Any investment in the dollars and cents world is a calculated risk. Essentially with a financial “bet,” the risks and rewards often rise with the amount of capital being wagered, er, invested. Baxter International Inc. understands this and is currently making a solid bet that the global market for plasma-based therapies will create a tremendous opportunity, not only for their organization, but for the millions of people worldwide suffering from a range of chronic and debilitating immune disorders and other critical conditions.
How big is big? How about a billion dollars? In April 2012, Baxter International announced that it would be making the biggest capital outlay in its corporate history; investing a billion dollars over five years to build a state-of-the-art plasma products manufacturing facility near Covington, Ga., one ready to meet the fast-growing demand for plasma-based Albumin and IG treatments. At the time, Robert L. Parkinson Jr., Baxter’s Chairman, said, “The announcement represents our confidence in the long-term global growth of our protein business.”
This confidence continues to be inspired, no doubt, by the robust market potential of IGs. Global Industry Analysts (GIA) recently released a comprehensive global report revealing the global market for IGs is projected to exceed $11.8 billion by 2018, driven in part by growing diagnostic awareness and an increasing number of indications for plasma-based therapies. Currently, an industry source pegged the 2012 market value of IGs at approximately$7 billion, climbing from an estimated $5 billion in 2010.
Playing a key and leading role in the inception of the Covington project, Julie Kim, the global head of BioTherapeutics for Baxter, took the opportunity to debut the project to the industry, addressing the attendees of this year’s International Society of Pharmaceutical Engineers (ISPE) 2013 annual meeting. In her keynote, Kim framed the business case for Baxter’s milestone investment but opened with a case study describing how effective and versatile IG treatments can be. The therapeutic benefits of IG are becoming better known, and diagnostically the medical community is gaining a greater understanding of its indications and outcomes.
As her remarks continued, the case study served as a compelling introduction to Baxter’s equally compelling business case for the Covington facility. “One way to think of plasma,” said Kim, “and not everybody likes this analogy, but it’s easy to understand — is similar to when you pull oil out of the ground. You can pull a number of different products out of that oil. The more products that you can pull out, the more beneficial it is …”
From a plasma perspective, she explained, one always gets Albumin, which next to IG, is one of the primary products Baxter will process at the Covington facility. Next come IGs, which are the driver of plasma fractionation volume, said Kim. Following those are a number of different plasma proteins — with a primary potential to treat rare diseases.
Over the years demand for these therapies has been increasing, said Kim. “Part of the demand growth is driven by the fact that you … have better awareness and diagnosis. Another [reason for demand growth is] one of the disease areas that we treat is primary immunodeficiency disorders. This group … represents approximately 200 or so specific disorders. Even in the United States the diagnosis rate is less than 50%, and on average it takes over 12 years for a patient to be diagnosed.” While conditions indicating IG are under-diagnosed, this trend will abate, giving way to increased penetration, explained Kim, a dynamic that will generate sustainable, long-term demand globally; a macro-market force sure to drive the exponential growth in plasma protein sales over the coming years. Expansion of healthcare in developing markets will also drive growth in countries like China, a nation touted to emerge as one of the leading Albumin-consuming markets.
USA: PLASMA CENTRAL
With demand for IG and plasma protein-derived therapies expanding globally, a strategic business decision of the magnitude Baxter is making might beg the question: “Why site the plant in the U.S. when China represents such a lucrative market? According to Kim, because IG is a product based on human plasma, it’s an issue of balancing supply with demand. In order to be able to manufacture therapies, explained Kim, a producer needs to have the “right” plasma available to process into IG. “The way the world works today,” intoned Kim, “unfortunately the only universal plasma that is accepted across the entire globe is from the United States. European plasma is accepted in certain geographies, but the U.S. supply is the only one that’s accepted universally. This represents a challenge for manufacturers in terms of being able to collect enough plasma to turn the plasma proteins into therapy.”
GREEN LIGHT TO BREAK RED CLAY
Baxter’s Kim explained there are many risks associated with creating and commercially sustaining such a large-scale production facility of this magnitude. Chief among them: correctly anticipating product supply and demand far into the future, staying current with advancing technologies and regulatory expectations, and operationally committing to relatively inflexible processing trains not easily or practically reconfigurable to pursue other biological products. With such a strong business case backing the project, support of both executive management and Baxter’s board was earned every step of the way, culminating in the corporate decision to green light the project and begin the monumental task of matching Baxter’s vision with reality.
