The FDA Modernization Act 3.0: Paving the Way for a New Era in Drug Development - or Just a Gentle Nudge?

In a significant step toward making drug development more patient-centric, the FDA Modernization Act 3.0 was introduced as a major piece of forward-looking legislation in February 2024 [1]. This legislation is the latest in a series of efforts to refine and modernize the regulatory framework for drug approval in the United States and will have implications for other countries as well. For stakeholders across the biopharmaceutical industry, including companies like InSphero that specialize in complex in vitro models, this legislation presents both promising opportunities and new challenges. Will it change things?

The FDA Modernization Act 3.0 introduces several initiatives aimed at accelerating the development and approval of new therapies while ensuring that these innovations are safe and effective. The most notable aspect of the Act is its strong endorsement and encouragement of the use of non-animal testing methods: One eligibility criterion is that the New Approach Method (NAM) must replace or reduce animal testing. Equally important, the method must either improve the predictivity of nonclinical safety and efficacy testing or reduce the development time of a drug. This applies not only to small molecules, but to any therapeutic modality.

As the scientific community increasingly questions the relevance and ethics of traditional animal testing, this legislation seeks to reduce reliance on these methods. Instead, it promotes the use of advanced alternatives, such as complex in vitro models like spheroids and organoids, in-silico modeling, and organ-on-chip technologies. To this end, the Act emphasizes regulatory flexibility and requires the FDA to evaluate and approve new test methods that can demonstrate efficacy and safety more quickly (in 180 days or less). This shift is particularly important for emerging NAMs technologies that may not fit neatly into the current regulatory framework.

Collaboration between industry, academia and regulatory agencies is also a cornerstone of the FDA Modernization Act 3.0, very much in line with our efforts at the International MPS Society (IMPSS) . Recognizing that the development and validation of new test methods requires a collective effort, the Act encourages greater collaboration among stakeholders. This, to me, has been one of the most impactful outcome of this. The realization for all companies working in this area,like us, that we have to collaborate in an ecosystem to move the field forward and encourage greater adoption into discovery pipelines has been a revelation.

Comparing the FDA Modernization Act 3.0 to its predecessor, Act 2.0, reveals several key differences that highlight the evolution of this legislative effort. While Act 2.0 laid the groundwork by promoting in vitro methods and establishing a level of equivalence between animal testing and NAMs, the 3.0 version unequivocally expands on these ideas in significant ways. While Act 2.0 introduced this concept, the latest version goes further by implementing specific mechanisms that require the FDA to quickly evaluate and approve new test methods. This is a critical step in keeping the regulatory environment in step with technological advances.

For companies like InSphero, the FDA Modernization Act 3.0 is both a catalyst for growth and a call to action. As a provider of complex in vitro models and services, InSphero stands to benefit from the increased demand for these technologies driven by the Act's push for non-animal testing methods. However, with this opportunity comes the responsibility to provide compelling evidence of the predictivity, sensitivity and specificity of NAMs to the highest scientific standards. In addition, reproducibility and interlaboratory variability will play a greater role in the evaluation and qualification of new assays. This is a good and necessary development in the emerging NAMs industry, which must rather under-promise and over-deliver than the other way around.

For this reason, InSphero is heavily involved in efforts to support regulatory acceptance of advanced in vitro models. We are involved in ongoing discussions and collaborations with key regulatory agencies to ensure that these models can prove themselves as credible alternatives to traditional animal testing methods. In addition, we are committed to supporting associations such as the IMPSS in their mission to educate the pharmaceutical and biotech industries, academics, students and other stakeholders about the benefits and applications of these technologies, helping to build a more informed and capable industry.

For pharmaceutical and biotech companies, the FDA Modernization Act 3.0 signals a shift toward faster, more efficient and patient-centric drug development processes. The acceptance of complex in vitro models and other NAMs promises to shorten development timelines, reduce costs, and improve the safety and efficacy of new therapies. However, these companies will also need to navigate the new regulatory environment, which will require them to invest in new technologies, be bold in their innovation, and adapt their development strategies if they do not want to be left behind.

The FDA Modernization Act 3.0 represents a pivotal moment in the evolution of drug development; it is definitely not just a gentle nudge. Can it be better? Yes, it can. For example, by providing clearer guidance on how new technologies will be evaluated and integrated into existing regulatory processes, it will reduce uncertainty and allow companies to plan and innovate more effectively.

While the legal process is underway, pharmaceutical and biotech companies do not need to wait for the FDA Modernization Act 3.0 to pass in order to start leveraging advanced in-vitro models and other proven non-animal testing methods. Some great technologies are already available and have been shown to accelerate R&D pipelines, improve the predictability of human outcomes, and reduce costs. By adopting these solutions now, companies can immediately enhance their drug development processes, stay ahead of the competition, and contribute to more efficient, ethical testing practices in the industry. Change is not a burden; it is an opportunity in an increasingly competitive industry.

[1] At the time of this writing (September 2024), the FDA Modernization Act 3.0 (H.R. 7248) has been introduced in the House of Representatives. The bill is sponsored by Representative Earl Carter of Georgia and has garnered bipartisan support, including 33 co-sponsors, split almost evenly between Republicans and Democrats. Currently, the bill has been referred to the House Committee on Energy and Commerce and is awaiting further consideration by the Subcommittee on Health.