JACOPO BUZZANCA1, MATEO BERTON2
1. CDMO NBD Manager, Farmhispania Group, Spain
2. Flow Chemistry Lead, Farmhispania Group, Spain

Abstract

Flow chemistry continues to emerge as an ever-growing area for research, development and manufacturing of Active Pharmaceutical Ingredients (APIs) / High Potent Active Pharmaceutical Ingredients (HPAPIs) within pharmaceutical and Contract Development and Manufacturing Organization (CDMO) industry. Although pharmaceutical industry still relies on multi-purpose batch or semi-batch reactors, the transition towards flow reactors and continuous manufacturing (CM) is more and more arising today. This significant interest arose from the possibility of accessing novel process windows and to explore new chemical reactions under conditions that are considered difficult (“forbidden chemistry”) or even impossible (“forgotten chemistry”) in conventional batch modality. This article discusses the advantages, as well as opportunities, of flow chemistry in today’s pharmaceutical sector. We will give an overview about a recent case study successfully achieved within Farmhispania Group (FHG), thus illustrating the potential of flow chemistry as a novel synthetic tool for development and cGMP manufacturing of new generation APIs / HPAPIs. Finally, some considerations on prospective future developments of flowchem research in the industry are briefly discussed.

INTRODUCTION 
Today, flow chemistry is playing an increasingly important role in the modern API process chemistry; A confluence of factors is driving the need for a paradigm shift in API manufacturing strategies in pharmaceutical and CDMO industry, where for over 100 years have long been carried out using batch-wise operations. Movement towards tailor-made drug therapy, rising generics competition, dramatically higher clinical trial costs and timelines, the shift away from blockbusters to niche products, the growing number of candidates with accelerated development designations (Fast Track, Breakthrough Therapy, Orphan Drug) and, last but not least, the rising phenomenon of “pharmaceutical nationalism” in the Western Countries post COVID-19 pandemic is catalyzing the momentum and magnitude of flow chemistry adoption as a novel toolbox for chemical development and cGMP manufacturing of new generation APIs / HPAPIs.   
   
In this article we focused our discussion only on a recent flowchem case study successfully achieved in FHG. The aim of this case study is to discuss the application of flow technology for the genesis and use ...