Month: August 2025

By Jim Corbett, CEO, Emulate 

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Drug discovery is at a crossroads. With nearly 90% of clinical trial candidates failing to reach FDA approval, the need for more predictive, human-relevant models has never been greater. That’s why Emulate recently launched the AVA™ Emulation System, the first self-contained Organ-on-a-Chip workstation designed to bring scale, reproducibility, and accessibility to this transformative technology. As the company’s CEO, Jim Corbett brings a unique perspective on how AVA will accelerate adoption across pharma, biotech, and academia—and why it represents a turning point for human-relevant drug discovery. In this blog post, Jim shares how AVA was built to overcome longstanding barriers in the field and what its introduction means for the future of drug development. 

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Rethinking Preclinical Models 

The pharmaceutical industry faces a staggering challenge: nearly 90% of candidate drugs that enter clinical trials fail to gain FDA approval. Traditional reliance on animal models has proven insufficient for predicting human responses, leaving researchers searching for more accurate and efficient solutions. 

Organ-on-a-Chip technology offers a transformative alternative by modeling human biology with unprecedented fidelity. Yet for years, adoption was constrained by scale and cost. That’s where AVA comes in. Designed as the first self-contained Organ-on-a-Chip workstation, AVA integrates high-throughput microfluidic culture, full environmental control, and real-time imaging—all within a compact benchtop unit. Supporting up to 96 Organ-Chip Emulations in a single run, AVA delivers insights at a scale that makes Organ-Chips viable as a standard tool in preclinical workflows. 

Building Confidence Through Scale and Reproducibility 

For Organ-on-a-Chip technology to impact drug development meaningfully, the data must be both accurate and reproducible. AVA enables exactly that. By allowing large-scale experiments, it empowers scientists to generate robust datasets that validate predictive models for efficacy and safety. The result: researchers can make more confident decisions about which drug candidates to advance, reducing costly late-stage failures. 

From Liver-Chip to AVA: A Foundation of Regulatory Trust 

A landmark 2022 study in Communications Medicine demonstrated the predictive power of Emulate’s Liver-Chip in identifying drug-induced liver injury. That study not only paved the way for the Liver-Chip’s inclusion in FDA’s ISTAND program but also set the benchmark for AVA. 

Building on that foundation, AVA incorporates equivalency studies designed to show performance on par with or better than previous generations of Organ-Chip technology. By combining this proven biological fidelity with higher throughput, AVA strengthens regulatory confidence while accelerating the path to qualification as a recognized tool for drug development. 

Empowering Pharma to Capitalize on Regulatory Shifts 

Regulators are now explicitly encouraging the inclusion of New Approach Methodologies (NAMs) like Organ-Chips in IND submissions. With AVA, pharmaceutical companies can generate human-relevant data at the throughput and scale required for regulatory acceptance. 

Importantly, AVA also complements other NAMs—such as computational modeling and omics-based approaches—by providing organ-level validation. This synergy creates a weight-of-evidence approach that strengthens submissions and supports the global movement toward reducing animal testing. 

Making Human-Relevant Research Accessible to Academia 

While industry adoption is critical, academic research plays a pivotal role in innovation. Historically, cost has limited Organ-Chip use in academic settings. AVA changes this dynamic by reducing the cost per sample by more than 75%, making it feasible for academic labs and core facilities to run Organ-Chip experiments regularly. The result is broader access to human-relevant models that can shape early-stage discoveries and future therapies. 

Overcoming Persistent Barriers: Scale, Cost, and Workflow Efficiency 

High-throughput and reproducibility have long been bottlenecks in Organ-on-a-Chip research. AVA was designed to overcome these barriers by automating workflows, integrating imaging directly into the system, and enabling seamless compatibility with robotic liquid handlers. This means researchers can scale experiments without sacrificing quality or disturbing biological conditions, producing harmonized datasets suitable for regulatory and industrial pipelines. 

Shaping the Future of Drug Discovery 

Looking ahead, AVA has the potential to transform how pharma and biotech approach drug discovery. From helping companies like Moderna pre-screen lipid nanoparticles for safety, to accelerating early-stage research in academic labs, AVA is enabling more efficient, cost-effective, and human-relevant workflows. 

The convergence of regulatory change and technological innovation makes this moment especially pivotal. With the FDA and NIH shifting expectations toward human-relevant data, Organ-on-a-Chip technology—uniquely capable of recapitulating organ physiology—stands at the forefront of this new era. By delivering high-fidelity datasets that fuel both regulatory decision-making and AI-driven predictive models, AVA is not just advancing science—it’s redefining the standard for drug discovery. 

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Ready to future-proof your pipeline?

Explore our portfolio of sophisticated and user-friendly platforms that make it easy to get started with Organ-on-a-Chip technology.

