Executive Summary

Transitioning an adeno-associated virus (AAV) vector from a research-scale, adherent-based protocol to a robust, scalable suspension culture system is a frequent point of failure in clinical translation. This asset outlines a systematic approach to process development for AAV production, focusing on de-risking the scale-up to 500L+ single-use bioreactors. The objective is to establish a reproducible manufacturing process that meets the quality and yield requirements for IND-enabling toxicology studies and subsequent clinical phases, aligning with an 18-24 month timeline to IND.

De-risking the Transition to Suspension Culture

A successful proof-of-concept in an adherent system does not guarantee viability at a commercial scale. A data-driven process development program is required to translate research protocols into a scalable manufacturing solution. This involves a methodical evaluation of upstream and downstream parameters to build a process that is both high-yielding and reproducible.

Our approach focuses on key optimization areas:

• Upstream Process Development: Systematic optimization of transfection parameters, media selection, and feed strategies for high-density suspension cell cultures. We conduct scale-up confirmation runs in smaller bioreactors (e.g., 2L, 50L) to validate process parameters before committing to large-scale production.

• Downstream Process Development: Implementation of platform-based purification methods designed for scalability. This includes refining chromatography steps and filtration techniques to consistently meet purity and potency specifications for vectors like AAV-Rh10 or custom capsids.

Establishing a robust and adaptable platform is foundational for successful clinical translation and regulatory acceptance.

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

Integrated Analytics and Technology Transfer

Analytical testing is integrated at every stage of process development. We utilize a comprehensive suite of platform assays to monitor vector genome titer, purity, percent full capsids, and impurity testing. This continuous data stream informs process adjustments and builds the data package required for regulatory filings.

This methodology results in a well-defined process that facilitates technology transfer. The same scientific team that develops the process for preclinical production can execute GMP manufacturing at a partner facility, ensuring continuity of process knowledge. This model has contributed to a 100% successful IND submission rate for programs initiated since 2019, with the Franklin Biolabs brand formally launching in 2024 to carry this legacy forward.

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