Proven Intelligence Accelerating Next-Generation Therapies.

Executive Summary

Maintaining adeno-associated virus (AAV) vector integrity, purity, and potency during manufacturing scale-up directly influences clinical program velocity. The transition from 2L proof-of-concept batches to 500L+ GxP-compliant production runs introduces process variability that can impact defined quality attributes (CQAs). A successful scale-up requires a manufacturing platform built on deep analytical characterization, serotype-specific process optimization, and robust control strategies to ensure product comparability between scales. This approach minimizes risk and supports an 18-24 month timeline to IND submission.

Franklin Biolabs: >100,000 sq ft of Specialized Facilities

The Challenge of Isomorphic Scaling

The biophysical environment within a 500L single-use bioreactor differs substantially from that of a 2L flask, presenting distinct scaling challenges. Maintaining vector CQAs requires a process designed for scalability from its inception, where parameters are defined to ensure product consistency regardless of batch volume.

Our approach is built on the scientific continuity of the team that transitioned from the Penn Vector Core. This institutional knowledge allows us to anticipate and mitigate scaling challenges for a range of AAV serotypes, including AAV8, AAV9, and novel engineered capsids.

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 provides integral scientific and manufacturing support for our AAV-vector based gene therapy candidate development, and we hope to continue the collaboration for years to come.
— Biotech Partner

Analytical Comparability as the Foundation

Demonstrating that the vector produced at 500L is comparable to the material used in IND-enabling toxicology studies is a regulatory expectation. This is achieved through a matrix of qualified analytical methods.

• Vector Titer & Purity: ddPCR assays are used to quantify vector titer and assess the ratio of full to empty capsids, an indicator of potential efficacy.

• Capsid Integrity: SDS-PAGE and Western Blot confirm the correct ratio of viral proteins (VP1, VP2, VP3) and overall capsid integrity.

• Potency Assays: Phase-appropriate, cell-based potency assays are developed to provide a functional measure of the vector’s ability to transduce target cells and express its transgene. This is the ultimate measure of biological activity.

• Impurity Profiling: Methods are established to detect and quantify residual host cell DNA, proteins, and plasmid DNA, ensuring the final product meets safety specifications.

Process Control for AAV Scalable Suspension

Our AAV scalable suspension platform utilizes single-use bioreactors to provide flexibility and minimize contamination risk. The process is defined by control over defined process parameters to ensure batch-to-batch consistency. Scalable Manufacturing Strategies Accelerating Clinical Production.

This platform is built on decades of experience, including the foundational work that established the unique transduction patterns of various AAV serotypes. This knowledge informs our serotype-specific optimization of upstream and downstream processes, ensuring high-yield production without compromising vector quality. The Franklin Biolabs brand launched in 2024, building upon a legacy that has achieved a 100% successful IND rate for sponsors since 2019.