• New PhysioMimix in silico tools unlock deeper functional insights from existing assays, advancing translation of MPS data to predict human ADME behavior
• End-to-end support from experimental design to data interpretation

These capabilities have been developed to enhance Absorption, Distribution, Metabolism and Excretion (ADME) profiling, for accelerated drug discovery and development workflows.

This launch represents the Company’s new in silico tools available to customers and is designed to enhance data generation from its range of predictive in vitro tools – unlocking deeper insights into key ADME parameters, including human bioavailability, and enabling more confident in vitro to in vivo extrapolation (IVIVE).

CN Bio’s computational tools combine the insights gained from microphysiological system (MPS) assays with powerful mathematical models. These tools complement the Company’s existing bioavailability assay based on its proprietary dual-organ Gut/Liver model, available via the CRS or as an off-the-shelf kit. The derived data is fully compatible with physiologically-based pharmacokinetic (PBPK) frameworks and can be used to extract additional data from preclinical studies, providing functional predictions of how compounds interact with human biology.

By working with CN Bio’s CRS team, customers gain access to broad support and expertise from both MPS and computational modelling specialists. The team collaborates closely with customers throughout the process, from ensuring robust study design to translating experimental data into meaningful ADME predictions. Raw data generated from projects is also translated into an easy-to-interpret format, suitable for supporting go/no go and drug dosing decisions.

Dr Yassen Abbas, Lead Scientist, CN Bio, said:

“This year, the FDA made significant changes to phase out animal testing requirements, signalling a clear shift towards the use of more relevant human approaches for preclinical safety and toxicity testing. We are providing the tools to ensure our customers stay ahead of these regulatory changes.” He added: “The launch of our Bioavailability assay last year was a major step towards improving understanding of the appropriate dose regimens for safe and effective new therapies. Now, by integrating advanced in silico modelling into our offering, we are enhancing this service to bridge the in vitro to in vivo translation gap for drug developers. By working with our expert CRS team, customers have access to dedicated support throughout the entire process.”

For more information on CN Bio’s ADME CRS portfolio, visit…

Historically, bioavailability estimates have relied heavily on animal studies, which are not only expensive but often fail to predict human in vivo outcomes accurately. Additionally, traditional approaches rely on isolated in vitro assays that also often fail to predict human drug absorption and metabolism accurately. This leads to costly late-stage failures with pharmacokinetics and bioavailability being the third most common cause of attrition (16% of failures) in Phase I clinical trials for compounds developed by major pharmaceutical companies (Waring et al 2015). Our blog explores how we are integrating in silico tools with Gut/Liver-on-a-chip to deliver more accurate bioavailability predictions that reduce our reliance on animal use.

The PhysioMimix^® advantage

At CN Bio, we’ve taken a novel approach to address these limitations by combining a primary human Gut/Liver microphysiological system (MPS, also known as Gut/Liver-on-a-chip) with advanced computational modeling. This integrated strategy bridges the gap between in vitro testing and in vivo outcomes, offering a more human-relevant alternative that:

• Improves prediction accuracy
• Reduces reliance on animal studies
• Delivers a more time- and cost-efficient process

Our PhysioMimix multi-organ Gut/Liver model uniquely allows for intestinal absorption and hepatic clearance to be studied in a single, interconnected system, unlike traditional approaches that assess these functions in isolation. This connectivity mimics human physiology and offers a holistic understanding of bioavailability.

A common concern researchers express is whether MPS platforms offer proven advantages over traditional models, and whether transitioning from familiar assays to organ-on-a-chip systems is too complex. This can be a daunting transition, but we are here to help you through it.

Our internal assay validation and adopter experiences have demonstrated that the PhysioMimix Bioavailability assay kit: Human 18 can be implemented without significant hurdles. The all-in-one Bioavailability assay kit contains everything you need to start running MPS experiments as a part of your pipeline in no time. However, we have noticed that certain questions around how to use the assay and its data consistently arise when corresponding with users.

Moreover, regulatory shifts are accelerating the adoption of New Approach Methodologies (NAMs) like the FDA Modernization Act 2.0. The recent announcement by the FDA on its decision to phase out animal testing requirements for monoclonal antibodies, with plans to extend these changes to other drug classes, is cementing MPS as a valuable approach in modern drug discovery pipelines.

Enhancing MPS with computational modeling

Integrating in silico tools with organ-on-a-chip workflows enhances the interpretation of our results and unlocks the ability to use MPS-derived parameters in downstream physiologically based pharmacokinetic (PBPK) modeling. The FDA has emphasized the growing importance of PBPK modeling in their roadmap to reduce animal testing in preclinical safety studies, highlighting the value of integrating experimental data with simulation tools.

Why mechanistic modelling matters

To facilitate the adoption of our advanced in vitro assays, we are developing, with a view to commercializing, computational models. Our computational models enable in silico simulation of experiments before they reach the wet lab. This predictive power allows us to optimize experimental design and refine dosing concentrations, sampling times, and other key variables, enabling our experimentalists to generate meaningful results more efficiently. Eliminating the guesswork in setting drug concentrations and time points for sampling, the PhysioMimix Bioavailability assay kit plus computational tools provides guidance at every step.

