To demonstrate a biological product is biosimilar to a reference product, we need to show that they are highly similar and have no clinically meaningful difference. Comparative clinical studies are often conducted to support the conclusion of no clinically meaningful difference, as a part of totality of evidence. The FDA has published several guidance documents to facilitate the development of biosimilar products. While the guidance documents define the role and objective of comparative clinical studies, they however do not provide details about the determination of the similarity margin. In this paper, we illustrate how a similarity margin is derived for comparative clinical studies conducted to support the development of biosimilar products of Neupogen.