Process and quality considerations for recombinant adeno-associated virus manufacturing platforms

Area of Science:

• Biotechnology
• Gene Therapy
• Process Development

Background:

• Recombinant adeno-associated virus (AAV) is a key vector for gene therapy due to its safety and efficacy.
• Scaling up AAV manufacturing presents significant challenges including complexity, cost, and quality control.

Purpose of the Study:

• To review common AAV suspension production platforms: transfection, infection, and stable producer cell lines (PCLs).
• To provide insights into the advantages and challenges of each platform for accelerated process development and informed selection.

Main Methods:

• Examination of common unit operations for each AAV production platform.
• Provision of typical ranges for critical operating parameters.
• Inclusion of high-level product quality specifications.

Main Results:

• Detailed analysis of transfection, infection, and PCLs as AAV manufacturing platforms.
• Identification of common unit operations and critical process parameters for each method.
• Presentation of product quality specifications relevant to AAV production.

Conclusions:

• Understanding the nuances of each AAV manufacturing platform is crucial for process optimization.
• Informed selection of a production platform based on clinical use and target product profile can accelerate AAV gene therapy development.