Plantwide design and economic evaluation of two Continuous Pharmaceutical Manufacturing (CPM) cases: Ibuprofen and artemisinin

Abstract

Increasing Research and Development (R&D) costs, growing competition from generic manufacturers and dwindling market introduction rates for novel drug products bolster the efforts of pharmaceutical firms to secure competitiveness by investigating Continuous Pharmaceutical Manufacturing (CPM). The present paper explores the CPM of two key Active Pharmaceutical Ingredients (APIs), ibuprofen and artemisinin: cost savings and material efficiency benefits are evaluated for CPM vs. batch processing, with two continuous options for each API. Capital Expenditure (CapEx) savings of up to 57.0% and 19.6% and corresponding Operating Expenditure (OpEx) savings of up to 51.6% and 29.3% have been determined for ibuprofen and artemisinin, respectively. Total projected cost savings for a 20-year plant lifetime can reach 54.5% and 20.1%, respectively. Environmental (E)-factors (mass of waste generated per unit mass of product) of 43.4 (for ibuprofen) and 12.2 (for artemisinin) have been computed, indicating environmental and material efficiency advantages for these conceptual continuous pharmaceutical processes.

Process modelling, design and technoeconomic Liquid–Liquid Extraction (LLE) optimisation for comparative evaluation of batch vs. continuous pharmaceutical manufacturing of atropine

“…We implement an established methodology for costing pharmaceutical manufacturing processes (Jolliffe and Gerogiorgis, 2016). All plant designs are assumed to be constructed and operated at an existing pharmaceutical manufacturing site with essential auxiliary structures already in place.…”

“…Continuous pharmaceutical manufacturing (CPM) is a new production paradigm for the pharmaceutical industry with the potential to revolutionise production by offering enhanced yields, purities, heat and mass transfer and mixing efficiencies, reduced waste and lower total costs (Jolliffe and Gerogiorgis, 2016;Dallinger and Kappe, 2017). While traditional batch methods have been historically implemented for their advantages of equipment flexibility, product recall ability, utility for rapid synthetic pathway discovery and having established, well-understood technology, batch techniques imply significant waste and low operational asset efficiency, leading to a lack of robustness and flexibility which has lead to drug shortages, presenting a threat to public health (Lee et al, 2015;Yu and Kopcha, 2017).…”

“…For both BX-and CPM-LLE considerations, process performances at multiple plant API capacities, Q API = {10 3 , 10 4 } kg API yr -1 , are compared; this is useful in theoretical modelling studies in the early stages of process development to elucidate process performance on different operating scales (Jolliffe and Gerogiorgis, 2016). We also consider different assumptions of attainable solvent recovery, SR = {30, 50, 70}%; solvent constitutes a major contribution of material in the CPM process considered here, and thus differences in attainable solvent recovery are an important design consideration.…”

Uncertainty‐conscious methodology for process performance assessment in biopharmaceutical drug product manufacturing

“…In recent years, researchers have intensively focused on the deterministic description and modeling of drug manufacturing processes, more specifically for small molecules. Jolliffe and Gerogiorgis presented economic and environmental feasibility studies of continuous manufacturing processes of ibuprofen and artemisinin . Rogers and Ierapetritou reported the potential for the industry to apply deterministic modelling and optimization through a case study in DP manufacturing .…”

Dynamic Modelling and Optimisation of the Batch Enzymatic Synthesis of Amoxicillin

“…All values of RME were relatively midrange with respect to typical pharmaceutical manufacturing processes [33]. The effect of scale-up on material efficiencies, as well as plant-wide costs, is an important consideration during process design and optimisation studies such as this one [34]. masses of starting materials (PHPGME (mPHPGME) and 6-APA (m6-APA)) at the start (t0 = 0).…”