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December 01, 2020

If you are looking to get a lentiviral vector (LVV) program off the ground, selecting the right contract development and manufacturing organization (CDMO) partner can be a game-changer. Expertise, production and equipment are three key considerations you should evaluate to determine if a prospective CDMO is a fit for your LVV program’s needs.  

Expertise 

Process development for LVV production takes specialized experience and know-how. A CDMO with expertise spanning all stages of LVV development –including upstream processing (USP), downstream processing (DSP), analytics and production in a Good Manufacturing Practices (GMP) facility – will provide an advantage. The best CDMOs will have a collaborative mindset and a creative team, allowing for the development of client-centric, end-to-end solutions. 

Your CDMO should be thinking about your process from start to finish. Technical experts will provide solutions to USP-related issues including the optimization of cell culture, scale-up, transfection and harvest of viral particles. Experts in DSP will tailor purification and concentration steps to achieve a final product that fits your end-use and specifications. Finally, your team will be thinking about the best analytical controls to apply to your process to meet specifications.  

Finding a CDMO with strong alliances can bring additional areas of expertise. Since January 2016, CCRM has partnered with Cytiva (formerly GE Healthcare Life Sciences) to expand its USP and DSP capabilities, including platforms for scalable and suspension-based LVV manufacturing at the Centre for Advanced Therapeutic Cell Technologies (CATCT). 

CCRM has also leveraged partnerships with government to build industry-leading capabilities. For example, CCRM has developed a process for LVV production using a suspension-adapted cell line supplied by the National Research Council of Canada (NRC). The ability to perform early product development and scale-up on suspension-adapted cell lines requires specialized expertise and is a unique offering in the industry. Through these partnerships, and work on over 30 projects since the establishment of CATCT, CCRM has built an experienced team with the capability to design flexible and scalable processes that can help clients get into the clinic quickly.

Production 

Look for a CDMO that is equipped to handle production challenges at all stages of LVV manufacture. During USP, the use of multi-plasmid transient transfection requires careful optimization to address the inherent variability in transfection efficiency. To address this critical aspect of LVV production, your CDMO should be focused on acquiring a stable supply chain of high-quality raw materials such as plasmid DNA and transfection reagents to ensure that you are starting your process with the best chance of success.  

The biggest challenge during DSP is efficient recovery of virus. Currently, the industry standard is 20 to 30 per cent overall recovery. Recovery of virus during DSP is a function of how well you can purify and concentrate the final product. Optimization of each unit operation is required to achieve the best results.  

Overall, your CDMO should provide access to equipment, materials workflows that close the manufacturing process, reduce reliance on manual manipulation and reduce the number of steps in production to ensure manufacturing is more cost-efficient.  

Equipment 

CCRM’s significant investment in equipment means scalability can be embedded in everything that we do. Our industry collaborations have allowed us to furnish the lab with an assortment of equipment from a variety of suppliers to provide maximum flexibility to clients. We have stirred tank bioreactors ranging from 200 mL to 1 L, and 10 L to 50 L. Our clients benefit from a unique ability to optimize USP at a small-scale before scaling up. Similarly, we have sourced scalable technologies for DSP that allow us to design custom solutions for each unit operation. Finally, CCRM’s integrated GMP manufacturing capabilities are a unique advantage that we offer to clients. CCRM ensures production of LVV at clinically-relevant scales with seamless technology transfer from the development stage and an eye toward commercialization to treat patients with unmet needs.

To learn more about how CCRM’s CDMO services can support your lentiviral program, please contact cdmo@ccrm.ca.

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