Our computational models, which are based on the mechanistic details underlying the Gut/Liver-MPS, allow us to extract meaningful ADME parameters from complex datasets, many of which would be difficult to quantify using traditional approaches. These can be used to better inform PBPK modeling, or in vitro to in vivo extrapolation (IVIVE).

From each replicate of an MPS experiment, we can now identify multiple pharmacokinetic parameters that would typically have required separate assays to determine. Mechanistic modeling also opens the door to deeper biological insights. It allows us to address critical questions like: “When does saturation occur?” or “At what concentration does the system show non-linear behavior?”.

By integrating in silico tools with organ-on-a-chip technology, we can answer these questions with greater precision at a fraction of the cost of the equivalent animal studies.

Integrating in silico tools with organ-on-a-chip: midazolam case study

In a peer-reviewed publication (Abbas et al., 2025), we demonstrate the workflow of using organ-on-a-chip data to determine pharmacokinetic parameters and the bioavailability of midazolam. From a single set of experiments, we were able to quantify the midazolam concentration over 72 hours. The data showed the compounds being absorbed, translocating the gut membrane and entering the liver compartment, where the liver metabolized most of the compound.

Following the acquisition of the experimental data, we developed mathematical models to describe the movement of midazolam throughout the MPS. This process allowed us to generate several feasible models with distinct assumptions, which were all fitted to the experimental dataset. Each model was then ranked according to a performance criterion and the best-performing model was chosen. Using Bayesian methods, we could determine the confidence intervals of key parameters such as intrinsic hepatic and gut clearance (CL_int,liver and CL_int,gut), apparent permeability (P_app) and efflux ratio (Er).

Using the output parameters from the model we were able to generate values for the components of bioavailability, F_a, F_g and F_h (the fraction absorbed, escaping the gut and liver metabolism, respectively) and, by finding the product of these three components, we estimated a value for oral bioavailability of midazolam. Our prediction fell within the observed range of clinical values.

Future outlook

Our method of estimating key ADME parameters allows for organ-on-a-chip experiments to be used in the pipeline of PBPK modeling, as the resulting parameters can be plugged into these more complex models to potentially inform first in human trials.

Conventional approaches to obtaining the necessary parameters for PBPK modeling can be time-consuming, inaccurate and expensive, especially when using animal models. Use of more relevant MPS-based experiments in conjunction with computational modeling offers a cheaper, more translatable method to elucidate important pharmacokinetic parameters of a drug. Further reducing animal studies in the process of lead optimization is another notable benefit of this method.

Our future work integrating in silico tools with organ-on-a-chip is dedicated to further validating the method to evidence the suitability of primary MPS-based assays for lead optimization and as a better alternative to historical methods.

Ready to Get Started?

It is no secret that there is hesitancy around adopting organ-on-a-chip technology into workflows due to experimental costs, relevant internal expertise to perform experiments and proof. However, with regulatory change on the horizon, the time is right to get started with your MPS journey. We have made the onboarding journey easier by developing an all-in-one kit that contains everything required to recreate our dual-organ MPS and bioavailability assay in your laboratory.

Additionally, we have developed and aim to commercialize the in silico tools described above. For now, you can access these tools by outsourcing to our ADME Contract Research Services. Our simulation software helps you to plan your MPS-based experiments, streamline your workflow and reduce experimental costs. The second tool provides an understanding of how to combine data generated using this fully human in vitro Gut/Liver model with in silico computational modeling to improve the quality of input parameters for PBPK modeling and more accurately estimate the in vivo pharmacokinetic parameters of orally administered drugs. A comprehensive overview of this workflow is published in Drug Metabolism and Disposition by Abbas et al., (2025).

How to rapidly integrate MPS into your workflow

There are a variety of options offered by CN Bio. If you are looking to modernize internal workflows, contact us for more information about our industry-proven PhysioMimix technology, plus Bioavailability assay kit: Human18. Alternatively, CN Bio also provides ADME Contract Research Services for experiments to be completed on our premises via our Team. These services can either be used to validate MPS for your specific context of use before investing in PhysioMimix technology in-house. Alternatively, you can outsource your project work to our team of experts to instantly benefit from MPS insights.

Related blogs and resources

Application notes

Connecting the gut and liver

News & Blogs

Evaluating Caco-2 cell’s gold-standard status in absorption, permeability and bioavailability Studies: Are Their Limitations Justified?

News & Blogs

How in vitro human Gut/Liver models increase confidence in ADME estimations before human trials 

Dr. Kleinstreuer emphasized that this shift reflects not only scientific advancement but a strategic and ethical imperative to modernize biomedical research. “True impact really requires a workforce trained in modern methods and data-driven decision-making to ensure that the most effective tools are prioritized,” she said. 

The NIH aims to establish a dedicated Office of Research Innovation, Validation, and Application (ORIVA) to support the integration of New Approach Methodologies (NAMs). This move builds on existing NIH efforts to scale technologies such as organoids, 3D bioprinting, AI-driven modeling, and microphysiological systems. 

“It’s not about shutting down animal labs overnight,” Dr. Kleinstreuer explained. “We’re creating the policy, infrastructure, and partnerships that make sustainable adoption possible.” 

NIH’s commitment marks a significant cultural and scientific shift toward more predictive, reproducible, and human-relevant research approaches—with the goal of transforming biomedical research from the ground up. 

