Imagine the scenario: your lab has six months to demonstrate that your new cell therapy is viable. You’re excited when your new bioreactor arrives, but then disaster strikes. Your CHO cells won’t grow. The oxygen transfer is inadequate, the mixing is wrong, and the pH control isn’t stable. Your six-month timeline just became impossible to meet.
However, this scenario is preventable. Successful bioreactor selection depends primarily on an application-first approach while ensuring organism compatibility. As Joel Eichmann, co-founder and managing director of Green Elephant Biotech, explains, "The first step is understanding the biological process you're trying to support. Flexibility matters—having the ability to rapidly test conditions, scale up or down, and easily integrate into existing workflows is more valuable than the largest throughput or the most complex automation."
With the industry experiencing an ever-growing shift to scale-out strategies, most acutely in cell and gene therapy applications, it is imperative to make informed decisions around bioreactor selection.
This article explores the top considerations when selecting your next bioreactor, breaking down the decision-making process into three fundamental steps:
- What am I growing?
- How much do I need?
- How will I operate it?
Understanding organism-specific requirements
Your choice of organism drives every aspect of your bioreactor selection. "Suspension-adapted CHO cells have different requirements than adherent stem cells or microbial strains," notes Eichmann. "Parameters like shear sensitivity, oxygen demand, and metabolic profile all influence the reactor type."
The primary decision factor is shear sensitivity. While CHO cells may tolerate moderate shear, stem cells are highly shear-sensitive, requiring a gentler rocking motion or wave-mixing as opposed to traditional mixing.
Oxygen requirements are also key. High-density microbial cell lines will require intense aeration, whereas mammalian cell lines need much more controlled oxygen delivery to prevent oxidative stress. Whereas in terms of culture format, adherent cultures require much more gentle treatment than suspension cultures. A mismatch in organism requirements with reactor selection leads to poor cell viability, reduced productivity, and extended development timelines. Getting this first step right is paramount to a streamlined, cost-effective process.
Rethinking your sizing strategy
Generally speaking, a bioreactor should be as small as possible while still making the material needed for further processing. However, with the shift toward emerging fields such as cell therapy, size considerations extend further than footprint requirements. As Eichmann explains, "Size is more than just a matter of footprint. In many labs, benchtop space is scarce, and a smaller, modular system often wins over bulky setups. For a long time, scaling up meant moving to bigger bioreactors, but in emerging fields like cell and gene therapy, scale looks different. The goal isn't a 1,000-liter stir tank, it's 100 smaller batches in parallel, each tailored for a specific patient or a small group."
While traditional advice focused on selecting a single large vessel that could be scaled up linearly, scientists are increasingly opting for smaller units to run in parallel, offering greater flexibility, reduced risk, and support for patient-specific production. Many benchtop options are now even GMP compliant, coming with GMP-ready configurations that simplify the transition from development to clinical manufacturing.
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Additionally, selecting smaller models is essential in labs that are increasingly limited in funding and benchtop space. By choosing a modular design, systems can easily be reconfigured, moved, or duplicated to meet a lab's changing needs with much more ease than selecting one large, fixed system. Scaled-down models offer labs a unique chance to increase developmental efficiency by ensuring your lab reactor meets the needs of the target production system.
Supporting considerations for successful bioreactor selection
Beyond the top considerations already highlighted, there are several key factors for bioreactor selection and long-term success.
Sustainability is an evolving consideration; it is no longer an afterthought. With many regions now seeing both procurement teams and regulators considering the environmental impact of their systems, it is key to evaluate the lifecycle impact of your system. Where single-use systems eliminate the need for cleaning validation and reduce contamination risks, they also generate large volumes of plastic waste. Reusable systems, by comparison, may have a lower overall impact across their operational lifetime, but do require the use of cleaning chemicals along with water and energy consumption for sterilization.
Understanding the cost and ROI of your chosen system is crucial, but it's also important to recognize that a system may initially seem economical but could become a bottleneck if it fails to support your future developmental or commercial strategy. Consider the total cost of ownership, including consumables and maintenance, as a slightly more expensive system that has the functionality to reduce development time, saves money in the long run.
There are many operational factors to consider, with one of the most vital being a vendor's technical support availability. Support infrastructures can vary significantly depending on your location, making this an important talking point during initial conversations with vendors. It is also important to determine their track record for resolving issues quickly by evaluating their application support capabilities beyond basic equipment troubleshooting.
Consider how user-friendly the system will be and assess the ability of your team to tackle this learning curve compared to the vendor resources or hands-on training that is available. Looking at vendor stability can provide insight into long-term integration success. Do they have spare parts available, and does this availability align with the expected lifetime of the system you are looking to purchase? Vitally, does the vendor still support older instruments once new products are introduced?
You should also evaluate how well the bioreactor can integrate with your existing data management systems and downstream processing tools. Choosing a system with robust data export capabilities can save time and reduce errors, while software compatibility with your existing systems ensures seamless data flow, which is key to maintaining audit trails.
Get the most from your bioreactor investment
The difference between project success and costly delays comes down to three fundamental considerations when choosing your next bioreactor: understanding your organism's requirements, choosing the right size system for your actual needs, and selecting a vendor who will support you through the inevitable challenges that come with scientific development. Getting these decisions right will ensure your bioreactor enables your research rather than hindering it.
