From conventional biologics-device combination products to advanced therapies: current state and future trends in patient-centric delivery.

Patient-centric Biologics-Device Combination Products (BDCP) improve patient experience and compliance, while enhancing therapeutic outcomes by enabling novel routes of delivery, tackling frequent dosing and large-volume delivery requirements, and/or by simplifying administration in a healthcare setting as well as in out-patient dosing (e.g. self-administration). They also present promising solutions to overcome vaccine immunization challenges, particularly in developing nations. The BDCP opportunities, however, are often tempered by intrinsic properties of biologics (e.g. stability, viscosity etc.) and devices (e.g. design control, human factor engineering etc.) which can be further compounded by regulatory complexity across multiple jurisdictions. This comprehensive review examines the current landscape of combination product spanning across the complexities of modality (e.g. proteins, vaccines, oligonucleotide, mRNA/lipid nanoparticle (LNP) and to a limited extent cell & gene therapy) and delivery (parenteral, oral, ocular etc.) through the lens of business drivers, phase-appropriate technical development, regulatory frameworks, and patient-centric design principles. Selected case studies and commercially approved products for each modality are also presented here. Continued investments in new and improved devices such as prefilled syringes, wearable pumps, pen devices, jet devices and autoinjectors for liquid and lyophilized products highlight the recent paradigm shift for integration of delivery devices from self-administration to personalized medicine. Persistent innovation in the field, for example, has enabled device integration beyond chronic conditions such as diabetes and autoimmune diseases and prophylactic vaccination such as flu to cancer immunotherapy. Furthermore, technical, clinical and regulatory successes in achieving novel routes of delivery (e.g. oral biologics, inhaled insulin, inhaled vaccines, intradermal vaccination etc.), smart delivery systems and digital technologies have further advanced the boundaries of BDCP to not only increase market penetration but create new markets. This not only benefits patients worldwide but also paves the way for precision medicine in the future.