Executive Summary

Achieving high-titer, high-purity AAV5 vectors for ocular indications requires a manufacturing process that is both robust and scalable. This asset outlines the technical challenges inherent in scaling AAV5 production, from upstream process optimization in suspension culture systems to downstream purification methods that ensure payload integrity and regulatory compliance for ATMP submissions in the EU. We detail a data-driven approach to process development that supports an 18-24 month timeline to IND.

From Process Development to Scalable Production

Transitioning an AAV5 vector from a research-grade protocol to a scalable manufacturing solution demands a systematic approach. Initial process development focuses on optimizing transfection parameters and media selection in smaller-scale suspension systems, confirming that productivity metrics can be replicated before committing to large-volume runs.

This phase is foundational for de-risking the entire clinical production campaign. By establishing a well-characterized process early, we generate the necessary data to support toxicology programs and subsequent regulatory filings. Our >100,000 sq ft facility provides the infrastructure to execute these parallel workstreams. While the Franklin Biolabs brand launched in 2024, our scientific lineage has contributed to a 100% successful IND rate for sponsors since 2019.

The transition of key scientific personnel from established academic vector cores, such as the UPenn Vector Core, to Franklin Biolabs ensures continuity for long-term development programs. For example, a 2023 collaboration to manufacture a foundational AAV vector for a gene therapy candidate was transitioned without interruption to our Research Vector Division. This program is now advancing into preclinical studies, demonstrating our capacity to serve as an integrated scientific partner for AAV-based therapeutic development.

Ensuring Vector Quality and Potency

The ultimate measure of a manufacturing run is the quality of the final vector product. For ocular gene therapies, this means achieving exceptional purity and a high ratio of full-to-empty capsids. Our downstream process development utilizes platform-based or client-specific purification methods to meet these stringent quality attributes.

• Vector Purity: Chromatographic steps are optimized to remove process-related impurities, including host cell proteins and residual plasmid DNA.

• Capsid Integrity: Analytical methods like ddPCR and AUC are used to quantify vector genome titer and determine the percentage of full capsids.

• Potency Assays: We develop and qualify gene-of-interest-specific, cell-based potency assays to confirm the biological activity of the vector, a key component of any IMPD or IND submission.

Long-term experience with various viral vector platforms, including adenovirus, informs our understanding of vector safety and biological response (PMID: 16243818). This historical knowledge provides a framework for anticipating and mitigating potential challenges in the development of novel AAV therapies.

Facility and Technology Showcase

This tour highlights our preclinical and bioanalytical facilities.

Navigating from Preclinical to Clinical Supply

Our manufacturing platforms, utilizing single-use bioreactors for suspension cultures from 2L to 500L+, are designed to produce sufficient material for IND-enabling toxicology studies and early-phase clinical trials. Scalable Manufacturing Strategies Accelerating Clinical Production are built on a foundation of rigorous process analytics and deep regulatory understanding. This integrated approach ensures that the vector used in preclinical evaluation is representative of the material that will be administered in the clinic, minimizing program risk.