Experience and process of pilot scale-up

Pilot test is the only way for products to move from conception to adulthood, and it is the link of product life. The intermediate experimental stage is to further study the change law of biological reaction conditions at each step in a device of a certain scale, and solve problems that cannot be solved or found in the laboratory.

At what stage of the experiment is the pilot test?

• The yield of the small test is stable, and the product quality is reliable.

• The experimental conditions have been determined, and the analytical test methods for the products, intermediates and principles have been determined.

• Corrosion resistance tests have been carried out on certain equipment, pipe materials, and general equipment is required.

• A material balance was made. There are preliminary ways to deal with the problem of three wastes.

• The specifications and unit consumption quantities of raw materials have been proposed.

• The requirements for safe production have been put forward.

The purpose of the pilot test

• Pilot test is a necessary transition link from small-scale test to industrial production;

• It is the process of using small production equipment for production, and the design requirements, selection and working principle of the equipment are basically the same as those of large-scale production;

• After the small-scale test is matured, the pilot test is carried out to study the feasible process for industrialization and equipment selection, so as to provide a basis for industrial design.

Pilot scale-up method

• Empirical amplification: Mainly by virtue of experience, the characteristics of the reactor are explored through step-by-step scale-up (small-scale plant-intermediate plant-medium-sized plant-large device).

• Similarity amplification: Mainly apply the similarity principle for amplification. This method has certain limitations and is only applicable to the scale-up of physical processes.

• Mathematical simulation amplification: It is the amplification of the application of computer technology, and it is the direction of future development. In addition, the development of micro-intermediates is also rapid, that is, the use of micro-intermediates to replace large intermediates to provide accurate design data for industrial installations. Its advantages are low cost and fast construction.

Tasks in the scale-up phase of the pilot test

• There are mainly the following 10 points, which can be carried out in a planned and organized manner according to different situations.

• Finalization of the routing and unit reaction operation methods. In particular, when the original selected route and unit reaction method expose major problems that are difficult to solve in the pilot scale-up stage, other routes should be re-selected, and then the pilot scale-up should be carried out according to the new route.

• Selection of equipment material and model. Special attention should be paid to the selection of materials for equipment that comes into contact with corrosive materials.

• Investigation of agitator type and stirring speed. Many reactions are heterogeneous, and the thermal effect of the reaction is large. Due to the small volume of the material and the good stirring effect, the problem of heat and mass transfer is not obvious during the small test, but in the pilot scale-up, it is necessary to pay attention to the influence of the stirring type and stirring speed on the reaction according to the nature of the material and the reaction characteristics, so as to select the agitator that meets the requirements and determine the applicable stirring speed.

• Further study of reaction conditions. Therefore, the main influencing factors, such as feeding rate, stirring effect, heat transfer area and heat transfer coefficient of the reactor, and refrigerant, should be studied in depth to grasp the change law in the intermediate device. to obtain more applicable reaction conditions.

• Determination of process flow and operation method. Consideration should be given to adapting reaction and post-processing methods to the requirements of industrial production. Special attention is paid to shortening processes, simplifying operations, and improving labor productivity. So as to finalize the production process and operation method.

• Perform material balances. When the reaction conditions and operation methods of each step are determined, the material balance should be carried out on some reactions with low yield, more by-products and more three wastes. The sum of the weights of the reaction products and other products is equal to the sum of the quantities of each material before the reaction, which is the degree of accuracy that must be achieved in the material balance. in order to address the weak links. Tap the potential of energy saving, improve efficiency, recover by-products and comprehensive utilization, and provide data for the prevention and control of three wastes. The chemical composition of the chemical composition without the analytical method is studied by the analytical method.

• Determination of physical properties and chemical constants of raw materials, intermediates. In order to solve problems in the production process and safety measures, the properties of certain materials must be determined.

• Formulation of quality standards for raw material intermediates. If the quality standards in the small-scale test are not perfect, they should be revised and improved according to the pilot test.

• Determination of consumption quota, raw material cost, operating man-hours and production cycle, etc. On the basis of the summary report of the pilot study, the infrastructure design can be carried out and the purchase plan of the model equipment can be formulated.

• Carry out the design and manufacture of non-shaped equipment, and carry out the plant construction and equipment installation of the production workshop according to the construction drawings. All production equipment and auxiliary equipment are installed. If the trial production is qualified and the short-term trial production is stable, the process specification can be formulated and delivered to production.

Pilot scale-up steps for APIs and intermediates

• According to the small-scale operation steps for material balance and pilot process. The material balance includes raw material consumption and production cost estimates. The raw material consumption table should include a recovery estimate of the recovered solvent. The process flow should be a comprehensive embodiment of the combination of operation steps and equipment.

• The installation of the pilot process device is carried out according to the flow chart and the pilot process. Among the important aspects include: in the modification workshop to consider safety, ventilation, heating, lighting, power distribution and other aspects. Arrange the operating platform according to the equipment layout. Equipment installation and commissioning.

• In the case of complete equipment, the pilot operation procedures are compiled according to the small-scale operation steps and processes.

• At the same time, cooperate with the operation training of workshop personnel to carry out test runs. The general principle of commissioning is to start with a step-by-step approach, examine the operation and commissioning of each step, and then proceed at the same time.

• Begin the formal experiment. The main items to be investigated in the process of formal experiments are: 1) Verify the process and stabilize the efficiency. 2) Verify the operation used in the test. 3) Determine the product refining method. 4) Verify the application of biological recycling. 5) Verification of the industrialization of special operating processes. 6) Observe the thermal effect of each step of the reaction in detail. 7) Determine safety measures. 8) The batch of preparation of intermediates and finished products is generally not less than 3~5 batches, so as to accumulate data and improve the pilot production materials.

• Propose the industrial production process plan and determine the large-scale production process. This is the ultimate goal of the pilot test. Based on the data provided by the pilot test, feasible process and equipment selection, industrial design, installation, commissioning, and formal production are carried out.