Inhalable and Nasal Biologics: Analytical, Formulation, Development, and Regulatory Considerations

Area of Science:

• Pharmaceutical Sciences
• Biotechnology
• Regulatory Science

Background:

• Inhalation and intranasal delivery of large molecules and biologics offer direct targeting, bypass metabolism, and convenience.
• Significant growth in research and development for inhalable and nasal biologics (INBs) is observed.
• Challenges in formulation, manufacturing, analytical testing, and regulatory review must be addressed for INB market entry.

Purpose of the Study:

• To summarize expert discussions on applying Chemistry, Manufacturing, and Controls (CMC) and bioequivalence (BE) principles to INB development.
• To review applicable literature and regulatory guidelines for INBs in the absence of explicit guidance.
• To explore the balance between INB requirements and established medical aerosol techniques.

Main Methods:

• Review of existing US FDA and EMA guidelines for biologics and small-molecule inhalation/nasal products.
• Synthesis of discussions from the 2023 International Society for Aerosols in Medicine (ISAM) and International Pharmaceutical Aerosol Consortium on Regulation & Science (IPAC-RS) workshop.
• Inclusion of recent developments and case studies on generic peptides, inhaled biologics, and viral-based products.

Main Results:

• Description of regulatory expectations for INB development.
• Guidance on selecting delivery systems and formulation types for INBs.
• Overview of analytical techniques for assessing INB product quality attributes.

Conclusions:

• INBs hold promise for treating diseases with unmet needs and reducing injection burden.
• Continued collaboration among researchers, developers, and regulators is crucial for advancing INB therapies.
• Successful development and regulatory approval of INBs will ultimately benefit patients and improve health outcomes.