SK Biotek is a world leader in development of custom cGMP Chemical Manufacturing of API and Intermediate by Continuous Flow Process. With state-of-art manufacturing facilities with scale-up abilities from kilos to multi-ton for biotech and pharmaceutical companies. Theoretical and practical benefits associated with performing reaction under continuous flow have been demonstrated for a number of common organic transformations, ranging from liquid-liquid to solid-liquid-gas systems. In particular, for pharma companies, a very attractive feature of continuous-flow processes is the elimination of the risks associated with failing to scale up a process because the reaction conditions set-up can be easily transferred to production scale without the need of re-optimization, either by running the flow-reactor for an extended time or by employing multi-channel parallel reactors.
The main advantages associated with the flow processes can be comprised in two broad classes. The first one is associated with the small dimensions of the channels and includes the precise control of the reaction conditions, the efficient mass and heat transfer, the possibility of working under superheating conditions. The second aspect is related to the continuous nature of the process and includes the simplicity in reaction scale-up, the possibility of performing sequential synthetic steps with independent control of reaction conditions, and the possibility of interfacing the reactor with in-line analysis devices for real time monitoring. In addition, continuous process is the perfect way to produce large volume of product. The use of flow chemistry techniques can also allow the conversion of very unstable intermediates into the desired products without loss of yields and side-reaction runaways, thanks to the exact control of temperature and mixing.
We can assess that continuous manufacturing offers over the classical batch manufacturing advantages and the drawbacks as Small dimension of the channels • Precise control of reaction conditions • Efficient mass and heat transfer • Superheating • Safer and more selective processes • Toxic and explosive intermediates are prepared in situ and directly reacted • Easy management of poorly stable intermediates • Decreased inputs and waste.
In addition, the continuous nature of the process provides possible use solid supported reagents or scavengers in-line and the reaction conditions can be independently varied during the experiment facilitating the reaction optimization process and the following scaling up. At SK biotek, we apply a phased approach when implementing new technologies. Initially, an in-depth literature review on the technology will be performed along with a feasibility study. Factors we consider during the early stages are safety, cost, throughput and reaction complexity.
These items determine the potential to utilize continuous flow process for a particular step. If appropriate, we develop the continuous flow process as a matter of priority. Each year, SK biotek produce tons of advanced intermediates in continuous mode. Our continuous reaction system is a fully validated cGMP facility (Process validation (2009), Japanese PMDA (2013) & US FDA (2014) approved and the construction of new plant in Sejong increased dramatically our production capacity per year.
