Angus Worthing, MD, FACR, FACP, clarifies key biosimilars terms.
Interchangeability, switching, substitution: there seems to be some confusion about these terms. Can you clarify?
Switching and substitution both refer to the process of moving from one drug to another; for example, from a biologic reference drug to a biosimilar drug. Substitution refers to the specific process in which a pharmacist receives a prescription from the doctor for one drug, for example the reference biologic. But instead of dispensing that drug, instead it dispenses a biosimilar drug or a different medication that has been FDA approved as an interchangeable drug. That pharmacist is in a state or jurisdiction in which that process has been regulated and laws have been put in place. So, the patient ultimately receives, for example, the biosimilar drug after the prescription was written for the reference biologic. In contrast, switching refers to a prescription being changed. So a physician, for example, is treating a patient with the reference biologic and instead decides—and usually we anticipate with the patient—to write a prescription for the biosimilar and then that prescription goes to the pharmacy and the pharmacist dispenses the biosimilar. Interchangeability is the condition of a biosimilar that makes it legal for the pharmacist in certain jurisdictions, to make a substitution and that’s a process that’s being developed right now at the FDA. FDA has issued what we, at the American College of Rheumatology feel are very good guidances about how to design a clinical trial to prove that a drug can be substituted—or in other words, that a drug in interchangeable with a reference biologic—because the clinical trial design involves switching back and forth and alternating 3 times from the reference drug to the biosimilar, back to the reference drug, then back to the biosimilar. So, 3 switches, and then deciding that the drug is safe and effective at the end of that process.