How to increase bioreactor efficiency and productivity

Bioreactors create complex environments that rely on multiple conditions to achieve optimal performance. Slight variations in several factors—cell viability, mixing efficiency, pH, dissolved oxygen concentration, and more—could affect productivity. But dialing in the efficiency of your bioreactor can lead to increased productivity, higher product quality, and reduced cost of goods.

Very often, all it takes are a few relatively simple adjustments to achieve better bioreactor performance. The key is to find out where your bioreactor has suboptimal conditions to determine exactly which adjustments will generate positive business outcomes without impacting product quality. Start with these 3 questions:

The challenge: how to improve your bioreactor’s productivity and efficiency

There are a number of reasons you may choose to evaluate your bioreactor’s productivity and efficiency. In fact, your team may already know there is a problem.

Manufacturers often register an issue inside their bioreactor during periods of transition. Maybe you’ve changed your cell inoculation protocol, or your process utilities have undergone an upgrade, or you’re expanding your product pipeline. It’s especially common for manufacturers to see a drop in efficiency during one of the greatest transitions of all: the transition from lab to commercial-scale production.

Larger bioreactors introduce new geometric and hydrodynamic challenges compared to smaller reactors, which can influence the health and productivity of the cell culture inside. Even details that may seem relatively minor—like the number of baffles in your bioreactor, or the bubble sizes emerging from its sparger—can have a cascading effect on cell culture production, which in turn impacts your operation’s profitability and efficiency. Deviations as small as a few tenths of a percent can make all the difference between achieving your desired yield.

Dialing in optimal operating conditions in a manufacturing environment can be tricky. Traditional approaches that your scientists might try, like bench-scale testing, often fall flat as operating conditions change drastically from bench-scale to a large-scale bioreactor. It quickly becomes impractical to perform testing at a large scale, due to the cost of procuring raw materials, fabricating multiple bioreactors or occupying bioreactors that should be supporting your production line. Rather than troubleshooting your bioreactors, subpar yields sometimes become your operating expectation and production baseline.

Potential causes of low bioreactor productivity

The lack of a single, standard root cause makes the issue of low bioreactor productivity especially difficult to solve. One of the most common issues has to do with selecting the right scale-up parameters. Specific power, dissolved oxygen concentration, oxygen uptake rate, mixing time, shear rates—the range of critical process parameters is broad, and choosing the specific criteria that are appropriate for your project goals is key to future success.

This due diligence helps your team engineer and modify an operating environment that’s appropriate for your situation while avoiding many of the conditions that can impair bioreactor productivity, including:

The bottom line: While your productivity problem may have a relatively simple solution, identifying that root problem in the first place requires a tailored approach.

Strategies for addressing low bioreactor productivity

What does a CFD bioreactor study typically reveal?

A CFD study culminates in a detailed description of tailored solutions and recommendations to help you meet your productivity targets. To support and contextualize these recommendations, your CFD team will provide quantitative results supplemented with rich data visualizations captured from their simulations, including contour plots, vector field plots, and animations.

These visualizations provide an up-close view of the environment inside your bioreactor, showing you how that environment responds to different design adjustments. The output of these simulations gives you the data and actionable steps necessary to improve your bioreactor’s operating conditions. Here are two quick examples of how the output of a CFD simulation has increased a bioreactor’s efficiency:

• We used CFD to optimize the agitation rate and sparge flow rate for a client’s existing 16,000L bioreactor. The adjustments required no additional capital and more than doubled the oxygen mass transfer coefficient, significantly increasing the yield per batch by intensifying cell productivity.
• In another instance of optimizing processes within an existing bioreactor, we used CFD to reduce virus blend time by 70% while keeping the shear rate low enough to prevent cell damage. Again, we optimized an existing bioreactor’s processes without CapEx by simply adjusting operating settings.

Typically, a CFD study and the visualizations it produces answer the three questions we highlighted earlier:

What will your CFD specialist need to run simulations?

If your CFD specialist has strong experience working with cell cultures in alternative proteins, vaccine or antibody production, they’ll be able to guide you toward the data and specifications that are necessary to get started. You’ll likely have most of that information at hand already, such as your vessel’s computer-assisted design (CAD) model and details about its current operating conditions.

With this background information to guide them, your CFD specialist can simulate your bioreactor and test different solutions, ultimately uncovering the precise parameters that will generate your target productivity rate.

Need help moving forward?

Download our CFD guide to get started or talk to our team of experienced CFD consultants to take your first step toward more productive and profitable operations.