For Pfizer, the Prescription is .NET



Trials have been run, FDA approval is at hand, and—at last—millions of people will soon be able to benefit from the latest drug discovery. Right? Well, not so fast.

From research lab to consumer, the process of bringing a life-enhancing drug to market can take more than a decade and cost as much as a billion dollars. Most people know that the required research and clinical trials are lengthy and time-consuming, but they may not realize that regulatory approval is only the start of what is arguably one of the most complex processes in any industry. Once the U.S. Food and Drug Administration (FDA) approves a drug, the hard work begins for pharmaceutical engineers, chemists, and plant managers, who must prepare for mass production.

The key element in drug production is what is known as the active pharmaceutical ingredient, or API. Until this point in the process, the API has only been produced in very small quantities to support clinical trials. Now the “recipe” for the API, which often exists only on paper or perhaps in a spreadsheet, must be scaled up many times to accommodate commercial production—a process that can take weeks or even a year.

Once the model is scaled for production, the results are still theoretical until put to the test. If a problem surfaces with the recipe when it is tested in the plant, it has to be reformulated, and precious time is wasted. Even when the recipe is perfected, it is exclusive to one plant. Because of the pharmaceutical industry’s history of mergers and acquisitions, almost every plant has a unique collection of equipment and systems. So a recipe that works in one plant doesn’t necessarily work in another.

And that’s just the design phase. Engineers must still physically manufacture the API, monitor the manufacturing process, and, when necessary, prepare investigative reports. Making high-quality drugs—while documenting the process in a way that stands up to the scrutiny of an FDA inspector—is not an easy task. A typical plant might go through this process for 25 or 30 different products a year. It’s enough to give a drug maker a headache.

A promising trial under way in Groton, Connecticut, could bring relief to the pharmaceutical industry. That’s where Pfizer, Inc. is rolling out a groundbreaking system, called Catalyst that could revolutionize pharmaceutical manufacturing and reporting, and help bring the industry into the twenty-first century.

The world’s leading drug maker, with U.S.$52 billion in revenues and 13 category-leading drugs, including Lipitor and Celebrex, Pfizer discovers, develops, manufactures, and markets leading prescription medicines. Several years ago, when Pfizer was building its new plant in Groton, it was looking to use the latest technology to automate the plant. Compared to its peers, Pfizer has always been a leader in using automation technologies in its plants. But there was definite room for improvement, notes Cathal Strain, Senior Director/Team Leader, API Automation & Information Management at Pfizer Global Manufacturing.

The pharmaceutical industry is notoriously antiquated when it comes to information technology. Strain likes to point out a September 2003 article in the Wall Street Journal that noted that pharmaceutical companies, despite being an innovative industry capable of churning out new drug breakthroughs, lags behind makers of potato chips and laundry detergent in their use of IT.

Part of the reason for the lag is an industrywide conservative culture that grew out of intense regulation and a subsequent attitude that the less things changed, the better. But even the FDA lately has been nudging the pharmaceutical industry to modernize. The agency, as part of its 21st Century Initiative, has published guidelines for Process Analytical Technology (PAT) to help coax pharmaceutical companies into the digital age.

Pfizer engineers involved in the Groton plant identified some specific technology gaps. Although shop floor machines and enterprisewide systems were fairly automated, the highly creative tasks of designing API processes and planning their production were not. In addition, chemists and engineers were spending too much time hunting down information and preparing documents, which took away from more productive work. The team of engineers also noted that there was little integration between existing systems.

The engineers had two main goals: 1) To reduce the amount of time and effort spent doing investigations and preparing documents, and 2) to increase management effectiveness by providing access to real-time information presented in a rich format and useful context.

When the team started looking at technology offerings in 2001, it became clear they would need several discrete applications to accomplish what they wanted to do, and they would have to integrate the solutions themselves. They began to conclude that it would be best to build a completely new system. In 2001, a Pfizer team visited the Microsoft® Technology Center in Austin, Texas. What began as a mere visit to take a look at technology quickly turned into a collaborative effort that led to Catalyst, a fully integrated suite of functionality that spans the API manufacturing process, including design, production planning, and analysis. The system was developed using software that takes advantage of Microsoft .NET connection software, including Microsoft SQL Server™ 2000, the Windows Server™ 2003 operating system, the Visual Studio® .NET 2003 development system, Web services, and the .NET Framework.

The Groton plant began beta-testing Catalyst in November 2004, and version 1 was installed in mid-2005. As Strain says, “Catalyst is a paradigm changer.”

Catalyst completely automates recipe design. Recipes are now highly structured models that are stored in a central SQL Server 2000 database so that they can be shared by other applications and users. Design Catalyst, the process-design component, takes into consideration all information about materials, reactions, and available plant equipment, and calculates a production recipe in a matter of seconds. It also validates the model. If there was an error made in the assumptions or input, Catalyst flags it. A new model can be recomputed in seconds. Now Pfizer’s chemists and engineers can get it right the first time.

