3 major approaches to implement in R&D to end pharmaceutical animal testing

Approach n°1: Using innovative technologies for in-vitro assays

In the present advancing era of technologies, alternative methods for animal studies are being developed through innovative technologies for in-vitro assays such as 3-Dimensional (3D) cell cultures, organoids, and Organ-on-a-Chip systems.

By growing cells in a 3D matrix that can better mimic an in-vivo environment than a traditional 2-dimensional (2D) cell culture, scientists have a more realistic environment to study cells in. The use of 3D cell culture models which represent a more physiologically relevant in-vivo environment of complex tissue are now being used more prominently to accommodate for better precision during drug discovery. Additionally, 3D cell culture models using human cells circumvent drawbacks of using mouse models, which are less accurate, and once again reduce the use of animal testing.

For a more complex system, tissue cultures have been grown by employing genetically engineered pluripotent stem cells to create organoids. With the detailed architecture and physiology of human organs, human organoids can offer near-physiological models to study human development and human diseases. With a complex human organoid, it is possible to develop a screening platform for drug discovery that is more cost-effective and precise for studying human diseases than using animal models, thus reducing their need. In the past few years, organoids have been described for a variety of organs including the digestive tract, prostate, lung, kidney, and the brain.

Furthermore, innovations in synthetic biology and microfabrication have been merged to create organ-on-a-chip (OoC) systems which mimic the structure and function of human organs. Although OoC systems might simplify the complexity of an organ compared to an organoid, they better simulate physiological conditions as they are able to provide interactions between organs in the body. Nonetheless, the two technologies can be combined to complement one another as tools in treating diseases by focusing on clinical efficacy predictability. In fact, these technologies are becoming widely accepted in preclinical research as in-vitro studies are becoming increasingly predictive.

Taking it a step further, patient-on-a-chip models have been demonstrated to combine multiple organ-on-a-chip systems to model the interactions of different organs. These multi-organ chips have been created with the aim of physiological communications between engineered tissues in order to simulate the complex and multi-faceted metabolism and effects of drugs on the human body.

Approach n°2: Using computational modeling and simulations in In-Silico Assays

In the last 20 years, machine learning and AI research has skyrocketed. Several novel technologies have emerged in the field of in silico assays, including machine learning and artificial intelligence (AI), metabolomics and high throughput screening. Computational algorithms have begun to play a key role in optimizing costs, increasing productivity and overall simplifying processes in R&D thus enabling the space for innovation. Furthermore, with a demanding need to reduce or replace animal testing, in–silico assays are also a useful testing method in which biological experiments are carried out through computer simulations.

Computational studies represent a novel approach to research and are not replicating living organisms, but still contribute to drug discovery and biomedical research. In recent years, AI-technologies are gaining prominence along the life cycle of drug discovery and development.

Computational modeling can be used as a predictive tool to model the effects of drugs on the human body. This includes simulating the interactions between molecules, predicting drug toxicity, and designing new drugs. With that, scientists are able to maximize efficiency during the drug development process and screen out potentially harmful substances before even performing any tests on animals and humans.

As an example, computational modeling can be used for pharmacokinetic (PK) simulations that predict the oral bioavailability of drug compounds based on their chemical structure and in-vitro dissolution behavior, resulting in the decrease of necessary animal and human testing performed during early clinical trials.

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Approach n°3: Combining AI with in-vitro

Although a single alternative method is not able to provide a 1-to-1 replacement for the toxicological evaluations provided through animal models, combining various techniques from in-vitro technologies with in-silico modeling can lead the scientific community to move forward and away from animal testing.

Innovative approaches of combining cutting edge in-vitro assays with in-silico methods have been investigated in recent years. For example, by combining patient-on-a-chip approaches with AI predictive tools, scientists were able to conduct physiological PK modeling of first-pass absorption, metabolism, and excretion of specific drugs in humans by using computationally scaled data from multiple organs-on-a-chip for predicting PK parameters.­­

Such models and simulations can be further utilized to create digital twins. Clinical trial digital twins can be used as virtual patients that reflect personal characteristics to simulate various patient outcome under different conditions, such as, for example, with different drugs at varying concentrations, to determine which would be most effective for a given disease.

The pharmaceutical industry is exploring novel technologies of in vitro testing and in silico technologies to reduce or replace animal testing. While animal testing cannot be entirely replaced at present, technologies such as cell or tissue cultures and computer simulations can effectively reduce unnecessary animal trials.  Such approaches can address concerns regarding patient safety, high costs, and ethical issues faced in drug development.

Although the road to animal-free testing remains long, regulatory bodies have begun to pave the way by developing frameworks, creating long-term visions, ensuring global harmonization, and improving information for more sustainable research. In 2022, both the FDA and EMA implemented new measures and proposals to minimize animal testing for medical development by encouraging the pharmaceutical industry to alternative approaches such as the ones we have mentioned above. Alcimed is happy to support its clients in deciphering the potential of these technologies for their business! Don’t hesitate to contact our team!

About the author, 

Sandra, Consultant in Alcimed’s Life Sciences team in Germany