This sentiment reflects the NIH’s formal press release on April 29th, citing their plans to reduce animal use in NIH-funded research, which landed just days after the FDA’s announcement on April 10th, citing their commitment to reduce animal testing in drug development.

“Ushering in a new era of innovation”, the NIH’s press release acknowledges that human-based research technologies “offer unique strengths that, when used correctly or in combination (with animals), can expand the toolbox for researchers to answer previously difficult or unanswerable biomedical research questions.”

The NIH plans to establish the Office of Research Innovation, Validation, and Application (ORIVA) to:

Coordinate efforts to develop, validate, and scale non-animal approaches across the agency
Serve as a hub for interagency coordination and regulatory translation for public health protection.
Expand funding and training in non-animal approaches and awareness of their value in translational success.
Expand infrastructure to make non-animal approaches more accessible to researchers.
Publicly report on research spending to measure progress toward reduced funding for animal studies and increased funding for human-based approaches.

View the full press release here: NIH to prioritize human-based research technologies | National Institutes of Health (NIH)

At CN Bio, we’ve spent over a decade developing and optimizing our PhysioMimix® OOC Systems and solutions, to better mimic human biology in the lab. These recent announcements affirm a transformative shift toward tools, such as OOC, which enable better predictivity and clinical translatability.

At the intersection of innovation, collaboration, and science lies an exciting new project led by the 3Rs Collaborative (3RsC) – and CN Bio is one of the collaborators. This effort brings together regulators, technology providers, end-users, and non-profits to advance the responsible use of microphysiological systems (MPS) in regulatory applications. 

In partnership with 3RsC, the FDA Center for Drug Evaluation and Research (CDER), 9 commercial providers, 1 end-user, NIH-NICEATM, and C-Path, we are embarking on a project to evaluate the use of Liver MPS to detect Drug-induced liver injury (DILI). Our goal is to assess variability across multiple platforms using the same experimental protocol, with the ultimate goal of enhancing confidence in the accuracy, reliability, and standardized characterization of these models. 

  Why this matters

This is more than a study. It’s a model for how different stakeholders such as regulators, developers, NIH and pharma end-users, can shape the future of drug development through the use of novel alternative methods. Our approach in this collaboration is focused on obtaining information that is human-relevant, data-rich, and aligned with the 3Rs. 

  What we’re doing

• Testing known hepatotoxicants & their controls across 9 unique, commercially available liver MPS platforms 
• Using real-world protocols to reflect what regulators might see in real submissions 
• Analyzing cross-platform data to inform best practices and future guidance 
• Submitting a collaborative letter of intent to FDA’s Innovative Science & Technology Approaches for New Drugs (ISTAND) program to qualify MPS for a specific context of use 

This is a first-of-its-kind, coordinated effort to harmonize innovation, good science while keeping regulatory considerations in mind—and it’s just the beginning. 

The future of science is collaborative

It highlights scientific rigor, innovation, and ethical considerations. And it’s already underway. 

Participating end-user:

Merck & Co, Inc. 

Participating model developers:

Axiom/LifeNet Health, BioIVT, CN Bio, DefiniGEN, InSphero, Lena Biosciences, Inc., PredictCan, TissUse, Xellar. 

Click the links to find out more about our Liver MPS (also known as Liver-on-a-chip), DILI assays powered by PhysioMimix technology and our cross-species DILI Contract Research Services.

CN Bio, a leading provider of Organ-on-a-chip (OOC) systems and solutions that accelerate drug discovery and development workflows, has introduced two new animal microphysiological system (MPS) models that enhance translatability in preclinical drug safety and toxicology assessments to its Contract Research Services (CRS).

Building upon the Company’s FDA-recognized drug induced liver injury (DILI) assay, the expanded offering enables rapid, comparative studies between commonly used animal and human models to flag interspecies differences early, and better informs in vivo study design.

Traditional human in vitro methods have limited capacity to accurately determine drug toxicity. Added to this, the discrepancies between these methods and in vivo animal studies make it challenging to accurately predict safety risks for humans during preclinical testing. Often, unsafe drug candidates are wrongly progressed, and potentially life-saving ones are misclassified and abandoned, ultimately impacting clinical progression. In response to growing market demand for tools that address these concerns, CN Bio has expanded the in vitro to in vivo extrapolation (IVIVE) capabilities of its established PhysioMimix^® DILI assay, adding the ability to easily compare results across human-, rat-, and dog-derived Liver-on-a-chip models. These assays offer a modernized workflow to generate predictive and actionable insights that mitigate the risk of costly, late-stage conflicting data, and reduce unnecessary animal use by providing early warning of hepatotoxicity/DILI prior to in vivo studies.

Accessible through the Company’s CRS, the new offering harnesses the longstanding expertise of CN Bio’s scientific team to provide detailed data analysis, optimized outcomes, and data-driven conclusions beyond what is achievable using existing in vitro models. The assay enables a broad range of longitudinal and endpoint testing for DILI-specific biomarkers from single- or repeat-dosing studies over a 14-day experimental window. This provides a more comprehensive overview of underlying mechanisms of hepatotoxicity or latent effects of drug candidates to improve IVIVE assessment and streamline clinical progression.

