Continuous pharmaceutical process engineering and economics
Investigating technical efficiency, environmental impact and economicviability
Continuous Pharmaceutical Manufacturing (CPM) emerges as a ground-breaking technology which can invigorate the global pharmaceutical industry by sustainably fostering its agility and the affordability of healthcare for large populations. Continuous production methods feature numerous significant technical advantages, which however need be ensured by robust, scaleable chemistry, systematic process design and efficient Process Analytical Technology (PAT) for control. Quality by Design (QbD) must be achieved by a relentless pursuit of efficiency in energy and solvent use, but above all the business case for a product must be strong enough to cover both synthesis and process R&D against competition. Remarkable corporate investments in production-scale CPM facilities illustrate the value and promise of this paradigm. This paper focuses on applications of process systems engineering methodologies (flowsheet modelling and simulation) toward evaluating the technical efficiency, environmental impact and economic viability of two continuous processes. Original final upstream separation results for ibuprofen and recent ones for plantwide CPM economics are discusse
Pharmaceutical processes are broadly distinguished in batch (the overwhelming majority) and continuous (a growing minority): in either case, a process comprises a primary (upstream) and a secondary (downstream) part: the first addresses production of the Active Pharmaceutical Ingredient (API or Drug Substance, DS), while the latter focuses on mixing the API with excipients to manufacture the final marketed formulation (Drug Product, DP).
The incentive for technically sound and economically viable CPM (1) depends on each business case, but also on technical advances in organic synthesis, multiphase flow units and process automation (2). The business aspect has paramount importance for deciding if a CPM process should even be evaluated (3). The economic viability is determined using several factors: the total manufacturing cost comprising capital (CapEx) and operating (OpEx) expenditures, the product selling price, marketing costs, and often product and/or technology licensing costs (4).
Batch organic synthesis of API molecules at laboratory and production scale is an arduous procedure, in which long seq ...