Viral vectors, such as lentivirus or adeno-associated virus (AAV), have taken on incredible importance in basic research, drug discovery, and clinical trials, and are essential for delivering genetic material in gene therapy.
While viral vectors are an exciting delivery method for gene therapies and drug discovery, their production brings challenges on different levels – from the manufacturing techniques and processes to cost efficiency and safety down to regulatory demands. These challenges are even more crucial to overcome when viral vector production is to be brought to a larger scale.
Key challenges in viral vector production
- Complexity of Production: Viral vectors are biologically complex, and production involves multiple stages—cell culture, transfection, harvest, purification, and concentration. Each stage must be optimized to ensure high yields without compromising quality.
- Low Yields: Achieving high titers (concentration of virus particles) is difficult. Inconsistent yields and the inability to easily scale from research to commercial levels are common roadblocks.
- Scalability: The production methods used in early-phase research often don’t scale efficiently. Moving from small batches to commercial-scale production can lead to inefficiencies, contamination risks, and decreased product quality. Selecting the proper manufacturing platform can thus ensure consistent quality and compliance with GMP standards.
- Purification: Viral vectors are prone to degradation. Purifying them without losing yield is a major bottleneck. Efficient purification techniques that can handle large-scale operations are needed.
- Long-term Storage: Efficient long-term storage of viral vectors ensures their viability and full functionality over extended periods, ready to use in critical applications. One of the primary challenges in long-term storage lies in formulation. The selection of excipients, stabilizers and optimal storage conditions are therefore of paramount importance.
- Regulatory Compliance: Scaling viral vector production must also meet stringent regulatory standards for consistency, traceability, safety, purity, and potency, which increases the complexity of scaling. Moreover, regulatory approval for clinical trials and eventual commercialization requires meticulous documentation, adherence to established protocols and transparency in reporting.
Solutions via Proper Equipment
- Bioreactors: Advanced bioreactors (e.g., single-use or perfusion bioreactors – i.e. Xcellerex XDR 50 to 2000 from Cytiva) are essential for scaling viral vector production. They allow precise control over culture conditions like temperature, pH, and oxygen levels, which can enhance viral yields and maintain consistency across larger batches. Perfusion bioreactors, for instance, provide a continuous supply of fresh media, enhancing productivity.
- Tangential Flow Filtration (TFF): TFF systems are crucial for the concentration and purification of viral vectors. They help process large volumes without compromising viral integrity, which improves scalability.
- Chromatography Systems: Advanced chromatography systems (i.e. ÄKTA systems from Cytiva) tailored for viral vector purification can enhance purity without significant losses in yield. Using high-resolution, single-use chromatography can make the process more scalable and reduce contamination risks.
- Automated Process Control: Using automated systems to monitor viral production processes (such as in-line sensors for real-time monitoring, i.e. UNICORN™ 7 control software from Cytiva) ensures consistency, reduces human error, and facilitates scaling while adhering to regulatory standards.
Addressing these challenges through advanced equipment and process optimization is essential to meet the growing demand for viral vectors in gene therapies and vaccines. At The Science Support, we have partnered with key technology providers to support every step of your viral vector production, from research to large scale. Find out more about our solutions to your production challenges at: https://thesciencesupport.com/en/applications-and-suppliers/biotechnology-biopharmaceutical-applications/.
Sources:
- Cytiva. Upstream bioprocessing for manufacturing viral vectors. Published on 27 September 2019. Accessed on 23 September 2024.
- McKinsey & Company. Viral-vector therapies at scale: Today’s challenges and future opportunities. Published on 29 March 2022. Accessed on 23 September 2024.
- Genetic Engineering & Biotechnology News. Viral Vector Capacity: A Biopharma Problem CDMOs Can Solve. Published on 17 August 2021. Accessed on 23 September 2024.