Current and Future Scale-Out Needs in Cell Therapy Manufacturing
Thomas Heathman, PhD, Business Leader, Technology Development, Manufacturing Development & GTP Services | November 15, 2016
The following is an excerpt from a paper originally published online in the journal Cytotherapy on October 26, 2016, entitled, “Bioreactors for cell therapies: Current status and future advances.” The paper’s authors are Shannon Eaker, Eytan Abraham, Julie Allickson, Thomas A. Brieva, Dolores Baksh, Thomas R.J. Heathman, Biren Mistry, and Nan Zhang.
Patient-specific cell therapies offer a new and exciting challenge for process scalability, where the manufacturing process must be scaled out to produce one batch per patient. The unique challenge of scaling out patient-specific cell therapy manufacturing processes is reducing the cost per dose, given that there are currently few economies of scale to exploit. Reducing the cost of these patient-specific therapies must therefore be achieved by advances in engineering and manufacturing technology to reduce the number of labor-intensive and open-process steps that are routine in cell therapy production. However, there are some strategies that can be implemented within the scale-out manufacturing model to control the cost per dose and ensure scalability, as illustrated in the table below.
Steps to achieve economies of scale within a scale-out cell therapy manufacturing process
Steps to achieve economies of scale
Understand the product quality profile
Enables management of comparability risk as the production rate is scaled and unit operations are modified.
Ensures the cost of failed batches is minimized by in process monitoring, allowing unsuccessful batches to be ended as early as possible.
Minimize the number of process unit operations
Reduces labor and equipment requirements by reducing process complexity, which reduces variability and costs, particularly as the number of batches increases.
Avoid peak capacity points by evenly distributing labor requirements across the process
Peak capacity points increase the overall labor cost as additional resources are required at peak times.
Reduces the cost efficiency of the process as the personnel cost per batch is increased.
Drive development to minimize variation and maximize product yield
Multiple input products derived from primary patient material are inherently variable.
Reduced variation allows for defined process times and effective scheduling
Maximizing product yield reduces process times which reduces the cost per batch.
Closed process steps
Allows for the concurrent manufacture of multiple patient-specific products.
Potentially reduces the grade of clean room, which significantly reduces operating cost as well as the cost of idle manufacturing capacity.
Reduces the potential for contamination and therefore the risk of batch failures.
Automated process steps
Reduces the labor requirements which becomes important as the production rate increases.
Reduces in-process variation and creates more reliable process transfer.
Shared infrastructure across multiple product manufacturing processes, in-house or externally
Manufacturing infrastructure such as quality testing, logistics and management can be shared across multiple processes.
Reduces the overhead cost per batch for each of these services.
Development of scale-down process models
Process optimization can occur at reduced scale, allowing for increased throughput.
Scale-down models must be based on sound engineering principals, to ensure they are comparable with commercial scale processes.
Incorporating the steps shown in this table will help to control the top-down facility costs and the bottom-up process costs associated with cell therapy product manufacture. Reducing these costs will minimize the overall production cost for the patient-specific cell therapy product and allow for strategies such as the exploitation of shared resources among multiple products to realize economies of scale in the scale-out manufacturing model. Given the high fixed cost associated with the manufacture of cell therapies, minimizing the cost of idle capacity will be critical to reducing the overall product costs when ramping up to commercial production. The ramp-up of additional manufacturing capacity must therefore be carefully managed and aligned with projected patient accrual rates or product sales projections.
If you have access to Cytotherapy, you can read the full paper online by clicking on the button.
Thomas Heathman, PhD, Business Leader, Technology Development, Manufacturing Development & GTP Services
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