Growing the Cells to Realize Probiotics’ Promise

| July 14, 2019
 
 
 
Growing the Cells to Realize Probiotics’ Promise

With demand for probiotics surging, DuPont engineers tackled the challenge of designing the world’s largest — and most innovative — fermenter. 

Dave Cress’ heart rate jumps at the same point in his commute into Rochester, New York, each morning: the moment he spots DuPont’s newly expanded facility just off the expressway. Most drivers probably don’t notice the nondescript industrial building, and those who do may not give it much thought. But Cress, a DuPont project team leader who moved to Rochester for college in 1992 and never left, knows the facility houses a momentous milestone in the city’s storied industrial heritage and represents a boon to probiotics.

The city that rose to prominence with the opening of the Erie Canal and then nurtured legendary companies like Eastman Kodak and Xerox now boasts the world’s largest probiotics fermentation unit. It produces healthy bacteria in novel ways for nutritional supplements, food, and beverages.

The market for probiotics is large and growing.  These beneficial microbes support more than gut and immune health — they have the potential to help solve major health challenges, such as the obesity epidemic and anxiety disorders. But the world can’t achieve those goals without enough bacteria.

No wonder Dave Cress gets excited. 

 
 
 

“When your product is a living organism, you have to reinvent nearly every step of the process to ensure you can grow them efficiently at four times the volume.”

Dave Cress, Project Team Leader | DuPont

 
 
 

Quadrupling production volume

Cress oversaw the recent expansion of the plant, which was part of a broader $100 million probiotics investment project at DuPont.  The company already produces the widest range of clinically documented probiotic strains in the United States. At the facility’s heart is a new stainless-steel tank that towers almost 50 feet above the ground. This new unit can produce four times more bacteria than the older units in the same amount of time.

This single tank will increase the facility’s production capacity by 70 percent, helping extend DuPont’s lead in probiotic manufacturing. Yet growing probiotics at the speed and scale the world now demands wasn’t just a matter of making bigger fermenters. Larger volumes presented new challenges. Cress and his team applied their decades of experience in bacterial fermentation to create a next-generation system that optimizes cell growth and viability on a grand scale.

“When your product is a living organism, you have to reinvent nearly every step of the process to ensure you can grow them efficiently at four times the volume,” he says.

 
 
 

Revolutionizing the process from seed to pellet 

The active ingredients for probiotic products are tiny, freeze-dried pellets — picture beige-colored Dippin’ Dots ice cream, Cress says — each containing 4 to 10 billion cells of good bacteria such as lactobacillus. Fermentation is the process that propagates these bacteria from a small “seed” batch to large quantities.

Probiotic fermentation itself sounds straight-forward — just add the seed organism, along with nutrients from natural origins, including sugar.  But everything else about the process is tricky, especially when expanding to such significant capacity. Bacteria can be fragile and finicky. They need a careful balance of temperature, pH, and oxygen to grow. They must be mixed, concentrated, and frozen for shipment carefully to ensure their survival and potency.

Developing that process at enormous scale required countless hours of brainstorming from Cress and his team, resulting in a fermenting tank that’s been redesigned from top to bottom — literally.

Managing fermentation can be nerve-wracking throughout the entire fermentation process, like trying to control a chain reaction. As bacteria consume nutrients and grow exponentially, they generate lactic acid — too much kills the cells. So, the fermentation team has to ensure the proper balance and maintain an ideal pH level while ensuring that the nutrients disperse evenly and efficiently throughout the tank.

To monitor this delicate process continually, Cress’s team designed and implemented a new automated control system. In an adjacent room, isolated from the heat and noise generated by the fermentation process, the team receives constant updates on various parameters within the tank, ranging from pH to temperature to agitation rate. The software monitors these variables and responds accordingly, such as adding small amounts of base at the right moments to ensure proper dispersion and optimum cell growth or increasing the cooling within the vessel.

“This new fermentation vessel design provides a wealth of information to help us manage and control internal tank conditions in an ideal way throughout the process,”says Cress. “Now, there’s a lot more feedback and independent automation within the system.”

That high-tech approach extends to another key step: cooling the solution before harvesting the cells.  “It’s like turning on your car’s AC on a hot day,” Cress says. “If you want to cool your whole body, you don’t just turn on the floor vents. You want cool air blowing from the dashboard, too.”

After fermentation, the bacteria are prepared for pelletization by adding a material that protects the cells during freezing. The new system has an innovative solution to allow mixing with the concentrated material in a way that minimizes unnecessary harm prior to pelletization.

 

“We intentionally designed the expansion to minimize the number of moving parts in our process,” Cress says. “We need to be gentle with the organism and not introduce any additional mechanical shear or heat.”

 
 
 
 
 
 

Meeting market demand for volume and quality

Every milestone in the fermenter’s nearly three-year development process validated the team’s hard work. But for Cress, perhaps the best moment was watching the first batch of pellets emerge from the pelletizer.  Having studied biotech at the Rochester Institute of Technology and worked on vaccine development for years prior to probiotics, Cress still marvels at these powerful organisms.

The new system not only allows for bigger batches overall, but it also frees up the smaller fermenters to meet changing market needs. In the past, a large order for might take up the entire capacity in the Rochester facility. Now, DuPont can fill that same large order with the new unit and still have tanks available to produce different strains of bacteria simultaneously. This flexibility will help speed new products to market as ongoing research identifies more uses for specific strains.  

Even as consumer demand for probiotics continues to grow, manufacturers won’t have to wait for bacteria to become available — Cress expects the facility to easily meet the need. Even better, they won’t have to worry that faster production might result in less effective ingredients. “The first material from the fermenter exceeded all the expectations for product quality,” Cress says. “The bacteria performed phenomenally.”

That’s something even a non-engineer can get excited about.