Clinical Qualification of Subcutaneous Injection Devices for Monoclonal Antibodies
Beate Bittner, Javier Muñoz, Sabine Frank, Michael Dolton, Renato Ravanello, Markus Dembowski, Aude Clement, W. Richter
Abstract
Subcutaneous autoinjectors serve as a convenient and user-friendly alternative to manual injection using prefilled syringes or handheld syringes, enhancing self-administration in decentralized care settings, patient compliance, and dosing accuracy. Autoinjectors consistently penetrate the skin to the same depth, and are, thus, expected to reduce variability in injection conditions as compared to more operator-dependent manual self-injection. Even with an established autoinjector platform, molecule-specific technical development requirements often preclude the availability of the automated device at the start of pivotal clinical studies. This necessitates manual injections during these studies and frequently subsequent pharmacokinetic comparability studies to transition to the autoinjector. A proposed Molecule-Independent Device Bridging Approach (MIDBA) aims to eliminate the need for dedicated pharmacokinetic comparability studies for each new monoclonal antibody developed with a previously validated autoinjector platform by referring to PK data from other mAbs with dosing volumes up to 2 mL. The rationale for this approach lies in the slow absorption rates of mAbs following SC injection, which is primarily influenced by the residence time in subcutaneous tissue and subsequent lymphatic drainage rather than the specifics of the injection method. A narrative review of clinical data from 29 pharmacokinetic comparability studies revealed that independent of the molecule and the injection device, comparable pharmacokinetic and tolerability profiles were achieved following manual and automated injection. The review supports the applicability of the MIDBA as a streamlined development pathway for autoinjector validation without molecule-specific pharmacokinetic studies. This framework is expected to present a novel methodology for efficient transition from manual to automated subcutaneous injections for biotherapeutics.