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Client-Specific Downstream Process Development for AAV Vectors

EXECUTIVE SUMMARY

Client-Specific Downstream Purification Method Design for Proprietary AAV Capsids

CELL & GENE | RNA | BIOLOGICS

Standard, platform-based downstream purification processes often fail to deliver the required purity and yield for novel or engineered AAV capsids. Franklin Biolabs designs and implements client-specific downstream purification methods tailored to the unique physicochemical properties of proprietary vectors. This bespoke approach maximizes full:empty capsid separation, removes process-related impurities, and establishes a robust, scalable process suitable for generating material for IND-enabling toxicology studies and subsequent clinical phases. This work is performed within our >100,000 sq ft facilities, leveraging the expertise that has contributed to a 100% successful IND rate since 2019 for programs led by our core scientific team, which transitioned to the Franklin Biolabs brand upon its formal launch in 2024.

A close-up of a gloved hand handling PCR tubes with blue liquid in a laboratory rack, with a blue color overlay.

Frequently Asked Questions

Why is a client-specific purification method necessary for a proprietary AAV capsid?

Engineered AAV capsids possess unique surface charge distributions, isoelectric points, and aggregation propensities. A generic, platform purification process developed for common serotypes like AAV8 or AAV9 may result in low recovery, poor separation of full and empty capsids, and inadequate removal of host cell or process-related impurities for your specific vector.

What is the timeline for developing a custom AAV purification process for IND-enabling studies?

The development and optimization of a tailored downstream process is integrated into the overall program timeline. Our model targets getting candidates to IND within 18-24 months, and this includes the necessary process development to produce high-quality vector for GxP toxicology studies.

How does downstream process development for AAV vectors align with global regulatory submissions?

We design purification processes with scalability and regulatory compliance in mind from the start. The methods and analytics are developed to meet harmonized international guidelines (ICH), ensuring the CMC data package is robust for multi-jurisdictional IND and IMPD submissions to agencies like the FDA and MHRA.

A close-up of a Pall Corporation single-use bioreactor system in a cleanroom environment, showing the control panel, vessel with cell culture media, and tubing.

Tailored Downstream Purification for Engineered AAV Capsids

The efficacy and safety profile of an advanced therapy is directly linked to the purity of the vector. For sponsors developing proprietary AAV capsids, relying on a one-size-fits-all purification platform introduces significant process risk. Each engineered capsid has distinct biochemical characteristics that demand a tailored downstream strategy to achieve the quality attributes required by global regulatory bodies.

A customized approach moves beyond basic affinity chromatography. It involves a systematic evaluation of multiple orthogonal methods to optimize the separation of full capsids from empty particles and other process-related impurities.

  • Capsid Characterization: Initial analytical assessment of the vector’s isoelectric point (pI) and surface charge properties to inform column and resin selection.

  • Chromatography Screening: Methodical screening of ion-exchange (anion and cation), hydrophobic interaction, and mixed-mode chromatography resins.

  • Buffer & Elution Optimization: Fine-tuning of pH, conductivity, and gradient conditions to maximize resolution and vector recovery.

  • Scalability Assessment: Ensuring the developed process is robust and transferable from development scale to the larger volumes needed for AAV scalable suspension cultures.

From Theory to High-Purity Vector

Understanding the target patient population informs vector design, which in turn dictates manufacturing strategy. For instance, data showing lower-than-expected seropositivity for certain AAV serotypes in specific patient cohorts (PMID: 26790480) reinforces the value of developing highly specific and potent vectors. Achieving that potency requires a purification process that can consistently deliver a highly pure final product, minimizing clinical risk associated with immunogenicity from process contaminants.

Our team’s deep history in vectorology, including collaborations with partners like our partners, provides the foundation for solving these complex challenges. This expertise is valuable when engineering a process for a novel capsid, a topic explored in our technical webinar on AAV program initiation.

The continuity of this scientific leadership ensures that complex programs maintain momentum. As one partner noted:

The transition of our core scientific team from their previous institution enables seamless continuation of established client programs. For example, a 2023 AAV manufacturing project provided the foundational vector for a partner’s gene therapy candidate now advancing to preclinical studies. This program transitioned without interruption, preserving critical project momentum and expertise.

This seamless transition of knowledge is fundamental to de-risking the manufacturing process for novel advanced therapies. Our work is designed to support your entire development lifecycle, from initial process development through to large-scale production.

Learn more about our comprehensive manufacturing capabilities at our parent hub page: Large-Scale AAV Manufacturing and Process Development.

Scientific Process Diagram

This content is for informational purposes. For guidance specific to your therapeutic program, please contact our team for a consultation.

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