Dr Emily Richardson, Lead Scientist, Safety and Toxicology, CN Bio, said: “Understanding safety risks is critical to successful drug development, however, fundamental physiological and biological differences between species can lead to inaccuracies in predictions, often causing drug candidates to be wrongfully abandoned as toxic, or worse, mistakenly classified as safe.” She added: “Having established our DILI assay as an industry leading option to garner more valuable insights across the development pipeline, we were in an ideal position to expand its capabilities and address this crucial gap in understanding hepatotoxicity using the most commonly used animal models. Partnering with us to utilize this powerful service not only ensures robust and reliable results but also provides access to a team of Organ-on-a-chip experts, who are invested in your success; to de-risk your pipeline and move it forward with confidence.”

Learn more about our cross-species DILI services

CN Bio, a leading provider of Organ-on-a-chip (OOC) systems and solutions that accelerate drug discovery and development workflows, today announced a strategic partnership with SCINCO, a specialist scientific instrument company based in South Korea. The agreement is the latest milestone in CN Bio’s international expansion, amplifying the Company’s presence in major Asian and Pacific markets and broadening access to its predictive human organ models.

Pharmaceutical and biotech companies are recognizing the potential of non-animal, new approach methodologies (NAMs) to improve preclinical efficacy and safety data generation in drug discovery and development workflows, leading to reduced failure rates of new drug candidates. In this pioneering field, the market is rapidly evolving in line with breaking regulatory developments, most recently the FDA announcing a shift toward human-relevant methods for drug development, replacing animal testing in the evaluation of monoclonal antibody therapies and other drugs¹.

Central to the Company’s ongoing growth strategy, CN Bio is establishing regional supply networks through specialist distribution partners to address growing demand for its FDA-recognized PhysioMimix^® OOC System and solutions. With the surge in South Korea’s biotech sector, driven by a series of billion-dollar licensing deals in early 2025 and the announcement of a new fund to support high-tech industries, the agreement with SCINCO uniquely positions CN Bio to support and expand operations in this high growth market. The partnership complements the Company’s wider network in the APAC region, including recently appointed Japanese distributor, Primetech².

CN Bio’s industry-leading benchtop PhysioMimix OOC range accurately mimics human physiology in the lab. Using advanced in vitro human organ models, these systems enable more accurate predictions of human drug responses to support the development of novel therapeutics with increased efficiency, whilst relieving the dependence on animal studies. These models provide insights into crucial aspects of preclinical drug development, including drug bioavailability, toxicology and disease modelling, providing information on how drugs will perform in patients and reduce the risk of costly late-stage failures in the clinic.

Soo Min Choi, Director, SCINCO: “Our dual-approach covering in-house development and the distribution of high-quality equipment from international manufacturers ensures we offer a comprehensive range of solutions to meet the diverse needs of all researchers, while leveraging unique insights to understand the scientific business landscape.” He added: “The global NAM market is growing at a rapid pace and to maintain the increased momentum across our industry, we believe adoption of these tools will become essential. We’re excited to be a part of the movement to bring CN Bio’s next-generation OOC solutions to the South Korean market.

Dr Paul Brooks, CEO, CN Bio: “Recent regulatory updates from the FDA are fueling a rapidly growing, global interest in human-relevant alternatives in drug development. Recognizing this, we are progressing an ambitious growth strategy to respond to market demand and put in place essential sales and support channels to ensure we remain ahead of the curve in addressing customers’ research needs. Partnering with SCINCO is an exciting development, allowing us to draw upon the team’s unique insights into the scientific and business landscape in South Korea to provide a strong footing as we expand further in the APAC region.”

1. https://cn-bio.com/important-fda-announcement/
2. Press release (13 January, 2025): CN-Bio Partners with Primetech to Distribute OOC Solutions

In part one of the blog, we unpicked the reasons behind the FDA’s decision to focus on mAbs first, and steps to ensure that a NAM-based approach will offer the same degree of safety as animals before their use is phased out.

If you missed it, read Part one “Why has the FDA loosened its grip on animal testing for mAbs?” here.

In “Microphysiological systems for mAbs”, we continue the commentary by taking a deeper dive into the PhysioMimix^® OOC range of microphysiological systems, also known as organ-on-a-chip (OOC). We explore how microphysiological systems address the shortcomings of animal models for mAb development and the role that CN Bio is taking to support your switch to a NAMs-based approach.

Use of microphysiological systems for mAbs to address animal shortcomings during development

At CN Bio, we have developed, characterized, validated and commercialized many PhysioMimix organ models and assays that have been successfully adopted by 16 of the top 20 Pharma. They can be used to test a range of drug modalities across disease modeling, safety toxicology and ADME applications, and are supported by “all-in-one” reagent kits to support rapid onboarding. Our customers have independently developed many more.

In their roadmap to reducing animal testing in preclinical safety studies, the FDA focuses much of their narrative on immune-related risk and how microphysiological systems can add a “crucial safety net that animal tests struggle to provide”. In principle, use of primary human cell-derived models avoids interspecies differences to reveal immune-related toxicological effects that are more relevant to humans; however, modeling the human immune system is challenging in all experimental setups – not just animals.

