Proven Intelligence Accelerating Next-Generation Therapies.

Executive Summary

A robust stability program is foundational to de-risking an AAV therapeutic’s path to clinical application and commercial supply. A comprehensive analytical strategy assesses capsid integrity, genome stability, and biological potency over extended periods, supplementing standard vector titer confirmation. Franklin Biolabs designs and executes GxP-compliant stability studies tailored to specific AAV serotypes (e.g., AAV8, AAV9, engineered capsids) and formulations, providing the data package required for Investigational Medicinal Product Dossier (IMPD) submissions and other global regulatory filings. Our approach ensures that vector quality established at large-scale production is maintained through long-term storage to the point of patient administration.

Defining Vector Integrity from Bioreactor to Clinic

Producing AAV vectors at scales of 50L, 200L, or 500L+ introduces complexities that extend beyond upstream and downstream processing. The final purified bulk vector substance must maintain its quality attributes from the moment it is aliquoted until it is administered. A failure to ensure long-term stability can invalidate data from expensive IND-enabling toxicology studies and delay clinical timelines.

Early gene therapy trials with viral vectors demonstrated that durable clinical responses are linked to the sustained biological activity of the vector (PMID: 16243818, PMID: 14977858). This principle of ensuring long-term functional integrity is directly applicable to today’s highly purified, high-concentration AAV products, forming the basis of scalable manufacturing strategies accelerating clinical production.

Core Components of a GxP Stability Program

A data-driven stability program is designed to meet global regulatory expectations, including those for Advanced Therapy Medicinal Product (ATMP) submissions in Europe. It is tailored to the specific vector and its intended clinical use.

• Formulation and Excipient Screening: We identify optimal buffer conditions (pH, ionic strength) and excipients (e.g., surfactants, sugars) to protect vector integrity for specific serotypes like AAV2, AAV8, or novel engineered capsids.

• Real-Time Stability Testing: The vector product is stored at its intended long-term storage temperature (e.g., -80°C) and tested at pre-determined intervals (e.g., 0, 3, 6, 9, 12, 18, 24 months).

• Accelerated Stability Testing: To model the impact of temperature excursions during shipping and handling, samples are stored at elevated temperatures (e.g., -20°C, 5°C) for shorter durations.

• Forced Degradation Studies: The vector is exposed to stress conditions (e.g., light, oxidation, agitation, multiple freeze-thaw cycles) to understand its degradation pathways and confirm the stability-indicating nature of the analytical methods.

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 has been instrumental in the development of our AAV-vector based gene therapy candidate, and we hope to continue the partnership for years to come.
— Biotech Partner

Phase-Appropriate Analytics for Stability Assessment

The analytical panel for a stability study must be robust enough to detect subtle changes in the AAV product over time. At Franklin Biolabs, our >100,000 sq ft facility is equipped to perform these phase-appropriate assays under GxP conditions, supporting programs on an 18-24 month timeline to IND.

This structured approach provides the necessary data to confidently define storage conditions and shelf life, a required component for any IMPD or IND submission.