December 12, 2017

Driving change in biomanufacturing

By Jenny Dunker, Global Product Marketing Manager, BioProcess Hardware at GE Healthcare

The large buffer volumes required for biomanufacturing can be a bottleneck, especially when scaling up. Just-in-time buffer preparation can be the solution.


Two commonly asked questions about in-line buffer preparation

Whatever the objective, driving change is a challenge. Implementing a new technology into a bioprocess is a big change. The new technology must be fully understood, all regulatory requirements fulfilled, the quality of the product output secured, and a thorough risk mitigation conducted.

Biomanufacturing require many unique buffers and some might be complex to prepare, posing challenges to planning for manning, logistics, and scheduling. With in-line conditioning (IC), buffers are prepared just-in-time, simplifying logistics and securing critical quality attributes.

Changing from traditional buffer preparation to IC would mean implementing a new control strategy—driving a change. Here, are the answers to the two most common questions from our customers that can help you drive the change of implementing IC at your facility.

Will our buffers work?

You can use an inline conditioning system for almost any buffer. The system is very flexible, and can be used for in-line buffer preparation from single-component stock solution, for in-line dilution of buffer concentrates, as well as for creating gradients.

Using GE Healthcare’s Inline Conditioning system, over 100 unique buffers of five different buffer systems, varying in pH, concentration, conductivity, and additives, have been formulated in line in an automated manner from single-component stock solution.

Table 1 shows phosphate buffers that can be prepared from the same three stock solutions. Glycerol mixtures with acetate and dilution gradients with potassium phosphate, for example, have also successfully been prepared using the Inline Conditioning system.

Table 1. Example of phosphate buffer range that can be prepared from only three stock solutions

Input

Output

Stock solutions Buffer conc. (mM) Salt conc. range (mM) pH range
0.3 M NaH2PO4 20 0–500 6.8–7.3
0.3 M Na2HPO4 30 0–500 6.8–7.4
3.5 M NaCl 50 0–500 6.8–7.4

How can we be convinced that buffers are made to specification?

With Inline Conditioning systems from GE Healthcare, advanced in-line feedback regulations by dynamic control ensures accurate formulations of the final buffer as it is being produced (Fig 1). The dynamic control feature will adjust for any incoming variability to deliver a consistent formulation.

The Inline Conditioning systems, including the control modes, are validated as any other type of bioprocess system. Process qualification includes preparation of the buffers used in a process, all according to regulatory requirements at a typical biomanufacturing facility.

A key aspect through validation is to document robustness of the process in the operating space. Studies, such as testing extremes of the operating space, obtaining models to predict variance, and perform failure mode risk analysis, are commonly made to provide data that justifies the change.

Fig 1. Correlation between in-line and off-line pH readings for buffers produced with ILC.

Let the IC system test and control your input stock solutions

Ensuring that buffers meet specification takes time. Moving the QC closer to the production floor can be a way to intensify this process. Let the IC system test and control your input stock solutions to save time and logistics spent on QC of these stock solution.

As correct formulation is crucial for success in production, sensors monitor the output, and formulation outside specifications is diverted to drain. All buffer data is stored as part of your result file for later review. Time stamps will help distinguish between buffers and batches.

Adjustments to the final formulation will be made according to the buffer recipe defined in the system. Three modes of feedback control can be used: recipe and flow; pH and flow; and pH and conductivity. Select the feedback mode that best controls your critical process parameters.

Learn more

Do you have more questions regarding in-line conditioning? Find the answers here or from our FAQ.

Sign up for upcoming posts! The next post will discuss single-use versus stainless steel equipment in downstream bioprocessing.