Analytical Control Strategy for Half-Life Extension Features of Biotherapeutics

Biotherapeutics are often designed with the addition of chemical or protein features to the active component of a biotherapeutic that extends the serum half-life thereby reducing the frequency of dosing needed to maintain therapeutic levels. A common feature that is naturally associated with antibodies is the Fc region that interacts with the neonatal Fc receptor (FcRn) to be recycled away from the lysosome degradation compartment and back into circulation enabling about 2-3 week serum half-life. For non-mAbs, one strategy is to attachment an immunoglobulin Fc region to the active component of the biotherapeutic. Other elements include features that bind to human serum albumin and chemical modifications such as pegylation. These features become product quality attributes that require attention during the manufacturing process to ensure proper safety and efficacy of the biotherapeutic. This talk will compare and contrast these half-life extending features and how to meet regulatory expectations for the proper analytical control strategy for these features.