The subjects of biosimilars has been discussed for decades and has been the focus of numerous continuing education programs, articles, editorials, and new media stories, but the time to decide what we are actually going to do with these products is now upon us.
The first of the approved biosimilars (filgrastim-sndz [Zarxio]; Sandoz, Inc.) should be available soon, unless legal maneuvers delay its introduction.1,2 Tbo-filgrastim was approved as separately licensed biologic and is not classified as a biosimilar.2,3 The delay between the passage of the law and the approval of the first biosimilar has been frustrating and confusing in the United States. Europe has allowed several biosimilar products to be marketed since 2005 without any apparent problems.4 The net result of the biosimilar approval process is to lower the acquisition cost of the product for the payor and the patient without compromising the safety and efficacy of the product.
A biosimilar is defined by the US Food and Drug Administration as a biologic product (eg, vaccines, blood and blood components, gene therapies, tissues, and proteins [except those that are chemically synthesized polypeptides]) that is “highly similar” to the reference product and is available in the same dosage form, strength, and route of administration.3–14 The definition of “highly similar” is not fully understood by most practitioners and regulators. These compounds are more difficult to produce, and small changes in the manufacturing process (eg, type of expression system, changes in environmental conditions, changes in the engineered cell line) may produce slightly different compounds that act differently within the biologic system or cause peptide denaturation, aggregation, oxidation, or degradation during the manufacturing process.8–11 An interchangeable product is a drug classified as a biosimilar to the reference product and “can be expected to produce the same clinical results as the reference product in any given patient.”2
In the case of Zarxio (filgrastim-sndz), the FDA new releases classify this drug as a biosimilar to Amgen Inc.’s Neupogen (filgrastim), and the FDA approved its use for the same indications as Neupogen.1 In this situation, Neupogen is considered the reference product and filgrastim-sndz is considered its biosimilar.2
How is your institution going to handle these products? Are you going to treat drugs approved as biosimilars differently than those approved as a separate licensed biologics? What changes are needed in the electronic medical record and ordering system to accommodate the new products? Are you going restrict their use to new starts for treatment-naïve patients or are you going to allow an interchange program? If an interchange program is available, how are you going to handle differences in the approved indications? Will the use of the biosimilar be restricted to its approved indications or will it be available for use for all of the same approved indications as the reference product? What about off-label indictions? If an adverse reaction occurs, will it be tagged back to the drug or the actual product the patient was receiving? These questions should be considered for each product prior to its formulary approval.3,4,14–16
What are the best sources for information in addition to the medical literature and the manufacturer? A starting point will be the FDA’s lists of licensed biological products with reference product exclusivity and biosimilarity or interchangeability evaluations, known as the “Purple Book.” This book provides a list of approved biosimilar licensed products and will serve as a useful tool for determining whether the drug is biosimilar to or interchangeable with a reference product.2,17
Concerns regarding immunogenicity, especially if the patient is switched between products, and therapeutic interchangeability will probably drive these decisions about biosimilars. It is generally hoped that neither of these will be a problem for the majority of the population. Pharmacists should help patients and other health care professionals to understand the differences between these products and, if problems are encountered, to report these problems to the manufacturer and the FDA.
References
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