Protein products are highly complex molecules. They can have significant heterogeneity associated with the primary amino acid sequence, post-translational modifications, and three-dimensional structure. In addition to structural complexity, the source materials and manufacturing processes for proteins may lead to a variety of product variants and impurities that can impact product quality. Knowledge of the relationship between specific protein attributes and clinical activity is key to the evaluation of different protein products. This presentation will focus on the many factors that need to be considered when evaluating the similarity of follow-on protein products, including comparative physiochemical and biological characterizations, understanding of protein mechanism of action, and product immunogenicity.