Buffer Stock Blending System

The full-scale, open-source prototype Buffer Stock Blending (BSB) System will potentially significantly reduce capital investment and manual operation costs, reduce the number and volume of buffer, and decrease time for buffer manufacturing.

Industry Need

Traditional batch buffer preparation during the manufacturing process is highly manual, space-intensive, and creates operational bottlenecks with scheduling and throughput limitations. Current approaches lack flexibility and scalability, making it difficult to meet the growing demand buffer needs in modern biomanufacturing facilities.

Approach

This project designed and built a mass-flow based, open-source Buffer Stock Blending System (BSB System) which was then tested at NIIMBL headquarters in Newark, DE. The system uses mass-flow to blend concentrated stock solutions enabling delivery of continuous or near real-time buffers eliminating the need for buffer storage space. The BSB System's open-source design allows it to be configurable and democratizes access for wider industry adoption. The system is also cGMP-ready and can integrate seamlessly with external equipment like chromatography skids.

Impacts

The BSB System supports the industry shift to integrated continuous bioprocessing (ICB) and enables rapid changeovers, significantly accelerating manufacturing timelines.

Next generation manufacturing facilities could operate with smaller buffer prep areas and utility requirements enabling more compact, modular plant designs.

With minimal buffer stock wastage and elimination of buffer hold steps, the BSB System supports industry sustainability goals.

The BSB Systems open-source design removes proprietary barriers to adoption of advanced buffer manufacturing.

Value Statement/Outcomes

The BSB System represents a paradigm shift from traditional buffer preparation to automated, continuous, and flexible buffer manufacturing, addressing speed, cost, and quality challenges in biopharmaceutical production. During testing at NIIMBL, the system demonstrated a 3-4x improvement in throughput compared to manual buffer prep. Buffers can be delivered within 30 seconds from start, enabling real-time release and eliminating lengthy hold times.

Outputs/Deliverables

Prototype Buffer Stock Blending System - Skid housed at NIIMBL headquarters

Design documentation, FAT, SAT, demonstration data, buffer recipe calculator tool

Publications

Ram, N., Johnson, J., Ardeshna, H., Camire, J., Campbell, R., Chau, D., Gardner, S., Gibson, K., Norikane, J., Randolph, P., Smith, K., Stafford, K., Swamy, R., Usery, S., & Lee, K. H. (2023). Evaluation of the Design, Development, and Performance of a Mass-Flow Based, Open-Source Buffer Manufacturing System. PDA Journal of Pharmaceutical Science and Technology, 77(2), 79-98. https://doi.org/10.5731/pdajpst.2021.012660