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The pharmaceutical and fine chemical industries are eager to strive toward innovative products and technologies. This study first derives hotspots in resource consumption of 2839 Basic Operations in 40 Active Pharmaceutical Ingredient synthesis steps through Exergetic Life Cycle Assessment (ELCA). Second, since companies are increasingly obliged to quantify the environmental sustainability of their products, two alternative ways of simplifying (E)LCA are discussed. The usage of averaged product group values (R(2) = 3.40 × 10(-30)) is compared with multiple linear regression models (R(2) = 8.66 × 10(-01)) in order to estimate resource consumption of synthesis steps. An optimal set of predictor variables is postulated to balance model complexity and embedded information with usability and capability of merging models with existing Enterprise Resource Planning (ERP) data systems. The amount of organic solvents used, molar efficiency, and duration of a synthesis step were shown to be the most significant predictor variables. Including additional predictor variables did not contribute to the predictive power and eventually weakens the model interpretation. Ideally, an organization should be able to derive its environmental impact from readily available ERP data, linking supply chains back to the cradle of resource extraction, excluding the need for an approximation with product group averages.

In this article, for the treatment of two specific pharmaceutical waste solvents the resource consumption of an on-site distillation process is evaluated and compared with an off-site incineration process. Both techniques are evaluated based on a thermodynamic quantitative method. The exergy approach and the cumulative exergy extracted from the natural environment (CEENE) are envisaged in order to evaluate the overall resource intake at different levels. Scenarios are constructed to make a fair comparison of both techniques. Two waste solvents, toluene (TOL) and dichloromethane (DCM), from the pharmaceutical industry which are frequently sent to distillation were evaluated. The functional unit for the comparison of both treatment alternatives is the treatment of 1 kg waste solvent + the incineration of W kg low calorific hazardous waste + the delivery of X kg “recovered” solvent + the production of Y MJ heat and Z MJ electricity. W, X, Y and Z depend on the waste solvent properties. In terms of resource requirements, distillation requires 17% (TOL) and 66% (DCM) less resources than incineration. It can be concluded that the waste solvent properties, the efficiency of the distillation process and the efficiency of the fresh solvent production process are of major importance on the resource consumption and the final choice between incineration and distillation. For a full environmental impact analysis of both treatment options, also the emissions should be taken into account. It also has to be stressed that in practice, only solvents go to incineration which cannot be distilled due to the type and degree of pollution/composition of the solvent. If distillation is not feasible, then such solvents are sent to incineration with energy recovery, according to the EU directive 2006/12/EG.

Rechargeable Li-ion battery applications in consumer products are fastly growing, resulting in increasing resources demand: it is for example estimated that battery applications account for nearly 25% of the worldwide cobalt demand in 2007. It is obvious that recycling of batteries may help saving natural resources. However, it is not straightforward to quantify to what extent rechargeable battery recycling saves natural resources, given their complex composition, and the complex international production chain. In this paper, a detailed analysis of a lithium mixed metal oxide battery recycling scenario, where cobalt and nickel are recovered and re-introduced into the battery production chain, is compared with a virgin production scenario. Based on detailed data acquisition from processes spread worldwide, a resource saving analysis is made. The savings are quantified in terms of exergy and cumulative exergy extracted from the natural environment. It turns out that the recycling scenario result in a 51.3% natural resource savings, not only because of decreased mineral ore dependency but also because of reduced fossil resource (45.3% reduction) and nuclear energy demand (57.2%).

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.

