The clinical use of in vivo lentiviral vectors requires considering the vector as final drug product, creating new analytical expectations. Legacy assays developed for ex vivo applications may not adequately characterize quality, potency, and safety, particularly as alternative envelope glycoproteins are introduced for tissue targeting. This presentation highlights key analytical gaps, regulatory drivers, and emerging strategies to enable robust characterization and clinical translation.

In recent months, there has been a notable shift from traditional ex vivo CAR T manufacturing toward strategies designed to engineer CAR T cells directly in vivo. This new class of products may consist of lentiviral vectors, or mRNA constructs, often formulated in lipid nanoparticles (LNPs). From a regulatory perspective, these products are more appropriately classified as gene therapies. I will discuss 1) key regulatory consideration: viral versus RNA/LNP approaches; 2) potential differences in manufacturing and CMC consideration; 3) pharmacology and toxicology considerations; and 4) clinical development plan.

Lentiviral vectors (LVVs) are essential tools for ex vivo applications such as CAR T therapy and are also being developed for in vivo therapies. Their size and complex structure make characterization challenging. USP has developed LVV standards for vector copy number quantification, residual HEK293 DNA quantification, and physicochemical characterization to support robust analytics. This talk will demonstrate how these tools can help streamline workflows and strengthen confidence in the quality of LVVs.

This presentation will explore approaches to process characterization within the compressed timelines of an accelerated Biologics License Application. Drawing on practical experience in vector process development and manufacturing science, it will consider how teams can prioritize studies, manage evolving knowledge, align cross functional stakeholders, and maintain regulatory readiness. Attendees will gain perspectives on balancing speed, scientific rigor, risk management, and documentation while building a robust characterization strategy supporting regulatory submission.

This presentation will focus on strategies for a late-stage AAV program for accelerated CMC development in support of the approval pathway. A case study and some data will be presented.

Novel capsids modify wildtype adeno-associated virus (AAVs) serotypes to improve efficacy and tissue specificity. This is often done with the placement of inserts onto the capsid. However, complex capsids require advanced analytics to properly characterize and assess lot-to-lot variability of manufactured batches. Here, several analytical methods focusing on the abundance, polydispersity, and function of the insert are used to elucidate attributes that may impact the quality of the final product.

This presentation examines the unique manufacturing complexities of dual AAV vector systems including vector design, co-packaging efficiency, and ensuring balanced expression of both halves. It highlights key control strategies for process optimization, analytical characterization, and product consistency. Emphasis is placed on developing robust, scalable workflows to maintain quality and regulatory compliance in dual-vector gene-therapy manufacturing.

In 2025, Baby KJ became the world's first patient to receive personalized CRISPR therapy in just six months. The critical next step is translating this breakthrough into scalable, cost-effective standard care for thousands with rare genetic diseases. This presentation explores the strategic and technical foundations for building scalable gene editing platforms, examines regulatory innovations that enable rapid deployment, and discusses how industry is reshaping the economics of personalized CRISPR therapy.

Since the first approval in 2012, there have been tremendous advancements in quality control for adeno-associated virus (AAV) therapies, including innovations in analytical methods for impurities, titer, and capsid content. To support emerging best practices, USP is collaborating with stakeholders and expert volunteers in developing <1067> Best Practices for the Manufacture and Quality Control of Recombinant Adeno-Associated Virus Gene Therapy Products and a growing set of standards, reference materials, and other tools to support quality strategies. Attendees will learn how to integrate these resources into a robust analytical quality-control strategy.

AAV vectors present unique stability challenges compared to traditional biologics with poorly understood structure-function relationships. Comprehensive stress testing using heat, pH variation, oxidation, and light exposure was conducted on AAV vectors using extensive analytical methods including potency assays, mass photometry, and peptide mapping. Vectors demonstrated significant sensitivity to temperature, light, and pH extremes, with temperature causing free DNA release, capsid emptying, and deamidation. These findings inform formulation optimization and CQA identification for gene-therapy development.

Lentiviral vectors are widely used in ex vivo and in vivo cell and gene therapies. Manufacturing generates lentiviral particles alongside heterogeneous membrane-bound species with similar properties, creating analytical challenges. Monitoring particle concentration, size, charge, and protein content across production, purification, formulation, and storage provides critical data to inform process decisions. This presentation highlights the use of multiple orthogonal analytical techniques, including DLS, NTA, and flow virometry, to characterize lentiviral vectors.

This presentation will explore the development and qualification of TCID50 as an infectivity assay for AAV programs, highlighting its role in supporting process development, analytical characterization, and product quality assessment. It will discuss key considerations in assay design, variability, robustness, and comparability, as well as broader lessons learned when implementing functional assays in a regulated environment. The session will offer practical insights for teams advancing viral vector analytics.

This session examines the regulatory and quality considerations that shape formulation strategies for gene therapies. It will explore how excipients are selected and justified, how regulatory principles should guide formulation studies, and how developers can build quality into product development. The discussion will also highlight common pitfalls, unintended consequences, and practical approaches for reducing risk while supporting product stability, safety, consistency, and regulatory acceptance throughout clinical and commercial development programmes.