Why successful cell therapy processes need to scale both ways
When it comes to cell therapy manufacturing, much of the industry is focussed on optimizing large scale manufacture – whether that’s scaling up larger batches for allogeneic therapies, or scaling out more batches for autologous therapies. This makes sense if the only issue in delivering cell therapies was the lack of manufacturing capacity. But with over a third of clinical stage cell therapies reporting issues ranging from safety and efficacy to CMC, and batch failure rates reportedly in the low double digits at commercial scale, understanding the whole development process is crucial.
To gain this insight Process Development (PD) teams often use Design of Experiment (DoE), varying process parameters in a combinatorial way to understand the impact on cells and determine critical process parameters. But there’s a problem.
Most cell culture tools are either designed for research OR manufacturing, meaning a process in a research tool won’t translate through to a larger volume manufacturing process and vice versa. Therefore, PD teams need to decide whether to continue with (often) manual research tools or jumping to (usually) automated manufacturing tools. And there’s pros and cons with each:
Optimizing a process with research tools
- Experiments can be kicked off quicker
- Reagent costs can be kept low
- Several experiments can be run in parallel
- Manual interventions generate variability
- There’s a lack of process data
- There’s a lot of re-work needed to translate the process for large-scale manufacturing
Optimizing a process with manufacturing tools
- Future proofs the process for large-scale manufacturing
- Can capture more data than manual processes
- High costs to run – one experiment can cost up to $30k in reagents because of the large volumes
- Can only run one experiment per device
- In-process analytics are basic at best
So what’s the solution?
We asked Lindsey Clarke, the latest member of the MFX team what was on her wish list.
“We need cell culture tools that can translate seamlessly – you won’t believe how many times I’ve been asked for this over the last decade. So many potential therapies work great at the research bench when you’re only thinking about getting the best cell, but then you try and scale them up and the biology doesn’t like it or you’re limited by what you can do at GMP, its improving as more tools companies realize this but it’s by no means seamless, especially when it comes to what you grow your cells in”
And what does it look like?
“An ideal research tool for me would be a perfectly scaled-down version of the manufacturing tool, capable of automatically running several dozen experiments, requiring very little reagents, and outfitted with live in-process analytics, so you can really understand the biology that’s happening when you change parameters.”
At MFX, we’ve been working on making this ideal world a reality. Our Cyto Engine™ performs automated cell culture in a research setting by multiplexing the exact same microfluidic chambers used in automated manufacturing, with each chamber carrying out a distinct experiment. This way, the cells are exposed to the same environment, no matter the scale.