With all the hoopla surrounding the passage of the Patient Protection and Affordable Care Act on March 23, 2010, relatively little notice was given to a piece of the legislation called the Biologics Price Competition and Innovation (BPCI) Act.
The BPCI established an abbreviated licensing pathway for drug firms to manufacture generic versions of biological drugs. The hitch was that they first have to prove the generic versions are similar to, or interchangeable with, an FDA-licensed reference product.
The law stipulates that a biological product can be demonstrated to be “biosimilar” if the data show that the product is “highly similar” to, and differs in no clinically meaningful way from, an existing approved biological drug. Because biosimilars are not direct copies of the original biologic drug, they are not the same as generic drugs — hence the name “similar.”
Biologics typically are liquid drugs used to treat cancer, rheumatoid arthritis, Crohn’s disease, and any number of other serious, often life-threatening ailments. Instead of being chemically synthesized like most drugs, biologics are made from living cells. Not surprisingly, they are costly and time-consuming to develop, and tend to be some of the most expensive drugs on the market. In addition, many biologics are used long-term by patients to treat chronic conditions.
By formally approving the notion of “biosimilars,” the law was, in effect, inviting drug manufacturers to take a stab at manufacturing generic versions of biologics as a way to reduce health care costs. However, as of May 2014, more than four years later, the Food and Drug Administration had yet to approve a single biosimilar.
So what’s the hangup? There’s certainly no lack of financial incentive. Patents on a host of leading biological medicines, with estimated global sales of $80 billion, are set to expire by 2020. Many big pharma firms, as well as some generic manufacturers, are preparing to jump into generic biologics manufacturing. Although the investment needed to get into this market is huge, the pot for the winners is well worth the ante, and maybe even a raise or two.
“You already see Big Pharma looking at jumping into this market,” says Dave Marks, a principal at DME Alliance, an engineering firm that designs manufacturing facilities and processes for the pharmaceutical and other industries. “And some, but not all, smaller generic manufacturers are looking at it, but the pathway to approval of biosimilars is still not clear.”
Drug manufacturers may be taking a wait-and-see attitude, holding back to get a better sense of the regulatory waters before taking the plunge. “A few companies are ahead of the curve and will cut their teeth on the market,” Marks asserts. “Once there have been a few successes, others will follow.” Adds Kim Wong, director of facilities and GMP support for bioprocess R&D at Sanofi Pasteur in Toronto, “After the first one or two products have been approved, it will provide greater comfort for the industry. The market will gain momentum with time and success.”
Perhaps the biggest single reason drug manufacturers have been slow on the uptake is the huge challenge involved in manufacturing a biosimilar. First, a biosimilar manufacturer must recreate a highly similar large molecule with similar makeup and characteristics as the innovator firm’s drug. Then they must prove their product is highly similar to the original in its effect on patients. And they have to develop a commercial-scale, high-quality process with controls tight enough to ensure that the drug won’t be altered in any way that could impact its efficacy or purity.
“There are some unique challenges associated with biologics products manufacturing,” Marks says. “Large molecule products are more difficult to characterize and reproduce. It requires that you reproduce a manufacturing process and demonstrate equivalency of the product.”
Others with experience in the business of creating and manufacturing biologics agree. “What I have learned working on biosimilars is that this is not easy — it’s scientifically difficult to manufacture biosimilars,” says Victor Fung, executive director for development of the biosimilars portfolio at Amgen in Thousand Oaks, Calif.
“Manufacturing biosimilars requires developing a process to match a reference product,” says Fung, who has more than three decades of experience in the industry, having started at Genentech in 1982, moving on to Immunex in Seattle, and later joining Amgen in 2002. “It requires making good decisions around the host cell and your process. You also need to keep your processes in control to maintain similarity. Developing biosimilars requires a high level of scientific rigor.”
The process hurdles alone are daunting. “You have to develop the process, then confirm the process can work in manufacturing, and then you have to execute the process — and make sure it’s in control,” Fung adds. “My role is to develop those processes and transfer them to our manufacturing network.”