During the COVID-19 pandemic, the public learned more than ever about the pharmaceutical cold chain. However, for bioprocessors, cold-chain workflows had already been changing.
“There has been a big transition for at least 10 years as bioprocessors turned stainless-steel workflows more towards the single-use technologies,” says Muhammad Siddiqui, life science application engineer at Entegris. “Still, in more recent years, there’s been a growing focus on the cold chain, actually treating it more as a unit operation of its own because some of the new developing therapies are temperature sensitive.”
In addition, Siddiqui notes that “growing attention to improving yield of existing biologic therapies—for example, monoclonal antibodies—is driving this change.”
In that chain, two of the key steps are freezing therapies and then thawing them, and the industry is “shifting toward adopting more controlled, reproducible, and scalable solutions that enable those operations,” Siddiqui says. Entegris helps bioprocessors incorporate those steps in a complete manufacturing workflow and played an important role in the development of the COVID-19 vaccines.
Cold chain challenges
In thinking of the overall challenges in the cold chain, John Lynch, PhD, vice president of the life sciences business at Entegris, describes two general categories: product and process challenges.
“Product challenges directly impact the biologics, and that’s the focus when manufacturers are doing their development work; process challenges arise when a manufacturer is scaling up to commercial production,” he explains.
So as a bioprocessor thinks ahead, a workflow must include equipment and containers, such as plastic bags, that work together to create a homogenously frozen product. “You don’t want the frozen bulk to have different regions of pH, salt, concentrations, and so on,” Lynch says.
To create the best cold chain for a therapy, a bioprocessor should include those steps in early planning.
“It starts with having a mindset on the process economics, making sure that whatever solution you end up adopting and scaling up can give you the best yields and lower costs—operating costs and capital costs—and even a more sustainable process,” Siddiqui tells GEN. “One of the best things you can do is really start assessing different solutions as early as possible in the process development.”
To give bioprocessors an opportunity to evaluate different cold-chain workflows, Entegris developed its Life Sciences Technology Center, where a bioprocessor can test various containers and devices for freezing, storing, and thawing samples.
“Here, a bioprocessor gets hands-on with those solutions, being able to see product demonstrations, test samples with your product, run some initial studies, and really be able to look at that small-scale evaluation, but also see how that solution can scale up to a commercial workflow,” Siddiqui explains. “That’s where you’ll start to see the economics work out.”
In fact, Entegris can develop economic models of different cold-chain workflows for comparison. “In this way, a bioprocessor can see what would really make the biggest impact and improvement without the need for physically testing different scenarios,” according to Lynch.
The recent focus on cold-chain workflows in bioprocessing is likely to keep evolving. As a result, bioprocessors need to consider these steps early and test variations whenever possible.
