Day Two

• Identifying key bottlenecks in purification and how adjustments in chromatography and filtration improve recovery and yield
• Evaluating the role of advanced analytical methods in confirming identity and consistency
• Sharing lessons on establishing platform QC methods that remain predictive and reproducible when applied to engineered capsids

• Investigating differences in manufacturability caused by AAV capsid modification.
• Discussing techniques to maintain process robustness across diverse capsids and payloads.
• Highlighting Affinia’s use of single-use clarification, affinity purification and ultracentrifugation to achieve full capsid enrichment to ensure batch consistency and regulatory confidence
• Presenting lessons from the transfer of AFTX-201 high yield process to a CDMO partner, including reproducibility of yield and capsid quality across sites 

• Considerations for phase-appropriate AAV characterization and release activities from pre-clinical to late-phase products. 
• Discussion on how to leverage platform analytics, client-specific methods and transfers, formulation verifications, tox material testing, and stability for early-stage and continued development activities, timing of method validation, IPC verifications, and data trending for late-stage. 
• Potential challenges in validation of late-stage analytics for PPQ and commercial testing and paths for maturation of platform and product-specific analytics.

• Addressing analytical gaps in viral vector identity, genome integrity, impurity profiles and batch comparability
• Evaluating the role of sequencing in identifying truncated genomes and sequence integrity that impact potency and safety
• Discussing how NGS can be adopted in cGMP environments to meet identity, purity, safety, and comparability requirements

• Outlining what regulators expect from PPQ runs in viral vector manufacturing: consistency, reproducibility, and demonstration of process control across multiple consecutive batches
• Sharing strategies for scaling processes developed at early-stage to commercialready platforms without compromising quality or timelines

An overview of how an integrated digital documentation platform supports scalability and control in complex, regulated scientific programs.

• Reviewing how to design GMP-compliant viral vectors tailored for a single patient’s treatment needs
• Discussing strategies for releasing viral vectors in <3 weeks for single-patient treatments
• Anticipate scaling up processes from n=1 vectors to 20-40 patient batches

• Comparing triple transfection and transient systems for their ability to rapidly support early-stage programs, while evaluating their scalability limits at clinical and commercial scales
• Exploring how plasmid-heavy approaches create supply challenges at large scale, and whether dual plasmid systems or stable cell lines can reduce dependency on GMP plasmid supply
• Debating which transfection or cell line strategy best supports PPQ runs, regulatory alignment, and robust COGs to ensure long-term viability of gene therapies

• Testing requirements for: cell banks, bulk harvesting, drug substance and drug product release

• Discussing how to integrate potency assay design into early R&D so that assays are relevant, reproducible, and fit for regulatory expectations at IND stage
• Evaluating how early potency assay choices reduce risk of late-stage delays, bridging studies, or regulatory feedback loops
• Reviewing emerging tools, including ddPCR-based functional assays, FACS, in vitro surrogate models, that allow faster and more reliable potency readouts

• Clarifying definitions of raw materials, starting materials, and ancillary components to enable global alignment and consistent quality expectations
• Discussing how industry and regulators can collaborate through pharmacopeial channels to anticipate evolving expectations
• Highlighting gaps and inconsistencies across regional guidance and how standardsetting organizations can help bridge interpretation differences

• How ICHQ12 provides a shared foundation for post-approval change management
• Comparison of post-approval variations framework across the FDA, EMA and PMDA
• Adoption of risk-based CMC review models across the three agencies