Scaling up cell culture media for your cellular therapy doesn’t have to be grueling; Nucleus Biologics simplifies formulation testing, scale-up, and re-ordering to make your life easier.
Last week, we discussed media potency and how changing even one cell culture component can impact the downstream performance of your cells. This week, we bring you the third pillar upholding the Krakatoa cell culture media system: Scalability.
Cell therapy is one of the fastest growing segments of pharmaceutical manufacturing. But delivering the remarkable benefits of a medical therapy based on living cells to a large patient population is not without its challenges. One of the primary pain points in the cell therapy industry is product scale-up.  Fresh starting material is needed throughout the cell therapy lifecycle, not simply for the therapeutic itself, but for process development and validation, quality testing, comparability runs, and more. Successful clinical candidates will need to be scaled up from small pilot studies to full-scale manufacturing in a bioreactor. Cell culture media, of course, supports all of these steps, and is crucial to product quality and consistency.
Defining media formulation
Cell culture media formulation is easily one of the most important tasks facing any cell therapy developer. Understanding the critical quality attributes (CQA) of your cell type and developing a growth media that will optimize and safeguard those attributes directly impacts downstream performance and patient outcomes.
Nucleus Biologic’s NB-AIRTM system is an AI-based, guided cell culture media formulation tool that is used to design cell-type specific media, based either on commonly used formulations, or completely customized formulations. NB-AIR identifies high-value compounds and their effect on cell performance and offers multiple custom formulations based on your cell type and CQAs.
Media formulation is rapid and reliable, informed by extensive peer-reviewed expertise on cellular function and performance. Clients have complete transparency of every component and its concentration in their media. Utilizing NB-Lux™, Nucleus Biologics configurator customers can guide formulations based on desired growth factors, pH, osmolality, and other important parameters. Customers can also pick which test results they would like to see on the certificate of analysis, for example, target pH, sterility, or mycoplasma testing.
Media formulations that are fully defined make it easier for scientists to control factors such as transduction efficiency, cytotoxicity, and yield. Media performance is consistent, and supply chain risk is much lower, since only a single vendor is involved. Regulatory compliance and quality validation are also simplified.
Small batch media validation
With NB-AIR and NB-Lux, clients can already quickly design, customize, order, and test small 2L batches of media that can be used to define their final formulation. The systems securely store formulations for future iterations or reordering at different volumes and quality – research use or cGMP. Our formulation and ordering systems make it easy to examine the impact of individual components or component concentrations. Testing multiple formula iterations early in process development reduces cost and waste, benefiting both the client and the environment. Nucleus Biologics also offers wet-lab services and in-house media manufacturing for more complex projects and process development.
With the introduction of Krakatoa, clients will be able to choose even smaller testing and iteration volumes. Powdered media will be available in 500mL biodegradable pods – the perfect volume for testing the efficacy of custom formulated media. When you have locked in your formulation, you can scale the production of that formulation from 500mL to 2000L cGMP lots with ease. Larger media volumes from 2L up to 2000L are available in drums, bottles, or bags in multiple configurations.
With Krakatoa, custom cell culture media, buffers, or balanced salt solutions can be manufactured on-site. Krakatoa pods can be shipped and stored at room temperature, eliminating the risk of cold chain disruptions, and reducing supply chain hazards, since media can be stored on hand without fear of degradation. Cell culture media manufactured at the point-of-use is at peak potency and quality, safeguarding cell performance and reproducibility of results.
Transitioning to large-scale production
All formulations generated by our clients are stored on their profile in a secure repository and are their intellectual property. Using NB-Lux, customized media can be ordered and re-ordered, with real-time pricing and delivery lead times available instantly. Clients can choose whether they would like cGMP or research-grade media. With ordering volumes up to 2000L, transitioning from research to process development, to large-scale production is simplified.
Scale-up comes with significant price benefits and can quickly become cheaper than off-the-shelf media. While custom media costs can be slighter higher than off-the-shelf options for small volume orders, cost savings associated with reduced formulation time, shipping, and storage quickly add up at higher volume quantities.
Stay tuned for our next blog when we discuss lifecycle cost of cell culture media- and how it can be significantly reduced! Meanwhile, visit the Nucleus Biologics website to learn more about our game-changing products.
- Sterling J. Scaling Up Cell Therapy Manufacturing. Genetic Engineering and Biotechnology News (2018).
- Ghassemi S., et al. Enhancing Chimeric Antigen Receptor (CAR)-T cell anti-tumor function through advanced media design. Molecular Therapy: Methods in Clinical Development (2020), doi: https://doi.org/10.1016/j.omtm.2020.07.008.