Bioprocess Scale-Up Solutions

We have some questions that come in from the web about how to progress to the scale-up bioprocess. Mainly when we talk about bioprocess, we’re talking about two main activities.

The first activity normally is fermentation or growth of microorganisms or microcells. The second step is to try to separate between the product that we want to have and the other parts of the cells that are not good for us, inside or outside the cell, it really depends on the biotechnology and bioprocess that the company is using.

But in general terms, the way to go to the scale-up in bioprocess is to identify the phases that are involved in the process and the process by itself that we want to progress because as a function of it, the conditions we need to provide to the materials to progress to the next step are well defined.

For instance, if we go to the first step which is fermentation and the reproduction of cells, the main goal is to provide the conditions for these cells to continue to live, develop themselves, and reproduce at a rate that will be good for us and will be possible for the equipment. And the way to do it is to identify the level of oxygen required in the liquid phase, the distribution of the nutrients that we are feeding into the tank, the pH that is required that should be well distributed in the tank, correction, and how long this process is progressing, that can be different in different sizes, because the high dependency of the diffusivity and the flow that we’re generating into the tank.

When we go to the second part of the process which is mainly the cleaning of the materials, the extraction of the materials to some stream that we can clean more and generate our last product, this is really dependent. We have normally the filtration, we have normally the precipitation, and we have normally some high shear rate that we need in order to break up the cells that will be required. And all of these activities are process activities that are regarding physics and physical properties of the media that you are using in order to separate the materials to the product required.

So, these are the two main ideas. To go for every one of them, you need to know what the unit operation and what is the main characteristic of this unit operation is from the point of view of the chemical affinity and the point of view of physics provided to the materials to interact and generate good results.

Bioprocess with Big Equipment

When we go into the industry, we need to take into consideration that we are going to big equipment, normally in the first step. And when we go to this big kind of equipment, the capability to transfer materials is better normally but should be controlled. We need to be sure that when we are in the step where we are consuming a lot of oxygen because the reproduction of these cells is at a high rate, the equipment will be able to provide you with the conditions. And sometimes it is not possible. For this, you need good appropriate mixing control equipment and the appropriate geometry of impellers that will distribute the gas in a good way. So, in terms of this first part.

The second part is more regarding the membranes you are using to the shear rate you need to apply to transfer the materials to the liquid phase or how to precipitate on the conditions that the solubility will be the control parameter that you need to take care of during the process because you will generate conditions that the probability will be not good and the material will like to be in the solid phase. And of course, the filtration and particle size will not be good enough to filtrate optimally. So normally, it is not enough to have some kind of calculator. Okay, we don’t have to be a process calculator. We have to simulate it, to understand how the process will be well-defined on the conditions that will be able to provide on a big scale, and for this it is fundamental to know what environment we’re generating. So, to know about flow and how to connect to the process. Normally, you know you process better than everyone. The biological phenomena are well known. The point is how to understand what are the limitations on the flow, regarding the process you want to apply. So, this is the main idea. For everyone at this stage, once we are focusing on understanding what are the phases involved and what we’re looking for, the point is how to understand the mixing parameters and the flow parameters. And for this, of course, you have VisiMix – the best mixing software to help you at any step.