Accelerated Adeno Associated Virus Upstream Process Development From High-Throughput Systems to Clinical Scale.

Area of Science:

• Biotechnology
• Gene Therapy Manufacturing
• Process Development

Background:

• Adeno-associated virus (AAV) is a key delivery vector in gene therapy.
• Current AAV manufacturing faces challenges including high cost of goods (COGs), scalability, and impurities like empty capsids.

Purpose of the Study:

• To present a streamlined approach for developing and scaling AAV upstream production.
• To optimize productivity, reduce impurities, and lower COGs per dose.
• To demonstrate scalability from bench to commercial volumes exceeding 1,000 L.

Main Methods:

• Utilized triple transfection for AAV production.
• Employed high-throughput technologies like the AMBR®15 system for rapid process development.
• Detailed direct scale-up methodologies to a 2,000 L single-use bioreactor.

Main Results:

• Achieved rapid upstream process development in under 2 months.
• Successfully optimized AAV production for increased productivity and reduced impurities.
• Demonstrated a streamlined process for scaling AAV manufacturing.

Conclusions:

• The presented streamlined approach enables efficient and scalable AAV manufacturing.
• High-throughput technologies accelerate process development and optimization.
• This method addresses key challenges in AAV production, paving the way for cost-effective gene therapies.