Historical Roots of Mandated Animal Testing

Animal use in U.S. biomedical research has been both guided and constrained by laws that date back to the 1938 Food, Drug & Cosmetic Act, which effectively required animal data before human trials could begin. Yet almost as soon as that mandate was in place, pressure to curb its excesses arose. In 1959, British scientists William Russell and Rex Burch articulated the now-canonical “3 Rs” (Replace, Reduce, Refine) in The Principles of Humane Experimental Technique, giving regulators and ethicists a common language for alternatives¹.

Through the 1970s and 1980s, advocacy groups such as the Humane Society of the United States, the Physicians Committee for Responsible Medicine, and later PETA turned laboratory animal welfare into a mainstream public concern. Their campaigns helped secure passage of amendments to the U.S. Animal Welfare Act and spurred the first congressional hearings on alternatives to animal testing in drug development.

The scientific establishment followed. In 1997, eleven federal agencies formed the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), and Congress cemented its role with the ICCVAM Authorization Act of 2000. ICCVAM’s charter is explicit: accelerate regulatory acceptance of test methods that replace, reduce, or refine animal use without compromising safety or efficacy².

Momentum grew when the National Research Council’s 2007 report, “Toxicity Testing in the 21st Century,” urged a wholesale shift toward human-relevant, high-throughput assays and computational models³. That vision seeded collaborative programs like Tox21, an EPA-, NIH-, and FDA-backed effort that screens thousands of chemicals in robotics-driven, cell-based platforms instead of rodents⁴. Across the Atlantic, the European Union’s phased-in ban on animal-tested cosmetics—culminating in a full marketing ban in 2013—proved that large markets could operate under strict animal-free requirements without stalling innovation⁵.

Why This Marks an Inflection Point

Despite this steady drumbeat, U.S. federal drug-development rules remained largely unchanged—until recently. Over the past 3 years, and especially within the last twelve months, a cascade of legislative and agency actions has transformed decades of advocacy into concrete policy. What once felt aspirational is now operational: sponsors are no longer merely allowed to submit New Approach Methodologies (NAMs); they are increasingly expected to do so. That rapid acceleration marks 2024-2025 as an unmistakable inflection point: one in which scientific maturity, public pressure, and regulatory authority have finally aligned to make human-relevant models the new default for preclinical research.

Over the past three years, the United States has moved from discussion to implementation in modernizing drug-development rules that were once completely reliant on animal testing. Catalyzed by bipartisan legislation, agency-specific pilot programs such as FDA’s ISTAND program, and mounting scientific validation of New Approach Methodologies (NAMs) such as Organ-on-a-Chip technology, a clear through-line has emerged: regulators now expect—and increasingly require—human-relevant tools to inform safety and efficacy in preclinical research. Below is a chronological look at the key milestones, followed by a recap of how Emulate has helped drive and shape this historic shift.

Recent Timeline of Policy Milestones

December 2020 — FDA launches ISTAND Program

Recognizing the need to facilitate the approval of beneficial technologies for drug development that fall outside the scope of existing Drug Development Tool (DDT) qualification programs, in late 2020, the FDA introduced the Innovative Science and Technology Approaches for New Drugs (ISTAND) Program. In their explanation of the ISTAND program, the FDA explicitly listed microphysiological systems such as Organ-Chips as an example technology that would qualify for entry into the program. Ultimately, technologies approved for a context of use through the ISTAND program can be included in IND and NDA applications “without needing FDA to reconsider and reconfirm its suitability.”⁶

December 29, 2022 — FDA Modernization Act 2.0 becomes law

Congress eliminated the Depression-era mandate that animal data be the default gateway to human trials, explicitly authorizing cell-based assays, microphysiological systems (MPS), and sophisticated computer models as equally valid evidence. The amending language accomplishing this was quite simple: the new act removed the phrase “preclinical tests (including tests on animals)” from the original law, and replaced it with “nonclinical tests”. Nonclinical test were further defined as “…a test conducted in vitro, in silico, or in chemico, or a non-human in vivo test that occurs before or during the clinical trial phase of the investigation of the safety and effectiveness of a drug, and may include animal tests, or non-animal or human biology-based test methods, such as cell-based assays, microphysiological systems, or bioprinted or computer models.”

While the changes to the original law were simple, their effects were profound. The statute not only empowers sponsors to use NAMs, it also instructs FDA reviewers to consider them on their scientific merits^7,8.

February 6, 2024 — FDA Modernization Act 3.0 introduced

Building on the 2022 breakthrough, the 3.0 bill directs the FDA to create a formal pathway for the qualification, review, and routine acceptance of non-animal methods. If enacted, it would put the agency on a clock to translate legal authority into day-to-day regulatory practice, closing any remaining gaps that slow the adoption of NAMs⁹.

