The preparation of a large number of buffers is becoming a challenge for the biopharmaceutical industry since buffer solutions are required in large quantities and within a short interval of time. It is also a critical operation as it has to be very specific in terms of concentration to get a high yield. Traditionally buffer used to be prepared by mixing buffer stock solution in fixed vessels or single-use mixers at the final required concentration ready for delivery to the process. But this mixing strategy accounts for a large proportion of a facility’s footprint, labour, equipment and operating cost.
Inline dilution (ILD) can overcome challenges to some extent such as reduction in floor space by the use of buffer concentrates that are diluted with water for injection (WFI)-grade water upon need. As buffers are multi-component formulations, the common ion effect will limit concentration grade when preparing stock solutions. The least soluble ion will determine the maximum concentration of the stock solution. Furthermore, the subsequent dilution will cause pH and conductivity shifts that need to be taken into consideration in the final buffer formulation. Concentrated buffers need to be precisely formulated as dilution will propagate any formulation error. Moreover, managing gradients is not possible with ILD.
To overcome all of the above challenges inline buffer conditioning (ILBC) techniques are developed. In ILBC buffers are formulated using concentrated stock solutions of required acid or base, WFI and salt. Unlike ILD, a wide range of buffer solutions can be made and it is not affected by Common ion effects (CIE). ILBC not only requires less space, but it also allows dynamic control i.e uses a variety of control modes. It also achieves higher dilution ratios. ILBC also addresses issues with buffer variability by allowing for feedback control of the buffer preparation process. It easily conditions buffers with gradient flow i.e step gradient, linear gradient etc. Automation reduces manual interaction with the system thus prevent risks of human error or contamination.
Nilsan Nishotech has wide-ranging experience in designing, manufacturing and customizing in-line buffer conditioning systems for very specific and critical needs of the Pharma and Biopharma industry. Our technology is based on using the most accurate mass flow and conductivity measuring devices and a specific control system to reach the highest reproducibility. These systems drastically reduce the volume and size of buffer tanks in Biopharma manufacturing plants.
Our in-line buffer conditioning systems include advanced, PAT (Process Analytical Technologies guidelines of the FDA) compliant features.
Advantages of NNSPL Inline Conditioning:-
– Automated buffer mixing system.
– Ratio of chemicals is easily controlled.
– Savings on labour due to reproducible buffer preparations.
– OpenX is less due to its low footprint.
– No loss of chemicals.
– Automation ensures less contamination.
– Reduced maintenance time.