Identifying better performing Active Pharmaceutical Ingredient (API) synthesis routes with reference to green chemistry and green engineering principles was of the highest importance in the pharmaceutical industry during the past decade. However, very little attention was paid to other life cycle stages such as the Drug Product (DP) production, packaging and distribution. In this case, the environmental sustainability of batch versus continuous granulation based tablet manufacturing is quantified from a resource point of view by conducting Exergy Analysis (EA) and Exergetic Life Cycle Analysis (ELCA) at three different levels in order to identify and locate resource losses throughout the pharmaceutical supply chain. Assessing the potential implementation of the continuous production line ConsiGma™ at the Janssen-Cilag SpA pharmaceutical manufacturing plant and thereby replacing the conventional batch manufacturing mode would result in a resource consumption reduction of 10.2% (65.6 to 58.9 kJex per tablet), 15.2% (111 to 94.0 kJex per tablet) and 2.2% (2.3 to 2.2 MJex per tablet) at the process (α), plant (β) and overall industrial level (γ) respectively. Focusing on DP production processes by excluding transiting exergy in API, excipients and packaging materials resulted in a reduction of 34.0%, 25.9% and 14.7% at the respective system boundaries. The API dose seemed to be the parameter with highest sensitivity towards environmental burden. From an emission point of view, a Carbon Footprint (CF) reduction of 2.0% (0.22 to 0.21 kg CO2-eq per tablet) was obtained at the γ level in shifting from batch to continuous manufacturing of Tramacet®. Focusing on DP production revealed a CF reduction of 16.2%.

In the pharmaceutical industry, there is always a desire to identify better synthesis pathways and technologies. Chemistry can be changed resulting in safer reactions, higher yields, better recyclability, etc. Also new technologies as for e.g. continuous flow reactors can be used allowing better heat transfer and better reaction efficiencies compared to batch reactors. It is these innovations that make green chemistry actually happen. However, according to the principle “you can only manage what you can measure”, also measuring methods are required for the evaluation of the innovative improvements. Many chemistry related measuring methods are available for the evaluation of the greenness, eco-efficiency or even sustainability of new developments. In this article, exergetic life cycle assessment is used on a real case from the pharmaceutical industry (three generations of Galantamine·HBr synthesis) to illustrate the importance of the continuous search for improved chemical processes and technologies and of using measuring methods in order to support, quantitatively, the decision making towards new, greener and more sustainable processes and technologies. From this case, it can be concluded that a reduction in the overall resource consumption can rise up to 41% by optimizing the first generation pathway by new chemistry and by a new technology, i.e. continuous flow reactors.

Today, environmentally responsible chemistry is of huge importance in the wake of sustainable production. In the field of the fine chemical and pharmaceutical industry, preparative supercritical fluid chromatography (Prep-SFC) and preparative high performance liquid chromatography (Prep-HPLC) are widely used chiral separation techniques. Prep-SFC is often named as a green alternative for Prep-HPLC without having a thorough assessment of the greenness. However, if metrics are used for process selection with respect to green chemistry, they mainly show three shortcomings: (1) a narrow system boundary approach is used; (2) energy requirements are barely taken into account and (3) if energy requirements are considered, there is a differentiation in mass and energy inputs. Taking into account these shortcomings, Prep-HPLC and Prep-SFC are now compared and evaluated for their integral resource consumption. The evaluation is performed on a specific enantiomeric separation using exergetic life cycle analysis within enlarging system boundaries α, β and γ. Within the α system boundary (process level), Prep-HPLC requires 26.3% more resources quantified in exergy than the Prep-SFC separation due to its inherent higher use of organic solvents. Within the β system boundary (plant level), Prep-HPLC requires 29.1% more resources quantified in exergy than Prep-SFC. However, the Cumulative Exergy Extracted from the Natural Environment (CEENE) to deliver all mass and energy flows to the α and β system boundary via the overall industrial metabolism shows that Prep-SFC requires 34.3% more resources than Prep-HPLC. The poor score of Prep-SFC in the γ system boundary is attributed to the high CEENE value related to the production of liquid carbon dioxide and the use of electricity for heating and cooling. It can be concluded that for this case, the most sustainable process as for the integral resource consumption is Prep-HPLC, unlike the general perception that Prep-SFC outperforms Prep-HPLC.