Executive Summary

For next-generation therapeutics, a generic, off-the-shelf potency assay is insufficient for building a robust regulatory submission package. The biological mechanism of action (MOA) for modalities like AAV gene therapies, CAR-T constructs, or LNP-delivered RNA is unique to the asset. This requires the development and formal validation of custom, biologically relevant cell-based potency assays under GxP conditions. A validated, MOA-reflective assay is a foundational component of the CMC data package required for Investigational Medicinal Product Dossier (IMPD) and IND submissions, directly impacting program timelines and minimizing clinical risk.

Frequently Asked Questions

The Requirement for Biologically Relevant Potency Measurement

A potency assay measures the specific ability of a product to achieve its intended biological effect. For complex next-generation therapeutics, this cannot be reduced to a simple analytical measurement of presence or quantity. The assay must be a functional, cell-based system that recapitulates a key aspect of the therapeutic’s MOA.

Developing such an assay is a multi-step process that moves from initial design and optimization to formal validation. This ensures the method is reliable, reproducible, and fit-for-purpose, generating data that will withstand regulatory scrutiny. Franklin Biolabs’ approach is built on a deep scientific foundation, leveraging a team whose track record contributes to a 100% successful IND rate since 2019. This history predates our formal launch in 2024 and reflects the continuity of our core scientific leadership and principal scientists in navigating complex regulatory requirements.

Phase-Appropriate Validation for IND and IMPD Submissions

A standard, one-size-fits-all preclinical testing template does not exist for these therapies. The validation of a custom potency assay must be phase-appropriate and aligned with the overall program goals.

• Early Development (Pre-Validation): Focus is on establishing the fundamental assay parameters, demonstrating proof-of-concept, and ensuring the system is sufficiently robust for initial characterization and comparability studies.

• IND-Enabling Phase (Formal Validation): The assay undergoes rigorous validation according to GxP principles. This involves executing a pre-approved validation protocol to formally document the method’s performance characteristics. This is the data set that will be included in the CMC section of an IND or IMPD.

• Post-IND (Lifecycle Management): The assay’s performance is monitored over time. Any significant changes to the manufacturing process may trigger a re-evaluation or re-validation of the potency assay to ensure continued suitability.

Our >100,000 sq ft facilities provide the specialized laboratory space

required to conduct these sensitive biological assays in a controlled environment, ensuring data integrity from sample receipt to final report.

Integrating Bioanalytics with Preclinical Reality

The data from a potency assay is most powerful when contextualized with in vivo results. The scientific rationale must connect the in vitro biological activity with the expected therapeutic effect in a relevant animal model. For instance, demonstrating potency of a CNS-targeted AAV vector is strengthened by preclinical data showing effective delivery to the target region. The development of standardized, clinically relevant delivery techniques, such as fluoroscopic-guided intra-cisterna magna administration in nonhuman primate models (PMID: 30032644), provides a robust in vivo context for the in vitro potency results, creating a cohesive and compelling narrative for regulators.

This integrated strategy is central to achieving an 18-24 month timeline to IND, connecting CMC analytics directly to the preclinical and translational services outlined in our parent Vector | CMC | Analytics Services hub.