Proven Intelligence Accelerating Next-Generation Therapies.

Executive Summary

Scaling adeno-associated virus (AAV) vector production from development to clinical-grade volumes requires a sophisticated analytical strategy integrated directly into the manufacturing workflow. In-process controls (IPCs) provide the data necessary to guide manufacturing decisions, ensure batch-to-batch consistency, and build a robust data package for Investigational New Drug (IND) or Investigational Medicinal Product Dossier (IMPD) submissions. This approach moves beyond simple final batch release testing, enabling proactive process optimization and minimizing the risk of costly batch failures at large scale. Franklin Biolabs leverages a comprehensive suite of platform assays to characterize vector identity, purity, potency, and quantity throughout the production cycle.

Integrating Analytics into Scalable AAV Production

Scaling an AAV candidate toward the clinic requires a proportional increase in analytical oversight alongside volume amplification. A manufacturing process without integrated analytical checkpoints operates with incomplete data, risking deviations in product quality that may only be detected during final release testing. Our approach embeds phase-appropriate analytics directly into the upstream and downstream workflow.

This methodology provides data on defined quality attributes (CQAs) at each unit operation. By monitoring vector genome titer, aggregation, and the removal of process-related impurities at each stage, our scientific team can ensure the process is performing as expected. This builds a comprehensive process history that supports regulatory filings and de-risks technology transfer.

“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 our key collaborator in our AAV-vector based gene therapy candidate development and we hope to continue the partnership for years to come.”
– Biotech Partner

Characterizing Purity and Product-Related Impurities

The purity of a final AAV vector preparation is directly linked to its performance and safety profile. Inadequate removal of impurities, such as residual host cell DNA or plasmid DNA used during transfection, can impact efficacy and elicit unwanted immune responses. Historical findings have underscored the importance of the transgene itself in safety profiles, making the removal of any potentially confounding biological material a priority (PMID: 16682254).

Our analytical services for large-scale manufacturing focus on precisely quantifying and removing these impurities.

• Empty and Full Capsid Ratio: We employ techniques like analytical ultracentrifugation (AUC) or transmission electron microscopy (TEM) to determine the percentage of capsids carrying the desired genetic payload.

• Process-Related Impurity Testing: Highly sensitive assays are used to detect and quantify residual host cell proteins, host cell DNA, and plasmid DNA.

• Aggregate Analysis: Size-exclusion chromatography (SEC-MALS) is used to identify and quantify vector aggregates, which can affect potency and immunogenicity.

This level of characterization, performed within our >100,000 sq ft facility, is integral to achieving the 18-24 month IND timeline our partners expect. It also forms the foundation of the CMC data package that has supported a 100% successful IND rate for programs initiated since 2019, with the Franklin Biolabs brand itself launching in 2024 to carry this expertise forward.

To learn more about capsid engineering and scalability, view the full webinar at: Vector Ready: Where AAV projects begin and how they succeed

From Process Control to Clinical Confidence

A well-defined analytical control strategy provides the process knowledge and continuity needed for successful clinical translation. By engaging the same scientific team from early process development through to GMP manufacturing support, we ensure a deep understanding of your vector’s specific attributes. This continuity is invaluable during interactions with regulatory bodies and during technology transfer to a CDMO’s GMP suite.

This integrated approach connects every manufacturing step with a corresponding analytical data point, creating a robust and defensible CMC narrative for global regulatory submissions.