There is no doubt that microphysiological systems with closed-loop microfluidic designs, which re-circulate media around cultures are best equipped for mAb immunogenicity testing. Our PhysioMimix Liver-on-a-chip, (also known as a Liver microphysiological system/Liver MPS) is the furthest advanced in terms of immunocompetency. A key customer has already reported the initial characterization of a fully immunocompetent drug-induced liver injury (DILI) model – including circulating peripheral immune cells alongside the liver microtissues – at the Society of Toxicology conference, demonstrating that the basic design of PhysioMimix technology is on point. The development of these fully immunocompetent microphysiological systems for mAbs development is on the horizon. With the ability to report inflammatory responses and resulting organ damage to drugs, they will be game changers!

From immediate effect, companies that include NAMs-based data into therapeutic submissions to the FDA will be rewarded, for example, toxicology studies using animal and NAMs methods which show no concerning signals in one month can be reduced from six months to three months. Through close collaboration and joint expertise, we are confident in our ability to supply effective microphyiological system-based assays required for these tests, so that you can benefit from the regulatory relief promised by the FDA.

CN Bio’s closely forged links to primary human cell suppliers, including LifeNet Health, position us well to address current market challenges surrounding immunogenicity testing, such as HLA donor matching of all primary cell types required. Plus, our latest collaboration deal with CRO giant Pharmaron provides us with a greater potential to meet market needs for microphysiological systems for mAbs testing more rapidly.

Immune-mediated liver injury associated with mAbs

There are four types of immune-mediated injuries associated with monoclonal antibodies:

Idiosyncratic Reactions

These are unpredictable and often not dose-related, meaning patients may develop DILI even at low drug doses.  

Autoimmune Hepatitis

mAbs can trigger an immune response that damages the liver. 

Other Immune-Mediated Injury

The primary effect of the mAb can trigger an immune or non-immune response that results in liver injury. 

Viral Reactivation

Immunosuppressive mAbs can reactivate latent viral infections, like HBV, which can cause liver damage. 

Use of concomitant medications, like aminosalicylates or methotrexate, can also increase the risk of DILI when used with mAbs, as does the presence of underlying liver disease and genetic predisposition. How can the use of microphysiological systems for mAbs testing reduce the risk?

Liver MPS’ potential to detect immune-mediated liver injury

Human Liver MPS (co-cultures of hepatocytes with non-parenchymal cells under perfusion) have human liver metabolic competency and recapitulate human-specific responses.  Our PhysioMimix Liver MPS has been extensively validated for predicting the DILI effects of small molecules, whilst proof of concept work evaluating their use for therapeutic antibody/small molecule drug-drug interaction responses, and the testing of newer, more human-specific drug modalities (where animal use is less suited) has also been demonstrated. Visit our DILI application page for more info.

A recent CN Bio blog, “Immune-mediated DILI – Predicting the unpredictable!, explores the additional benefits of a fully immunocompetent Liver MPS, where peripheral immune cells are incorporated into the system’s fluidic flow to circulate around liver microtissues. Assays utilizing these models facilitate the detection of cytokine release, T-cell activation, or other immunotoxicity, such as hepatocyte damage via clinical liver function test (LFT) markers. They enable effects that only manifest in human tissue to be detected, overcoming the limitations of animal tests. For more information, visit our immune-mediated liver injury webpage.

Although CN Bio’s fully immunocompetent assay is not yet widely available, the concept is verified, and the approach is built upon proven pedigree. A co-publication with the FDA’s CDER group concluded that data derived using PhysioMimix systems is appropriate for use in drug safety and metabolism applications, evidencing its enhanced performance versus standard techniques. It substantiated CN Bio’s position as a leader in the Organ-on-a-chip (OOC) field with reliable and robust cutting-edge technology, ready for widespread adoption across the pharmaceutical industry (Rubino et al., 2021).

Furthermore, healthy human models can also be induced to common liver diseases such as Metabolic dysfunction-associated steatohepatitis (MASH) to explore increased DILI susceptibility due to the presence of underlying disease. As our PhysioMimix MASH assay also has proven calibre, having supported Inipharm’s INI-822 for metabolic liver disease treatment now in clinical testing, you can rest assured that investing in PhysioMimix OOC microphysiological systems for mAbs development represents a safe future bet.

What role is CN Bio taking in supporting the transition away from animal testing?

CN Bio has been, and remains, actively involved in numerous consortia, groups, and networks that are driving change to facilitate broader adoption of microphysiological systems within our industry (see examples below). This includes direct and indirect work with agencies such as FNIH, ICCVAM, and C-PATH, which are working with the FDA to facilitate interagency coordination and accelerate the process by pooling expertise, data, and resources across the US government and other relevant agencies.

• CEN-CENNELEC – OOC working group  
• The Predictive Safety Testing Consortium (C-PATH) – Qualification workshops 
• FNIH VQN (validation qualification network) – Complement-AIRE programme 
• 3RsC MPS Working Group  & 3RsC-FDA DILI Project to build confidence in Liver MPS for DILI and regulatory applications.
• NICEATM (National Toxicology Program Interagency Centre for Evaluation of Alternative Toxicological Methods) ICCVAM (Interagency Coordinating Committee on the Validation of Alternative Methods) 
• NC3Rs NAMs network 
• CAMs (Cambridge Alliance on Medicines) network 

But ultimately, our success in supporting the transition away from animal testing towards more predictive and cost-effective workflows is entrenched in our customers’ success, and we will never lose sight of that fact! We offer exemplary customer support irrespective of whether customers choose to adopt CN Bio’s validated models and assays or wish to develop their own novel approaches using our platform.

