Proven Intelligence Accelerating Next-Generation Therapies.

Executive Summary

A robust, scalable downstream process is a prerequisite for AAV vector clinical translation and commercialization, particularly when navigating European regulatory pathways. This asset outlines a platform approach to AAV purification designed to manage serotype-specific challenges, enhance product quality attributes, and align with Investigational Medicinal Product Dossier (IMPD) expectations. The focus is on creating reproducible processes that de-risk technology transfer and accelerate timelines, leveraging our >100,000 sq ft facility to support programs aiming for an 18-24 month IND timeline.

Establishing a Scalable AAV Purification Blueprint

Developing a purification strategy for an AAV vector requires a forward-looking approach that anticipates future manufacturing and regulatory demands. A non-platform, ad-hoc process developed for early research material often fails during scale-up, leading to significant delays. The objective is to establish a purification train that consistently delivers a high-purity, high-potency product, irrespective of the upstream production system.

The regulatory journey of early gene therapies in the European Union provided a clear lesson: process is product. As outlined in the review of Glybera’s market authorization, a well-characterized and consistent manufacturing process is fundamental to a successful submission (PMID: 23808604). This history informs our development of Strategic Process Blueprints Accelerating Technology Transfer.

Mitigating Biological Variables Through Process Design

The inherent biology of AAV vectors directly influences purification strategy. Preexisting immunity to AAV capsids can impact in vivo efficacy, making the removal of immunogenic impurities a primary process objective (PMID: 16219492). A robust downstream process must effectively clear host cell proteins, residual plasmid DNA, and process-related impurities that could potentiate an adverse immune response.

Our platform addresses these variables by focusing on:

• Serotype-Agnostic Capture: Utilizing affinity chromatography resins (e.g., POROS CaptureSelect AAVX) that bind a wide range of AAV serotypes, including AAV1, AAV2, AAV5, AAV8, and AAV9, creating a standardized first step.

• Targeted Polishing Steps: Employing anion-exchange (AEX) or cation-exchange (CEX) chromatography to separate full capsids from empty capsids and other product-related impurities.

• Orthogonal Clearance Methods: Incorporating tangential flow filtration (TFF) for buffer exchange and final formulation, which also serves as an additional, orthogonal step for impurity removal.

Learn More: Watch the full webinar, “Vector Ready: Where AAV projects begin and how they succeed”

“We started collaborating with UPenn Vector core in 2023 and the AAV vector which they manufactured laid a foundation for development of a gene therapy candidate which will enter soon preclinical studies. The key people from UPenn Vector Core joined Franklin Biolabs and our partnership transitioned without interruption from UPenn Vecor Core to Franklin Biolabs Research Vector Division. Franklin Biolabs is a key collaborator in our AAV-vector based gene therapy candidate development and we hope to continue the partnership for years to come.”
— Biotech Partner

From Development to GxP Readiness

The Franklin Biolabs team that executes early process development and preclinical production remains engaged to support GxP manufacturing at a strategic partner’s CDMO suite. This continuity of personnel and process knowledge minimizes risks during technology transfer. This model ensures that the process developed at small scale is the same process that will be implemented under GxP conditions, a key consideration for regulatory bodies like the MHRA. This approach is informed by our team’s 100% successful IND rate for programs initiated since 2019, with the Franklin Biolabs brand itself launching in 2024 to carry this expertise forward.