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This article, entitled “Why it is time to ‘Think Different’ about nasal delivery of biologics,” looks into the potential and challenges of nasal delivery for biologics. As the pharmaceutical industry continues to evolve, the focus is shifting towards innovative delivery methods. Nasal delivery of biologics is one such method that promises significant benefits, including the potential for prophylactic therapies against threats like SARS-CoV-2 and the ability to deliver molecules to the CNS to treat neurodegenerative diseases. However, the path to realizing this potential is fraught with challenges. Biologics are sensitive to aerosolization and shear stress, and their interaction with excipients used in typical formulations can lead to issues such as protein agglomeration and precipitation. The article emphasizes the importance of an integrated approach to formulation and device development, taking into account the characteristics of the API and the device, as well as patient behavior and needs. It also highlights the potential of emerging technologies, such as ‘connected’ nasal devices, which could revolutionize the management of chronic conditions. The article serves as a comprehensive guide for anyone interested in the future of biologics and nasal drug delivery.