In terms of pharmacokinetics, IV appear to be superior to SC injections due to faster absorption, higher bioavailability, short time to reach maximum serum concentration (T_max) and similar elimination half-life (Table 1) (Matucci, Vultaggio, & Danesi, 2018). Subcutaneous route results in slow absorption, with a slow increase in plasma concentration and delayed time of T_max, ranging from 1.7 to 13.5 days (Ortega, Yancey, & Cozens, 2014; Ryman & Meibohm, 2017; Zhao et al., 2013). The longer T_maxassociated with slow lymphatic uptake is due to the limited flow rate of 1-2 mg kg^-1h^-1 in the thoracic duct (Zhao, Ren, & Wang, 2012). While the SC route offers more convenience to patients compared to IV administration, it was reported that SC administration resulted in higher risk of immunogenicity (Hamuro et al., 2017). This observation was investigated by comparing the immunogenicity profiles of marketed mAbs by monitoring the formation and persistence of anti-drug antibody (ADA) events with either SD- or IV-formulations (Hamuro et al., 2017). ADA events can potentially impact the pharmacokinetics of the product by increasing or decreasing drug clearance or affecting its pharmacodynamics and efficacy. Tocilizumab (Actemra®), a humanized mAb against interleukin 6 receptor (IL-6R) for the treatment of rheumatoid arthritis (RA) was studied by IV and SC RoA in a phase 3 study in a Japanese cohort. After 24 weeks of treatment, ADAs were detected in 3.5% and 0% of patients for SC or IV administration, respectively. Trastuzumab (Herceptin®), a humanized IgG1 mAb against HER2 was first approved for IV injections and became the standard treatment for patients with HER2-positive breast cancer. A SC formulation was offered as a fixed-dose alternative to the weight-adjusted IV-formulated product, and a 2-fold increase in ADA incidence was observed for SC (14.6%) compared to IV (7.6%) route. Rituximab (MabThera®), an anti-CD20 chimeric IgG1 approved for non-Hodgkin’s lymphoma, has a similar SC formulation to trastuzumab, but no difference in ADA incidence was reported between SC and IV routes (Hamuro et al., 2017). Further examples comparing IV and SC routes for therapeutic mAbs are described in literature (Blair & Duggan, 2018; Matucci et al., 2018). Additional examples of dosing and administration methods of FDA-approved mAbs are listed in Table 2. Despite the majority of therapeutic mAbs being administered through IV or SC routes, early drug development programs are still exploring novel delivery systems for biopharmaceuticals. Examples of these delivery systems are ones that can pass the intestinal tract without being digested, or administration through pulmonary or nasal routes (Anselmo, Gokarn, & Mitragotri, 2019; Bequignon et al., 2019; Kumar et al., 2018; Mitragotri et al., 2014).

Table 2 : Characteristics (route of administration, mode of delivery and dose strength) of several therapeutic mAbs approved by the FDA. Abbreviations: RoA : route of administration,IV : intravenous, SC : subcutaneous, IVP : intravenous pyelogram, PFS : pre-filled syringe, AI : autoinjector. Information gathered from MedScape (2020).