![]() Small columns have a higher surface area to media ratio meaning a larger fraction of the media is touching the wall helping to give support to the bed as it resists the compressive effects of flow. As the diameter of the column increases, wall support decreases. Understanding column wall support is also important. For example, the relationship between pressure and flow and knowing the resins critical velocity (the point at which the pressure-flow relationship is no longer linear) is very important during scale-up. So, how does one achieve a well-packed column? Although the details often vary, several important principles remain the same. On top of all this, tight deadlines often require the packing to be “right the first time.” ![]() In addition, the large number of available media precludes a “one-size-fits- all” procedure for varying experimental situations. Often, each manufacturing step has different physical constraints (space considerations, ceiling height and pump size to name a few) and requires alterations in vendor-recommended procedures. Packing a process-scale column can become more of an art than a science. Although the chemistry remains the same, going from discovery to process-scale conditions can be quite challenging procedurally. Also cGMP manufacturing spaces often use a closed system to avoid contamination. Moving to process-scale, a column 2 meters in diameter generally utilizes pack-in-place technology where media is added without requiring removal of the top flow adapter (closed system): at these larger sizes, the piston is often very heavy and can require a hoist to lift it. When performing at a pilot scale, the column might be 10-45 cm diameter but the packing procedure can still be comparable to the laboratory scale. The purification process will likely be by flow packing with manual compression. For example, a small-scale column of 0.5-5 cm in diameter may include an open system where the operator takes the column top off to add media. The differences in the size of equipment used will require changes to some aspects of the method. When scaling up, although the chemistry usually stays consistent, procedural differences are often overlooked. Here we discuss a few key considerations when transitioning from small to larger-sized columns. With larger diameter columns, issues with irregularities in media packing, pressure and flow can occur. Columns range in size from a few millimeters in diameter for laboratory-scale to two meters or more for process-scale. Some issues start with column selection and transitioning the workflow protocol smoothly. However, many challenges exist in this activity. ![]() Scaling up from laboratory-scale to process-scale purification is one of the most important manufacturing activities for the pharmaceutical industry. Column chromatography has been used for many years to successfully characterize, purify and manufacture products for the food and drug industries. ![]()
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