ABSTRACT
ABSTRACT Unlike most small-molecule drugs, biological products are known to have a large variability although this variability does not impact its purity, potency, and safety in any clinically meaningful ways. This unique fact creates challenges in assessing similarity of a follow-on biologic and its reference product. A biosimilar follow-on biologic should be “highly similar” to its reference product. But how similar is highly similar? How do we measure the similarity? These are hard questions and there has been no consensus on how to address these questions. This chapter discusses different metrics to measure the similarity and puts forward two scientic principles, which can be used to establish the threshold for similarity in each metric. The rst principle is that a biosimilar criterion should be determined in a way that it allows the reference product to claim similarity to itself with a high probability. And the second is that all commercial lots of the reference product should meet a preset lot consistency criterion with a high probability. Following the proposed metrics and established thresholds, the corresponding statistical approaches are proposed for evaluating the similarity. Simulations are provided to compare different statistical approaches given at the end of this chapter.
