Amgen Set to Double Production of Enbrel
The patient waiting list already had soared to tens of thousands for the rheumatoid arthritis drug Enbrel when Amgen Inc. sent its biotech SWAT team of 100 experts to Rhode Island last spring on a critical mission: to clean up a drug factory and get it ready for production by year-end.
On Monday, the mission was accomplished when the Food and Drug Administration signed off on the two-story plant that houses a network of stainless-steel vats connected by 25 miles of pipe.
The agency’s approval of the West Greenwich plant means that Amgen now could double its shipments of Enbrel, which analysts said would add up to $700 million to Amgen’s projected $7.8 billion in overall revenue next year. The drug also is made at a factory in Germany.
Making biotechnology drugs is not like stamping out Barbie dolls or assembling cars. Companies splice bits of DNA into live cells, which in turn pump out the medication. Throughout the process, a biotech factory has to meet FDA cleanliness standards, which are far more rigorous than those of hospitals.
The Rhode Island plant “would never have passed FDA inspection” without a major overhaul, said Fabrizio Bonanni, the Amgen senior vice president who led the SWAT team.
Amgen acquired the factory and a potential blockbuster in Enbrel when it purchased biotech rival Immunex Corp. for $9.6 billion in July. Enbrel was approved for sale in 1998, and the drug is seen as an effective tool to combat serious joint damage and disability so severe that a person can end up in a wheelchair.
When Amgen inherited the Enbrel factory, more than 40,000 people suffering from arthritis were on a waiting list for the drug. Unable to obtain it, doctors had begun prescribing an alternative made by Johnson & Johnson called Remicade, which also combats joint damage and pain but has more serious side effects. Patients and their insurers pay about $12,000 a year for twice-weekly injections of Enbrel.
Thousand Oaks-based Amgen, the world’s largest biotech company, was convinced that if it could find a way to keep up with the demand for Enbrel, the drug could be a $3-billion-a-year product.
But first it had to whip the Rhode Island factory into shape.
Amgen’s start was inauspicious. Bonanni arrived at the plant outside Providence in January, just after the Immunex deal had been announced. Personnel there, he recalled, refused to share key information with him, forcing him to develop a set of plans for improvements based largely on conjecture and intuition.
When Bonanni’s SWAT team showed up a few months later, one of the most important mysteries they needed to solve was why so many batches of Enbrel were going bad. The FDA requires a minimum success rate of 60% of all drug production runs, and the Rhode Island factory was below that minimum. (By contrast, Amgen says its other factories have a 90%-plus success rate.)
The team eventually discovered that there was no one reason for the failures. Rather, there was a litany of problems.
For instance, leaky valves and ill-fitting filters caused Amgen to throw out batches of Enbrel that could have been stockpiled for patients. And clean rooms where the drug was prepared and processed were full of trace bacteria and mold.
Adding to the troubles was that the 350 workers at the factory were insufficiently trained, Bonanni said.
Once, noticing Enbrel dripping from a tank, Bonanni scolded the production crew for “wasting gold.” He further humiliated them by crawling on the floor to find the source of the leak. After that, he said, crews made sure the valves on the tanks were closed.
Bonanni and his team brought two decades of biotech experience with them to Rhode Island. One of the first things they changed was how the janitors wiped down the factory walls and mopped the floors to remove contaminants. He also assigned Amgen supervisors to shadow Immunex factory workers until they mastered their daily tasks.
The hamster cells used to make Enbrel are grown in large vats that contain a broth of nutrients and vitamins, kept at just the right temperature. The smallest change in conditions can kill cells or reduce their ability to make the drug.
“There are a zillion ways things can go wrong,” said Deb Chakravarti, a professor at the Keck Graduate Institute of Applied Life Sciences in Claremont. “A mistake in the wrong place can wipe out the whole lot.”
The timing of the factory approval is important for Amgen. Abbott Laboratories Inc. is preparing to introduce a similar medication that is likely to appeal to many of the same patients that have been waiting for Enbrel. Amgen’s stock closed Monday at $51.64, up 16 cents, on Nasdaq. The FDA’s approval was announced after the market had closed.
Amgen’s chief executive, Kevin Sharer, hailed completion of the factory and credited Bonanni with getting the job done. “The smartest thing I did was sending Fabrizio in early,” he said.
For his part, Bonanni noted that it took some time to gain the trust of the Immunex employees in Rhode Island. But in the end, all but a dozen or so have stayed on with Amgen.
