At the beginning of this year, the U.S. welcomed a law no longer necessitating animal testing for pharmaceutical pre-clinical trials. However, industry officials expressed skepticism as many technologies that can replace animal testing are still in their infancy.

The Ministry of Food and Drug Safety (MFDS) also announced in October that they were preparing additional guidelines for alternatives to animal testing for cosmetics. In March, the MFDS started preparing standardization requirements for alternative animal test methods specific to pharmaceuticals.

Still, the latest announcements from the government have given biopharmaceutical companies a sufficient incentive to accelerate the development of alternative platforms for animal testing.

Alternatives to animal testing 

Cell-based assays were regarded as one of the first methods to replace animal testing but failed to accurately mimic the 3D human environment because it was difficult to observe the complex interactions of drugs in a petri dish of cells alone. 

However, this later gave birth to another emerging technology that could better replicate cell-cell interactions in the body for replacing animal testing, organoids, and organ-on-a-chip. Other methods include in silico tests and bioprinting.

In Korea, MESPGEN, Next&Bio, Organoid Science, and T&R Biofab are just a few companies engaged in building such platforms.

MEPSGEN is developing organ-on-a-chip models that mimic human organs and can be mass-produced.

In addition to cancer organoids, Next&Bio is engaged in the development of new drug efficacy platforms and alternative analysis services for animal testing, with the goal of standardizing organoid culture and analysis technology for precision medicine.

Organoid Science is developing treatments for incurable diseases based on organoid models for each organ and disease of the human body.

T&R Biofab possesses a 3D bioprinting technology for creating skin, liver, and heart organoids.

Although most companies are actively engaged in researching organoid platforms, the value of in silico modeling is also being realized by microbiome company, KoBioLabs, to ensure that genes reported to be highly correlated with microbial toxins and antibiotic resistance are not present in the microbial genome.

How ready is the organoid platform?

Organoids are tissue-engineered cell-based in vitro models that recapitulate many aspects of the complex structure and function of the corresponding in vivo tissues in human beings.

“Organoids can better simulate the function of specific organs in the human body, which can greatly reduce the risk of candidate drugs in clinical trials," said Choi Nak-won, a senior researcher at the Korea Institute of Science and Technology (KIST), at a recent event to celebrate Clinical Trials day. "For organoids to completely replace animal tests, standardization of organoid production technology must be achieved first."

Accordingly, the MFDS is also conducting various studies to prepare toxicity evaluation methods using organoids and is promoting the standardization of evaluation methods through the registration of the Organisation for Economic Co-operation and Development (OECD) internationally recognized test methods.

Next&Bio and KIST also jointly developed an in-vitro brain model platform to replace animal tests used to confirm safety, which was provided as a standard operating procedure (SOP) to the MFDS.

The FDA Modernization Act 2.0 to replace animal testing is just the beginning, an official from Next&Bio told Korea Biomedical Review.

“It will take several more years to replace decades of animal testing in drug development that is directly linked to human life,” the official said. “We have built several organoid-based drug evaluation platforms and are working to develop related technologies that could eventually replace animal testing entirely.”

However, the company is using a phased approach to achieve animal-free testing methods.

“First, we developed a tissue chip-based tumor microenvironment (TME) including organoids that represent cancer patient tissues,” the Next&Bio official shared. “Currently, we are developing technologies that can accurately validate various treatment strategies, including immune-checkpoint inhibitors.”

Acknowledging that organoids cannot completely confirm absorption, distribution, metabolism, and elimination (ADME) which can be verified in animal tests, Next&Bio is conducting research to merge organoids onto a chip to more accurately embody the human microenvironment.

What about in silico modeling?

On the other hand, in silico modeling is a newer technology that can simulate the effects of drugs or chemicals on the human body using data from various sources, including prior experiments, to predict their impact without the need for animal testing.

KoBioLabs is using an in silico toxicity platform in its non-clinical testing.

“The platform is especially applied to verify that there are no microbial toxins or antibiotic-resistant strains in the genome by conducting genomic analysis of its microbiome candidates and comparing it with reported databases,” a KoBioLabs official said. “Additional verification through toxicity experiments using organoids and other cell models is also utilized if required, but presently, in silico methods cannot completely replace animal tests.”

When will alternative methods replace animal testing? 

Regarding a potential timeline for these platforms to replace animal testing, the KoBioLabs official replied, “It is still necessary to present toxicity data based on animal testing to regulatory agencies such as the FDA to obtain approval.”

However, the official admitted that as prediction techniques related to the expression of toxic factors in microbial genomes quickly become more advanced, together with the development of in vitro human body simulation models, a wider acceptance of organoid and in silico platforms is expected.

The Next&Bio official estimated that a full replacement for animal testing could be established as early as 2035, in line with the U.S. Environmental Protection Agency's (EPA) 2035 animal testing ban.

The official also noted that the FDA has relaxed its stance on mandatory animal testing requirements, saying, “The FDA recently allowed Neuralink's BCI technology to enter clinical trials which gives hope that alternatives to animal testing may be adopted sooner than expected.”

However, the official maintained that there is still no perfect alternative to animal testing but organoids and organ-on-a-chip technologies appear to be forerunners with the FDA also expressing similar sentiments.