The various products between the APIs are pharmaceutical intermediates, and the synthesis of drugs has a strong dependence on intermediates. Pharmaceutical intermediates are important raw materials for the production of APIs, which belong to the category of chemical products, and the manufacturer does not need GMP certification. However, its production has certain particularity, and GMP related requirements should be strictly followed in plant site selection, layout planning and plant design. Different from the general chemical production process, the production process of pharmaceutical intermediates has the characteristics of miniaturization, single batch intermittency and multifunction.
1. Miniaturization
The production of pharmaceutical intermediates is characterized by miniaturization. The miniaturization is characterized by small reactors, few raw materials and precise requirements. In particular, the amount of liquid materials added in the reaction process is very small and needs to be controlled. For example, the common hydrogenation reaction process in the production of pharmaceutical intermediates is a small-scale batch reaction, which mainly includes feeding process, replacement process, reaction process, pressure relief process after reaction and discharge process. Hydrogen, solid materials and liquid materials are all hydrogenation reaction process materials. The general process is to add solid and liquid materials first, and then add hydrogen under a certain pressure for reaction. In the feeding process, it is necessary to control the addition of solid and liquid materials outside hydrogen, which is also a fine chemical process.
At present, large pharmaceutical enterprises are more focused on improving their core competitiveness and paying attention to drug research and development and sales. In order to shorten the cycle of new drug research and development and reduce the cost of new drug research and development, they often customize the production of tundish in vitro, and some companies provide customized synthesis services for intermediates. Medici provides customized synthesis services for intermediates, which can synthesize reference compounds, intermediates, candidate drugs, impurities, metabolites and other small molecule chemicals for customers, with the scale ranging from mg level to kg level (including GMP quality). His team is proficient in new route design and route optimization, with skilled problem-solving skills and a high success rate of the project.
2. Single batch intermittent
The general chemical production process is mostly continuous production. The difference is that the production process of pharmaceutical intermediates is mostly single batch intermittent, usually frequent single batch production, which requires repeated pre-treatment and post-treatment, and these processes need to meet the requirements of the pharmaceutical production quality management specification. In the continuous process, raw materials continuously pass through a group of special equipment, each of which is in steady-state operation and only performs a specific processing task, and the product has been output in a continuous flow manner. Intermittent production refers to the processing of raw materials according to the specified processing sequence and operating conditions, and the output of products in a limited manner. The essence of batch process is dynamic, and the operating conditions and product quality will change with time.
3. Multifunction
The reaction kettle in the production of pharmaceutical intermediates usually needs to carry out multi-step reactions or multiple processes, which requires different temperature control or pressure control in different stages. In order to complete the precise control of these processes, the characteristics of large-scale regulation need to be considered in the design of control scheme and instrument selection.
Batch processing using batch reactors is the dominant method in the pharmaceutical industry. The reactor with agitator used in this method is suitable for unit operations in most pharmaceutical industries, such as reaction, extraction, distillation and crystallization. More decisions need to be made in designing batch processes. The continuous processing method provides a more predictable amplification path, as well as some additional operational advantages. These advantages make more and more pharmaceutical enterprises begin to apply continuous processing as a new method to the actual production process of pharmaceutical intermediates and active pharmaceutical ingredients.