We are proud of our product portfolio’s ability to rapidly and easily onboard customers with a microphysiological system-based approach and are committed to broadening its scope through future model, assay and kit development via our internal R&D efforts and strategic partnerships. Through our inclusion in regulatory and standardization agencies and resultant projects, we will continue to innovate and validate models for applications most urgently needed in the drug discovery/development pipeline.

So, what are you waiting for?

Like the FDA, we believe that integrating more predictive NAMs methods into early decision-making will enable companies like yours to begin the process of reducing non-clinical animal use costs (up to $7.2M in NHP savings alone for mAb development) and be better positioned to make more informed go/no go decisions regarding which therapeutics to advance.

We are here to support your journey so that you can benefit from cost and time savings benefits earlier! So that leaves us with a question. Are you ready to make the change and adopt microphysiologcal systems for mAbs development? Contact us here to get started.

Infographic

Top tips for integrating organ-on-a-chip technology into your workflow

Keep a lookout for part three in this blog series exploring the new era of drug development. Coming soon.

Associated with their announcement was a 5-year roadmap outlining their plan to reduce animal studies from the norm to exceptions in the standard drug development process.

This historic and pivotal moment also included much-anticipated regulatory guidance and incentives for using data from New Approach Methodologies (NAMs), including Microphysiological Systems (MPS) and in silico approaches, for regulatory applications with immediate effect.  

Why has the FDA loosened its grip on animal testing for mAbs?

Several key factors behind the FDA animal testing phase-out for monoclonal antibodies (mAbs) are cited as reasons behind this decision including:

Advancing Public Health

Improve drug safety and accelerate the evaluation process by using more effective, human-relevant methods 

Reducing Animal Experimentation

Due to their limitations in accurately modeling human health and disease and their predictivity for whether a drug may be safe or effective in humans.

Cost Efficiency

Leveraging AI-based computational models and lab-grown human organ-on-a-chip/ organoids, to reduce R&D costs and lower drug prices 

Ethical Considerations

The shift aligns with broader ethical concerns about animal testing and promotes more humane testing methods 

In this first blog in a series of three, we explore highlights from the FDA’s roadmap and why mAbs were chosen as the starting point. We dig into the topic of NAMs and plans to ensure that they offer the same degree of safety as animals before focusing down on the important role of predictive human MPS in the successful outcome of this process.

What does the FDA animal testing phase-out for monoclonal antibodies (and other drugs) roadmap look like?

There’s no doubt that the FDA’s implementation roadmap for reducing toxicity testing in animals in favor of a NAMs-based approach is ambitiously proactive. Their roadmap plans are outlined in a document released alongside the press release, which can be read in full here, however the short- and long- term highlights are summarized below.

Short-term (1-3 year) priorities

Leveraging existing international data, encouraging NAM IND data submissions in parallel with animal data, developing an international open-access data repository of toxicology data from animals and humans, reducing timelines for primate mAb and other drug toxicity testing, and tracking quantifiable changes.

Long-term (3-5 year) efforts

Aim to make animal studies the exception rather than the norm by switching to a “NAM-based default” for pre-clinical safety & toxicity testing.

Despite the initial shock regarding the boldness of the FDA’s decision, when you investigate the detail, their initial focus on monoclonal antibodies represents a cautious first step. mAbs are relatively safe and well-tolerated by humans. But they (and any other new human-specific drug modalities) pose development challenges due to inter-species differences that render the use of animals less suited or even unsuited for their testing. This can result in adverse effects being discovered in the clinic, or during post-approval marketing. But there’s more than just safety concerns behind their decision.

Why did the FDA choose to focus on phasing out animal use for mAbs first?

Monoclonal antibodies specifically target molecules and cells in the body, making them highly effective for treating a plethora of diseases. They are well-characterized and have a long half-life, meaning they can provide sustained therapy over extended periods. And importantly, compared to traditional therapeutics, generally have fewer side effects due to their specificity. For reasons such as these, the mAbs clinical pipeline represents the largest of all new modality classes, with 2,700 mAbs in clinical trials as treatments for a wide variety of diseases according to a 2024 report from BCG.

Although mAbs have a relatively good safety profile, the FDA specifically calls out reasons why mAbs represent a promising area for reducing preclinical animal use in their roadmap. These include the shortcomings of animal models, which render testing workflows vulnerable, plus practical considerations centered around “skyrocketed” costs, as quoted below.

Immunogenicity & interspecies differences

“Animals often mount immune responses to human mAbs, which can alter exposure and confound toxicity interpretation. However, animal immunogenicity is not predictive of human immunogenicity due to interspecies differences in immune systems. In addition to inherent biological differences, stress of laboratory life and use in research can impact immune function, inflammatory responses, metabolism, and disease susceptibility and progression.

Moreover, some safety risks may go undetected in animals – a notable example is the mAb TGN1412, which caused a life-threatening cytokine release syndrome in human volunteers despite appearing safe in preclinical monkey studies. That tragedy highlighted the limitations of animal models for certain immune-activating mAbs and spurred efforts to develop in vitro assays to better predict human-specific responses”.

