Less expensive, “generic” versions of biologic medications are a step closer to appearing on pharmacy shelves – although the road to federal approval of so-called “biosimilars” could still be a long one.

The U.S. Food and Drug Administration (FDA) in 2012 released draft guidelines that define the oversight and approval process for companies that want to make and sell biosimilars. These medications will be similar substitutes for biologic products already used to treat a variety of conditions, including rheumatoid arthritis, cancer and diabetes.

A new approval pathway is needed for biosimilars because, unlike most medications, which are made from chemical molecules, biologics are proteins produced by gene-based technology from biological components such as living animal, or human or microorganism cells. So, unlike generic forms of chemical drugs, they are not exact replicas of the original drug.

“The protein has a complicated, three-dimensional structure and it’s much larger than a regular chemical drug, so it’s very tricky to make it exactly the same way every time,” explains Donald Miller, professor and chair of pharmacy practice at North Dakota State University in Fargo. “The original manufacturer has a patent on the process to make the protein, and they put in a lot of work to make it reproducible, so someone starting from scratch has a lot of work to do to make the identical protein.”

A provision in the federal health care reform law, signed by President Obama in March 2010, mandated the creation of an abbreviated regulatory pathway for the approval of biosimilars. To come up with that pathway, the FDA met with pharmaceutical companies and other interested parties (including patient advocates and doctors) and held hearings. The draft guidelines are result of that process. They outline the scientific and quality expectations the FDA has of any drug company making a biosimilar, such as how similar it must be and what safety studies must be conducted.

The FDA says the exact requirements, to be determined on a case-by-case basis, will vary from one product to the next. Small differences in drug formulation, delivery devices and containers will be allowed, but those differences cannot be clinically meaningful from the original, or “reference” product. The government reserves the right to require clinical trials if it deems them necessary – something not required of most generic drugs.
 

“This is a completely new paradigm, and so it was very important to us to get the message out to the public – including industry, patients, consumers and physicians – to fully understand what these products are, what they mean. We want to make sure people understand that they are safe and effective and in no way any less meeting our rigid standards than the originator product,” says FDA spokesperson Karen Mahoney.

Rheumatologist Robert Katz, MD, professor of medicine at Rush University Medical Center in Chicago and Northwestern University’s Feinberg School of Medicine, says this is uncharted territory. “It’s like the FDA discovered a new continent. We have to explore this,” he says. “Before, we had drugs [for which] we knew their chemical makeup; you could make a reproduction of it and we could evaluate it. [With biosimilars], you are almost redesigning it.”

Dr. Katz would welcome a cheaper biologic alternative for his patients, but he wonders just how affordable they will really be. “I’m not sure they’ll be able to do it [inexpensively], because the manufacturing and evaluation process could be lengthy, complicated and very costly,” he explains.

Typically, a generic drug is 50 to 70 percent cheaper than the brand-name version, but biosimilars are expected to still be pricey. In a 2009 report, the Federal Trade Commission, or FTC, estimated that a biosimilar would be initially introduced at a price 10 to 30 percent less expensive than its reference biologic. “That is still pretty expensive,” Dr. Katz says. “Twenty thousand dollars a year is average for many biologics.”

Any price reduction might be enough for some patients to try biosimilars, he says, but he also believes patients will be wary.

“If you’ve got something working really well, certainly some people will be reluctant to change if they have insurance coverage,” Miller says. “It will probably make more of a difference for people just beginning a biologic. If they can get a cheaper drug or their insurance will cover a cheaper version, that’s the one they might start on.”

The American Medical Association released a statement from its president, Peter W. Carmel, MD, saying the group applauds the FDA’s efforts to prioritize “product efficacy and patient safety” in the draft guidelines by establishing rigorous standards by which a biosimilar might be considered interchangeable with the original.

But Dr. Carmel’s statement indicates that some issues still need to be addressed. “We look forward to clear guidance from the FDA about the naming of biosimilars to avoid confusion among prescribers and patients, and strategies for physician and patient education on these products,” it says.

Original biologics have patent protection in the United States, generally for 12 years. As patents near expiration, some companies may be able to get extensions, which could delay biosimilar versions of their products getting to U.S. markets. For example, Amgen and Pfizer’s patent on etanercept, or Enbrel, had been set to expire this year, but – mainly due to a technicality – the FDA in November granted the drug makers a new 17-year patent. More than 30 branded biologics are set to lose patent exclusivity between by 2015.

The FDA stresses that this is just the start of the process. Although biosimilars are already available in Europe, no regulatory pathway is in place yet in the U.S.