Scale-Up and Postapproval Changes in Orally Inhaled Drug Products: Scientific and Regulatory Considerations

Area of Science:

• Pharmaceutical Sciences
• Regulatory Science
• Drug Delivery Systems

Background:

• Approved drug products often undergo changes (e.g., batch size, manufacturing sites) requiring regulatory assessment.
• Existing Scale-Up and Postapproval Changes (SUPAC) guidelines from the FDA cover solid oral and semisolid formulations but not orally inhaled drug products (OIDPs).
• OIDPs are complex drug-device combination products, necessitating specific considerations for post-approval changes.

Purpose of the Study:

• To provide a seminal contribution towards developing SUPAC guidelines for orally inhaled drug products (OIDPs).
• To discuss the scientific aspects and regulatory bases for addressing SUPAC in OIDPs.
• To outline considerations for evaluating the impact of changes on OIDP performance, safety, and efficacy.

Main Methods:

• Review of existing FDA SUPAC guidelines for other dosage forms.
• Discussion of the unique challenges posed by OIDPs as drug-device combinations.
• Analysis of scientific and regulatory factors influencing post-approval changes in OIDPs.

Main Results:

• Identified a gap in current regulatory guidance for SUPAC in OIDPs.
• Highlighted the need to consider changes in drug substance, formulation, and device components of OIDPs.
• Emphasized the compound effect of multiple changes on OIDP safety and efficacy.

Conclusions:

• Formal regulatory guidelines for OIDP SUPAC are needed and this article provides a foundational discussion.
• Development of OIDP SUPAC guidelines requires multidisciplinary input from industry and regulatory agencies.
• Case-by-case evaluation by authorities will determine applicable guidelines for OIDP SUPAC.