To that end, on Aug. 1, 2012, Baxter formally broke red Georgia clay for its billion-dollar baby, beginning construction early in 2013 at a 162-acre site 40 miles from Atlanta. The campus will eventually span approximately 1.2 million square feet of developed space including three primary manufacturing units as well as a warehouse, utilities buildings, administrative facilities and laboratories.
Brien Johnson, program executive and vice president for program management, described how the plant fits into Baxter’s overall production portfolio. “It really complements the network we have today,” he says. “It not only expands our capacity for these products and also our plasma testing capability for our plasma collection network, but provides redundancy for a number of these operations. Today, [for] some of [Baxter’s manufacturing] activities and some of [Baxter’s] products we have single sources. So this will provide us with some redundancy ...” Johnson notes that Covington will eventually create jobs in Illinois because Baxter will be shipping Albumin to its Round Lake facility for fill and finish operations.
GEORGIA ON MY MIND
Since the project’s site selection was made clear, state and local officials have been lauding Baxter’s choice and it is clear Georgia is glad to have them. “We picked the location for a number of reasons: logistics, geographic diversity compared to our other plants, the skill base of the people and the attractiveness of the site for people to relocate,” says Johnson. “And the state has some great programs,” he notes, “such as the Quick-Start training program. They’re building their first biopharmaceutical training site adjacent to our site and helping us in a lot of different ways.”
Over the last several months, construction tempo has increased significantly. By March 2014, according to a local news report, some 2,200 workers will be on site, fielded by the primary construction contractors Fluor and Turner Construction. The first manufacturing buildings are expected be finished in 2015 with additional construction concluding in 2016.
Obviously for Baxter, the risks (as well as the potential benefits and financial rewards) associated with building a green field, state-of-the-art manufacturing and research facility were well understood. What makes Baxter’s Covington Biologics Manufacturing facility a ground breaker? It’s a combination of a number of things, really, ultimately a whole greater than the sum of its parts. From its bank-busting billion-dollar price tag and its coming role in the biopharmaceutical revolution, to its incredibly well organized project implementation practices and sustainable operational aspects, every facet of the program is superlative in one way or another. Fueled by finely tuned Lean Six-Sigma-informed internal project management processes and organizational acumen, as well as the swagger factor gained by the architect, engineering and construction teams Baxter selected, the Covington facility is truly groundbreaking.
Here are the broad strokes framing the project. As noted, Baxter is investing more than $1 billion to establish this million-square-foot facility to support its global growth prospects with a major operation supporting plasma fractionation and purification, fill and finish and testing and R&D. Once construction and validation/commissioning are completed in 2015 and 2018, respectively, the Covington facility will have created about 2,000 new jobs across Baxter’s manufacturing network.
In an interview appearing in ISPE’s Pharmaceutical Engineering, Baxter’s Kim explains that the Covington facility will be more vertically integrated than the company’s other sites, combining new technologies and the best demonstrated practices from its other plants at one site. “We’re adopting single-use technologies, where appropriate, to reduce contamination risk, and improve operating costs and efficiencies. The latest and emerging trends in GMP (environmental and viral) controls are also being incorporated in the facility design.”
AN INTEGRAL QBD APPROACH
Baxter has taken great pains to ensure its facility will be forward leaning when it comes to overall operational and process design, innovating to strategically position the plant as a compliance leader through best GMP and QbD practices. Eric Schnake, engineering director for the Baxter Covington facility explains: “We are incorporating quality-by-design principles into the project, and it primarily starts with our validation strategy and validation master plan, which includes a number of components like process risk assessments.
Ultimately, what we do in this QbD approach is identify a process control strategy — the attributes of the process that are important for quality as in critical quality attributes. We’ve tied that to our design and our specific equipment requirements, all of which are a very alive and thriving part of our approach here.”
When fully operational, the Covington facility is projected to add up to three million liters of new capacity annually with the flexibility and infrastructure ready to support emerging global market needs. To the executives leading this project, the intent from the beginning was always to fashion a plant that was state-of-the-art for Baxter, not necessarily the industry. Part of this attitude comes from the company’s 60-year legacy of manufacturing excellence and operational experience.
What’s innovative? Johnson went first, offering that “it’s a couple of things; for one it’s the level of automation we’re incorporating into this facility, not only in process control but in the electronic batch records. We’re not retrofitting a facility. We’re building it with automation from the ground up.” Secondly, Johnson points out that, on a humanistic level, Baxter is creating an environment that will be uniquely pleasant to the folks working there. “For example, we are making extensive use of natural light … from almost any place you’ll be working, you’ll be able to see daylight. Very often, facilities of this type force people into environments that are not only controlled, but closed in. I think [the design of the plant and its extensive use of natural light] will make a nicer environment for our employees.”
