MANUFACTURING
“Within the next several years, the industry will define which system is more efficient. We should expect high production titers and faster delivery of final products.”
sign the contract for the entire project upfront. This should prevent penalties for project termination if you are not satisfied with outcomes along the way. However, I would recommend balancing the project components with CMO capacity utilization to prevent project delays.
Q. Industry experts are decrying a general shortage of cell/gene therapy expertise. How does that complicate CMO selection? A. I would have agreed with this statement three or five years ago. At that time, there were just a handful of CMOs working on gene and cell therapy, with a facility availability lead time of 12 – 18 months. The suddenly increased demand for viral vectors led to ironic situations, with some CMOs being acquired at an incredibly high price and others selling manufacturing timeslots in their inexistent or just-planned commercial facilities two or three years ahead based on the client projections. Fortunately, the situation is changing fast, particularly with the production of viral vectors, due to the following reasons. First, I see an increasing number of small-scale CMOs and GMP units being placed directly in hospitals and universities, offering their services in a fast and efficient manner. Second, the majority of gene therapy studies are in early-stage clinical trials. At this stage, the structure of viral vectors is still being modified, the number of patients is relatively low, and the number of doses being administered to patients is frequently limited to one. Unlike the kg-scale batch of the DS and several thousand vials of DP used in the clinical manufacturing of monoclonal antibodies, the phase 1 – 2 gene-therapy study can be covered by 100 – 200 vials of the DP and another hundred vials used for the release and stability studies. Third, the manufacturing technology for viral vectors is evolving rapidly and is currently
balancing between the planar systems used for adherent cells, bioreactors for cell suspensions, and a kind of hybrid system. Within the next several years, the industry will define which system is more efficient in the standard manufacturing process. We should expect higher production titers, reduced volumes and size of manufacturing suites, and faster delivery of final products. Single-use disposable systems and highly efficient cell lines have replaced the large-scale stainless-steel bioreactors used for recombinant proteins within the past 10 – 20 years. The same changes are occurring now with the manufacturing of viral vectors for gene therapy. Meanwhile, autologous cell therapy products still require the production of a separate batch for each patient, which drives the prices up. It will take time to establish new CMOs and optimize manufacturing and analytical techniques, and the supply chain, to make them more affordable. Also, the development of allogeneic cell therapy products should free up some CMO capacities.
Q. What else would you recommend for successful partnering with CMOs? A. As a sponsor, you should consider CMOs as a flexible extension of your company, which gives you a great opportunity to address changes quickly. Meanwhile, it is important to build and maintain a partnership with the CMO through clear communication of your goals and expectations, and a willingness to understand their limitations. I would recommend the following: • Visit CMOs frequently. Face-to-face communication is the most efficient way to resolve technical and business-related issues. Travelling to CMOs costs less than a delayed or failed product.
• Make sure the CMO is currently working with the required technology. Their past experience is irrelevant due to the high turnover of personnel.
• Analyze the background of the development team offered by CMO. Choose the A-team or be prepared to change the team members to ensure the success of your project.
• Be on top of your project and update the CMO with relevant information or suggestions to resolve complicated issues.
Ultimately, you are the project owner and the CMO is the tool in your hands. Choose the right tool to sculpt your drug development project.
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