Speed-Swimming in a Data Swamp

The vision of IT-driven drug manufacturing, like that of the paperless office, is far from a reality for most companies today. In that vision, sophisticated computer programs, guided by design engineers and research chemists, would generate mounds of data that define new production plants. The data would flow seamlessly through each program as the plant is built, validated and commissioned. And when commercial production began, production data would flow in the reverse direction, matching plant capacity with production equipments, and meeting corporate regulatory, accounting and business goals.

The reality? Design and construction programs output paper documents that are handed over to a new plant's owner. A new data-gathering effort then begins to meet validation and production goals. Then, as production begins, more databases are created, each requiring constant attention. IT and automation budgets soar, time is wasted and regulators begin asking, "who's in charge here?"

The need to speed time to market is driving more corporate managers to move from the reality to the vision. Vendors of everything from design and engineering systems, to control systems, to corporate ERP, all propose solutions that combine program execution or calculation with a database for storing the program's data as well as the information flowing forward and backward across an organization. These products have traditionally come under the rubric of plant (or product) life cycle management (PLM) solutions, but are increasingly being referred to as "asset management" tools.

Whichever label you use, the idea of getting everything within such a system to talk to all its parts is a challenge. "Without going really crazy with the money, you could justify almost any level of IT costs to accomplish this, simply because you want to get to market fastest," says Drew Wildman, team leader, IT systems, at Eli Lilly & Co., Indianapolis.

Vendors may be leaping forward with product offerings, but they're encountering some resistance from pharmaceutical companies. Drug manufacturers have been slower to adopt new IT systems than other process industries, observers say, but the situation is changing.

"Being [part of] a regulated industry, pharmaceutical companies tend to be conservative," notes Mark Wheeler, a life sciences market manager at Aspen Technologies, Cambridge, Mass. He cites the current emphasis on modernization of facilities coming from FDA Commissioner Mark McClellan as one driver; another is the growing difficulty of meeting documentation and validation requirements without having modern IT tools.

But the trump card is time to market: "Passing clinical trials is still the controlling factor with new drugs, but once that happens, the problems in dealing with all the information to design and build a plant, and keeping all the paper and e-mails flying around in synch, becomes very difficult," Wheeler concludes.

Like their counterparts in other industries where chemical reactions are the source of products, pharmaceutical process designers work with process simulation tools. Unlike other process industries, however, most of the process design is batch-oriented, and"tends to be dominated by scheduling unit operations, rather than by the kinetics or reaction rates of the processes, according to Dimitri Petrides, president of Intellign, Inc., Scotch Plains, N.J.

Intelligen offers two tools, SuperPro and SuperSchedule, to model pharmaceutical processes. Petrides says that typically, a user would develop a flow diagram "based on the process recipe "in SuperPro, then shift the data to SchedulePro for scheduling and debottlenecking the process. Utilities, such as clean-in-place (CIP) skids, buffer solutions and the like, are often the bottleneck, especially when production is being scaled up. Most recently, Intelligen has developed an equipment database, based on Microsoft Access, to store asset information.

Aspen has a batch-oriented offering called Batch Plus. Following Aspen's acquisition of Hyprotech in 2002, the company is in the process of integrating components of Hyprotech's Batch Design Kit into Batch Plus. According to Aspen's Wheeler, Batch Plus is part of Aspen's Engineering Suite, which allows data-sharing between the recipe management of Batch Plus and the kinetics or distillation features of Aspen Plus.

In addition, Aspen has invested heavily in asset-management and supervisory process-control tools, such as its Electronic Batch Records System (EBRS), and Info Plus 21, to allow for data to move from one application to the next. "The idea here is to work collaboratively," Wheeler explains. "Years ago, manufacturing experts would not have been brought into the design process until a drug had passed Phase III trials. Now, process engineers and researchers can synchronize their workflows better." Besides "time to market," he stresses, companies need to plan for "time to volume" "the time it takes to ramp up production, especially during a crucial product launch.

Some of these activities could be seen in action at Merck kGa, a pharmaceutical intermediates and fine-chemicals producer in Darnstadt, Germany. There, according to Michael Grund, head of process development engineering, the largest multipurpose batch plant in Europe has been developed and built over the past several years.

Aspen's Batch Plus was used early in the design process to reduce the 250 distinct chemical reaction pathways into 12 design recipes that allow a range of products to be produced while sharing appropriate process equipment. Besides helping plan the batch scheduling, says Grund, Batch Plus provided the documentation necessary to win regulatory approvals. "When you can show all the mass balances accurately calculated and consistently presented, you speed up the review process," he says. "One wrong mass balance and the regulatory review stops."