A nondescript factory just off Hwy. 610 in Brooklyn Park is quietly churning out batches of high-tech biologic drug ingredients in a quest to become the largest working biotech pharmaceutical plant in the state.
The plant is owned by Japanese drugmaker Takeda Pharmaceuticals International Co., one of the 20 biggest drug companies in the world. Takeda has been working for years to bring a sophisticated facility online in Brooklyn Park that will become its first U.S. manufacturing site and also serve as a corporate center of excellence where Takeda can study and develop "large-molecule" biologic drugs of the future.
"Getting into the biologic space was new for Takeda, and it has helped us to appreciate the complexity of biologic manufacturing," said Uthra Sundaram, a senior vice president in Takeda USA's specialty-drug division, which plans to make its hot-selling gut-inflammation drug Entyvio in Brooklyn Park starting next year.
Biologic drugs are produced by living cells instead of from chemical synthesis, which is why the north metro plant is home to gleaming 10,000-liter bioreactors where complex proteins like those in Entyvio can be created under carefully controlled conditions.
Biologics make up a fast-growing sector of the drug market. The Iqvia Institute, which tracks drug spending, said that five consecutive years of double-digit revenue growth propelled sales of biologic drugs past $120 billion in the U.S. last year.
About 46 "biopharmaceutical" plants have been opened or upgraded in the U.S. and Puerto Rico since February, according to an analysis of federal data by Washington-based industry trade group PhRMA. More than 1,000 drug plants in total operate in the U.S. and its territories.
Minnesota is home to pharmaceutical companies such as Upsher-Smith Laboratories in Maple Grove and ANI Pharmaceuticals in Baudette, but Takeda's plant in Brooklyn Park will be the largest biotech pharma site in the state, with more square footage than a SuperTarget.
The Brooklyn Park plant is working on its "process performance qualification" batches for Entyvio, and data from those test batches will be used to pass the Food and Drug Administration's standard drug-plant inspection process. Takeda acquired the 14-year-old plant in Brooklyn Park from Baxalta in December 2015, and has been working to bring it online since then. By roughly this time next year, Takeda hopes to be making real doses of the active ingredient for Entyvio.
"When you look at the scope for the facility that we had around the renovation and starting Entyvio manufacturing, the timeline that we have for Brooklyn Park is very aggressive," said Eric Hahn, the site head for biologics operations at the Brooklyn Park plant. "Takeda plans to license the Brooklyn Park facility to supply the U.S. market first. Once approved, we plan to expand licensing to other regions, so that we can serve patients around the world."
Last year Takeda sold $1.2 billion worth of Entyvio in the U.S. that was made at sites outside the country. Takeda chose to centralize that manufacturing in Minnesota because of the Baxalta facility, and the area's ecosystem of workers familiar with life-sciences manufacturing.
Entyvio is approved domestically to treat inflammatory bowel conditions like Crohn's disease and ulcerative colitis through a 30-minute infusion. Other ways of administering it, like injection, are being investigated. The drug, also known as vedolizumab, is being investigated in small, early-stage trials for celiac disease and HIV, according to the National Library of Medicine database of clinical trials.
When the first batch of Entyvio ingredients rolls out of the 215,000-square-foot facility next year, it will be the culmination of more than three years of work by Takeda to establish a new global center of excellence for its biotech business. It will also be the first of Takeda's 20 drug-manufacturing plants to be located in the United States, which made up more than a third of Takeda's total $16 billion in annual revenue last year.
Takeda is a 237-year-old drug company based in Tokyo that employs about 30,000 people worldwide, including 220 in Minnesota. The local workforce will eventually reach about 250 as commercial production ramps up.
The Takeda project received a legislatively directed $2 million forgivable loan from the Minnesota Investment Fund and a sales-tax exemption for the facility, contingent on capital spending and creation of 190 jobs at the facility. The Brooklyn Park Economic Development Authority said in meeting minutes that Takeda planned to invest at least $190 million into the plant "to offset the extraordinary costs associated with the FDA certification process."
Like all drugs made of monoclonal antibodies, Entyvio is not easy to manufacture.
Entyvio's active ingredient is an antibody that binds with another protein in the body called alpha-4 beta-7 integrin. That interaction blocks the movement of specific cells to the GI tract that can cause inflammation, and helps to control symptoms of ulcerative colitis and Crohn's disease, Takeda says. The drug has clinical studies backing its effectiveness and examining rates of adverse events.
Compared to a traditional drug like aspirin, which involves manufacturing a product by chemically synthesizing components, creating the active ingredient in a biologic drug like Entyvio requires a manufacturer to carefully control cells in industrial-scale bioreactors and then purify the byproducts.
"Monoclonal antibodies are produced using cell-culture processes. Manufacturing for these types of products is complex and can take up to 45 days of continuous processing to complete" a single batch, Hahn said.
On a recent plant tour, company officials declined to take visitors into the part of the facility where the drug will be made once the FDA inspectors approve.
But site manager Hahn and senior director of technical operations Mike Gramer did open the doors to smaller-scale development lab at the site, which includes small-scale bioreactors that could play an important role in Takeda's future.
"Having these development capabilities and the commercial manufacturing capabilities positions us well to support Takeda with bringing in additional products from the pipeline," Hahn said. "We have capabilities to produce product for clinical trial in this facility ... Also, we have the capabilities to commercially manufacture products as well, as they transition out of clinical trials and become approved products."