Techno-economic analysis of separation processes for continuous pharmaceutical manufacturing: assessing process performance, material efficiency and economic viability
The pharmaceutical industry is currently dominated by the traditionally implemented, yet wasteful and inefficient, batch production paradigm. Continuous Pharmaceutical Manufacturing (CPM) shows potential to bring technological innovation, cost savings and environmental benefits to pharmaceutical production. This paper describes the process modelling and simulation of CPM of two active pharmaceutical ingredients (APIs): diphenhydramine (a globally-marketed antishistamine) and artemisinin (an important antimalarial drug), with focus on implementing a continuous separation process for each. The continuous liquid-liquid extraction of diphenhydramine and continuous crystallisation of artemisinin are compared to the batch methods, in order to demonstrate the benefits of material efficiency and economic viability of continuous separations in pharmaceutical manufacturing.
Batch manufacturing methods have historically dominated the pharmaceutical industry, with benefits of versatile equipment usage, specific batch recall, long residence times for exploring different reaction pathways (1), and well-established regulatory protocol (2). However, batch manufacturing necessitates large equipment, intensive labour (3), limited automation and frequent plant reconfiguration (4). Additionally, costs associated with R&D and bringing new drug products to market have drastically increased over previous decades (5). Increasing competition from generics manufacturers also poses a significant threat to pharmaceutical firm profitability. Technological innovation is required to ensure sustainability for pharmaceutical enterprises (6).
Continuous Pharmaceutical Manufacturing (CPM) is a new production paradigm receiving attention from the highest regulatory levels due to its potential for reduced costs, lower material requirements and waste handling and smaller footprints (7). CPM offers enhanced mixing and heat transfer efficiencies, safer operation under hazardous conditions and improved yields (8). However, CPM is ye ...