That amounts to a huge timesaving. But it’s only the beginning. Catalyst will also automatically adapt the recipe for other plants and their unique capabilities, which helps with the second phase, production planning. Planning Catalyst can assess current production status at plants around the world, identify what equipment is available, and rank each piece of equipment based on its ability. The system can determine whether a vessel is in use or fallow and note special characteristics—for example, if a vessel or tank is glass lined, which might be desirable when dealing with corrosive substances. “Catalyst provides a level of information integration that was not possible before .NET,” says Adam Lalonde, Pfizer’s Catalyst Development Manager.

When Catalyst is fully deployed, engineers will be able to draw upon Pfizer resources around the world to split up production between plants while maintaining quality and consistency. Catalyst gives Pfizer, which operates a dozen API plants around the world, an unprecedented and highly efficient means of scheduling production and optimizing capacity on a global scale. That capability can greatly reduce the time it takes to get a drug to market once it is approved—not an insignificant factor, considering Pfizer plans to submit 20 new drugs for FDA approval by 2006. “Catalyst opens the door to a truly global planning process,” says Majdi Rajab, a technology consultant to Pfizer since the beginning of the envisioning process that resulted in Catalyst.

There’s a final piece to the API manufacturing process, and it is a significant one: Analysis. To comply with pharmaceutical industry regulations (which include environmental and safety regulations in addition to those of the FDA), companies must generate an endless stream of reports and documentation. In API manufacturing, any anomaly triggers an internal investigation and a “Notice of Event” to the FDA. Depending on the outcome of the investigation, the company can be fined.

To understand how Catalyst has affected analysis, imagine that a batch of Lipitor API exceeded the normal temperature. When such an event is discovered, an investigation is triggered. Before Catalyst, conducting an investigation typically required an employee to hunt down documentation and interview people to piece together the situation. This is a time-consuming and manual task as the records are scattered in different places, often not in electronic form, and rarely linked together in any meaningful way.

Furthermore, a week or more can go by before an employee has time to go back and review the situation. In the meantime, more batches were run and, chances are, the same problem affected those batches as well.

As it does with design and planning, Catalyst brings a new level of automation to the analysis or “exploring” phase. For the first time, all the information relating to production is collected and stored in a central database, so engineers have all of the data they need, in a rich context, at their fingertips. Instead of taking weeks and hundreds of work hours, investigations can take days or merely hours. “That’s the kind of business-changing impact we are trying to make,” says Strain.

Drug makers are also required to prove to the FDA that they manufactured a substance the way they promised they would. Catalyst creates an electronic record of the process, which can be submitted to the FDA and compared to the original version. The analysis component, known as Exploring Catalyst, not only helps with compliance and internal investigations, but also supports Pfizer’s broader goal of regulatory excellence.

For all of its outsized capability, Catalyst was built by a relatively small team of developers from Pfizer, Microsoft Services, and the Microsoft Technology Center in Waltham, Massachusetts. The system is based on a multi-tier, distributed .NET architecture using Web services, XML messaging, SQL Server 2000 and a rich graphical user interface (future versions will make use of SQL Server 2005). It is currently being deployed in Pfizer’s Groton plant, where it will ultimately be used by a couple hundred employees. By early 2006, Catalyst will be rolled out to a second plant in Ringaskiddy, Ireland, and then to plants in Puerto Rico and Singapore, allowing for truly global capacity planning. The initial four plants represent Pfizer’s most complex API manufacturing sites.

Strain has been busy presenting the system to Pfizer’s far-flung plants. The reaction so far? “Incredible,” says Strain. “I’ve never enjoyed going out and doing demos so much!”

Pfizer estimates that Catalyst will pay for itself in 6 to 12 months by saving time, effort, and inventory. And it may well establish Pfizer as the first of the big pharmaceutical companies to meet the FDA’s challenge to modernize. “I think the FDA is going to be very pleased with what they’re seeing here,” says Strain. “It should set a new paradigm for the industry.”

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Pfizer Inc., a U.S.$52 billion company based in New York, discovers, develops, manufactures, and markets leading prescription medicines for humans, animals, and many of the world's best-known consumer brands. Its products are available in over 150 countries.

“Catalyst opens the door to a truly global planning process.”

—Majdi Rajab, Technology Consultant to Pfizer

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“Catalyst provides a level of information integration that was not possible before .NET.”

—Adam Lalonde, Catalyst Development Manager, Pfizer

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“It should set a new paradigm for the industry.”

—Cathal Strain, Senior Director/Team Leader, API Automation & Information Management at Pfizer Global Manufacturing

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