Geert Van der Vorst

Exergetic life cycle analysis for the selection of chromatographic separation processes in the pharmaceutical industry: preparative HPLC versus preparative SFC

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.

Exergetic sustainability assessment of batch versus continuous wet granulation based pharmaceutical tablet manufacturing: a cohesive analysis at three different levels

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%.

Environmental sustainability assessments of pharmaceuticals: an emerging need for simplification in life cycle assessments.

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.