How to Select the Right Platform for Your Vaccine Production Process

Roller bottles, stacked vessels, microcarriers, bioreactors — researchers are flush with choices when selecting adherent platforms for vaccine production. Making the right choice requires scientists to consider a range of factors, from surface area to scale.

How you approach your choice can make or break a project's success — so think through your goals and test out your options. Thorough due diligence at the start will lead you to make the most effective choices and put you on track to achieve outcomes that match your expectations.

"Process optimization can look different for different research objectives, which means required materials and modalities can, too," said Chris Suarez, Ph.D., a field application scientist manager at Corning Life Sciences. "I always advise people to start with the end in mind. What are your objectives for your cell lines, and how do you envision your terminal seed train? These initial considerations can help drive platform selection."

As far as which factors to consider and why they make a difference, Suarez has suggestions.

Start at the Surface

Two big things matter when considering the right vessel for your cell line: the desired surface area and the optimal surface treatment. You could make most vessels work for your desired surface area and scale, but they might not always be feasible. For example, you could use either roller bottles or stacked vessels for a process requiring a large yield of cultures — but the former might take hundreds of bottles, and a stacked solution might be more efficient.

Surface treatments are trickier. Because different vessels offer different coatings and modifications, Suarez says the first things researchers should consider are what surfaces are available and how their cell lines will perform on them. If you're not sure, ask your supplier.

"Across all different platforms—whether that's a roller bottle, stacked vessel, or fixed bed bioreactor—there's going to be an associated surface or characteristic that's unique to the vessel," he said. "These can vary between surface modifications, which are material changes to the vessel, and surface coatings, which are applied to the vessel."

"For surface modifications," he continued, "you might want a tissue culture-treated vessel, which is standard for most needs, or you might choose something like a Corning® CellBind® surface that maintains cell attachment while being able to withstand multiple media exchanges. For surface coatings, you might feel your cell line would thrive with a collagen coating, for example. But not all treatments are available on all vessels, so there are trade-offs to consider at the outset."

If you're ever in doubt about your chosen platform, Suarez says, the best practice is test it out.

"You'll want to undergo small process development testing before you get too far down the path of committing to specific platforms," he said. "The outcomes of these tests can help researchers understand the timing of their planned cell expansion; optimize conditions for cell viability, adherence, and maximum yield; and ultimately determine the best surface for that exact cell line before doing things at scale."

Consider Your Scale

Depending on the number of operators and amount of facility space available, some vessels are more practical than others. Biotech and industrial labs incur heavy labor costs, so time-intensive tasks such as monitoring, changing media, and harvesting from hundreds of roller bottles can be inefficient and unprofitable. They also tend to have more facility space to accommodate high-capacity reach-in incubators, designed to hold large quantities of stacked vessels. Closed-system solutions like stacks, microcarriers, and bioreactors offer more surface area and automation potential, so they might be the better investment.

Academic labs may have different considerations. Often, space is more constrained and prevents installation of multiple high capacity reach-in incubators. While there are large numbers of researchers, there are often shared resources, such as biosafety cabinets and smaller format incubators. This means that scale up strategies must be tailored to maximize use of the incubator space while minimizing the time needed inside a biosafety cabinet.

In each scenario, choosing the appropriate size and quantity of vessels is something to consider during early stage planning of your cell expansion strategy.

Other labor considerations matter, too — especially now. During the COVID-19 pandemic, many labs have had to stagger schedules to limit close contact. If your lab can't safely accommodate the number of people it needs to support labor-intensive vessels, upgrades in vessel type and automation could help keep research on track.

Consider the Contamination Risk

Suarez estimates that as much as 70 percent of the vaccine production process is focused on quality control. Much of that is dedicated to minimizing contamination risk, which can cut into profitability and affect culture performance. That's why the vessel selection process should also include closed-system configurations against open-system configurations.

"In vaccine manufacturing, you always want to reduce the risk of contamination — not only from the small scale but throughout your entire seed train to the endpoints in your process," Suarez said. "But with certain open-system platforms, like roller bottles, you do introduce more risks when you open and close the caps and use pouring and pipetting techniques to add or remove media."

Closed-system vessels are a more efficient way to mitigate risk while promoting cell line quality, he says.

"With closed systems, you're able to maintain a more sterile and validated process workflow thanks to aseptic connectors or tube welding," Suarez said. "Depending on your timeline, budget, and labor, implementing closed systems could be the more cost-effective way to ensure quality end to end, even if they require more processing time to weld and connect different tubing."

Making the Right Decision

There's a lot riding on your adherent platform selection, especially because types and treatments vary from vessel to vessel and supplier to supplier. Don't be afraid to ask your vendor for detailed configurations from their catalog or for help formulating small-batch tests at the outset.

Choosing the right vessel could be the difference between cells that die and cells that thrive. Take the time and make the effort to understand those factors that will result in the most efficient scale up strategy for your cells.

Looking to optimize your cell culture platform? Explore Corning's lineup of vaccine production equipment.