A Systematic Evaluation of the Resource Consumption of Active Pharmaceutical Ingredient Production at Three Different Levels

Abstract

In this paper, the development and the advantages of a methodology which allows the systematic assessment of the environmental impact on the resource side of specific pharmaceutical production processes with limited data entry is presented. The quantification of the process-specific mass and energy balances over three different system boundaries (process, gate-to-gate, and cradle-to-gate) is based on the methodology explained in Van der Vorst et al. (Ind. Eng. Chem. Res.2009, 48(11), 5344-5350). These mass and energy balances are now coupled with the thermodynamic term exergy allowing the quantification of the resource efficiency at the process and gate-to-gate level and the environmental impact at the cradle-to-gate level. The advantages of such a calculation tool for the resource evaluation are illustrated with five consecutive pharmaceutical production steps which are part of the galantamine (anti-Alzheimer medication) pathway. It is shown that such a quantitative and systematic evaluation tool allows a detailed and relatively fast evaluation of the resource efficiency of active pharmaceutical ingredient (API) production processes at the three different levels. Combining thermodynamics and the systematic data inventory methodology for the quantification of the resource efficiency first allows results to be merged into a single impact value (exergy loss/mol API or CEENE/mol API) for fast benchmarking and evaluation of different API production processes. Second, it also allows results to be divided over different categories depending on the users' interest and make thorough analysis of processes in order to pinpoint process improvements and quantitatively justify the introduction of second generation production processes or production techniques.

Rules and benefits of Life Cycle Assessment in green chemical process and synthesis design: a tutorial review

“…They applied this measure also in the context of life-cycle based evaluation of pharmaceutical processes. 27,28 Life cycle interpretation…”

10. From green chemistry principles in flow chemistry towards green flow process design in the holistic viewpoint

“…This evaluation step is followed by a characterization and quantification of environmental impacts associated with those inputs and outputs. They also applied this measure in the context of life-cycle based evaluation of pharmaceutical processes [35,36]. At this, the magnitude as well as the potency of the impacts is taken into account using equivalence factors in relation to a reference compound.…”

“…Van der Vorst et al [35,36] performed an exergetic LCA of a Galantamine⋅HBr synthesis for anti-Alzheimer medication. They searched for environmental improvements within the overall synthesis pathway of the active pharmaceutical ingredient (API) in three processing alternatives (first-third generation).…”

Towards a Multidisciplinary Approach on Creating Value: Sustainability through the Supply Chain and ERP Systems

“…that were found by De Soete et al (2014) and adopted by the Sustainable Development Unit (SDU) of the British National Health Service (NHS) were tested on their feasibility to be integrated in customized ERP applications [14,35]. It was proven that by combining MES data from batch reports (e.g., time duration of a chemical synthesis step), line sensors (e.g., operating temperatures), Bill of Materials (BOM) (e.g., raw material use), indicators for environmental sustainability could be derived (e.g., Cumulative Exergy Extracted from the Natural Environment, CEENE and the Carbon Footprint, CF) [36][37][38][39][40][41][42]. Ideally, these aforementioned correlations, engineering modules, design software such as ASPEN are to be built in in a customized ERP application for LCA (as visualized in Figure 2) in order to couple primary engineering data, Life Cycle Inventory databases (LCI, e.g., ecoinvent) and Life An ERP system is generally customized for a certain enterprise.…”

“…Exergy Extracted from the Natural Environment, CEENE and the Carbon Footprint, CF) [36][37][38][39][40][41][42]. Ideally, these aforementioned correlations, engineering modules, design software such as ASPEN are to be built in in a customized ERP application for LCA (as visualized in Figure 2) in order to couple primary engineering data, Life Cycle Inventory databases (LCI, e.g., ecoinvent) and Life Cycle Impact Assessment Methods (LCIAM, such as CEENE and CF).…”