Franklin Biolabs Achieves CLIA Certification for AAV NAb Testing
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Accelerating Tech Transfer and Scale-Up of AAV Manufacturing
EXECUTIVE SUMMARY
Programmatic Asset
CELL & GENE | RNA | BIOLOGICS
The translation of a research-grade adeno-associated virus (AAV) production method into a robust, scalable manufacturing process is a primary determinant of success for in-vivo Chimeric Antigen Receptor T-cell (CAR-T) programs. This requires a data-driven process development strategy focused on shifting from adherent to scalable suspension culture systems, establishing phase-appropriate analytical controls, and ensuring technology transfer into GxP-compliant environments. The objective is to produce AAV vectors with consistent purity, potency, and yield to support an accelerated 18-24 month timeline to IND submission.
Frequently Asked Questions
What are the primary manufacturing challenges when scaling AAV vectors for in-vivo CAR-T applications?
The main challenge is achieving high-titer, high-purity production in a scalable format, typically moving from adherent cell culture to a controlled AAV scalable suspension bioreactor system. For in-vivo CAR-T, this includes ensuring the vector serotype has the correct tropism and that the process minimizes empty capsids, which can increase immunogenicity and reduce therapeutic efficacy.
How does Franklin Biolabs de-risk the technology transfer process for AAV manufacturing?
We minimize clinical risk by maintaining process knowledge continuity. The same scientific team that develops the scaled-up process and produces material for IND-enabling studies provides direct oversight during transfer to a GMP manufacturing partner. This approach, which has contributed to the core team’s 100% successful IND rate since 2019, prevents the loss of key process insights between development and clinical production.
What analytical assays are required for an IND-enabling data package for an AAV-based therapeutic?
A comprehensive analytical package is needed to characterize the vector’s identity, purity, and potency under GxP conditions. This includes vector genome titer, capsid titer, aggregation analysis, residual impurity testing (e.g., host cell DNA/protein), and a qualified, gene-of-interest-specific potency assay to ensure biological function.
AAV Process Scale-Up for In-Vivo CAR-T Therapies
Proven Intelligence in Scalable Vector Manufacturing.
The manufacturing process for an AAV vector intended for in-vivo CAR-T delivery dictates its ultimate clinical viability. A process that is sufficient for small-scale research and discovery is rarely adequate for producing the quantity and quality of material required for IND-enabling toxicology studies and subsequent clinical trials. A tailored, science-driven approach to process development is necessary to navigate this transition.
The objective is to establish a scalable and reproducible manufacturing platform early in development. This often involves adapting processes from adherent systems, like flasks or fixed-bed bioreactors, to single-use suspension bioreactors. This shift provides superior control over process parameters, enhances batch-to-batch consistency, and enables production at scales sufficient for late-stage clinical programs.
From Research Protocol to IND-Ready Process
Our approach begins with a thorough evaluation of the existing research-grade protocol to identify parameters for optimization. This includes transfection efficiency, media and feed strategies, and serotype-specific purification methods.
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Upstream Process Development: We focus on optimizing cell growth and vector productivity in suspension culture, utilizing platforms such as single-use bioreactors from 2L to 500L+.
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Downstream Process Development: Purification strategies are refined to maximize the recovery of full, potent capsids while effectively removing process- and product-related impurities.
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Analytical Comparability: A phase-appropriate analytical strategy is implemented to demonstrate that the scaled-up process yields a vector comparable to the original research material.
A biotech partner commented on the team’s expertise: “Wonderful services. Excellent team to work with. Vast knowledge in all aspects of vector production and analytics.”
Analytical Rigor and Translational Foresight
A robust analytical package is the foundation of a successful IND submission. Beyond standard assays for titer and purity, we develop methods that provide insight into the vector’s expected in vivo performance. The ability to develop non-invasive reporter systems to quantify gene transfer in preclinical models provides substantive data on vector efficiency (PMID: 16390274). Similarly, establishing systems that demonstrate long-term, regulated gene expression in nonhuman primate models informs predictions of clinical durability and control (PMID: 15761258).
This level of analytical depth ensures that the manufacturing process is not only scalable but also produces a vector with the desired biological characteristics for clinical success. Optimizing these processes is key to reducing timelines and costs.
Franklin Biolabs operates from a >100,000 sq ft facility, leveraging a deep history of vectorology that includes collaborations with organizations like our partners. While Franklin Biolabs was formally launched in 2024, the core scientific leadership and principal scientists carry forward a track record that includes a 100% successful IND rate since 2019, consistently moving programs toward clinical evaluation within an 18-24 month timeline. This expertise is central to our work in Large-Scale AAV Manufacturing and Process Development.
This content is for informational purposes. For guidance specific to your therapeutic program, please contact our team for a consultation.