What Is Surge Manufacturing And How Can Biopharma Companies Prepare For It?

By Life Science Connect Editorial Staff

In response to the COVID-19 pandemic, numerous biopharma companies accomplished a near-miraculous level of mass manufacturing of vaccines and other biologics. One approach to this rapid scale-up of manufacturing has been dubbed surge manufacturing. In the wake of the pandemic, many more pharmaceutical companies are looking into if and how they can prepare themselves to adopt the concept.

On a recent edition of Bioprocess Online Live, Matt Pillar, editor of Bioprocess Online, spoke with two leading minds on the topics: Kayla Hannon, manager of process engineering at TFF Pharmaceuticals, who was on the front lines at Moderna when it faced the challenge of ramping up COVID-19 vaccine production; and Zoltán Kis, Ph.D., a lecturer at The University of Sheffield and a leader at the Wellcome Leap R3 Readiness + Response project.

The concept of surge manufacturing was largely unknown or not well understood by many of the listeners, as gleaned from questions submitted to the panel in advance. As such, Hannon and Kis spent much of the webinar discussing what it is and what is required to execute it effectively.

Setting A Surge Strategy

There are several scenarios that could justify surge manufacturing in the biopharma space, including raw material supply chain shortages, natural disasters, product recalls, and manufacturing plant emergency shutdowns. However, in response to a polling question, most audience members indicated that the most compelling reason to have a surge manufacturing plan is the risk of another pandemic.

According to Hannon, surge manufacturing requires flexibility to scale up processes. “Having a site or a process that you're able to reconfigure quickly or move around and scale up quickly is definitely something that's going to help enable surge manufacturing. Looking at things like single-use technology, how can you turn over things quicker and rapidly mobilize scale-up?” she said.

Kis suggested that having excess manufacturing capacity could be a key component of surge readiness. However, he noted that there are trade-offs to having excess capacity, asking, “What do you do with this capacity right now when there’s no product to make? How do you finance that?”

Hannon quickly added her affinity for process trains and the ability to swap out smaller equipment for larger ones, such as a 50-liter single-use mixer for a 100-liter single-use mixer. Both panelists agreed that another viable solution is to have equipment with a higher maximum capacity than needed, for example, running 20-liter volumes in 50-liter tanks, so that the volumes could be increased rapidly without leaving machinery idle.

Staffing For Surge

Effective surge manufacturing is more than just a production capacity problem; it’s also a manpower and expertise problem. In particular, multiple audience members asked how they could “surge” personnel. Hannon said that during the pandemic, Moderna relied heavily on consultants to help start up new equipment and train existing staff on its operation. In addition, the company leaned on operators to take on multiple shifts to keep equipment running as often as possible.

However, process automation, she said, was critical to success then and will be for any future surge manufacturing. She recommended that biopharma companies figure out how to automate their processes as early as possible. Early product development is very manual, she admitted, but once product parameters are tied down, she said, “being able to automate a system helps immensely.”

Kis expanded on this to note that real-time monitoring along with automation can go a long way to closing hiring gaps under normal circumstances, but particularly during surge manufacturing. Speaking to work his team is doing at R3, he said, “We're looking at building all sorts of kinetic models, for example, that can predict degradation in real time based on things that are happening in the process like pH, temperature concentration of certain components. We use this information to even forecast degradation ahead of time.”

Leveraging Resources

The conversation turned to the role of outsource capacity and its role in surge manufacturing. Both panelists agreed that CMOs and CDMOs are a critical resource, but the question was whether they could meet potential surge demand. Hannon pointed out that “you can also use multiple CDMOs or multiple rooms to be able to scale up.”

However, even when working with one or more CDMOs, Hannon asserted that biopharma companies may need to prioritize their production lines in order to surge. “You might have to step down your clinical process to meet the demand of the pandemic,” she said. “So, pausing one thing in Phase 1 or really early product development to then increase [manufacturing] to what you need to meet [demand] today. And that’s kind of part of the risk assessment.”

Kis flipped the script and said that the CDMO may have to consider its own options in the event of a future pandemic. “[A CDMO’s] capacity is very valuable for surge manufacturing, but their capacity is utilized in non-pandemic times or non-outbreak times already,” he said. “So, if you switch their facilities to making dynamic response products, you disrupt their other activities.”

The answer there, he suggested, is for CDMOs to maintain stockpiles of certain products whose production could be paused during an emergency in order to open lines for a surge.

Kis rejected the idea that universities could fulfill capacity needs for surge manufacturing. In addition to having small footprints, he said, “Universities very rarely have GMP-grade facilities.”

Navigating Regulatory Challenges

Pillar posed the question of how government regulations could stymie efforts to surge effectively or even at all. Hannon mentioned that during the COVID-19 pandemic, the FDA was very amenable, allowing electronic filings and being more generous with emergency authorizations. Even with these, Hannon emphasized the value of single-use equipment in proving no cross-contamination.

Kis suggested that since mRNA is a platform technology, it would be worthwhile for regulators to consider a prequalification process. “Basically, the process doesn't change if you have a platform,” he said. “So, with that approach, I think the regulatory workload could decrease as well. They would not have to do it every time for every product when not much changes in the process.”

Surging Forward

While the pandemic was a challenge for everyone worldwide, the panelists concurred that there were many valuable takeaways that have since benefited the biopharma industry. “I would say how quickly we were able to use a novel science like mRNA to come out with a vaccine so quickly -- that showed really great effectiveness. And then being able to scale that growth and continue to show effectiveness at different scales was very noteworthy,” said Hannon.

Kis lauded the number of initiatives focused on improving mRNA technology and biopharma production overall, specifically citing the WHO mRNA Technology Transfer Hub. “That’s quite ambitious, and that would also aim to establish a manufacturing capacity distributed in multiple countries, mostly low- and middle-income countries,” he said.

He went on to say that the COVID vaccine has effectively proven mRNA’s value as a platform technology, stating, “It’s really nice to see multiple mRNA-based products coming on the market and how this becomes a platform, then combining that with automation and more efficient processing to reduce the footprint of these production lines.”