Feasibility and pharmacokinetic evaluation of a needle-free injector for delivering high concentration antibody formulations. A Josowitz, AS Manoj, D Laiacona, M Pelletier, D Molano, S Jennings, C Ng, CAntoni, G Chan, R Mahoney, S Patel, E-M Koehler-Stec, M Retter, J Kantrowitz, B Rayaprolu, E Holowka, AS Bhalla, M Shameem.
This research report presents the evaluation of a novel NFI for the SC delivery of high concentration mAb formulations. This new, 2 mL design addresses some of the challenges patients and healthcare providers experience as industry has continued to shift toward SC delivery from IV. Furthermore, this evaluation utilizes ex vivo and in vivo porcine models to approximate the characteristics of human skin rather than small mammal models.
Abstract: The increased preference amongst health care providers and patients for subcutaneous (SC) administration of biologics has necessitated the development of higher concentration formulations to maintain doses similar to intravenous (IV) products. These formulations possess manufacturing and administration challenges; particularly high concentration monoclonal antibody (mAb) formulations push the limit of injectability. Furthermore, patient-centric considerations, such as pain and fear of needles (trypanophobia), can lead to compliance deviations for long-term treatments.
This study presents a set of evaluations of a novel computer-controlled, needle-free injector (NFI) design that can deliver 2.0 mL of a high viscosity (50 cP) mAb formulation into the SC space. Critical attributes such as antibody purity, aggregation, color, turbidity, and charge heterogeneity were evaluated before and after ejection and demonstrated minimal change compared to ejection from a 27-gauge needle and syringe (N&S). Furthermore, the device functionality was evaluated in a novel ex vivo pig skin model, demonstrating the ability to accurately deposit a 2.0 mL dose at an appropriate depth in the SC tissue, though requiring 8% greater fill volume than an N&S. An in vivo Yorkshire pig model was used to understand the pharmacokinetic (PK) profile of the NFI in comparison to a N&S. Clearance (CL), the observed peak concentration in serum (Cmax), the time until Cmax (Tmax), area under the concentration-time curve extrapolated to infinity (AUCinf), and half-life (t1/2) were all within 1.2 fold and considered similar between the NFI and N&S. A non-significant difference in Tmax was also observed. Bioavailability relative to IV administration was similar between the NFI (80.0%) and N&S (79.5%) groups. No concerning clinical observations and injection site reactions were observed.
Ultimately, the NFI represents an advancement in SC delivery of high concentration mAb formulations with patient-centric design. This device could facilitate clinical and at-home use while complementing efforts to bridge IV and SC formulations.