The US Food and Drug Administration’s (FDA) decision to phase out mandatory animal testing is widely hailed as a historic turning point for pharmaceutical research. To understand what this means in practice, Discover Pharma spoke to Patrick Smith, senior vice president of translational sciences at Certara, a leader in model-informed drug development and biosimulation.

Smith discusses how the FDA’s move accelerates adoption of New Approach Methodologies (NAMs), the growing role of computational modeling in early-stage drug development, common misconceptions about non-animal strategies, and how Certara is preparing to support companies through this transition.

The FDA’s decision to phase out mandatory animal testing is being called historic. From your perspective, how significant is this move for the pharmaceutical industry?

While the 3Rs (reduce, replace, refine) of animal testing have been a goal for decades, the FDA’s decision nevertheless marks what may be a pivotal moment for the modernization of drug development. From a historical context, it often takes a push from regulatory agencies to drive meaningful changes and adoption of new approaches. This move by the FDA encourages and incentivizes the pharmaceutical industry to embrace New Approach Methodologies (NAMs), such as in silico modeling. To stay competitive, they’ll have no choice but to adapt to the new roadmap and modernize their clinical research processes.

What role can model-informed drug development play in de-risking early-stage programs previously reliant on animal data?

Model-informed drug development (MIDD) uses in vitro, preclinical, and clinical data to build mathematical models of how drugs act in the body. Having such a model becomes an enormously valuable tool to help inform decision-making. It allows for the simulation of clinical trials to predict how drugs will perform from both a safety and efficacy perspective. It helps determine which drugs are worth moving into the next phase of development and informs how clinical trials are optimally designed without the need for costly and time-consuming animal research. The more information and data available, the better a model performs, resulting in better decisions. MIDD provides that intel, de-risking drug programs for developers and potential investors. At Certara, in addition to major pharmaceutical companies, we work with venture capitalists (VCs) and early-stage biotechs to pressure test drug attributes and provide data on the value of their assets. This helps VCs decide which programs to invest in, and how to de-risk those investments through modeling and biosimulation.

Certara has long advocated for biosimulation — what types of modeling techniques do you see gaining the most traction as alternatives to in vivo studies?

Quantitative Systems Pharmacology (QSP) and physiologically based pharmacokinetic (PBPK) models enable mechanistic simulation of human and preclinical PK, pharmacodynamics (PD), drug-drug interactions, toxicity, and anti-drug antibody (ADA) responses in humans. They integrate physiological, biochemical, and molecular data to simulate how a drug will impact the body and diseases, predicting drug behaviors, drug-drug interactions, first-in-human dosing, and more. These findings support species translation, optimize study design, and significantly reduce reliance on animal testing in line with evolving regulatory guidance. For a long time, these modeling techniques have been essential for translating animal results into humans. Going forward, they will be even more essential to translate the results from NAM methods, such as organ on a chip, to humans.

What are the biggest misconceptions pharma and biotech companies may have when transitioning to a non-animal testing strategy?

The primary concern for developers is that regulatory agencies won’t accept results from NAMs as animal testing has been the standard for decades. In such a high-stakes industry with millions on the line, they are hesitant to deviate from the way things have been done historically. However, 90% of new drugs do not make it from Phase 1 to approval – a clear indicator that our current drug development process isn’t working, and something has to change. The perception that regulators do not support NAMs is outdated. For example, regulators themselves already leverage PBPK models to independently review and verify drug label claims.

Another key misconception is that animal testing is better at assessing safety and efficacy than computational models and/or NAM approaches. Although fully embracing and trusting new technologies can cause hesitation for some in pharma and biotech, the truth is that these models have been developed over decades and are informed by a plethora of historical data and research.

How does this shift impact clinical timelines or R&D costs for companies who are early adopters of these tools?

Biosimulation and modeling yield significant time and cost savings during the drug development and clinical research process, especially when brought into the fold early. Eliminating or reducing animal testing also cuts costs, saves time, and avoids supply chain limitations (such as scarce non-human primates). A recent study from Pfizer found the use of MIDD saved on average 10 months of cycle time and $5 million per program.

How is Certara preparing to support clients in meeting evolving regulatory standards that no longer require animal data?

At Certara, we recently announced the launch of Non-Animal Navigator (NAN), a new solution designed specifically to help biopharma companies in the transition away from animal testing. Certara’s drug development and regulatory experts, along with the modeling experts, work with clients to identify a NAM strategy for development programs and assist in approaching and gaining alignment with FDA prior to execution.

Certara’s NAN program provides toxicology options as well as AI-enabled biosimulation options for developers of monoclonal antibodies and antibody-drug conjugates (ADCs) to predict human outcomes requiring the minimal amount of animal studies. NAN’s core capabilities include virtual trials, QSP modeling, data integration, and regulatory and toxicology support.

Looking ahead, how do you envision Certara’s role in shaping regulatory science as these alternative methods become more mainstream?

Certara’s role will be to provide the biosimulation software and expertise necessary to execute on NAM approaches, and to advise the industry on how best to leverage MIDD and how to prepare MIDD-based submissions for regulatory approval.