Continuous flow : An emerging alternative
Dr Sripathy Venkatraman , head of R & D operations at Curia , shares some insights on continuous flow processing as an alternative to conventional batch mode
Pharmaceutical companies have traditionally been very riskaverse and have adopted safe and well-established processes . This probably has its roots in the fact that the regulatory agencies in general have been very conservative and less approving of novel methodologies being used in the process unless absolutely necessary .
However , this is now changing . With the growing complexity of drug molecules and the need to involve newer , harsher reaction conditions that were once thought of as unfriendly in process chemistry , continuous flow chemistry and processing ( Figure 1 ) offer a proven alternative pathway .
The last decade has also seen the growth of several companies providing commercial continuous flow units for research to large-scale production . Some of these , which are fully GMPcompliant and offer the ability to scale up rapidly have multiplied the interest in and access to continuous flow .
Until recently , continuous flow chemistry mainly focused on reaction chemistry and isolation , largely followed a batch process . More recently , with the availability of lab-scale processing units , the concept of chemistry followed by continuous isolation of the product has seen growing interest .
Many fine chemical manufacturers with thin margins have used flow technologies to take advantage of the efficiencies continuous processing provides when batch mode would have been cost-prohibitive . With biotech companies turning more towards orphan indications and the shrinking appetite for traditional drugs , manufacturers have also been more receptive to the idea of alternative , more selective options .
Increased competition from generic drug manufacturers and falling R & D productivity rates have forced pharmaceutical companies to find faster , more efficient ways of developing and manufacturing new products . Many companies have reduced in-house capacity and outsourced to CMOs in a bid to cut costs .
Initially , only basic manufacturing operations were outsourced . However , it is now common for a drug company to hand everything from discovery through clinical development and commercial production to a contractor . This demand for comprehensive services has driven consolidation in the sector , with large CMOs acquiring smaller specialists to expand and differentiate their offerings .
Drug substance
In flow chemistry , substrates and reagents react in a highly reproducible environment where parameters such as heat and mass transfer , mixing and residence times are controlled . Reactors are customised for each reaction and are assembled from specialised components .
For API and intermediate syntheses with reaction kinetics that are suited to continuous flow , there are numerous potential advantages over batchbased production . These can be split into three broad categories : quality , innovation and safety .
The US FDA requires APIs to meet purity specifications and manufacturers to implement systems for managing quality at each stage of production . Process safety information based on risk assessment not only
Figure 1 - Concept of continuous flow processing
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16 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981