Five questions for.....Andries van der Meer
The Future of Organ-on-Chip: Innovation, Standardization, and Collaboration
In this interview, we speak with Andries van der Meer, professor at the University of Twente and lead researcher in the field of Organ-on-Chip technology. Andries shares his insights on the crucial role of standardization in this field, the challenges and opportunities for further development of Organ-on-Chip models, and the impact of the NXTGEN Hightech project on his work. He discusses how collaboration between academic institutions, companies, and regulatory bodies can contribute to accelerating innovations and implementing this promising technology in the pharmaceutical industry.
Why is standardization important for Organ-on-Chip and how is the international community responding to it?
"Standardization is crucial for the further development and implementation of Organ-on-Chip technology. It helps create guidelines for collecting and interpreting measurement data, which is essential for the reproducibility and reliability of the data. This is especially important for the pharmaceutical industry and regulatory bodies such as the FDA and EMA, which use this data for drug development and toxicology testing.
I am personally heavily involved in this process. At the European level, organizations CEN and CENELEC have set up a focus group to explore standardization for Organ-on-Chip.
I chaired this focus group for two years, during which we wrote a roadmap with about 70 to 80 experts. This document, which is freely downloadable, maps out which aspects of the technology can be standardized and where we should prioritize. Together with NEN, the Dutch Institute for Standardization, we are working to embed these standards at the ISO level. "
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"There are two main ways to look at standardization in this domain. First, there is a strong demand from end-users and regulatory bodies to develop standards for the data that Organ-on-Chip models produce. This helps in interpreting and comparing data with existing data, such as that from animal models. Standards ensure that measurement data is robust and reproducible, facilitating the acceptance and implementation of these models in drug development.
Second, standardization plays a role in innovation. To accelerate the development of more complex models, we need to agree on how different components of an Organ-on-Chip can be integrated. This includes biological components, technical elements such as microelectronics and fluidics, and materials derived from human tissues. By making basic agreements on quality control and form factoring, we can develop new applications and models more quickly.
Internationally, there is broad support for standardization. During a recent workshop by the C-Path Institute*, a key advisory body to the FDA, the importance of standardization for the implementation of Organ-on-Chip models in drug development was emphasized.
The focus here is mainly on providing guidelines for measurement data and reproducibility.
Companies worldwide, whether from the US, Germany, Korea, or the Netherlands, all see the need for standardization. Although they have developed their own platforms and gained market share, they realize that the market potential is enormous and that collaboration in a pre-competitive domain is essential. This means that companies need to exchange components and knowledge to come up with new applications and innovations more quickly.
The international community is responding positively to these developments. The establishment of a new ISO subcommittee for Microphysiological Systems and Organ-on-Chip underscores the value of standardization. This subcommittee is working on standards in the areas of terminology, biological components, experimental design, data management, and engineering. This pioneering work forms a solid foundation for further international standardization."
* Critical Path Institute - The Path Forward in Drug Development
Why is it taking so long for Organ-on-Chip to become a major market and what is its relevance?
"The main application domains of Organ-on-Chip are biomedical and pharmaceutical research, such as the search for new therapies and understanding human diseases. Currently, preclinical pharmaceutical research is almost entirely dominated by animal models. This means that human diseases are simulated in animals such as mice or dogs, after which candidate drugs are tested for efficacy and safety.
The system is set up for this, and regulatory bodies often require extensive animal testing. However, many new therapies are human-specific, such as cell therapy for cancer and gene therapy. These therapies often do not work in animal models because they target unique human aspects.
Additionally, animal models have limitations such as high costs, inefficiency, and low predictive value for human responses. The success rate of clinical trials in the pharmaceutical industry is very low, indicating the limitations of animal models.
Organ-on-Chip technology offers a solution by mimicking the complexity of the human body in a controlled laboratory environment. This makes it possible to study human responses more accurately. The technology is cost- and time-efficient and can be optimized for future generations of models.
The relevance of Organ-on-Chip lies in the ability to better understand and develop human diseases and therapies. This is especially important because many new drugs and therapies are human-specific and cannot be properly tested in animal models. Organ-on-Chip technology can significantly improve the predictive value of preclinical research and reduce the reliance on animal testing.
