MPS World Summit 2024 Recap

By Breanne Kincaid & Yiguang Zhu | July 11th, 2024

Introduction 

Members of the Toxicology Policy Team recently attended the Microphysiological Systems (MPS) World Summit in Seattle, Washington, where they were able to discuss their own research, attend presentations, and moderate sessions. 

MPS is the umbrella term that encompasses organoids, organs-on-a-chip, and other diverse bioengineering technologies that mimic the structure and functionality of organs in vitro. They are powered by advancements in stem cell technology, allowing for patient-derived miniatures of human tissues on which to test the toxicity and efficacy of drug candidates, consumer products, and environmental or occupational contaminants. While many of the MPS presented at the conference are still in the model development stage or being implemented as companion tools in early compound discovery and toxicity screening phases, they have a promising application in risk assessment across many disciplines. 

Two team members discuss the MPS work that they presented at the conference, and the major takeaways from the sessions they moderated. 

Yiguang: 

I presented my work on the validation framework for MPS models. Earlier this year, the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) published a report titled Validation, Qualification, and Regulatory Acceptance of New Approach Methodologies (NAMs), proposing a validation framework for NAMs. We assessed this framework's applicability to MPS models and identified several key hurdles, including the limitations of the fit-for-purpose strategy and unclear allocation of responsibilities. To address these issues, we proposed an improved framework, dividing the validation process into two phases: Phase 1, where interagency bodies like ICCVAM validate the biological relevance and technical characterization of MPS models and catalog them in a library; Phase 2, where end users such as federal agencies select appropriate models from this library and qualify them for specific applications. In my presentation, I used two flowcharts to compare the ICCVAM framework and our proposed framework side by side, demonstrating why our approach could accelerate the validation of MPS models and reduce redundant work. 

I also moderated a session titled 'Case Studies of MPS Use that Informed Regulatory Submission,' which featured five insightful presentations showcasing innovative applications of MPS in drug development and regulatory processes. Dr. Kevin Healy from Organos Inc. presented a high-throughput 3D heart microtissue system for arrhythmogenic drug evaluation. The MPS combines tests on cell behavior and computer models to predict heart toxicity, helping to make drug development safer. Dr. Heather Hsu from Inipharm, Inc. discussed the nonclinical development of INI-822 for treating a liver disease called “MASH”, emphasizing the use of MPS to measure anti-fibrotic effects and highlighting how liver MPS models provide superior insights compared to traditional mouse models. Dr. Sai Grandhi from GSK presented a novel MPS assay system to study cancer immunotherapy, demonstrating its potential for high-resolution investigations into immune cell functions within tumor microenvironments. Dr. Giulia Raggi from AlveoliX AG, shared advancements in using MPS to evaluate drug-induced liver injury, showcasing the system's ability to mimic human liver physiology for more accurate toxicity assessments. Lastly, Dr. Mario Beilmann, representing the European Federation of Pharmaceutical Industries and Associations (EFPIA), gave a presentation on MPS applications in regulatory submissions, highlighting successful case studies where MPS data informed regulatory decisions, underlining the critical role of these systems in modern drug development and safety evaluation.EFPIA), gave a presentation on MPS applications in regulatory submissions, highlighting successful case studies where MPS data informed regulatory decisions, underlining the critical role of these systems in modern drug development and safety evaluation. 

Attending the conference provided a deep understanding of the connections in drug development, pathophysiological research, and MPS validation, all seen through a critical regulatory lens. This experience demonstrated how regulatory considerations are crucial at every step, from the initial development of MPS to the thorough validation required before these systems can be used for real-world application. Many presentations highlighted the need for a regulatory framework that supports innovation while ensuring that new methods meet strict safety and efficacy standards. 

Breanne: 

My work with the Johns Hopkins Center for Alternatives to Animal Testing (CAAT) uses a human brain MPS to characterize how exposure to industrial contaminants (arsenic, cadmium, chromium, and lead) alone and as a complex mixture can impair the formation and function of neuronal connections in the developing human brain. The brain MPS – which we informally call our “mini brains” – allows me to look at key events in neurodevelopment such as the assembly of synaptic proteins, the extension of neural projections called neurites, and the dynamic handling of calcium that’s necessary for a neuron to fire. Broadly, my research has found that the combined toxicity of low levels of these contaminants doesn’t seem to be more harmful to neurodevelopment than the compounds individually. My work is still ongoing, and I hope to gain additional insights into deviations from additive toxicity, since we are exposed to thousands of compounds as mixtures every day. 

My involvement moderating the session on food, cosmetics and consumer products' industry experience in MPS implementation allowed me to take a step back from neurodevelopmental models and learn about MPS that model the lung, skin, and intestine. 

During the session, presenters discussed some of the ways organ-on-a-chip and complex in vitro models are being applied to early research and development within their companies. Marisa Meloni with VitroScreen explored the role that MPS may be able to play in generating evidence for cosmetics and nutraceutical claims substantiation, while Johanna Ritter of Beiersdorf AG and Ji Eun Lee of MEPSGEN discussed their own strategies of layering biological complexity onto their in-house skin MPS models. Robert Moyer with Battelle discussed using an air-fluid interface to assess inhalation toxicity of a chemical intended to replace a compound known for causing popcorn lung in occupational settings, while Gretchen Mahler of Binghampton University gave a presentation on macromolecular absorption through a small intestine chip cocultured with gut microbiota for application in food additives research. 

Overall, I was impressed by the cross-disciplinary efforts focused on bringing MPS to the forefront of toxicity testing outside the preclinical space. In attending the MPS World Summit and other conferences and webinars, it is increasingly clear that MPS developers and end-users would all benefit from clearly enumerated regulatory requirements describing what benchmarks must be met in order for MPS data to be accepted for particular use contexts. 

The mention of companies and products in this blog post is for information only.  No endorsement of such companies and product is implied. 

The views expressed do not necessarily reflect the official policy or position of Johns Hopkins University or Johns Hopkins Bloomberg School of Public Health.