Practical challenges

“The cost of drug development can vary by therapeutic class, with a market report noting the cost to develop a mAb at $650-$750 million and taking up to 9 years. Typical mAb development programs typically use 144 non-human primates (NHPs). In recent years, costs of NHPs have skyrocketed, up to $50,000 per NHP. The time and cost of long-term animal studies slow down delivery of new therapies to patients.”

This is where it gets interesting, by forcing the hand to “plug” this weakness – alongside animals initially – testing workflows can be made even safer than today!

Before animals are fully replaced, the FDA plan also allows time for lessons to be learnt, gaps to be identified and NAMs to become further developed, validated and entrenched into workflows. Plus, the FDA acknowledges the importance of updating international guidelines so that companies do not face different rules in different regions to alleviate adoption barriers.

This approach also begins the important process of reducing both the cost, and the time required to bring novel mAb therapeutics to patients to lower the price of drugs, whist also preparing workflows for the inclusion of additional drug types going forward.

What are NAMs and how do we ensure that they deliver the same degree of drug safety as animals?

In their roadmap, the FDA provides an overview of key NAM categories and their applicability to drug development. There are many definitions for NAMs but the FDA refers to them as:

“tools to assess safety, efficacy, and pharmacology of drugs and therapeutics without traditional animal models. NAMs include in vitro human-based systems such as organs-on-chips, “in silico”, or computer-based modeling, as well as other innovative platforms that can collectively evaluate immunogenicity, toxicity, and pharmacodynamics with high relevance to human biology. The FDA and the broader scientific community recognize NAMs as a means to obtain faster and more accurate human risk assessments while reducing animal use”.

The FDA acknowledges that the transition to a NAMS-based approach will require careful planning, robust science, and collaboration. It lists specific actions that the FDA is considering for validating and integrating NAMS safely into their regulatory process.

They also recognize that, while computational models can be used to predict human-relevant outcomes, in vitro test systems will be needed to confirm and improve predictions. Amongst the in vitro-derived systems cited by the FDA are organoids and microphysiological systems (MPS), often called organ-on-a-chip (OOC).

MPS can be thought of as next-generation organoids because they more accurately recapitulate human organs. The differences between organoids and MPS are explored in more detail in our blog “Taking organoids to the next level”, however, the most important differentiators are the incorporation of microfluidic flow, mechanical forces, and multi-cell primary human co-cultures on a bioengineered chip to recapitulate the in vivo environment.

Compared to self-assembling organoids cultured in static conditions, MPS deliver higher functioning microtissues that deliver greater assay sensitivity, the reporting of clinically relevant biomarkers for enhanced in vitro to in vivo extrapolation (IVIVE), plus prolonged culture longevity (for up to a month using PhysioMimix^® OOC solutions) to facilitate repeat-dosing studies in vitro. Furthermore, they can be interconnected to form multi-organ networks that simulate pharmacodynamic effects systemically, human processes such as drug absorption and metabolism, or used to understand interactions between organs, such as inflammation, which drive disease and cause unexpected toxicities.

Many of the organ systems affected by mAbs are available, including liver, heart, lung and kidney. However, despite these technological advances, certain scientific challenges are yet to be overcome before animal tests can be fully replaced. For example, in vitro or in silico models are not able to represent a complete biological system, and further advances are required in the field to recreate the full complement of the human immune system.

Despite these challenges, it is important to acknowledge that, although animal use is a current mainstay of drug development, when first utilized they were never fully validated before being adopted. By comparison, the ongoing validation of non-animal methods, including MPS, for predicting human drug responses is highly rigorous. It is also a well-understood fact that, for certain read-outs, animal responses are no better than the toss of a coin on whether a drug may be safe or effective in humans. Frequently, different answers will be reported by different species, which makes the final assessment of drug safety difficult. In addition to safety concerns, this lack of clarity also causes safe human therapeutics to be unnecessarily dropped from the pipeline out of caution.

In our extensive experience, MPS-based PhysioMimix assays are more predictive of human responses than animal tests (see example publications and application notes for more info).  Our findings are echoed by the FDA’s CDER group who concluded that data derived using PhysioMimix is appropriate for use in drug safety and metabolism applications, evidencing its enhanced performance versus standard techniques. Their publication (Rubino et al., 2021) substantiates CN Bio’s position as a leader in the field with reliable and robust cutting-edge technology, ready for widespread adoption across the pharmaceutical industry.

To provide further confidence in the human predictivity of MPS models, we are also developing animal equivalent MPS models/assays. They enable developers to recreate in vivo outcomes in vitro alongside human assays to prevent good assets from being abandoned. However, rather than just using these to troubleshoot, our future vision for MPS-based cross-species assays is for upstream lead optimization to reduce unnecessary in vivo animal use.

Despite the positive outcomes of our MPS validation tests using “fallen angels” it is also imperative to remember that, like animals, no one NAMs method will be 100% accurate or applicable for every question, especially given the fact that no human is identical. Therefore, we believe it is important to adopt a broad range of NAMs to predict human behavior. The skill to acquire here is determining which combination of alternative approaches should be used in combination to determine a drug’s safety. At CN Bio we will continue to explore and demonstrate the advantages of combining MPS plus in silico tools ourselves, with further announcements planned later this year.

