Route of Administration (RoA)
For pharmaceutical products, the preferred RoA is generally through oral administration (non-parental) due to increased safety, good patient compliance, ease of ingestion and cost-effectiveness. However, the pitfall of macromolecular biopharmaceuticals is their limited bioavailability of only 1-2% by oral administration due to limited penetration across the intestinal epithelium, and increased susceptibility to enzymatic degradation in the intestinal lumen (Ovacik & Lin, 2018; Zhao, Ji, Li, Roy, & Sahajwalla, 2013). In recent years, therapeutic antibodies with diverse RoA have been approved for treatment of diseases. The most common RoA for mAbs are intravenous (IV), intramuscular (IM), or subcutaneous (SC) administrations, with injections being the principal source of delivery (Table 1) (Zurdo, 2013). Other administration methods, e.g. ocular delivery, also exist for site-specific drug administration and lowering of side effects by localized therapy (Homayun, Lin, & Choi, 2019; Mandal et al., 2018). When compared to SC or IV, IM administration is not the ideal route of administration for mAbs due to low bioavailability (Homayun et al., 2019). IV administration is generally used for mAbs, whereas IM injections are most commonly used for vaccines (Mitragotri et al., 2014). Compared to other parental RoAs, SC injections are the most convenient as they facilitate patient self-administration and are the least invasive (Mitragotri et al., 2014; Zurdo, 2013). Despite that however, SC formulations place considerable constrains in terms of stability, aggregation and viscosity due to the need of high concentrated doses in low injection volumes (Viola et al., 2018; Zurdo, 2013).
Table 1 : Characteristics of different route of administration (RoA) for monoclonal antibodies. Data gathered from Ortega et al. (2014), Ryman & Meibohm (2017) and Zhao et al. (2013).