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FDA's Current Perspectives on the Propellant Transition: Work Towards Global Harmonization

Bielski E, Newman B, Luke M.

Respiratory Drug Delivery 2025. Volume 1, 2025: 72-75.

Abstract:

The transition from hydrofluoroalkane (HFA) propellants to the next generation propellants (NGPs) presents scientific and global regulatory challenges for metered dose inhalers (MDIs). Through engagement with key stakeholders from academia, industry, and regulatory agencies via a public workshop, alignment on data requirements to support an NGP transition of MDIs was gained in certain areas. However, several challenges remain surrounding certain data requirements and appropriate submission pathways for United States (US) applications. Based on the workshop outcomes and current scientific understanding, the US Food and Drug Administration (FDA) has considered updates on recommended data requirements to support the propellant transition and facilitate better global harmonization efforts. The updates on nonclinical, product quality, pharmacokinetic (PK), and clinical data considerations are provided. An emphasis of understanding propellant safety, establishing in vitro comparability, and building upon in vitro–in vivo relationships are considered key to support a streamlined approach. Remaining challenges on varying global data requirements are also identified. While the data requirements to support an NGP MDI application across regulatory bodies is not fully aligned, leveraging existing knowledge and experience, minimizing changes to the MDI product where possible, and understanding NGP safety profiles will likely evolve with time and build towards a more globally harmonized approach for the transition.