Proven Intelligence Accelerating Next-Generation Therapies.

Executive Summary

For AAV-based therapeutic programs targeting UK and EU regulatory submissions, establishing robust data integrity for potency assays is a primary determinant of timeline adherence. A potency assay must reflect the vector’s mechanism of action (MOA), and its development requires a GxP-compliant framework from the outset to prevent costly delays during IMPD review. This involves defining quality attributes, implementing controlled data capture systems, and ensuring a complete, auditable data trail that aligns with MHRA expectations. This approach, executed within our >100,000 sq ft facility, is built on the same principles our team used to establish an 18-24 month average timeline to IND.

The Challenge of AAV Potency Assay Variability

AAV potency is a composite of multiple vector attributes: capsid-mediated cell entry, intracellular trafficking, uncoating, and transgene expression. An assay that measures only one aspect, such as viral genome titer, fails to capture the complete biological function. This creates significant risk during regulatory review, as inconsistent or non-representative potency data can lead to questions about product consistency between manufacturing lots.

Developing a reliable potency assay requires a science-based strategy tailored to the vector’s specific MOA. This process must be governed by stringent data controls to ensure that the results are reproducible, accurate, and defensible under regulatory scrutiny.

“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 a key scientific collaborator in our AAV-vector based gene therapy candidate development, and we hope to continue the partnership for years to come.”
— Biotech Partner

A Framework for Data Integrity in Assay Development

A defensible data package for UK and EU submissions is built upon a systematic, integrated framework. This model requires several interconnected components working together to ensure audit readiness.

• Phase-Appropriate Validation: The rigor of assay validation increases as a program advances. Early-stage development focuses on qualification to demonstrate the assay is fit-for-purpose, while later stages require full GxP validation to support lot release.

• Controlled Data Capture: All raw data, from plate reader outputs to imaging files, must be captured and stored in a secure, unalterable format. The use of validated electronic laboratory notebooks (ELNs) and laboratory information management systems (LIMS) is standard.

• Audit Trail Functionality: Systems must automatically record all actions, including data entry, modifications, and deletions, with user identification and timestamps. This provides a transparent history of the data lifecycle, a key requirement for MHRA inspections.

• Defined SOPs and Training: Standard operating procedures must govern every aspect of the assay, from reagent preparation to data analysis. Personnel must have documented training on these procedures to ensure consistent execution.

From Complex Biology to Quantifiable Potency

The requirement for a functionally relevant potency assay becomes more apparent with vectors designed to elicit complex biological responses. For instance, AAV vectors engineered to modulate cellular pathways influencing tissue architecture (PMID: 27937051) have effects that cannot be measured by simple protein expression. The potency assay for such a product must quantify a downstream biological event that is directly linked to the therapeutic outcome.

Building these complex assays requires a deep understanding of the vector biology and a robust analytical development process. The data integrity controls are what connect the sophisticated biological measurement back to the quality control environment, ensuring that each manufacturing lot possesses the same functional attributes as the material used in pivotal IND-enabling toxicology studies. This continuity is a requirement for building a successful IMPD submission for the MHRA.