State-level legislation on follow-on biologic substitution

INTRODUCTION In 2009, the Biologics Price Competition and Innovation Act (BPCIA) paved the way for market entry of generic biologics by establishing a pathway for their regulatory approval. Proliferating with the advent of recombinant DNA technology, biologic drugs are derived from living organisms to create vaccines, blood products, allergenic products, monoclonal antibodies, cytokines, growth factors, enzymes, immunomodulators, thrombolytics, proteins, arsphenamine (and derivatives), toxins, and antitoxins.1 Larger andmore complex than traditional pharmaceuticalmolecules, biologics are moredifficult to create (and replicate) than small-molecule drugs.2Their clinical effects are determined not only by their primary chemical structure but also by glycosylation patterns found in their structural folds.3 Thus, follow-on biologics, also referred to as biosimilars, can never be exact replicas of a reference product.4 Unlike generic drugs, biologics with pharmacokinetic equivalence may nevertheless exhibit varying pharmacodynamics, clinical efficacy, and immunogenicity (the product’s power to cause an immune reaction), not only between follow-on and reference products, but also within a particular reference product manufactured at different times or locations.5 The BPCIA defines biosimilars as biological products that are highly similar to reference products with no clinically meaningful differences in terms of safety, purity, or