Patient compliance
At the core of drug development and the intended use of an antibody is patient centricity. While some formulations were developed for improved PK/PD properties or safety concerns, others were developed for increased patient compliance. The subcutaneous route has shown to be most convenient route of administration due to self-administration possibilities, with increased flexibility and potential to reduce costs for patients, payers and providers. The use of autoinjectors, PFS or mini-needles for SC administrations has led to increased patient acceptability and compliance, with the exception of potentially eliciting a higher immunological response (Datta-Mannan, 2019; Homayun et al., 2019). Using trastuzumab as an example, the re-formulated SC trastuzumab allows for administration using a hand-held syringe or single-use injection device (Jackisch et al., 2015). A study by Pivot et al. reported that 88.9% of patients treated with trastuzumab, both IV and SC, preferred administration by SC route, with “time saving” being the main reason for their preference (Pivot et al., 2014). Nevertheless, potential higher immunological ADA response, needle-associated phobia and pain, unsafe needle use and improper disposal must also be considered (Homayun et al., 2019).
Considerations for the intended use of an antibody must also be suitable for treatment of the desired disease. While parenteral administration is preferred for acute and emergency responses, non-parenteral and less invasive methods are more suitable for sustained therapy and chronic delivery (Homayun et al., 2019). Patient adherence is an important aspect in achieving successful treatment outcomes. Reports have revealed that patient adherence rates for chronic therapies in developed countries are only 50%, being even lower in developing countries (Li & Easton, 2018). Considering this, novel technologies have been developed, such as large-volume wearable injector device (LVD), allowing self-administration of a drug at a flexible time and location, with the hope of joining patient factors and promoting consistent use of a drug in chronic diseases (Li & Easton, 2018). In an effort to increase patient compliance and reduce invasive treatments, promising advances have been reported by assessing different RoA for mAb treatment of diabetic retinopathy and potentially other chronic retinal pathologies in mice (Barcelona et al., 2018).
Special populations must also be examined, particularly if there is a certain correlation between a disease and a given population. The disease status of patients with renal or hepatic impairment, or paediatric or elderly patients will not only influence a drug’s PK properties, but may also impact safety and efficacy of a drug (Mould & Meibohm, 2016). Defining patient’s physical and cognitive limitations and capabilities could also impact the ability to use a certain drug delivery device safely and effectively. Such impairments could include visual, cognitive or manual dexterity. For example, patients with rheumatoid arthritis or those eliciting involuntary hand movements due to Parkinson’s disease may not be capable of using fine motor skills to control and stabilize a syringe with a narrow needle (Strochlic & Davis, 2017). The high costs of monoclonal antibody therapy by achieving patient-convenient self-administration formulations may also hamper the success of a drug on the market (Li & Easton, 2018). Thus, when evaluating the intended use of a therapeutic monoclonal antibody, all these attributes must be taken into consideration in order to find the balance between the needs, interests and limitations of both the patient and process development.