Modeling approaches play a valuable role at various stages of development and life-cycle management of biopharmaceutical products. In Quality-by-Design (QbD) paradigm, quality needs to be designed into the product rather than merely confirming it through end product testing; this requires in-depth understanding of the product quality and impact of manufacturing process on product quality (Group IEW 2005. Modeling strategies in support of QbD paradigm for biologics are particularly important because of the costs involved in the development of biologic products (Group CBW 2009; Fissore and Antonello (Qual Des Biopharm Drug Prod Dev 18:565-93, 2015)). This mini-review focuses on the application of mechanistic models in the development of biologic drug products as ready-to-use solutions or lyophilized drug products. The choice of the modeling approach is dependent on the specific processes involved in the unit operation as well as intent of application of modeling. The application of models to unit operations in biologics drug product processing such as mixing (compounding), membrane transfer (ultrafiltration/diafiltration), freeze-thaw, and lyophilization, to characterize the quality risks, define the design space, provide input to control strategy, and build robustness in the process will be discussed.