The market for Organ-on-Chip is potentially enormous, and it is important to capitalize on this technology now to maintain momentum and increase its impact on biomedical research and drug development."
What do you expect from the NXTGEN Hightech Biomed 03 Organ-on-Chip project and what is its importance?
"What we are doing in Biomed 03 is setting an example for the entire field of how it can be done. The field of Organ-on-Chip is relatively young, and it is impressive how much has already been achieved in 10 years. What started as an academic exercise is now a technology in demand from the market, with commercial activities in the form of Organ-on-Chip companies.
However, these companies have all developed their own platforms, with different systems for pumps and readouts. This makes it difficult to innovate quickly and develop new applications. What we are doing now with NXTGEN Hightech is recognizing that the market potential is much greater, but that a different approach is needed. Instead of closed platforms, we are creating a pre-competitive domain in which companies and academic institutions collaborate and bring in their expertise.
By combining components and using standards, we can switch and innovate more quickly.
This concept already works on a small scale in academic settings, such as at the University of Twente. The goal now is to make this scalable and manufacturable, so that it meets the current and future market demand.
There are specific challenges per component, such as miniaturization of sensors and quality control of cells. The NXTGEN Hightech project helps us identify and address these challenges. We are building an ecosystem in which different parties collaborate and share their expertise. This can lead to a market player acting as an integrator, or a level playing field in which companies serve multiple markets.
The exciting thing about this project is that we are discovering together where the bottlenecks are and how we can overcome them to successfully develop and commercialize Organ-on-Chip technology."
What do you think would be ideal to accelerate the maturation of the Organ-on-Chip market? What should be the major steps?
"To accelerate the Organ-on-Chip market, we need to talk to the intended end-users, such as the pharmaceutical industry. They are already using some existing Organ-on-Chip platforms, but the learning curve is steep, and the systems take up a lot of valuable lab space. These platforms often do not fit into the normal workflow of the labs, which are used to standardized microtiter plates.
To increase adoption and implementation, we need to address these challenges. This means focusing on standardization so that the form factor and standards align with what end-users are used to. Additionally, automation is crucial so that the systems can be used as turnkey solutions without extensive training.
Miniaturization and parallelization are also important. The promise of Organ-on-Chip is that we can test hundreds of chips with different concentrations of candidate drugs in one study. Currently, we are far from that, with studies yielding only a few data points. There are Organ-on-Chip companies that have taken scaling up as a starting point, although they make concessions in terms of complexity.
The current Organ-on-Chip companies can still get away with this because the pricing is comparable to animal testing. But to really grow, we need to move to a model like in microelectronics, where we go from large, bulky systems to compact, efficient devices. This will significantly accelerate implementation and adoption."
What has the NXTGEN Hightech project brought you so far, besides financial support?
"Besides financial support, the NXTGEN Hightech project has brought me many insights and experiences. I am involved in both the Organ-on-Chip project and the One-stop-Shop project. The One-stop-Shop project focuses on creating an ecosystem in which multiple players and suppliers collaborate to develop working and manufacturable products. Standardization is an explicit part of this project.
What struck me most is the enormous energy in the field to work on the challenges of standardization. It took relatively little effort to get this off the ground, thanks to the involvement of parties such as NEN and the companies within NXTGEN Hightech.
Additionally, I am heavily involved in the facilities and infrastructure within the One-stop-Shop project. This is a challenging puzzle, especially since we at the University of Twente are investing in open facilities and infrastructure that are accessible to partners in the ecosystem. The goal is to give companies low-threshold access to complex cell biological assays and microfabrication techniques.
This experience has made me much more aware of the challenges in making this technology manufacturable and scalable. In my daily practice, I am often busy developing new Organ-on-Chip models in the lab. But through this project, I have become much more aware of what it takes to translate these innovations cost-effectively into real products.
The project has also shown me how important collaboration is with high-tech and biotech companies, mechatronics companies, and engineering firms. It has made clear what our role is as a university and researcher in this ecosystem, and how we need each other to be successful.
There is also a lot of synergy with other domains of NXTGEN Hightech, such as Smart Industries and Semicon. Many of my colleagues are interested in photonics, Digital Twins, and optimizing production techniques. Now and in the future, these are aspects we need to incorporate in the early development of new technologies to ensure they are scalable and manufacturable."