FDA Modernization Act - Drug Trials in a Dish and the Cloud

This month, the Senate unanimously voted to pass the bipartisan legislation authored by Senators Cory Booker (D-NJ) and Rand Paul (R-KY) that will alter how drugs are discovered and developed.

In 1938, Congress passed the U.S. Federal Food, Drug, and Cosmetic Act, mandating animal toxicity testing. Since then, science and data have shown that in some products, animal testing is a highly inconsistent predictor of toxic responses in humans; in contrast, animal testing on any single pharmaceutical product often requires killing hundreds of animal test subjects.?Since then, several non-animal tests have been developed that predict the human response to drugs.??

This bill allows a new drug candidate to use methods other than animal testing to establish the drug's safety and effectiveness in its application for market approval. Under this bill, alternative methods may include lab-grown human cells, mini-organs, and computer modeling (official language here ).

This carries enormous implications for the biotechnology and pharmaceutical industries aside from the progressive animal rights movement, particularly in treating chronic and complex diseases such as aging and age-related diseases. Many, if not all, don’t have high-fidelity animal models, and where the lack of biological overlap can impede efficient drug discovery and development. Problems with animal models in drug discovery are elaborated further in 1Pager “Longevity Science Lost in Translation”

As expected, the bill was met with resistance from traditional drug discovery companies (notoriously referred to as “Big Pharma”), who have relied mainly on conventional FDA compliance's financial and regulatory burdens to cap the development of emerging biotechnology companies from becoming worthy competitors. For instance,?Pfizer notes on its website ?that the “use of animals in research is currently an essential component of the drug discovery process. Animals help us advance our scientific understanding, serve as models to study disease, and help us develop and test potential new medicines and therapies.” However, it should be reiterated here that the bill does not ban or discredit the use of animal testing in any way but instead opens the regulatory process to consider alternative evidence to evaluate safety and efficacy.

Drug trials in the cloud

The idea that “humanized” computer simulations could not only replace but outperform animal models in drug testing was, until recently, a moonshot vision. The rise in stem cell technology and “omics” analysis with integrated healthcare data has created an environment where this is feasible and currently in progress. Companies specializing in computer models for the pharmaceutical industry, such as In Silico , Cytoreason , and several others, use computer models of human physiology to characterize molecular changes in disease and match those with equal and opposite drug-induced changes to develop new compounds that reverse disease and age-related decline. By incorporating biomarkers and clinical data, researchers can predict if a drug candidate will impact a specific molecular pathway and model how the downstream effects of that interaction correspond to drug efficacy and side effects. This is somewhat similar to how engineering software can model different designs of structural integrity in the face of various stressors (earthquake, wind, weight, etc.) and identify the most suitable structure for a given location and purpose. However, in biology, these “trials in the cloud” will be particularly useful in identifying insidious side effects like nausea, fatigue, and lightheadedness that mice often fail to report.

Drug trials in a dish

Trails in a dish are essentially testing medical therapies for safety or efficacy on cells collected from a representative sample of human patients before moving into actual clinical trials. Recent advances in stem cell technology enable researchers to grow miniaturized organs from these cells to test how drugs can impact the entire organ function and not just cells in isolation. To go even further, multiple mini-organs can be connected in parallel using microfluidics to investigate how drugs interact with entire organ systems without putting a single patient in harm’s way. Many predict it won’t be long before drugs are routinely tested on your mini-multi-organ-doppelganger as a pre-screening measure before ever ingesting/injecting a drug candidate in clinical trials.

Why this matters now

Earlier this year, Insilico Medicine ?announced the start of the world’s first Phase 1 clinical trial of a drug developed from scratch using AI. Its end-to-end platform applies AI to biology for target discovery, and to chemistry for drug design. Intriguingly, the company believes the drug may have?anti-aging properties ?as well as an immediate therapeutic effect. A Phase 1 trial is when a drug is first tested in humans at the dosage level required for therapeutic effect. It tests safety, not clinical effectiveness. Before that, drugs go through preclinical trials on animals, and Phase 0 trials in sub-therapeutic doses. In Phase 2 and Phase 3 trials, a drug is tested for effectiveness, first with a small sample of a few hundred people, and then with a larger sample of thousands.

Should the algorithms prove successful in their ability to predict safety and effectiveness, this could pave the way for expedited drug development in the complex and chronic diseases plaguing the world today.