The Future of Buffer Management: On-Demand Dilution at Point of Use

Buffer flow

The following case study describes how dilution at point of use is utilized to reduce the floor space required, decrease buffer production cost, and make buffer management more time-efficient.

The Role of On-Demand Buffer Dilution

The biopharmaceutical industry is undergoing significant changes, including process intensification, higher product yields, and the need for multi-product facilities. This has led to a greater demand for process buffers, which must be prepared in a way that is cost-effective, efficient, and safe. Additionally, the industry is trending towards continuous bioprocessing, which requires different buffer demands. These changes have led to an increased volume and diversity of buffers required, highlighting the need for improved solutions and technological advancements in buffer preparation. The BioPhorum Technology Roadmap for the Biopharmaceutical Manufacturing Industry has recognized buffer preparation as an area that requires attention and innovation to meet the evolving needs of the industry.

Pain Points Caused by Traditional Buffer Preparation

  • Large quantities of buffer are necessary
  • Requiring significant floor space for manufacturing and storage
  • The process of buffer preparation is inherently labor-intensive

Benefits On-Demand In-line Dilution

  • A decrease in buffer production cost per liter (up to 12%)
  • 75% reduction in floor space required for buffer storage
  • Integrated point-of-use delivery can make buffer management more time-efficient

Traditional buffer preparation is challenging due to its labor-intensive nature, large quantity of chemical reagents required, and significant footprint within a manufacturing plant. Buffer preparation dictates plant capacity and drives biopharma plant schedules, leading to time-consuming bottlenecks. Forward-thinking production teams are seeking effective ways to manage the buffer process to avoid being slowed down by these challenges. To address these challenges, utilizing in-line dilution of buffer concentrates, along with Single-Use fluid handling and mixing solutions, can be effective. This involves preparing multi-component buffer solutions in fixed vessels or Single-Use mixers at high concentrations and then diluting them for use in the process.

Bioreactor Dilution Point
Bioreactor buffer management control


An example of skid capable of delivering the benefits listed is the Cytiva Allegro™ Connect Buffer Management System [31]. The main CPP are pH and Conductivity, monitored respectively with Hamilton SU OneFerm Arc 120 and Conducell 4USF Arc 120.

pH Dilution Point Graph
Conductivity Dilution Point Graph

CPPs: Conductivity and pH measurement stabilization before filling the biocontainer with triplicate in-line dilutions of 0.2 M Tris-HCl 1 M NaCl pH 8.1 by 20x and 0.1 M Tris-HCl 0.5 M NaCl pH 8.0 by 10x

Hamilton Products Used

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