Proven Intelligence Accelerating Next-Generation Therapies.

Executive Summary

Adeno-associated virus (AAV) vector aggregation is a recurring challenge in Chemistry, Manufacturing, and Controls (CMC) that directly influences product quality, potency, and the potential for immunogenicity. A robust analytical control strategy is required to detect, characterize, and mitigate aggregation throughout the vector production process. This necessitates a multi-method approach using orthogonal techniques to build a comprehensive data package supporting regulatory submissions for Advanced Therapy Medicinal Products (ATMPs) in European and global markets. Our analytical services provide the high-resolution data needed to de-risk development and accelerate programs toward their 18-24 month IND timelines.

Characterizing AAV Aggregation in CMC

Controlling the aggregation state of AAV vectors is a fundamental aspect of process development and product characterization. Aggregates can form at any stage, from upstream production to final fill-finish, potentially compromising the quality and biological activity of the final product.

An unstable vector preparation complicates the accurate determination of dose and potency. This principle is underscored in foundational preclinical work that establishes effective doses based on well-characterized vectors (PMID: 30112420). Without a clear understanding of aggregation pathways, programs risk generating inconsistent batches, leading to development delays and challenges during regulatory review. The objective is to build a data-driven process that ensures a homogenous and stable vector product.

An Orthogonal Analytical Approach

A single analytical technique is insufficient to fully characterize AAV aggregation. We deploy a suite of orthogonal methods to build a complete picture of vector quality, ensuring all data is generated within a GxP-compliant framework suitable for regulatory filings.

• Initial Screening: Dynamic Light Scattering (DLS) is used for rapid, early-stage assessment of hydrodynamic radius and polydispersity, identifying potential issues in process development.

• Quantification & Sizing: Size Exclusion Chromatography (SEC), often coupled with MALS, UV, and Refractive Index (RI) detectors, separates and quantifies monomers, dimers, and higher-order oligomers.

• High-Resolution Characterization: Analytical Ultracentrifugation (AUC) provides definitive data on the sedimentation velocity of different species in solution, resolving complex mixtures without the potential artifacts introduced by a stationary phase column.

Data Packages for Regulatory Submissions

The data generated from these aggregation studies are integral to the CMC section of an Investigational Medicinal Product Dossier (IMPD) or Investigational New Drug (IND) application. Regulators require a clear demonstration of product consistency and a deep understanding of quality attributes, with aggregation being a primary quality attribute for AAV vectors.

Our approach ensures that the analytical methods are developed and qualified in a phase-appropriate manner. This provides the robust data package necessary to justify product specifications and demonstrate manufacturing control. While the Franklin Biolabs brand launched in 2024, our scientific leadership’s work has contributed to a 100% successful IND rate since 2019.

Our scientific teams provide comprehensive expertise across all aspects of vector production and analytics, fostering a collaborative, data-driven approach for each partner program.

Our teams operate within a >100,000 sq ft facility designed to support these complex analytical workflows alongside preclinical programs, creating an integrated path to regulatory submission.