Aligning In Vivo Potency Assays with MHRA Regulatory Frameworks.

Executive Summary

Developing a robust in vivo potency assay for cell-based therapies requires a strategy that aligns the therapeutic’s mechanism of action with clinically relevant endpoints and satisfies stringent MHRA and international regulatory expectations. A successful Investigational Medicinal Product Dossier (IMPD) submission depends on demonstrating consistent biological activity in a suitable animal model. This involves selecting appropriate in vivo systems, defining meaningful functional readouts, and ensuring the assay is sufficiently qualified for its intended purpose within a GxP framework.

Defining Biological Activity for Living Therapeutics

For cell-based therapeutics, including CAR-T, TCR-T, and iPSC-derived products, establishing a matrix of assays to define potency is a foundational regulatory requirement. An in vivo potency assay is a functional measure of the product’s ability to execute its intended purpose, confirming that complex biological activity observed in vitro translates to a therapeutic effect within a living system.

The design of these assays must be tailored, as a standard template does not exist. The scientific strategy begins with the specific mechanism of action (MoA) of the therapeutic candidate.

• For CAR-T/TCR-T cells: Assays are often designed around xenograft tumor models, where endpoints include tumor growth inhibition, survival, and persistence of the engineered cells.

• For Stem Cell Therapeutics (iPSCs, MSCs): The assay must measure the intended regenerative or immunomodulatory function, such as tissue repair or suppression of inflammation in a disease-relevant model.

• For Gene Editing Systems (CRISPR, Base Editors): Potency is linked to demonstrating the desired genomic modification in target cells in vivo, leading to a measurable physiological change.

Aligning with MHRA and International Regulatory Frameworks

For UK and EU submissions, the Investigational Medicinal Product Dossier (IMPD) must contain a robust data package supporting the product’s quality and consistency. The MHRA places significant emphasis on the relevance of the potency assay. The data must convincingly demonstrate that each batch of the cell therapy product will perform as expected clinically.

Our approach ensures that assay development is conducted with regulatory expectations in mind from the outset. This includes phase-appropriate qualification and validation, establishing clear acceptance criteria, and ensuring the method is transferable to a GxP environment for lot release testing if required. This forward-looking strategy is part of the integrated approach that has supported our core scientific team’s 100% successful IND rate since 2019, a track record established prior to the formal launch of Franklin Biolabs in 2024.

Translating Scientific Principles into Defensible Data

The core principle of a successful potency assay is its ability to measure a specific biological function. Historical work on engineered proteins, for instance, established that systemic delivery could block an intended biological process throughout an organism (PMID: 14668502). This principle of measuring a direct, systemic functional outcome is directly applicable to modern cell therapies. The goal is to create an assay that provides an unambiguous, quantitative result directly linked to the therapeutic effect.

A well-designed in vivo potency assay is a key component of a defensible data package, providing regulators with confidence in product consistency and biological activity. The responsible development of next-generation therapies requires a rigorous and transparent approach to data generation and interpretation (PMID: 40643951).