Feasibility: Barriers To Cell Therapy Automation

Today, we feature an excerpt from BioProcess International from David A. Brindley, I.B. Wall, and K.E. Bure.  The article Automation of Cell Therapy Biomanufacturing: Minimizing Regulatory Risks and Maximizing Return on Investment was featured in the March 2013 Supplement of BioProcess International.

Feasibility: Barriers To Cell Therapy Automation

Manual bioprocessing techniques (notably, cell culture) are critically important in terms of skill development for employees in industry and students within academia. Such skills provide a foundation for navigating future automation and operation strategies such as cell characterization studies (2). Further, in addition to capital investment costs, the management of automated biomanufacturing equipment in academic settings can be challenging. For example, access to resources must be shared amongst multiple parties with different work schedules, funding structures, and process materials. 

In some situations (e.g., autologous cell therapy production), manufacturing limitations render automation extremely challenging, in part due to inherent interdonor source material variability. For example, populations of bone-marrow–derived mesenchymal stromal cells (BM-MSCs) from different individuals (where the start population of cells comprises a heterogeneous mix of subclones) will age at different rates and have variable replicative lifespans. This is due largely to intrinsic telomere dynamics, difference in donor ages, oxidative stress status, and stochastic events (3, 4). A single
defined set of automated process parameters for cell expansion will not discriminate among individual samples. Consequently, products will exhibit different source material characteristics after amplification of the start population. 

Further, the start material will exhibit some variability if it is in the form of a tissue biopsy obtained by a navigating future automation and operation strategies such as cell characterization studies (2). Further, in addition to capital investment costs, the management of automated biomanufacturing equipment in academic settings can be challenging. For example, access to resources must be shared amongst multiple parties with different work schedules, funding structures, and process materials. 

In some situations (e.g., autologous cell therapy production), manufacturing limitations render automation extremely challenging, in part due to inherent interdonor source material variability. For example, populations of bone-marrow–derived mesenchymal stromal cells (BM-MSCs) from different individuals (where the start population of cells comprises a heterogeneous mix of subclones) will age at different rates and have variable replicative lifespans. This is due largely to intrinsic telomere dynamics, difference in donor ages, oxidative stress status, and stochastic events (3, 4). A single
defined set of automated process parameters for cell expansion will not discriminate among individual samples. Consequently, products will exhibit different source material characteristics after amplification of the start population. Further, the start material will exhibit some variability if it is in the form of a tissue biopsy obtained by a clinician. This is a consequence of the physical nature of the tissue being subject to variability between donor sites in terms of accessibility, tissue quality, surgical/sampling accuracy, and the exact quantity of tissue removed (5). Therefore, skilled technicians will isolate and plate cells from tissue biopsies and conduct morphological assessments to evaluate the likely risks and benefits arising from processing a particular patient sample. 

Any suitable automated biomanufacturing platform requires significant process flexibility to accommodate unique constraints of individual cell populations, in many respects similar to the flexibility required historically in MAb manufacturing strategies to accommodate variability in product titres and glycosylation profiles (6). For some cell lines that are particularly unamenable to automation, however, there has to be a tipping point at which costly process development is pushed aside in favor of focusing on first-to- market advantages that such highly unique therapies offer.

Read the rest of the article here. 

If you'd like to find out more about single use technologies and cell therapy bioprocessing, Richard Eglen, Ph.D., Vice President and General Manager, Corning Incorporated, will be on hand at the Cell Therapy Bioprocessing Event to present the technology workshop Optimization of Single-Use Technologies in Cell Therapy.  For more information on this session and the rest of the program, download the agenda.  Would you like to join us in Bathesda, Maryland this coming October 21-22? As a reader of this blog, when you register to join us and mention promo code BX13188JP20, you're eligible to save 20% off the standard rate! 

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