Concluding thoughts

So, as we wrap up this first (of three) blog post FDA announcement, three things are certain. Firstly, it is well known fact that drug development failures are due to lack of efficacy or unexpected safety issues that were not evident in standard in vitro or animal tests. Secondly, the largest global regulator has sent a clear message regarding their plans to phase out animal testing to save significant costs (up to $7.2M for NHP use alone/mAb) and reduce development cycle times. Thirdly, the FDA’s timeline to modernize drug development workflows is short.

The key way for pharmaceutical companies to enhance the human predictivity of workflows and keep pace with these changes is to invest in several NAM approaches. By becoming familiar with the types of data they generate and understanding where their limitations lie, you can decide which combinations of NAMs-based tests are required to fully investigate the safety and efficacy of a new drug entity.

So, having explored the FDA animal testing phase-out for monoclonal antibodies (and other drugs) roadmap, and what is being done to ensure that the collective use of NAMs offer the same degree of safety as animals before their use is reduced and replaced – are you ready to get started now and incorporate OOC/MPS into your workflows to avoid being left behind?

Contact us here, to find out how we can support your journey with PhysioMimix so that you can reap the cost and time-saving benefits earlier.

Infographic

Top tips for integrating organ-on-a-chip technology into your workflow

In part two of this blog series, we take a deeper dive into how MPS address the shortcomings of animal models for mAbs development and the role that CN Bio is taking to support the switch to a NAMs-based approach. Continue reading here.

Cambridge, UK, 24 April 2025: CN Bio, a leading provider of Organ-on-a-chip systems and solutions that accelerate drug discovery and development workflows, today announced the establishment of a strategic partnership with Pharmaron, a premier R&D service provider for the life sciences industry. Under the agreement, Pharmaron will validate CN Bio’s PhysioMimix^® technology across existing applications and collaborate on integrating OOC technologies into its R&D platform. The partnership will also explore the development of new applications to address unmet needs in drug discovery and development.

The initial phase of the collaboration will focus on validating CN Bio’s PhysioMimix technology for current applications in disease modelling, toxicity testing and absorption, distribution, metabolism and excretion (ADME) studies. Following successful validation, the companies will work together to adopt the platform in priority R&D areas and co-develop novel applications to expand the capabilities of OOC technologies.

Pharmaron is a global drug R&D service platform, providing end-to-end services across drug discovery, preclinical, and clinical development. Through the partnership, CN Bio will install PhysioMimix instruments at Pharmaron’s facilities across the globe, enabling the joint development of cutting-edge OOC solutions tailored to evolving R&D challenges.

Dr Paul Brooks, CEO, CN Bio, said:

“Pharmaron is a global, premier and trusted service provider for the life sciences industry. As such, Pharmaron were the ideal partner for CN Bio as we look to accelerate the growth of our OOC solutions portfolio in new and existing application areas. By working closely together and leveraging the industry-leading expertise of each company, we can share resources that enable us to progress new, innovative solutions from concept to global market deployment more effectively than ever before.

Dr Tomasz Kostrzewski, CSO, CN Bio, commented:

“The developments this partnership will enable are especially important given the recent FDA announcement, outlining their plan to phase out animal testing requirement for monoclonal antibodies and other drugs with more human-relevant models. Our platform is best placed to serve current market gaps including testing for immune-mediated organ damage. Together we can expedite this key development in line with global momentum for more ethical advancements that reduce costs and improve human health.”

Dr Hua Yang, CSO, Pharmaron, added:

“We are committed to continuous innovation that enhances the quality of our services and accelerates drug discovery and development. Organ-on-a-chip technology holds significant potential to advance translational science by improving our understanding of drugability at the preclinical stage. We are pleased to collaborate with CN Bio to explore how this technology can add meaningful value to our partners’ development programs.”

In the press release, the FDA cites their promotion of lab-grown human organoids, or organ-on-a-chip systems, to test drug safety because these models can reveal toxic effects that could remain undetected in animals, providing “a more direct window into human responses”

Read the press release to learn more about the key benefits of replacing animal testing in monoclonal antibody safety evaluation with human-based lab models and advanced computer simulations, including:

• The FDA’s roadmap for implementation
• Regulatory incentives to encourage investment in modernized testing platforms
• Long-term proposal (3-5 years) to make animal studies the exception rather than the norm by switching to a “NAM-based default” for pre-clinical safety/toxicology testing

“The recent announcement from the FDA is really a watershed moment for the biopharma industry, with a clear call to action for drug developers to move away from traditional animal safety testing and replace them with human-relevant methods such as organ-on-a-chip.

This change will really accelerate the adoption of organ-on-a-chip (OOC) and other new alternative human methods by drug developers, ultimately leading to faster drug development, reduced R&D costs and more cost-effective medicines for patients.

It is humbling to see the many years of hard work by the CN Bio team and our partners being recognised by the announcement and the roadmap laid out by the FDA leadership.” Dr Tomasz Kostrzewski. CSO, CN Bio

Visit our Immune-mediated liver injury application page for more information about how PhysioMimix_^® OOC assays support the safety profiling of mAbs and your response to the FDA’s roadmap.

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