Computer modeling is set to replace traditional testing methods 
The researchers want to show that computer modeling can be used to improve the quality of medical devices and the speed with which they reach the patient. They will demonstrate this technology using implantable devices from two representative areas which also happen to be the focus of developmental activities by relevant industrial partners: trans catheter aortic valve implantation (TAVI) and pulmonary artery pressure sensors (PAPS). The proof of concept will consist of a comparison between the old and new procedures – so long as everything works out as planned. “We will only be successful if we are able to demonstrate that our in-silico models produce better and/or more accurate results than traditional testing methods,” says Prof. Kühne. At what point ‘better’ represents a distinct improvement will be calculated by the research group’s statisticians. According to Prof. Kühne, a 0.5 percent improvement would definitely be considered insufficient. A 20 percent improvement would be desirable and “an entirely realistic goal”.

Exploiting the potential of virtual patients
Achieving this could reduce the duration and size of animal-based research and, in some cases, replace the use of animals altogether. In terms of the potential to reduce the need for animal research, the SIMCor project lead says: “We are aiming for a reduction of around 30 percent, both in terms of sample size and study duration,” says Prof. Kühne. In fact, the SIMCor study lead believes that specific stages of the development process may even reach 100 percent. This is because “not every single experiment has to be completed using animal-based research.” Clinical trial requirements may also be slimmed down. Similar reductions in both study duration and numbers of participants may be possible if new products can be tested using virtual patient cohorts with a wide range of pre-existing conditions and anatomical characteristics. The aim is to make sure medical implants are also suitable for pediatric use.
The researchers have three years to develop the relevant methodology. The researchers also plan to develop device-specific models which can be used to predict the safety, efficacy, and user-friendliness of medical devices. It is an ambitious timeline for an endeavor which aims to set new standards. Ultimately, the new testing and validation procedures have to be able to convince regulatory bodies such as the European Medicines Agency (EMA), the U.S. Food and Drug Administration (FDA), TÜV (Germany’s product inspection and certification body), notified bodies and ISO certification bodies. Prof. Kühne believes there is a long and difficult road ahead before regulatory bodies will say: Yes, we will approve that. However, the SIMCor researchers know they have an entire community behind them whose demand matches theirs: namely, to give computer modeling a more prominent role in the regulatory approvals process for drugs and medical devices.

Digital transformation supports the ‘3R’ aims
In the area of testing and validation, the medical field clearly lags behind many other sectors. Without relevant computer-based modeling, no airplane would take to the skies, and no car would be permitted on the road. However, medicine is beginning to catch up in the digital field. In this particular case, with backing from the European Union. Brussels is well aware of the potential of computer modeling to make many things better, faster, and more cost-effective, and that digital transformation is the future. The fact that it can also reduce the need for animal research is a welcome side effect. 
Titus Kühne does not believe that animal research can be eliminated completely. “Overall, however, we will be able to drastically reduce the number of animal-based experiments, and that is another added value of this project.”
 

(Text: Beatrice Hamberger)

Links

Institut für kardiovaskuläre Computer-assistierte Medizin

SIMCor-Verbundprojekt

Contact