High throughput screening of particle conditioning operations: I. System design and method development

Area of Science:

• Biotechnology
• Process Development
• Chemical Engineering

Background:

• The biotechnology industry faces pressure to reduce time-to-market and development costs.
• Regulators require increased process understanding for novel therapeutics.
• High throughput process development (HTPD) offers a solution by using small volumes and parallel processing.

Purpose of the Study:

• To describe an ultra scale-down (USD) system for high throughput particle conditioning (HTPC).
• To enable parallel evaluation of 96 reaction conditions for biological product recovery.
• To facilitate enhanced process understanding and reduce development costs.

Main Methods:

• Development of an HTPC system using off-the-shelf components.
• Integration of a temperature-controlled microplate with magnetic stirrers and a liquid handling robot.
• Parallel processing of 96 conditions, including centrifugal clarification, with high throughput analytics.

Main Results:

• The USD system successfully evaluated HTPC at a 1 mL scale using vaccine polysaccharide fermentation broth.
• Response profiles were compared to pilot-scale performance (3 L reactor).
• A comprehensive suite of analytics measured product titer, quality, impurity clearance, and particle characteristics.

Conclusions:

• The described USD system enables rapid, cost-effective optimization of particle conditioning processes.
• This approach supports improved developmental productivity and deeper process understanding in biomanufacturing.
• The system is scalable and applicable to industrially relevant vaccines.