Day One

• Discussing why COGs, not efficacy, may be the greatest barrier to gene therapy adoption
• Sharing lessons from current commercial products: what the numbers really tell us about cost, pricing, and scalability
• Identifying high-impact levers for cost reduction across upstream, downstream, and release processes
• Bridging innovation and economics: what types of investment and collaboration are needed to enable sustainable manufacturing

• Evaluating how early-stage manufacturing strategies for novel delivery platforms can be adapted for large-scale production without compromising quality or cost
• Exploring how automation, AI-driven design, modular unit operations, and raw material standardization can streamline process transfer and support scalable, reproducible manufacturing across diverse modalities
• Assessing technology transfer and process intensification approaches to enable costefficient, high-yield production for clinical and commercial supply

• Extending supply chain risk mapping to strengthen continuity of critical raw and starting materials
• Exploring collaborative inventory models to bridge shortages and prevent delays to batch release and clinical timelines
• Standardizing materials across products to streamline inventory, lower cost and accelerate procurement

As this community reunites for the fourth time, this session will provide valuable networking time with your peers, enabling you to forge new and lasting connections.

• Contrasting scalability limitations across vector types and how physical constraints shape commercial strategy
• Discussing trade-offs between driving higher titres versus maintaining potency and how these challenges can differ across vector classes
• Deciding between ‘scaling up’ and ‘scaling out’ and how this can be affected by modality, indication, and regulatory expectation

Following a short presentation, participants will take part in a guided roundtable discussion to share perspectives on defining acceptable impurity limits, aligning analytical methods across sites, and ensuring compliance amid shifting standards. This interactive format aims to foster collaborative learning and actionable takeaways that link analytics, safety, and CMC strategy.

• Linking analytics to safety: Examine how advanced quantification methods (dPCR + NGS) deliver deeper insight into impurity identity, size, and packaging- and what this means for dose safety and consistency
• Understanding regulatory misalignment: Discuss where current impurity thresholds and definitions inherited from biologics or vaccine frameworks fail to align with gene therapy products
• Upstream implications: Identify how analytical findings can inform plasmid design, ratio optimization, cell substrate, and nuclease strategies to proactively reduce impurity burden

• Reducing complexity in upstream workflows: assessing the potential for novel plasmid systems to streamline production
• Presenting insights from Affinia’s adoption of a novel plasmid system – Improving VG titres and reproducibility across capsid serotypes
• Discussing how a novel plasmid system can reduce GMP plasmid demand, simplify raw material supply chains, and lower COGs – directly accelerating time-to-clinic for rare disease programs
• Evaluating potential for scaling up through transfection volume, process timing and control

• Benchmarking productivity, scalability, and cost-effectiveness between AAV and LV manufacturing systems
• Evaluating upstream strategies: transient transfection vs. stable producer lines and implications for yield and consistency
• Assessing downstream purification challenges: recovery, impurity clearance, and platformability
• Identifying shared analytical standards and CQAs to ensure comparability across vector types