Optimising Gene Therapy: Leveraging HTPD and DoE for Efficient AAV Manufacturing
Poster Authors:
Nicholas Pearman, Damon Ho, Robert Olliver
Pharmaron Gene Therapy | Estuary Commerce Park, Speke, Liverpool, L24 8RB, United Kingdom
Accelerated Process Development for Gene Therapy Platforms
Pharmaron’s advanced gene therapy platform is revolutionizing how AAV-based therapeutics are developed. Through the strategic application of High Throughput Process Development (HTPD) and Design of Experiment (DoE) methodologies, the company has engineered a streamlined, adaptable approach to AAV process optimization, tailored to diverse serotypes and product profiles. These advanced tools reduce time-to-clinic and elevate quality and yield for gene therapy candidates. The poster presented at the 28th Annual ASGCT Meeting outlines how Pharmaron uses a flexible, modular downstream process—featuring depth filtration, capture and polishing chromatography, and sterile formulation. By integrating robotic automation (e.g., Biomek? i7), up to 17 experimental conditions can be evaluated simultaneously, enabling rapid, resource-efficient decisions.
Advanced DoE for Chromatographic Optimization
In-depth statistical DoE assessments revealed that loading density strongly influences AAV products’ monomer content and capsid yield. Notably:
- Higher loading density → Higher monomer content (DLS)
- Lower loading density → Greater capsid recovery (ELISA)
Despite pH and residence time having minimal impact on yield, Pharmaron confirmed the optimal conditions using predictive models and experimental confirmation, leading to more precise capture chromatography control. This process enables faster iteration and reduced development cost while ensuring consistency.
Why It Matters for Gene Therapy Manufacturing
By integrating HTPD and DoE with cutting-edge analytics like multi-angle dynamic light scattering (MADLS) and ELISA, Pharmaron’s approach supports:
- Scalable, GMP-compliant plasmid production
- Reduced vector impurities and aggregation
- Enhanced capsid quality for therapeutic-grade AAVs
The result is a robust, scalable gene therapy platform optimized for clinical success.
Dive deeper into Pharmaron’s innovative approach. Download the full poster presented at ASGCT 2025 to explore detailed data, predictive models, and how our HTPD+DoE toolbox transforms AAV gene therapy development.