Biological Activity Assays for Antibody Therapeutics

Abstract

The measurement of biological activity is required for therapeutic antibodies at release of a new manufacturing batch and throughout the product life cycle. However, the applicable regulatory guidelines provide relatively little advice with respect to the number and types of bioassays to be employed. For example, 21CFR610.10 states that potency tests “shall consist of either in vitro or in vivo tests, or both, which have been specifically designed for each product so as to indicate its potency in a manner adequate to satisfy the interpretation of potency” where potency is “the specific ability of capacity of the product, as indicated by appropriate laboratory tests or by adequately controlled clinical data obtained through the administration of the product in the manner intended, to effect a given result.” ICH Q6B lists animal-based biological tests, cell culture-based biological tests, biochemical tests and ligand and receptor binding tests as examples of biological tests. However, neither guideline provides any assistance on how to select the most appropriate bioassay format(s) for a given product. Since biological activity is determined based on individual product characteristics and mechanism of action, there is considerable decision-making involved when selecting, developing, switching, and maintaining appropriate bioassays. This chapter discusses the types of biological assays, the current practices and regulatory expectations regarding the potency test format. A key question for antibody therapeutics that acts as agonists or antagonists of a ligand-receptor interaction, is the question of cell-based versus binding assays. Development and validation considerations for biological assays will also be discussed. This chapter will particularly focus on special considerations for biosimilar antibody therapeutics and provide a strategy for the biological testing methods, plan, and statistical assessment for the assessment of functional biosimilarity. Key differences in the application of a battery of in vitro biological activity assays between a biosimilar and a novel biologic, and case studies will be discussed.