Scientific factors for assessing biosimilarity and drug interchangeability of follow-on biologics

Abstract

Biological products are therapeutic agents produced using a living system or organism. In practice, access to these life-saving biological products is limited due to their expensive cost. In the next few years, patents of the early biological products will expire. This provides other biopharmaceutical/biotech companies the opportunity to manufacture follow-on biologics. For the conventional pharmaceuticals of small molecules, regulations and statistical methods for the assessment of bioequivalence for generic approval are well established. How-ever, unlike the conventional drug products, the complexity and heterogeneity of the molecular structure, complicated manufacturing process, different analytical methods, and the possibility of severe immunogenicity reactions make evaluation of equivalence (similarity) between an innovator and its follow-on biologics a great challenge for both the scientific community and regulatory agencies. This article reviews past experiences for the assessment of bioequiva-lence for conventional drug products. Detailed descriptions of the fundamental differences and assumptions between the chemical generic products and follow-on biologics are given. An overview of current regulatory requirements for assessing biosimilarity of follow-on biologics is provided. Statistical considerations for scientific factors for assessing biosimilarity and drug interchangeability of the follow-on biologics as posted at the recent FDA Public Hearing on Approval Pathway for Biosimilar and Interchangeability Biological Products are discussed. In addition, current statistical issues that are commonly encountered when assessing biosimilarity of follow-on biologics are reviewed.