Congress passed the FDA Modernization Act 2.0 last week removing the requirement to use animal testing in drug development. This will allow drug companies the option to use alternative safety-testing models when making new drug submissions.
This is important because the Federal Food, Drug and Cosmetics Act of 1938, which is still in force, mandates animal testing for every new drug development protocol. Advocates of non-animal experimentation have argued that the cost of animal research is high—in dollars, in time, and in delays in approvals of beneficial drugs for human use. They also maintain that some drugs that were deemed safe by animal studies went on to cause harm in human subjects in clinical testing, although this last position is poorly quantified.
Once the FDA Modernization Act 2.0 is enacted, a transitional moment will follow. The section of the House bill that allows for alternatives to animal use to be incorporated into pre-clinical testing outlines approaches most likely to predict human response based on scientific evidence. These include cell-based assays; organ chips and microphysiological systems; and sophisticated computer modeling. Several of these approaches allow drug developers to incorporate safety assessment alternatives that are robust enough to convince regulators that a program has been adequately de-risked.
The bill comes at a pivotal time; modern toxicity testing has been moving away from a reliance on animal studies. One substitute has been mechanism-based testing strategies, such as cell-based assays. These are already being used as research tools to support the interpretation of in vitro toxicity data, as well as the design of in vitro experiments, and considerable progress has been achieved in making assays available and deployable in a user-friendly form.
So-called organ chips and microphysiological systems began to be used more frequently during Covid-19 drug and vaccine testing, which reportedly helped researchers to better understand how Covid-19 interacted with human organs and elicited an immune response. Using human cells and engineered structures, these approaches create an environment that mimics or models the function of organs, and they may have application in testing drug efficacy in genetically diverse human populations using human genetic material.
The average cost of bringing a drug to market is about $2 billion, of which more than half is spent on clinical trials. But before trials are conducted, researchers are increasingly employing computer modeling, a technology that has been expanding for several decades and which provides several benefits.
Sophisticated modeling that uses in-silico, computer-based testing with virtual patients, biosimulation is fast and relatively inexpensive and reveals rich information about how a drug would perform and how to best design a trial before the drug is ever tested in patients. Biosimulation also offers the flexibility of computer-based testing, allowing developers to optimize trial design and dosing for different patient populations.
By easing regulatory requirements for animal testing, the Act allows scientists to use innovative, leading-edge technologies more fully in future drug development strategies. These alternatives are not yet the complete answer, but by increasingly taking a “totality of evidence” approach where the combination of multiple data points can be used to assess whether a confidence threshold is reached in relation to the safety of a drug at a particular dose, regulators are allowing developers to accelerate the process.
Now that Congress has passed the FDA Modernization Act, drug companies should consider how to take advantage of the translational tools outlined above, which can be an important part of the drug developer’s arsenal. Depending on how they are used, they can result in researchers more cost-effectively developing the lifesaving drugs and vaccines that patients need, faster.
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