For years now, observers have said that pharmaceutical manufacturing must become more agile and that the industry faces a “sea change” in the way that it handles R&D and manufacturing. The last decade, like those that preceded it, has been marked by mergers, and many large, single-product facilities have been closed down. Yet, on the surface, little appears to have changed. Facilities have not become automated, “lights out” plants, continuous manufacturing is still relegated to specific niches, and PAT and QbD have not started a revolution, although they are gradually being applied, or at least studied by more companies.
However, the scene has been set for drastic change. In the U.S., discussions of healthcare reform bring the prospect of higher production levels and lower drug prices, while the likely approval of follow-on biogenerics promises to shave years off the marketable life cycle of biotech drugs. Is this the calm before the post-blockbuster storm? “We talk about personalized medicine but it doesn’t seem like we really believe it’s coming. Is it this year? Is it next year?” Lars Petersen, Genentech’s vice president of automation, asked peers at a life sciences panel discussion at the 2009 Emerson Global Users Exchange earlier this fall. “The most important factor will be the responsiveness of pharma facilities to changing demand,” he continued. “The key question is: How do we create more agility?”
In this article, we’ll try to answer that question, as experts share their views of how drug manufacturing facilities will change to become more agile, what technologies will drive flexibility and how this will affect the industry. We've also made our extended discussions with various experts available via links provided throughout the article, and in the box at right.
Drivers for Flexibility
Several major trends are driving less-expensive, more flexible pharmaceutical plant designs, says Bob Bader, senior manager of technology for pharma and biopharma at Jacobs Engineering (Conshohocken, Pa.). First, we don’t need that much product anymore, he says. “We’re not talking about 2000 kilograms but 200 to 300 kilograms per year,” he says. At the same time, in biotech, titers are going up. As a result, the upstream portion of bio facilities has become smaller and the extent to which single-use equipment can be used has increased to a point where 100% single-use becomes possible. “It gives you a lot of flexibility but also simplifies design, automation and fixstraed capital costs,” he says.
Bader’s colleague Deepak Agarwal, director of pharmaceutical technology at Jacobs, sees pharma engineering projects aiming to:
- minimize the cost of goods and the total installed cost
- further accelerate scheduling for design, build and
- make facilities more flexible and adaptable for a range
- continue to make high-quality product.
But cost containment is only one facet of pharma flexibility. There’s also a very real need to minimize financial risk and liability early in the drug value chain, a need that is driving increased use of disposable process equipment, Bader says.
“If you think of all the curve balls that can come at you when you have drugs in the clinic, plunking down $500 million that you won’t even use or see for the next five years, given the uncertainty that the drug will make it to market, is an incredibly risky proposition,” says Parrish Galliher, CTO of Xcellerex, Inc. (Marlborough, Mass.). Galliher responded to this problem not only by designing a “Biotech Monopoly” board game, but starting up Xcellerex six years ago, to address some of the most frustrating problems he’d seen in three decades of bringing new drugs, and plants, to market. At the heart of the company’s work is the FlexFactory biomanufacturing platform, a system that uses disposable bioreactors and mixers and collapsed cleanrooms around process equipment, and which grew out of a prototype that Galliher developed while at Millennium Pharmaceuticals in 2001. [Click here for more from Galliher.]