Two leading biotechnology companies are competing to be the first to implement cheaper, faster processes for producing drugs inside living cells, making it easier to manufacture human proteins, antibodies, and other medications.
The new approaches will be “disruptively different” says Robert Bradway, the CEO of Amgen, one of the companies pursuing a manufacturing breakthrough. Today’s systems for producing drugs in bacterial or animal cells and then isolating them are hugely expensive and can take months. With more efficient processes in place, companies could swiftly increase production of drugs in high demand, and they could produce medicines for rare diseases more cost-effectively as well.
Amgen, of Thousand Oaks, California, the largest biotech company in the United States, has been mostly quiet on the subject of its manufacturing ideas since May, when Bradway, also its president and board chairman, announced during a lecture at MIT that he believes we are “on the cusp of a major change in how we manufacture proteins.” An Amgen spokesperson declined to elaborate on the technology.
But its competitor, Genzyme, acknowledges the urgent effort to develop new methods. “There’s a race going on,” says Konstantin Konstantinov, vice president for late-stage product development at the company, which is based in Cambridge, Massachusetts. “We’re trying to come up with the dominant design.”
At Genzyme, a subsidiary of French drug giant Sanofi, Konstantinov leads a team pursuing an idea called continuous manufacturing. The switch from inflexible “batch” production processes to continuous ones has already wrought huge changes in other industries. Steelmakers, which used to mold molten metal into individual ingots, achieved a transformative jump in efficiency when they made the transition to extruding steel bars.
But change isn’t easy in the drug industry. Startup companies are focused on trying to discover new medicines, not new approaches to manufacturing. And the U.S. Food and Drug Administration, which regulates drug plants, keeps pressure on companies to stick with safe, tried-and-true methods.
The manufacture of a biotech drug usually begins in a large stainless-steel vessel where cells are grown. As they’re fed, they excrete a protein into the surrounding liquid. In a typical batch process, the cells are fed until they start to die off; whatever protein they have produced at that point is the batch. The bioreactor needs to be big to make enough of the desired compound—usually 10,000 to 20,000 liters in capacity, or about the size of a gasoline tanker. Then come several purification steps to isolate the protein.
In December, Konstantinov’s team at Genzyme published two technical papers (here and here) outlining for the first time their ideas for a revamped process. Konstantinov says his team’s main innovation is linking a smaller bioreactor to a type of chromatograph that can continuously separate the protein from the surrounding liquid.
Konstantinov says he’s been successfully running the process for several months now, although he declined to show the setup to a reporter. “There are some elements which are pretty obvious, which we decided to share because they are going to be incredibly important to the biotech industry,” he says. “[But] some things are secret.”
Konstantinov says he can get rid of about half the usual equipment and has squeezed a production line of steel vessels and piping down from something approaching the size of a football field into a space the size of a squash court.
With such compact manufacturing units, biotech companies could make more types of drugs, or they could quickly scale up production of blockbusters by adding units as needed. In his talk, Bradway said new technologies would let Amgen be “much more diverse, much more adaptive, moving in and out of different products more quickly.”
More flexible manufacturing could help prevent damaging drug shortages. The FDA reported 251 drugs in short supply in 2011; for medicines that are injected, as most biotech products are, it said that about 20 percent of the time, the problem was that companies’ manufacturing capacity fell short.
The pharmaceutical industry has typically paid little attention to innovations in manufacturing, but because Genzyme and Amgen have kept manufacturing capacity near to their labs in Boston and California, they’re now well positioned to implement new ideas. “We have the right scientists, the right engineers, the right suppliers in the U.S. I’m hopeful the U.S. will continue to be a leader [in] this new technology,” Bradway said during his remarks. “What we are doing brings technology and innovation to the heart of our manufacturing enterprise.”
It’s not clear how long it will take until patients receive drugs made through the new processes. At Genzyme, Konstantinov thinks that the main technical barriers have been overcome, so it’s now a business decision. “We’re pushing this very hard,” he says.