Bold Manufacturing Strategy Soon to Pay Off for Human Genome Sciences

After 18 years, Human Genome Sciences (HGS, Rockville, MD) may soon have its first drug on the market. And thanks to a bold scale-up strategy, HGS's manufacturing organization is ready.

In early June, HGS filed for approval in the US and Europe for Benlysta (belimumab), a human monoclonal antibody (MAb) for systemic lupus, developed in partnership with GlaxoSmithKline. If approved, Benlysta will be the first new treatment for lupus in more than 50 years, which means the potential demand for the drug is high.

That potential demand, along with a possible commercial dose of 10 mg/kg, means HGS could suddenly find itself producing large quantities of drug for the first time.

Scaling up the production of Benlysta won't be a problem, however, because of a decision made seven years ago to scale up early, when Benlysta was entering Phase 3. HGS then used that large-scale equipment, including two 20,000-L bioreactors, to manufacture material for Phase 3 trials. The rest was produced in 5,000 and 1,600-L bioreactors.

"A significant percentage of the drug that went into Phase 3 was produced at commercial scale," says Curran Simpson, senior vice president of operations at HGS. That means HGS doesn't have to worry about demonstrating the comparability of the drug produced at small and large scale without the benefit of clinical experience, a hurdle that some firms have had trouble overcoming.

"That was a gutsy call by our CEO, Tom Watkins," Simpson adds. "It meant spending a few million dollars on raw materials like Protein A resin when we still didn't have an approved drug."

As a result, the company's main challenges in preparing for commercial production relate not to scale, but to the total volume of production-shifting from making 10 to 20 batches a year to more than double that. HGS has already hired the additional staff needed-about 50 people-and training is underway.

Industry analysts calculate the potential patient population for Benlysta around 120,000 patients, who would consume a total of about 1,000 kg of drug per year. Simpson calculates that HGS's in-house manufacturing capacity can serve between 45,000 and 60,000 patients a year-enough for the first year or two. "That means we must be prepared to expand our capacity two or three-fold," he adds.

He plans to do that through a contract manufacturing organization or possibly excess capacity at an innovator company. According to Simpson, it's a good time to be on the market for manufacturing space. "We are one of the few companies looking for large-scale capacity right now," he says.

Whatever site is chosen, technical transfer should be fairly straightforward, because Benlysta is made using a standard MAb manufacturing process. That was also an important part of the company's strategy.

"Given that this was our first product, we took a fairly conservative route," Simpson explains. "We didn't want to present something unique for our first potential approval."

Nevertheless, HGS was an early adopter of one innovative manufacturing technology: the Celsius freeze–thaw system (Sartorius-Stedim, Goettingen, Germany). In this system, the product stays evenly distributed within the solute during freezing, thus avoiding product aggregation, which can be caused by the cryocentration often seen in carboys or stainless steel vessels.

"We were one of the first people to cut their teeth on this technology, and it has worked very well for us," Simpson says. "Also, the frozen material is in the form of a flat plate, which makes it more efficient to ship bulk drug to another site for fill–finish."