A Guide to Follow-on Biologics and Biosimilars with a Focus on Insulin

Abstract

Many healthcare providers in the U.S. are not familiar with follow-on biologics and biosimilars nor with their critical distinctions from standard generics. Our aim is to provide a detailed review of both, with a focus on insulins in the U.S. regulatory system. Literature has been reviewed to provide information on various aspects of biosimilars and a follow-on biologic of insulin. This will include structure, efficacy, cost, switching, and legal issues. Biologic products are large, complex molecules derived from living sources. Follow-on biologics are copies of the original innovator biologics. It is not possible to copy their structure exactly, leading to possible differences in efficacy and safety. Thus, regulations involving biologics are complex. Follow-on biologics are regulated under two Federal laws until March 23, 2020: the Public Health Service Act (PHS Act) and the Federal Food, Drug, and Cosmetic Act. Biosimilars are follow-on biologics which have been approved via the PHS Act. They consist of those which are "highly similar" to the reference drug and those which are "expected" to produce the same clinical result as the reference drug (interchangeable biosimilars). Interchangeable biosimilars have been determined by the U.S. Food and Drug Administration to be substitutable by the pharmacist "without the intervention" of the prescriber. From the patient perspective, switching to a follow-on biologic may necessitate a change in delivery device, which may create issues for patient adherence and dosing. Although they present several challenges in terms of regulation and acceptance, follow-on biologics have the potential to significantly reduce costs for patients requiring insulin therapy. BLA = biologics license application EU = European Union FDA = Food and Drug Administration FD&C = Food, Drug, and Cosmetic HCPCS = Healthcare Common Procedure Coding System INN = internatinal nonproprietary name NDA = new drug application PHS = Public Health Service.