[Reading Science] Are Organoids Ready to Replace Animals?

As the cost of failure grows, making experiments more human-like becomes an obligation, not a choice

Organoids are one of the fastest-spreading concepts in life sciences over the past decade. The idea of culturing human cells in three dimensions to partially reproduce the structure and function of organs has shaken the long-standing assumptions of new drug development.

Today, the key question around the industrialization of organoids has shifted from “Is this a new technology?” to “Can it actually be used in the field?” What matters now is not whether the technology can succeed once, but whether it can produce the same result every time.

Surgical scene using bioartificial organs. The photo is for illustrative purposes to aid understanding of the article and is not directly related to the article's content. Provided by Yonhap News

The technology is already feasible; the question now is whether it can be used

The numbers in new drug development are unforgiving. A candidate entering clinical trials does not automatically become a drug. According to an analysis of the global new drug development database Citeline covering the last 10 years (2014-2023), only an average of 6.7% of candidates that started in Phase 1 clinical trials made it all the way to final approval. In other words, 93.3% of candidates dropped out during clinical trials, with only a tiny fraction ultimately succeeding.

A 2025 study that recalculated clinical and approval data from the top 18 global pharmaceutical companies between 2006 and 2022 found that the average final approval rate was only 14.3%. The remaining 85.7% failed. The figures differ, but the conclusion is the same: structurally, there is a high rate of failure in new drug development.

The problem is that this failure does not end at the clinical stage. As failures accumulate, companies demand more extensive verification in the preclinical stage, which comes before human clinical trials. The most widely used method in this phase is animal testing. As the number of experiments increases, the number of animals used also rises.

This is why the debate over animal testing first emerges as an ethical issue. Researchers and industry are increasingly held accountable to society to explain “Why are so many animals necessary?” At the same time, the burden of time and cost grows. Ultimately, the field has been forced to confront the reality that it must find experimental models that more closely resemble the human body.

The more failures there are, the more human-like experiments must become

It is at this point that organoids enter the picture. Organoids are often called “mini-organs,” but in practice they are closer to experimental biological models that use human cells to reproduce some organ functions in order to observe drug responses. Rather than completely replacing animal testing, they represent an attempt to better anticipate how humans will respond.

Jongman Yoo, CEO of Organoid Science and regarded as a pioneer in the industrialization of organoids in Korea, noted, “In the past, organoids were more of an option to supplement animal testing. Now, they are being recognized as a core alternative that can change the very paradigm of animal-experiment-centered drug development.”

He believes that the criteria for judgment have shifted since the enactment of the U.S. Food and Drug Administration (FDA) Modernization Act (MA) 3.0 in 2025. “Previously, it was important how much animal testing data you submitted,” Yoo said. “Now, in new drug reviews, a more important criterion is how much standardized human-derived data you can present.” He added, “The key questions in collaboration are whether the experimental method satisfies reproducibility and statistical reliability, and whether data can be supplied in a stable and consistent manner.”

Photo to help readers understand the article. Provided by Pixabay.

As failures accumulate, experimental methods also change

Hans Clevers, a professor at the Hubrecht Institute in the Netherlands who helped establish the concept of organoids, has expressed a similar concern. In a 2023 interview with a Nature-affiliated journal, he stated, “The key question is no longer whether organoids are possible, but whether they are reliable enough to be used repeatedly throughout the drug development process.”

The historical role of animal testing cannot be denied. Animal models have long been the regulatory standard for safety assessments and toxicity testing. However, as new drug development has grown more complex, questions have intensified about whether animals can adequately substitute for human responses. Species differences clearly manifest in areas such as drug metabolism and immune responses.

For this reason, industry is moving in two directions. One is to conduct more animal testing. The other is to reduce animal use while seeking new experimental methods that can better predict human responses. The latter is what the U.S. FDA’s modernization framework has institutionally recognized as “New Approach Methodologies (NAMs),” or non-animal alternative testing methods.

In April 2025, the FDA unveiled a roadmap to gradually reduce reliance on animal testing in preclinical safety evaluations and instead employ AI-based computational models, cell-based assays, and organoid-based toxicity testing. This is a clear signal that the existing animal-test-centered framework must change.

How many animals are being used: visible and invisible numbers

The debate over animal testing becomes clearer when viewed through numbers. According to the “EU statistics on animal use 2022” released by the European Commission (EC), 9,237,542 animals were used in the 27 EU member states and Norway for scientific purposes such as research, testing, and education. Depending on the classification method, this is sometimes rounded to about 9.3 million animals, but it is clear that the annual scale is close to 10 million.

The United States is believed to use even more animals, but the scope that can be confirmed through official statistics is limited. According to the “Annual Report Animal Usage by Fiscal Year 2023 - Research Facilities” summary published by the Animal and Plant Health Inspection Service (APHIS) under the U.S. Department of Agriculture (USDA), research facilities covered by the Animal Welfare Act (AWA) reported using about 1.6 million animals in 2023. However, this statistic does not include rodents such as mice and rats, which are the most commonly used animals in experiments.

Drawing on sources such as the Merck Veterinary Manual, a standard reference in U.S. veterinary medicine, and related academic literature, the annual use of rodents in the United States is estimated at 25 million to 30 million. This means that the official statistics represent only a portion of the total.

The message conveyed by these numbers is straightforward. The more experiments conducted before drugs are administered to humans, the more animals are used. Within this trend, organoids are both an ethical alternative and a realistic option that industry can hardly avoid choosing.

The challenge of moving organoids from “technology” to “the field”

This does not mean that organoids are a万能 solution that can immediately replace animal testing. It is difficult for them to fully replicate whole-body responses or complex interactions between organs. Thus, organoids are better positioned as tools that complement existing experiments and enhance accuracy.

The remaining challenge is not the technology itself, but ensuring that there are no issues when it is used continuously in real-world settings. Miyoung Son, head of the National Agenda Research Division at the Korea Research Institute of Bioscience and Biotechnology (KRIBB), who has long studied organoid differentiation and manufacturing technologies, identifies the biggest challenge in scaling to industry as “the ability to reliably produce the same results.”

“In the laboratory, we focus on finding conditions that work well, but in industry, the same quality must always be achieved,” Son explained. “Small variables such as the initial state of the cells, culture conditions, or ‘culture medium lot differences’-subtle compositional differences between batches of the same medium produced at different times-can significantly disrupt results. That is why it is crucial to clearly define process and quality standards.”

Industry insiders warn that unless these issues of reproducibility and standardization are resolved, it will be difficult for organoids to move beyond research tools and be used in actual new drug development settings.

In the end, the key question is not whether organoid technology is ready, but whether the environment necessary to use this technology properly is in place. The issue has now moved beyond the laboratory; it is something that industrial sites and regulatory systems must answer together.