GFI highlights chicken-and-egg conundrum facing cultivated meat industry

With a 78% drop in funding in 2023, and two major players pausing plans to open large-scale commercial facilities in the near future, how will cultivated meat transition from a loss-making novelty served at a handful of high-end restaurants to a commercially viable alternative to animal agriculture?

Speaking at a webinar hosted by The Good Food Institute this week, Dr. Elliot Swartz, principal scientist, cultivated meat, acknowledged that like all new industries, cultivated meat producers are stuck in something of a chicken-and-egg situation right now.

Or as chemical engineer and engineering consultant Dr. Dave Humbird observed more bluntly last year, “None of this stuff makes any commercial sense until everyone’s eating it.”

According to Swartz: “While costs for growth factors [pricy signaling proteins used in cell culture media for cultivated meat] are still high today, the bottleneck is one of markets, not technology: no single manufacturer is ready to purchase kilograms of FGF2, IGF1, or TGFb.

“But suppliers by definition need to scale alongside the growth of the cultivated meat industry that they are serving. And this is inherently going to limit how fast certain costs can be reduced, because no one is going to invest the capital needed to create 100 large-scale facilities for growth factors [pricy signaling proteins used in some media formulations] if the industry really only needs to be serviced by five right now.”

Meanwhile, he said: “The bulk of cellular biomass in proliferating cells is made from amino acids [which are used in basal media formulations for cultivated meat]. Today, amino acids used to feed cells come primarily from individual fermentation processes, only some of which are sufficiently scaled.”

‘Cell density as a single metric doesn’t tell you the full story’

He also acknowledged that much of the work on sourcing lower-cost alternatives to certain media components—for example non recombinant sources of albumin or amino acids such as plant protein hydrolysates—is still at the research stage.

“Really everyone needs to know the answers to these questions, or else we’re going to see a lot of duplicative wasted research and efforts. So this is really one area that I think is ripe for publishing results, protocols and methods openly even if you’re a private company.

“With that said, there’s also a big opportunity for these questions to be addressed through collaborative public private work through some of the consortiums that have been formed already in the cultivated meat industry, since these challenges are not easy to solve.”

Overall, reducing media costs will come from economies of scale; switching from pharma to food-grade ingredients; finding cheaper sources of key media components such as albumin; and from developing more efficient cell lines that can thrive with fewer, less expensive inputs, said Swartz.

And the latter is key, he said: “For example, cells can be engineered in various ways to eliminate the need for certain [expensive] growth factors such as FGF2, so I think you will see more and more genetic engineering and editing tools become incorporated into the process to address some of these scalability concerns.”

“Millions of kg of albumin could be needed to supply less than 1% of global meat production volume.” Dr. Elliot Swartz, principal scientist, cultivated meat, GFI

‘Cell density as a single metric doesn’t tell you the full story’

When it comes to assessing the progress of companies in the space, he noted that while metrics such as cell density or media costs per liter are important, they shouldn’t be judged in isolation.

If high cell density is only achieved by using a lot more media, for example, it may not be very meaningful, he said.

Similarly, if some cells can flourish with fewer inputs, the price per liter of media would need to viewed through a different lens. What matters ultimately, he said, is how much does it cost to produce a kilo of meat?

“The question to ask is: what amount (mass) of media ingredients is necessary to produce 1kg of cultivated meat in your production process?”

Scaling up or scaling out?

As for optimal infrastructure for cultivated meat production, he said, “there’s not much primary data to go on, because companies are really just beginning to build their first facilities.” But based on modeling work done to date, large-scale facilities using stir tank bioreactors could cost anything from $300 million to well over $1 billion, with capital costs per ton ranging from $45k to $109k , prompting research into alternative bioreactor types and cheaper plant design.

“If cultivated meat companies are able to start demonstrating successful production runs at volumes that are larger than 25,000 liters [the highest scale known for mammalian cell culture], this could potentially be a de-risking event for the industry, because it indicates that these companies would be able to capitalize on these economies of scale,” said Swartz.

“However, when it comes to scale up, there’s a lot of risk. When you get to larger scales, delivery of oxygen and nutrients equally to all the cells in the vessel becomes more challenging. Additionally, as you increase the size of your vessel, there’s pressure differences that get introduced to cells at the bottom versus the top, which can impact viability.

“One of the things that I think is interesting, but I have no idea about tractability, is the use of nanobubbles for oxygenation, which could be some interesting that could address potentially address oxygenation at very large scales.”

The larger the reactor, meanwhile, the greater the losses should contamination occur, he said. “And if you don’t use pharmaceutical cleanrooms [to save money], this potentially exposes [your operation] to higher rates of contamination. But there are different philosophies. Some skeptics believe that growing cells at large scale in production batches that take weeks in a non-pharmaceutical environment is a dead end.

“Others believe this is not really that big of a hurdle, it’s just never been done before. People are also looking at other potential solutions where things like antimicrobial peptides can act as a second layer of defense if they’re added into the cell culture media to prevent contaminations.”

Above all, he said, “More efficient production processes [faster cell doubling times, increased cell densities, reduced media costs] means fewer bioreactors needed in the facility and fewer personnel to operate and maintain the equipment, reducing the overall cost burden.”

Modes of operation

As for modes of operation (batch, fed-batch, perfusion etc), the best choice may depend on your cell lines, he said. “We know that many companies are developing continuous or perfusion processes, but according to an analysis by Ark Biotech, these might have limitations as you increasingly scale up your bioreactor size, or if you cannot lower your media costs sufficiently.

“The question is how do we increase cell density while simultaneously decreasing media costs?”

Viability

Right now, said Swartz, “I don’t think we actually know the cost of cultivated meat production. There are a lot of different production scenarios and approaches being pursued, and so a single number really is hard to provide.

“I think it’s also critical to provide context for the product and whether or not it’s a hybrid [combining plant-based and cell cultured meat], especially when discussing how costs compare to conventional meat, as well as overall viability.”

If companies are pursuing a high-end product such as foie gras or Bluefin tuna toro, a 100% cultivated meat product can be a tractable approach to cost competitiveness, said Swartz. “If companies are pursuing commodity meats such as chicken, pork, beef, and certain seafoods, then hybrid products at low inclusion rates offer the most tractable way to approach cost-competitiveness. However, the timeline is uncertain.”

Watch Dr. Swartz’s presentation below: