Bioreactors in Bloomington: the start of a biotech drug cluster?

A FLEDGLING BLOOMINGTON company set to begin production later this year draws upon a long history of manufacturing and life sciences in Indiana.

Cook Pharmica LLC, the newest manufacturing company under the Cook Group umbrella, is spending much of this year going through the lengthy regulatory approval processes required for pharmaceutical manufacturing. By this fall, company officials hope to be in production, turning out ... well, they're not quite sure yet.

The company hopes to ride a growing wave in the pharmaceutical business: contract manufacturing of drugs for other companies. "There has been a trend in the pharmaceutical industry in the last 10 years where people have been moving to contract manufacturing," says Cook Pharmica's president, Jerry Arthur, who came to Bloomington-based Cook Group about a decade ago after spending three decades at Eli Lilly & Co. in Indianapolis. "One major reason is the high, capital-intensive cost of a pharmaceutical plant. It can be better used if it makes several products."

Cook Pharmica will go beyond manufacturing, employing a stable of Ph.D.'s specializing in product development--adding critical value to someone else's pharmaceutical discovery by coming up with a way to manufacture it on a mass scale. Thus, says Arthur, when it comes to R&D, "we have the 'D.'"

"There are many companies out there that are just coming up with products and don't have manufacturing capabilities," says Roger Brunkow, Cook Pharmica's director of operations. "That product has to be put into a process to make it."

Cook Pharmica, he says, will help client companies by developing the manufacturing process when necessary. "What we really want to do is distinguish ourselves from competitors by being much better at making a scaleable process," Arthur adds. In fact, Cook Pharmica's aim is to design for its clients a manufacturing process that's flexible, scaleable and transferable, a process clients can take back to their own facilities if they desire.

On the other hand, some potential customers may have already developed a manufacturing process for their product. "We'll be able to serve them by using our manufacturing capacity," Brunkow says. Cook Pharmica will therefore be able to market to both small biotech firms without their own manufacturing capacity as well as larger biopharmaceutical companies that require additional capacity. The current Cook Pharmica facilities aren't big enough to meet demand for the next blockbuster drug, but they can support smaller-scale commercial production as well as clinical-trial uses.

The Cook Pharmica operation is growing within Bloomington's old Thomson Consumer Electronics facility, once the world's largest color television factory In some 124,000 square feet, Cook Pharmica has constructed a high-tech manufacturing operation, including a pair of 2,500-liter bioreactors which are used to reproduce active pharmaceutical ingredients.

"The plant has been designed to produce monoclonal antibodies, just as the human body makes antibodies," Brunkow says. Monoclonal antibodies are highly specific antibodies mass produced by clones of a single, laboratory-created hybrid cell. The antibodies are typically aimed at single, specific antigens--foreign substances in the body such as toxins, viruses or bacteria. "We'll be making single antibodies to treat a disease state, such as a cancerous growth," Brunkow says.

According to Cook Pharmica, there are hundreds of monoclonal antibody drugs currently in preclinical and clinical trials. Yet there's only a limited amount of manufacturing capacity designed to produce these kinds of drugs, and U.S. Food and Drug Administration approval of just a small percentage of the drugs now being studied could quickly exhaust that capacity Cook Pharmica stands ready to help fill that need.

The plant will boast the latest innovations to allow a flexible manufacturing environment, able to move from one product to another relatively quickly Many current facilities can handle one or two of these production "campaigns" a year, according to Brunkow. "We hope to be able to run five to six campaigns in a year," he says.

One major factor that can limit the number of different products turned out in a year is the downtime between production campaigns. In many facilities, that downtime can stretch into months as machinery is cleaned and prepared to produce a different drug. "We're building this plant differently, with the idea that we can change over in two to three weeks," Brunkow says. Among other things, Cook Pharmica will employ single-use, disposable-bag technology to slash cleaning requirements. "We eliminate the time required to clean and prove that it's clean and validate that it's clean. We have a tremendous advantage."

In a contract-manufacturing industry first, the manufacturing process will be transparent. "We are installing Web cameras in our control rooms and our production rooms so our customers can watch their products being made," says Arthur. With client approval, Cook Pharmica also will allow the FDA and foreign regulatory agencies to monitor validation and production activities over the same secure Internet connections.

The hope is to achieve the highest levels of quality control and customer satisfaction, and perhaps even streamline approval processes. According to Arthur, "transparency is critical in the biopharmaceutical field. Customers need to have as much confidence in our work as they have in their own."

Cook Pharmica's plant has been developed on the fast track. The company was launched April 2004 and within months was working on plant design. Plant construction was under way by early 2005 and was completed within 10 months, much faster than the 18 to 36 months typical for a project of its type.

Currently, the plant is undergoing a validation and commissioning process, confirming that its equipment and processes will function properly If all goes well, production could commence as early as September. Meanwhile, product-development services may begin as early as this spring.

The Cook Group, of which Cook Pharmica is a part, has been known for years as a maker of a wide range of medical devices, grafts, stents, biomaterials and other related products. But Cook Pharmica is not its first pharmaceutical venture in Bloomington.

About a decade ago Cook launched Cook Pharmaceutical Solutions, a contract-manufacturing operation that offered parenteral formulation, fill and finish services. It took drug compounds manufactured by others and formulated them into final strengths and doses intended for injection or intravenous delivery Like Cook Pharmica, Cook Pharmaceutical Solutions was an innovator in transparency and openness--the first contract drug manufacturer in the world to invite customers to come watch their products being made.

"One of our key customers was Baxter Healthcare, and Baxter needed to expand," recalls Cook Group chairman Steve Ferguson. Cook Pharmaceutical Solutions fit Baxter's needs, was already FDA-approved and had a trained workforce, so Cook Group sold the business to Baxter in 2001. It has turned out to be a positive move for the local community, Ferguson says, noting that the Cook Pharmaceutical operation had just over 400 employees when it was sold and has roughly doubled its workforce as part of Baxter.

"At the time we sold to Baxter we were thinking of looking at other pharmaceutical opportunities," Ferguson continues. "In that research process we found biotech companies that needed manufacturing."

Though it's also a contract-manufacturing operation, Cook Pharmica is significantly different from Cook Pharmaceutical Solutions, Arthur observes. The earlier company put the finishing touches on drug compounds already manufactured by others, while "this time we're making the bulk drug itself," he says.

Arthur also was president of the earlier Cook pharmaceutical venture, having come to the Bloomington organization after accepting an early-retirement buyout from Lilly in the early 1990s. Brunkow also had a lengthy Lilly career, leaving the company in 2000 and consulting for a while before joining Cook.

At year-end, Cook Pharmica had more than 60 people on the payroll, and the hope is to employ about 200 by the time the plant is in full production mode. But that could be just the beginning, as the Cook Pharmica plant was designed with expansion in mind. "We started with a $45 million design but increased that to $70 million to put in the utilities and the physical facilities to allow us to expand with only the costs of the process itself," Arthur says.

Company executives foresee significant growth in manufacturing capacity if all goes well. Though plans are far from finalized, the next major build-out could add a pair of 10,000-liter bioreactors, boosting total capacity by a factor of five. Eventually, Cook Pharmica could occupy as much as 450,000 square feet of the former Thomson facility and employ several hundred.

That would be welcome news for a region that has lost hundreds of manufacturing jobs through the closing of the TV plant and layoffs at several other major manufacturers. Ferguson notes that the loss of Thomson and other manufacturing jobs was especially hard on the counties to the south of Bloomington that provide much of the community's manufacturing workforce. "We're in a lot of respects making up for that," he says of Cook Pharmica and other Cook Group growth. "Over half of our employees come from the counties to the south of us."

The new Cook Pharmica jobs, however, are likely to require skills that weren't necessary for the kinds of manufacturing jobs that the area has been losing. "About 60 to 70 percent of our employees will be college graduates, including between 15 and 20 Ph.D.'s," Arthur says.

Among the solutions to the need are coordinated biotechnology programs at Ivy Tech Community College and Indiana University Ivy Tech has developed an associate's degree in biotechnology, with credits that may be transferred to a bachelor's program at IU. "These types of degree programs are going to fit very well with the needs at Baxter and Cook," Ferguson says.

"We're finding that Indiana is remarkably well-suited for this type of business and this type of industry," Arthur says. It offers not just solid programs for preparing life-science workers but also a wealth of university research resources, including IU and Purdue University. "Indiana has the basis to support this industry It's a fertile ground. It's the right place at the right time."