Noteworthy also is the plant’s central utility spine, a design feature mentioned by Kim in her ISPE keynote and highlighted in a later panel discussion at the annual meeting chaired by Johnson and attended by Schnake, as well as representatives from Baxter’s team of architect and engineering firms. This aspect of the plant’s layout creates a “super highway” of sorts for utilities and provides straightforward employee and material access to fractionation trains, fill and finish operations as well as allowing architects to segregate manufacturing from supporting operations without creating a rabbit’s warren of closed interior spaces.
Schnake agrees, explaining that process and work flow attributes are better by design aiding everything from quality control to safety. “We’ve got some pretty robust designs in terms of facility segregation. In our business, passage and safety is a concern that we have to design around. We have built in some [relatively] unique GMP concepts around how we isolate the clean rooms. We build out progressively from that until we get to the outside.” Schnake recommends likening the plant’s general design to a shell: “There are layers of the shell from the outside environment down to our cleanest clean rooms — that we’ve baked into our design. We’re also using state-of-the-art filling and isolator technologies for IG filling operations.”
“This is large-scale fractionation processing,” adds Johnson, and is therefore stainless-steel-centric as far as process infrastructure is concerned. “So at this scale, [process design] does not easily lend itself to a lot of disposable technologies. However, we do have some applications in the design where we are using disposable [systems] where it makes sense and where it fits with our operational needs.”
OPEX FROM INFORMATICS
Best practice fractionation, finishing and filling technologies, as well as defense in-depth pathogen safety principles highlight the plant’s layout. But it’s the highly integrated and pervasive nature of Covington’s informatics and data systems which will connect the process and plant floor automation data to the back office and go a long way supporting both compliance and operational excellence. In pharma, data is everything, but its value is zero if it is not processed and disseminated correctly. “The highly integrated nature of our automation helps produce a consistent product quality — as well as enhancing our process safety, personnel safety and reducing manual operations. We want to implement an appropriate level of automation because, in the end, the manufacturing people run this process. You’ve got to find that right balance.”
Johnson and Schnake agree there’s automation that can assist you — keeping sensitive vulnerable process away from the human element, whether it’s to mitigate contamination opportunities, or sparing employees from mundane, repetitive routines. But ultimately humans can’t be divorced from manufacturing operations and this is what Johnson was referring to. “We try not to take the operator out of the operation. And at the same time, we want to put in the appropriate level of automation to take care of routine and actions that are repetitive. It’s always a balancing act, but that’s basically the goal: to keep the operator in the manufacturing process, but add the appropriate level of automation that allows him or her to monitor and still be in charge of the process.” Similarly, through robust data information handling, the data from automation can provide operators with decision support in real time. “Including the ability to historize some of that data,” said Schnake, “and be available to come back later to facilitate investigations or support compliance queries.”
A PART OF SOMETHING GREATER
For everyone involved at Baxter, it’s immediately apparent how proud they are of this project and how motivated they are to see it to its ultimately successful conclusion. “It is pretty great,” says Johnson. “I think, including myself, a lot of people — maybe nearly everyone on this program — has been attracted by the various aspects of the program.” First, he explains, is the fact that Baxter is doing it to make some pretty critical drugs that help people: “Save and sustain lives, as we say, at Baxter.” That’s the No. 1 thing that attracts people, he says. “They’re doing something that’s very rewarding. On top of that, it’s such a monumental project in terms of size and complexity. People see this as a really once-in-a-career type of program that they get to work on — really challenging.”
To be a part of something greater like this is certainly a peak career-making experience. “This is, for sure, a once-in-a-lifetime opportunity,” adds Schnake, “to be part of something this complex and this large. That’s an attraction right there.” But it’s not the only attraction, he says. “To be building something from scratch where before there was a forest of trees — soon to become a manufacturing plant that produces a product that saves people’s lives — to be part of that from the ground floor, I think, is every engineer’s dream.” To get involved in something like that, says Schnake, and to do it for a company like Baxter, is icing on the cake. “It’s been a tremendous challenge. I’ll say that; it’s a labor of love is what it is. You have to work at it, but you’re excited about doing it. And even when it’s tough and it’s hard, you still love it.”