What is an integrated solution?
Integrated manufacturing solutions for gene therapy provide scalable, well-characterized processes where individual unit operations are synchronized and coordinated to deliver a defined, consistent result. Integrated solutions provide a comprehensive outcome when multiple disciplines are combined to achieve distinct results. They help simplify and streamline manufacturing processes, expediting time to market, as well as reduce overall cost of goods.
Gene therapy is relatively new and the industry is still evolving to manufacture consistent, scalable, and cost-effective products to meet commercial demand. Current practices used by the biopharmaceutical industry are unable to meet manufacturing demand and deliver low yield product. This is not a problem for some medicinal targets such as rare genetic disorders of the eye where only a small percentage of the population is impacted and doses needed per patient are low (~1011 vg AAV/eye). On the other hand, diseases like hemophilia and Duchenne muscular dystrophy, where both patient population and number of doses required per patient is high (~1015 vg AAV/patient), require larger batch sizes to meet the demand.
Importance of integrated solutions for gene therapy commercialization
Gene therapy commercialization is comparable to other therapeutics where the manufacturer focuses on managing and balancing risk of investment during development phase. Investing very early in manufacturing technology before the product has been fully characterized can lead to issues of manufacturing the incorrect product. Alternatively, investing late in development can lead to challenges of scaling up the process to meet the demand. Production processes could also become risky and expensive. There are several decisions a manufacturer needs to make at every step, from early development through to manufacturing stages.
One of the core manufacturing decisions a company needs to make is either to work with a contract development and manufacturing organization (CDMO) or to invest in in-house manufacturing capabilities. Irrespective of which route a manufacturer takes, cost-effective and efficient manufacturing processes can be implemented by using integrated manufacturing solutions.
At present, many gene therapy products are being manufactured using traditional practices. These involve manual open steps, which result in process inefficiency and heightened risk of product contamination. These problems can be resolved by incorporating integrated solutions, such as scalable single-use, automated, and closed-system platforms.
Benefits of integrated solutions include:
- Improved process efficiency through using single-use components, which decrease the time required for cleaning and validating a cleaning cycle
- Reduced operator intervention and minimized operator error due to automated processes
- Improved product reproducibility and decreased risk of batch failure due to the consistent process control provided by automated processes
- Consistent and contamination risk–free products, produced by coordinating and connecting individual process steps in continuous modes, together with scalable, automated, single-use platforms
Applying integrated solutions to gene therapy manufacturing
Even though integrated solutions can offer substantial value to manufacturing processes, it requires experience and expertise associated with manufacturing process, equipment automation, and engineering for operational execution. The most proficient way of incorporating integrated solutions is to work with end-to-end solution providers who have skilled process experts and resources to manage the entire project. The provider also ensures the project is managed based on process requirements rather than fitting the process on selected equipment by offering compatible solutions.
Modular integrated solutions can add further benefits to gene therapy manufacturing. These include delaying the initial capital investment and saving time by providing cleanrooms fitted with automated instruments required for their unique manufacturing process. These prefabricated containment cleanroom systems will provide a flexible and speedy approach to fulfill industry and regulatory authorities’ demand for cleanrooms at lower capital cost. In addition, they facilitate more time to evaluate clinical trial data to make an informed decision before proceeding to commercialization.
Our integrated solutions team combines engineering expertise, in-depth industry knowledge, and a diverse portfolio of equipment to deliver end-to-end solutions within time and budget. It is important to consider that the quality of an integrated solution depends on a well-characterized manufacturing process. For gene therapy manufacturers who seek further expertise to develop their processes, our Process Development Services team is available to apply their expertise to develop and scale up processes for manufacturing viral vectors.