Chemical Process Scale-Down

Chemical process scale-down is a strategy that was generated in the last 20 years, based on the fact that chemical engineering calculations can become easier and more accessible to every chemical engineer or process chemist that is in charge of transferring a process to the production step. The main idea is to define as precisely as possible the environment that the materials are in, the interaction between them in any process, and if the equipment will be on a laboratory scale or pilot scale in low volumes (we’re talking about one of 50 ml, 1 L). We can give the process similar conditions during the production step, and simulate the same process but in very small quantities. In this way, we are saving time and money at the development stage, and are able to better understand the process and focus on ensuring there is as low a risk as possible at the next step. Success depends on these activities.

The capability to implement these kinds of metronome methodology has become more and more accessible because the equipment has improved, and simulation calculations have become more exact and closer to the realistic situation in the equipment.

The main problem faced when we talk about scale-down is the interdisciplinary aspect that exists among all the professionals involved in scale-up or scale-down activities. During a scale-up, there are chemists or biologists coming from the scientific side, production staff coming from the business and operational side, and analytical staff coming mainly from the side of quality assurance and the quality control process. Together, all of these professionals should understand what the process is and how to ensure that the small scale is representative of and relevant to what will be done at the next step. Once this is done, it will be possible to progress with a better understanding of the process.

Now, what is the main change that we face when transferring a process to the next step? If we have the same raw material, process, and interpretation, then the only reason a deviation in the quality, productivity, and operation of the process would occur is because the interaction between the materials is different in one piece of equipment versus another. The only way to ensure that these interactions are under control, and to forecast the next step well, is by considering the reason behind these interactions. The only reason that we are generating this kind of interaction is the flow and understanding of the process.

So, when we put our materials in our reactor, we have some fluid that is moving, and the flow that we’re generating in this fluid is the flow mechanics or the mixing parameters that are controlling the process. Once we know that the mixing we’re implementing is generating the kind of interaction acceptable for the quality productivity operation, we will be able to ensure that the process will develop satisfactorily. This is the reason that we would scale down. Scaling down means running a process on a very small scale, keeping fixed the chemical affinity between the materials and the kind of interaction we are able to generate between the materials. When we are using different sizes of equipment, of course, we have a difference in the geometry, and of course we have a difference in the pathway of the fluid elements that are interacting between the materials. Inside them, we have molecules, and there are some interactions inside and outside of the fluid elements.

This is the reason why we cannot talk about miniaturization or simplified rules when on a small scale, but divided by 10 only, because all these interactions between the flow and the chemicals, and the chemical affiliating, are nonlinear. The interaction is very nonlinear, and the fluid mechanics by itself is nonlinear, with interactions between different flow directions and sizes we are generating in the tank. Inside this condition, we have molecules that are smaller than any fluid element. So, we need to consider the fluid elements in combination with the molecular size, and how this group of fluid elements move in the tank and interact. For this reason, we are not talking about the miniaturization schedule of some equipment that we have. We are trying to apply all the knowledge about the process and how to combine different elements.

In the pharmaceutical industry, we’re talking about thousands of liters per batch regarding fine chemicals, or black busters, in the biotechnology. Of course, we’re talking about thousands and tens of thousands of liters, because we are talking about fermentation and all the downstream, all the crystallizations, and all the separation or purification of the materials involved in the industry. So, this is the main reason for a chemical process scale-down. With VisiMix, we provide all the tools that will quickly help you understand what flow is being used at any stage, how to combine it with the materials, and what the most important mixing parameters are that control the different process or chemical parameters, including reaction rates, dissolution, crystallization, mass transfer, and heat transfer.

The methodology on the role of mixing in the industry, and how to support this kind of scale-down, was developed by me and has been implemented in the industry. Additional doctoral work has been done regarding the implementation of this kind of methodology in the mechanical field; in my case, the type of manufacturing was in big quantities, in an environment that was a mixing and sterile vessel equipment. These kinds of processes involved solid phase in liquid phase, where the reaction was happening in the interaction between solids and liquids and involved 10, 12, and 15 different reactions in series, showing how to achieve a conventionally higher productivity.