Proven Intelligence Accelerating Next-Generation Therapies.

Executive Summary

Developing a robust, quantitative in vitro potency assay is a mandatory component for AAV vector characterization and release, particularly for Investigational Medicinal Product Dossier (IMPD) submissions to European authorities like the Paul-Ehrlich-Institut (PEI). A successful assay must reflect the vector’s specific mechanism of action (MoA) and be qualified or validated under phase-appropriate GxP conditions. This process involves MoA-based strategy, custom cell line engineering, and rigorous analytical qualification to ensure the data reliably predicts in vivo biological activity and supports an accelerated 18-24 month timeline to IND.

Defining the Mechanism of Action for AAV Potency

A scientifically sound potency assay moves beyond simple vector titer or transgene expression measurements. It provides a quantitative assessment of the biological activity directly linked to the therapeutic hypothesis. This requires a deep understanding of the transgene’s function to design a system where the AAV-mediated activity can be isolated and measured with high precision.

The development process follows a data-driven strategy, tailored specifically to the AAV serotype, promoter, and transgene payload. This ensures the resulting analytical method is a reliable surrogate for the expected in vivo effect, satisfying regulatory expectations in Germany and across the EU.

Phase-Appropriate Assay Development for IMPD Submissions

For sponsors targeting European clinical trials, aligning the CMC analytics package with PEI expectations is a primary objective. Our approach focuses on developing and qualifying these complex cell-based assays within a GxP-compliant framework.

Our >100,000 sq ft facility provides the specialized laboratory space and infrastructure to support these activities, from initial cell line engineering to final assay qualification.

A GxP-Compliant Framework for Qualification and Validation

The path to a qualified potency assay involves several distinct stages. This GxP-compliant framework enables rapid assay development accelerating quality control, generating the data needed for IMPD submissions.

• Cell Line Development: Selection or engineering of a biologically relevant cell line that responds to the AAV vector and its transgene product.

• Assay Optimization: Systematic refinement of parameters such as cell density, vector concentration (MOI), and incubation times to achieve a robust signal-to-noise ratio.

• Pre-Qualification: Initial assessment of the assay’s performance characteristics, including precision and range.

• Formal Qualification: Execution of a pre-approved protocol to formally document the assay’s specificity, accuracy, precision, and linearity, demonstrating it is fit-for-purpose for product release.

“We started collaborating with UPenn Vector core in 2023 and the AAV vector which they manufactured laid a foundation for development of a gene therapy candidate which will enter soon preclinical studies. The key people from UPenn Vector Core joined Franklin Biolabs and our partnership transitioned without interruption from UPenn Vecor Core to Franklin Biolabs Research Vector Division. Franklin Biolabs is an integral collaborator in our AAV-vector based gene therapy candidate development, and we hope to continue the collaboration for years to come.”
— Biotech Partner

Linking Vector Biology to Assay Design

A comprehensive understanding of AAV biology informs superior assay design. For instance, knowledge that AAV vectors can avoid certain inflammatory signals necessary for immune-mediated clearance (PMID: 20234342) reinforces the need for an in vitro system that isolates the vector’s direct biological effect from other potential confounding variables. This focus on the primary MoA produces cleaner data and a more reliable analytical tool for CMC programs. This is a core component of our approach, which has contributed to a 100% successful IND/IMPD rate for programs initiated since 2019, with the Franklin Biolabs brand itself launching in 2024.