A modular and multi-functional purification strategy that enables a common framework for manufacturing scale...

Area of Science:

• Biopharmaceutical Manufacturing
• Process Engineering
• Downstream Processing

Background:

• Biopharmaceutical manufacturing is shifting from traditional batch processes to integrated and continuous biomanufacturing (ICB).
• Achieving the full potential of ICB is challenging due to complex supply chains, reliance on customized single-use components, and extensive buffer requirements.
• Existing commercial equipment often struggles to meet the demands of integrated, multi-supplier systems.

Purpose of the Study:

• To introduce and evaluate SymphonX™, a novel downstream processing skid designed to overcome challenges in ICB.
• To demonstrate the capability of SymphonX™ for flexible, multi-product, and multi-process cGMP (current Good Manufacturing Practice) facilities.
• To validate SymphonX™'s performance in a manufacturing-scale proof-of-concept for ICB.

Main Methods:

• Development of SymphonX™ skid featuring advanced buffer management, a single generic disposable flow path, and a unified interface.
• Utilization of an Apollo™ X CHO-DG44 mAb-expressing cell line in a steady-state perfusion bioreactor for continuous product harvesting.
• Implementation of downstream processing using SymphonX™ with single-column chromatography (Protein A, cation exchange, anion exchange) and batch virus inactivation, employing surge vessels between unit operations.

Main Results:

• Successful continuous harvesting and processing of monoclonal antibody (mAb) product for 6 days.
• Production of 0.54 kg/day of drug substance with consistent product quality attributes.
• Demonstrated effective bioburden control across unit operations operating in continuous mode.

Conclusions:

• SymphonX™ provides a flexible and robust platform for integrated and continuous biomanufacturing.
• The system facilitates plug-and-play operations, reducing operational risks and enabling multi-product capabilities.
• This study validates the feasibility of manufacturing-scale ICB with consistent product quality and bioburden control.