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.