The various products between the production of active pharma ingredients (API) are known as pharma intermediates. The synthesis of drugs depends strongly on intermediate products. pharma intermediates are important raw materials for the production of APIs and belong to the chemical industry. The production plants do not require GMP certification, but their production is still subject to strict GMP-related requirements in terms of site selection, layout planning, and plant design.
Unlike general chemical production processes, the production process of pharma intermediates is characterized by miniaturization, batched intermittent processes, and multifunctionality.
The production of pharma intermediates has the characteristics of miniaturization, miniaturization is characterized by small reaction kettle, less raw materials and precise requirements, especially the flow of liquid materials added in the reaction process, the amount needed is very small and needs to be controlled.
For example, the common hydrogenation reaction process in the production of pharma intermediates is a small-scale intermittent reaction, which mainly includes the process of adding material, 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 certain pressure for reaction, which is a fine chemical process that needs to control the addition of solid and liquid materials outside of hydrogen.
At present, large pharma companies focus more on improving their core competitiveness and pay attention to drug development and sales. In order to shorten the cycle of new drug development and reduce the R&D cost of new drugs, they often outsource the custom production of pharma intermediates and cooperate with companies that provide custom synthesis services of intermediates.
Most of the general chemical production process is continuous, but the production process of pharma intermediates is mostly single batch intermittent, usually for frequent single batch production, need to repeatedly pre-treatment and post-treatment, and these processes need to meet the specification requirements.
In a continuous process, raw materials are continuously passed through a set of specialized equipment, each of which is in steady-state operation and performs only one specific processing task, with the product output in a continuous flow. Intermittent production, on the other hand, means that the raw materials are processed according to a defined sequence and operating conditions, and the product is output in a limited manner. The nature of the intermittent process is dynamic, with operating conditions and product quality changing over time.
The reactor in the production of pharma intermediates usually needs to carry out multi-step reaction or multiple processes, requiring different temperature control or pressure control in different stages. In order to complete the accurate control of these processes, it is necessary to consider the characteristics of meeting the wide range of regulation when designing the control scheme and instrument selection.
The pharma industry is currently dominated by batch processing methods using intermittent reactors. The reactors with stirrers used in this method are suitable for most unit operations in the pharma industry, such as reactions, extractions, distillations and crystallizations, and more decisions need to be made in designing intermittent processes. The continuous process approach, on the other hand, offers a more predictable scale-up path, as well as some additional operational advantages.
These advantages have led more and more pharma companies to adopt continuous processing as a new approach to the actual production of pharma intermediates and active pharma ingredients.