Regulatory landscape for inhaled biologics: Considerations and guidelines

Despite significant scientific interest, only a small number of inhaled biologics have reached regulatory approval, reflecting the complex interplay between the inherent structural fragility of biologics during the aerosolization steps intrinsic to inhaled administration and the absence of inhalation-specific regulatory guidance. This review examines the key scientific and technical considerations that influence the stability, safety, and performance of inhaled biologics, including aggregation, chemical degradation, immunogenicity, device compatibility, and the limited availability of inhalation-qualified excipients. Existing regulatory frameworks in the United States and Europe for biological products, inhalation products, and delivery devices provide substantial foundations for inhaled biologic development. Their application requires an integrated assessment of the final formulation-device pairing, particularly where aerosolization alters molecular integrity, biological activity, or pulmonary exposure. This review connects these considerations with clinical experience and proposes a scope for dedicated guidance addressing quality, pulmonary safety, device performance, and clinical benefit. A survey of ongoing clinical trials reveals a growing but constrained pipeline dominated by mRNA therapeutics, protein-based agents, and viral-vectored vaccines, underscoring both progress and persistent formulation barriers. Together, these insights emphasize the urgent need for a harmonized regulatory paradigm tailored to inhaled biologics that integrates biologic-specific analytical expectations, aerosolization stress testing, and clear pathways for excipient qualification.