September 24, 2024 — First Organ-on-a-Chip admitted to FDA’s ISTAND Pilot Program

FDA’s ISTAND initiative, created to qualify novel Drug Development Tools, accepted the first Organ-on-a-Chip submission: a liver MPS designed to predict drug-induced liver injury (DILI). This seminal acceptance signaled that complex microfluidic models can progress through the same evidentiary pipeline as traditional models¹⁰.

April 10, 2025 — FDA announces phased elimination of routine animal testing & releases Roadmap

In a pair of same-day actions, the agency published:

1. A policy plan to “reduce, refine, and ultimately replace” animal studies, prioritizing MPS data and AI-driven toxicity modeling in Investigational New Drug (IND) submissions.
2. A detailed Roadmap that lays out short-, mid-, and long-term steps—validation standards, cross-agency collaborations, and pilot incentives—to mainstream NAMs across all Centers.
   Taken together, the documents move the conversation from permission to expectation, stating that animal use should become “the exception rather than the rule.”^11,12

April 29, 2025 — NIH shifts funding priorities toward human-based technologies

America’s largest source of funding for biomedical research launched an initiative to prioritize grant applications that incorporate Organ-Chips, organoids, or computational models—an early indication that future paylines will reward researchers who leave “animal-only” study designs behind¹³.

May 29, 2025 — U.S. Navy ends cat and dog experiments

The Department of the Navy formally stopped all biomedical research on companion animals, citing the availability of advanced human-based platforms and ethical stewardship of federal resources. Although limited in scope, the decision adds military pressure to the broader federal trend away from animal models¹⁴.

July 7, 2025 — NIH bars funding for animal-only studies

Just nine weeks after its technology push, the NIH announced that proposals relying exclusively on animal data will no longer be eligible for agency support. Investigators must integrate at least one validated human-relevant method, accelerating the scientific community’s pivot toward NAMs¹⁵.

Emulate’s Contributions to the Sea Change

1. Giving NAMs a Voice on Capitol Hill
Before Congress voted on the FDA Modernization Act 2.0, Emulate submitted formal testimony underscoring how Organ-on-a-Chip technology can improve translational accuracy while reducing animal use. The company’s perspective helped lawmakers grasp the real-world readiness of NAMs and the economic upside of faster, failure-proof pipelines¹⁶.

2. Generating the Evidence Base
In the largest head-to-head study of its kind, Emulate’s peer-reviewed Nature publication demonstrated that the human Liver-Chip S1 outperforms animal models for predicting DILI, showing 87% sensitivity and 100% specificity for a set of hepatotoxic drugs that animal models had deemed safe. Those data have since been cited by regulators and pharma R&D teams alike as proof that chips can surpass conventional in vivo benchmarks^17,18.

3. Achieving the First-Ever ISTAND Acceptance
The Emulate Liver-Chip S1 became the first Organ-Chip welcomed into FDA’s ISTAND Program—setting a procedural precedent for all future MPS tools. Emulate’s submission not only opened the door for chip qualification; it provided the cross-disciplinary dossier that FDA reviewers will use as a template^19,20.

4. Being the Only Organ-Chip Manufacturer Cited in FDA’s Roadmap
When FDA mapped its strategy to cut animal testing, it highlighted Organ-Chips—specifically referencing Emulate’s platforms—as validated NAMs ready for wider deployment. That acknowledgment elevated the technology from promising to actionable in the eyes of regulators, funders, and biopharma stakeholders^21,22.

5. Convening Thought Leaders Around the New Rules
Shortly after the Roadmap’s release, Emulate hosted a fireside chat with FDA Senior Advisor Dr. Tracy Beth Høeg, Wyss Institute founder Dr. Don Ingber, and Moderna scientist Dr. Samantha Atkins to unpack what the policy means for sponsors. The session offered pragmatic guidance on designing IND packages that lean heavily on human-relevant data—effectively turning policy into a playbook^23,24.

Looking Ahead

From Congress to the lab bench, momentum now aligns toward a future where Organ-on-a-Chip technology, advanced in silico models, and other NAMs form the backbone of drug safety assessment. Through our early advocacy, scientific rigor, and collaborative posture, Emulate is proud to have played a role in shifting the regulatory tides. As agencies implement their roadmaps and funders enforce new criteria, technologies that accurately recapitulate human biology will become indispensable. The era of relying on animal proxies is closing; what follows is a more predictive, ethical, and efficient research ecosystem—one that Emulate is excited to be a part of!

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Ready to future-proof your pipeline?

Explore our portfolio of sophisticated and user-friendly platforms that make it easy to get started with Organ-on-a-Chip technology.