August 10, 2016
The FDA is starting to approve biosimilar drugs—medications that are expected to be on the leading edge of a major shift in the world of biologics in the United States. Many physicians, payers, and patients will face new choices and new challenges.
What about pharmacists? For the time being, most pharmacists will rarely, if ever, need to fill prescriptions for biosimilars. But those who help develop formularies may find themselves at the center of the changing times. They’ll need to educate themselves about what exactly biosimilars are and—just as important—what they are not.
For one thing, they’re not generics, although they can easily be mistaken for the non-branded drugs since they act in a similar way and aim to offer the same benefit of lower costs. For another, biosimilars may not function in exactly the same way as the reference products that they’re designed to replace.
As a result, it will be critical for pharmacists working on formularies to understand these and other complexities posed by biosimilars, said Evelyn R. Hermes-DeSantis, PharmD, BCPS, a clinical professor of Pharmacy Practice & Administration at Rutgers, The State University of New Jersey, and director of the Drug Information Service at Robert Wood Johnson University Hospital.
In addition to understanding the unique science of biosimilar drugs, Hermes-DeSantis said pharmacists on Pharmacy & Therapeutics (P&T) committees will face issues that range from biosimilar naming systems to potential challenges in dispensing and costs. As she explains, “it’s not always as straightforward as we’d like to think.”
What sets biosimilars apart
Biosimilars are close imitations of biologics, a wide category of medications derived from natural sources that includes vaccines, gene therapies, and tissues. Biologics treat a variety of diseases including cancer, rheumatoid arthritis, anemia, leukopenia, inflammatory bowel disease, and psoriasis.
As FDA notes, “most biologics are complex mixtures that are not easily identified or characterized,” making them much different from traditional small-molecule drugs derived from chemicals.
“Every single molecule of captopril is the same as every other molecule of captopril,” said Hermes-DeSantis. “But when we’re talking about biologic agents, there may be slight differences in the molecular weight or how long a particular chain is. It’s not as homogeneous a product.”
To complicate things further, she adds, there is more secrecy around the production of biologic drugs. When it comes to captopril, for instance, “the way you make the drug is not a trade secret.” But the manufacturing process of a biologic may be extremely confidential.
So how do you create a generic version of a biologic drug? You don’t. At least, not exactly. Manufacturers must rely on guesswork to create a “similar” version—a biosimilar.
Evaluating biosimilars: What you need to know
What do pharmacists need to understand when they consider whether biosimilars belong on formularies? It’s crucial to examine and evaluate the clinical and scientific evidence behind them, said Mary Jo Carden, RPh, JD, vice president of government and pharmacy affairs with the Academy of Managed Care Pharmacy (AMCP).
“For example,” she pointed out, “what do the data suggest about the bioequivalence of the biosimilar and the reference biologic? This information,” Carden explained, “may be found through an examination of the package insert and other evidence submitted through clinical trials and often in other countries.”
James G. StevensonJames G. Stevenson, PharmD, FASHP, a professor with the Department of Clinical Pharmacy at University of Michigan College of Pharmacy, said pharmacists may need to help colleagues understand the shortened approval process for biosimilars and the fact that there is no requirement for a full array of clinical studies.
“My advice is to help professionals understand the foundational structure and function analyses that are done to assure that the biosimilar is very similar to the reference product,” said Stevenson, who is president of the consulting company Visante. “The more similar the compounds are at this level, the fewer clinical evaluations are needed to help remove any residual uncertainty about them producing a similar clinical effect.”
Labels, sterility, stability
Labels are important, too. “Pharmacists should also understand that the label may include information about adverse effects and immunogenicity issues related to the reference biologic, the biosimilar, or both,” AMCP’s Carden said. “It may also include extrapolated indications from the biologic product that were not specifically submitted by the biosimilar maker.”
Robert Wood Johnson University Hospital’s Hermes-DeSantis suggests that pharmacists who work on formularies give plenty of attention to “a lot of the practical issues that may get lost otherwise.”
For example, she said, her hospital was exploring the use of the biosimilar Zarxio (filgrastim-sndz) as an alternative to Neupogen (filgrastim) and discovered that Zarxio only came in syringes.
That raised a red flag for its use in pediatric patients, who need a small amount of the drug, she said. It wasn’t clear whether the biosimilar Zarxio in the syringes could be divided into smaller doses in a sterile way. Neupogen, by contrast, came in vials.
This situation spotlights the importance of sterility in formulary evaluations of biosimilars.
Stability is another major concern given the way biosimilar drugs, and biologics in general, are manufactured and administered—most biologics are injected drugs, Hermes-DeSantis said. “A few are orals, but we haven’t seen any biosimilars for those yet.”
Watch for naming, pricing issues
AMCP’s Carden advised pharmacists working on formularies to also keep a close eye on how biosimilars are named.
Last year, FDA released a proposed rule suggesting that all biologic agents—biosimilar or not—have a name followed by a random 4-letter suffix. For example, the original Neupogen biologic would be known as filgrastim-jcwp, while the biosimilar Zarxio would be filgrastim-sndz.
Debate continues over whether this naming system is a good idea, with some critics hoping for suffixes that actually have meaning.
Moving forward, Carden said, “If FDA adopts the randomized 4-letter suffix for all biologic products, pharmacists must understand that the suffix is an identifier unique to the product and is not necessarily related to whether or not the product is interchangeable.”
Pricing is an area of added complexity in the biosimilar arena. Hermes-DeSantis said pharmacists will need to monitor costs closely and be on the lookout for complications.
For example, she noted, a biosimilar’s apparent savings might vanish if a hospital must buy two syringes to get the same amount of drug that previously came in a single vial. “It’s not always as straightforward as we’d like to think,” Hermes-DeSantis reiterated. “We may need to not just consider milligram vs. milligram but also examine the cost of being able to get this drug.”
Pharmacists as advocates?
Sarah L. Scarpace, PharmD, MPH, BCO, an associate professor of Pharmacy Practice with the Albany College of Pharmacy and Health Sciences, thinks pharmacists should advocate for biosimilars in light of their potential to reduce drug costs.
“Biosimilars have been available in other countries for a long time,” said Scarpace, who serves as president of the Hematology/Oncology Pharmacy Association. “Many of these therapies actually are or will be manufactured by the innovator company or an affiliate which has manufacturing processes that we can trust.”
She is concerned that cost savings from biosimilars will be reduced or eliminated if interchangeability rules forbid substitution unless more clinical trials are reported. The prospect of these rules has divided the pharmaceutical industry, pitting the upstarts who want to produce biosimilars against the companies behind the original biologics.
“The decision about substitution is left to institutional Pharmacy and Therapeutics committees,” Scarpace said. “Some companies are lobbying states to prevent substitution of biosimilar products for their own. This is unfortunate and reminiscent of the days when generic drugs were first coming to market.”
She predicted that in another decade or two, “we will be surprised there was even controversy related to the use of biosimilars.”
But for now, the debate seems to be only in its early stages with much more discussion—and drama—to come.
Disclosures: Drs. Hermes-DeSantis and Carden have no relevant disclosures. Dr. Stevenson has been a consultant for Amgen and Pfizer and a speaker for Abbvie. Dr. Scarpace is on speakers bureaus for Eli Lilly, Merck, Pfizer, and Boehringer Ingelheim.
Randy Dotinga is a medical writer based in San Diego.