As the process of bringing new drugs to market is extremely challenging, with an average cost of $2.6billion and a maximum of 12 years, it is crucial for pharmaceutical companies to optimize the drug discovery and development process to maximize the drug life cycle before the patent expires. The obvious benefits provided by continuous flow chemistry may reduce costs and reduce the time it takes to bring new drugs to market.
In July 2021, ICH released the highly anticipated Q13 guidance on continuous manufacturing of APIs, which provides in-depth and comprehensive guidance in many aspects, including coverage and discussion of technical issues. ICH Q13 consists of a main guideline and five appendices. The guideline clarifies the concept of continuous manufacturing, describes scientific methods, and proposes regulatory considerations for the continuous manufacturing of APIs.The guideline applies the batch definition of ICH Q7 to continuous manufacturing. A batch can be defined according to the quantity of output materials, the quantity of input materials, or the running time under a determined mass flow. At the same time, a batch can be defined as a range.
Flow chemistry using microchannel technology has many advantages, such as: super heat and mass transfer ability, horizontal flow reaction, small liquid holdup, intrinsic safety, easy scale-up, high pressure resistance and corrosion resistance, and can be connected to online IR, online Raman spectrum, online nuclear magnetic and other equipment to monitor the reaction.
In the process of large-scale production of global pharmaceutical enterprises, they will use some cutting-edge technologies: flow chemistry technology, enzyme catalysis technology, metal catalysis technology, and AI technology. For the design process, if these technologies can be combined, it will have a great impact on the promotion of the launch of products and the reduction of costs.
Using flow chemistry to optimize the reaction can improve the process efficiency. The precise control of reaction parameters, such as time, temperature, molar ratio of reagents, etc., can be easily screened by using automated methods, so that chemists can leave and continue to engage in other work. Compared with the usual traditional time-consuming method, the flow chemistry method can meet many conditions that chemists want to see by using only one reactor.
Since flow chemistry can provide chemists with benefits - such as better reaction control, greater selectivity, and increased chemical space - it is an excellent way to rapidly synthesize a large library of compounds, and has been adopted by all top pharmaceutical companies in some form by companies around the world. The drug compound library can be rapidly synthesized and screened using an automatic sampler, thus avoiding manual loading of reagents between two experiments, and a flow chemical reactor can automatically run more than 100 experiments in the shortest set time. In addition, once found successful, it is very easy to re synthesize the compound for further research. Flow chemistry technology is also very useful for the generation of compound libraries, screening reactions and optimization studies, because it is easy to handle a small number of compounds, which is important when using expensive materials such as enzymes.
Flow chemistry, as an important supplement to the traditional batch process of APIs, has excelled in enabling dangerous reactions, stimulating process potential and releasing production capacity, and has comprehensively assisted the research and development of new drugs from the perspectives of safety, quality, speed and cost. The application rate of flow chemistry technology has increased significantly in the field of green development of pharmaceutical process.
