From Animal Models to Patient Samples: The Regulatory Rise of Functional Assays under the FDA Modernization Act 2.0
The FDA’s regulatory shift away from animal testing has opened new avenues for preclinical innovation. Functional assays using native patient samples now offer a clinically translatable, ethical alternative for early drug evaluation. Learn how this paradigm is being implemented at Vivia Biotech to bridge discovery and clinical development.
The traditional reliance on animal testing in early drug development has long been a subject of ethical, scientific, and regulatory scrutiny. With the enactment of the FDA Modernization Act 2.0 (2022), the agency now formally recognizes validated non-animal methods—including cell-based assays and microphysiological systems—as acceptable tools for preclinical efficacy and safety evaluation.
Scientific Rationale for Functional Human Assays
Among the alternatives, patient-derived functional assays represent a significant advancement. Unlike standard cell lines or xenograft models, these ex vivo systems preserve the heterogeneity, cellular context, and immune landscape of the patient’s original tissue.
The use of ex vivo pharmacology assays provides several scientific advantages:
- Higher clinical translatability: Responses are measured directly in human primary cells within their native microenvironment.
- Mechanism-based insights: Simultaneous readouts of multiple cellular responses (apoptosis, proliferation, immune activation) allow MoA deconvolution.
- Personalized modeling: Assays can be stratified by genetic background, disease subtype, or prior treatment exposure.
Regulatory Implications
By reducing the dependency on animal models, these platforms align with the FDA’s evolving expectations for human-relevant data in IND-enabling studies.
Functional assays can be particularly impactful in:
- Early-phase candidate selection: Ranking compounds based on efficacy and selectivity across patient-derived cohorts.
- Preclinical justification for first-in-human studies: Demonstrating activity in native human tissue with defined biomarkers of response.
- Bridging data for rare or high-risk populations: Where preclinical models poorly reflect human disease biology.
Conclusions
The FDA’s policy shift opens the door to more predictive, ethical, and mechanistically informative models in preclinical development. Functional ex vivo assays—especially those using native patient samples—offer a scientifically rigorous complement or alternative to animal testing, accelerating the path from discovery to clinical translation.
Implementation at Vivia Biotech
At Vivia Biotech, we have adopted this paradigm through the systematic use of functional ex vivo assays in native patient samples, across hematologic malignancies, solid tumors, and autoimmune diseases. Our platform enables the evaluation of drug activity, mechanism of action, and immune modulation under physiologically relevant conditions, supporting early decision-making with clinically translatable data. By integrating this approach into preclinical workflows, we help bridge the gap between discovery and the clinic in line with current regulatory expectations.