Recent Advances in Co-processed APIs and Proposals for Enabling Commercialization of These Transformative...

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Chemical Engineering

Background:

• Optimizing physical properties of active pharmaceutical ingredients (APIs) is critical for robust drug product manufacturing and consistent quality attributes.
• Many APIs possess unmanageable physical properties through conventional methods like form selection, crystallization control, or milling.
• Innovative approaches are needed to enhance API physical properties for improved manufacturing processes.

Purpose of the Study:

• To explore the potential of co-processed APIs, integrating nonactive components during drug substance manufacturing, to control and enhance API physical properties.
• To highlight the opportunities and growing interest in co-processed APIs, supported by academic research and industrial examples.
• To advocate for co-processed APIs to be considered drug substances from a regulatory standpoint and identify areas for regulatory strategy development.

Main Methods:

• Review of academic research and industrial examples demonstrating the benefits of co-processed APIs.
• Analysis of how incorporating nonactive components during drug substance manufacturing can modify API physical properties (e.g., bulk, surface, mechanical).
• Discussion on the potential of co-processed APIs to enable advanced manufacturing techniques like continuous direct compression.

Main Results:

• Co-processed APIs offer unique opportunities to control API physical properties beyond traditional methods.
• This approach can lead to simplified and more robust pharmaceutical manufacturing, including continuous processing for both small and large molecules.
• Co-processed APIs can enable continuous direct compression for small molecules.

Conclusions:

• Co-processed APIs represent a promising strategy for overcoming challenges associated with API physical properties.
• Further development of regulatory strategies is essential to facilitate the commercialization of co-processed API technologies.
• Treating co-processed APIs as drug substances is recommended from a regulatory perspective to streamline their integration into pharmaceutical manufacturing.