The approval process for biosimilar erythropoiesis-stimulating agents.

A biosimilar drug or follow-on biologic drug is defined by the Public Health Service Act as a product that is "highly similar to the reference product notwithstanding minor differences in clinically active components and there are no clinically meaningful differences between the biologic product and the reference product in terms of the safety, purity and potency of the product." The advantage of biosimilar drugs is that they are significantly less expensive than the reference products, allowing for increased accessibility and cost savings. Recognizing these advantages, the US Congress passed the Biologics Price Competition and Innovation Act in 2009 as part of health care reform. The Biologics Price Competition and Innovation Act allows sponsors of biosimilar agents to seek approval by showing structural and functional similarity to the reference agent, with the extent of required clinical studies to be determined on the basis of the degree of biosimilarity with the reference product. The goal is to bring biosimilar agents to the market more efficiently while still protecting the safety of the public. The European Union has had such a process in place for a number of years. Two biosimilar epoetin agents have been approved in the European Union since 2007, and their companies are conducting trials to seek approval in the United States, because Amgen's patent protection for epoetin alfa expires in 2014. Trials completed for European Union approval of both agents showed similar efficacy and safety to the reference epoetin alfa. As with all biologics, immunogenicity concerns may persist because of the fragility of the manufacturing process and the worldwide experience with pure red cell aplasia as a result of epoetin therapy. The uptake of biosimilar epoetins after approval in the United States will depend on the balance of cost advantage against safety concerns. Competition in the marketplace will likely decrease the cost of the reference agent as well.