Wouter De Soete

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.

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

Manufacturing Resource Planning (MRP) is a widely used approach through manufacturing environments in a variety of sectors. With a tendency to go to specialized, smaller lot sizes in several industries (e.g., the pharmaceutical sector), companies are dealing with capacity bottlenecks if the planning rhythm wheel is not well calibrated or when production lines are not flexible enough in terms of changeover (C/O) and set-up times (S/U) (OEE is too small). A well-established communication system including other enterprise resources or production factors (e.g., Enterprise Resource Planning, ERP) is favorable to any extent. More and more questions arise from stakeholder communities and end-users on whether or not supply chains and manufacturing environments are sustainable and safe. Departments such as Environmental Health, Safety & Sustainability (EHS & S) and Product Stewardship are too often at the “blind” side of the ICT interface. When it comes to product and organizational sustainability, data seems to be lacking in order to conduct sustainability assessments proficiently. Years of intensive research and experience proved that primary data to perform sustainability assessments often are measured through equipment control sensors (e.g., flow rates, temperatures, etc.) and sent to PLCs and many other systems. Nevertheless, these data measurements are in many cases simply not penetrating through the Manufacturing Execution Systems (MES) because these bottom-up engineering data seems to be of little value to planning, procurement, etc. This communication paper deals with how sustainability assessments can be embedded in business operational management systems. After all, who does not want a “live Carbon Footprint” for process improvements and external sustainability reporting instead of a series of expensive resource consuming studies of 4 to 6 months digging into data logs in traditional Life Cycle Assessment (LCA)? This communication paper has taken one step further in coupling business ERP systems with environmental sustainability of products, services and enterprises.

Human health benefits and burdens of a pharmaceutical treatment: Discussion of a conceptual integrated approach

The effects of a pharmaceutical treatment have until now been evaluated by the field of Health Economics on the patient health benefits, expressed in Quality-Adjusted Life Years (QALYs) versus the monetary costs. However, there is also a Human Health burden associated with this process, resulting from emissions that originate from the pharmaceutical production processes, Use Phase and End of Life (EoL) disposal of the medicine. This Human Health burden is evaluated by the research field of Life Cycle Assessment (LCA) and expressed in Disability-Adjusted Life Years (DALYs), a metric similar to the QALY. The need for a new framework presents itself in which both the positive and negative health effects of a pharmaceutical treatment are integrated into a net Human Health effect. To do so, this article reviews the methodologies of both Health Economics and the area of protection Human Health of the LCA methodology and proposes a conceptual framework on which to base an integration of both health effects. Methodological issues such as the inclusion of future costs and benefits, discounting and age weighting are discussed. It is suggested to use the structure of an LCA as a backbone to cover all methodological challenges involved in the integration. The possibility of monetizing both Human Health benefits and burdens is explored. The suggested approach covers the main methodological aspects that should be considered in an integrated assessment of the health effects of a pharmaceutical treatment.

Resource recovery from residual household waste: An application of exergy flow analysis and exergetic life cycle assessment.

Exergy is based on the Second Law of thermodynamics and can be used to express physical and chemical potential and provides a unified measure for resource accounting. In this study, exergy analysis was applied to four residual household waste management scenarios with focus on the achieved resource recovery efficiencies. The calculated exergy efficiencies were used to compare the scenarios and to evaluate the applicability of exergy-based measures for expressing resource quality and for optimizing resource recovery. Exergy efficiencies were determined based on two approaches: (i) exergy flow analysis of the waste treatment system under investigation and (ii) exergetic life cycle assessment (LCA) using the Cumulative Exergy Extraction from the Natural Environment (CEENE) as a method for resource accounting. Scenario efficiencies of around 17-27% were found based on the exergy flow analysis (higher efficiencies were associated with high levels of material recycling), while the scenario efficiencies based on the exergetic LCA lay in a narrow range around 14%. Metal recovery was beneficial in both types of analyses, but had more influence on the overall efficiency in the exergetic LCA approach, as avoided burdens associated with primary metal production were much more important than the exergy content of the recovered metals. On the other hand, plastic recovery was highly beneficial in the exergy flow analysis, but rather insignificant in exergetic LCA. The two approaches thereby offered different quantitative results as well as conclusions regarding material recovery. With respect to resource quality, the main challenge for the exergy flow analysis is the use of exergy content and exergy losses as a proxy for resource quality and resource losses, as exergy content is not per se correlated with the functionality of a material. In addition, the definition of appropriate waste system boundaries is critical for the exergy efficiencies derived from the flow analysis, as it is constrained by limited information available about the composition of flows in the system as well as about secondary production processes and their interaction with primary or traditional production chains. In the exergetic LCA, resource quality could be reflected by the savings achieved by product substitution and the consideration of the wastes upstream burden allowed for an evaluation of the wastes resource potential. For a comprehensive assessment of resource efficiency in waste LCA, the sensitivity of accounting for product substitution should be carefully analyzed and cumulative exergy consumption measures should be complimented by other impact categories.

Challenges and recommendations for environmental sustainability assessments of pharmaceutical products in the healthcare sector

With healthcare representing a significant portion of the global economy, it is important to be able to understand the environmental impacts of this industry due to its size and nature of its operations. Interviews with people who have intimate knowledge of the healthcare industry indicate that significant efforts and advances have been made over the past ten to fifteen years in developing environmental impact assessment methods and tools tailored for the sector. These methods and tools have been important in helping to improve the overall environmental sustainability of the sector. However, comprehensive literature searches reveal that only a limited portion of the environmental impact assessment work has been published and/or is publicly available. This lack of visibility to the full scope of environmental impact assessment methods and the results of application of those methods can impair the advancement of these methods. To help facilitate further advancement of environmental assessment methodologies in the healthcare sector, Ghent University and the European Commissions Joint Research Centre, Sustainability Assessment Unit (JRC IES SA) undertook a study to map current challenges in conducting assessments, identify best practices in assessing and advancing the state-of-the-art, and to develop recommendations and priority action points based on the study learning. The study was accomplished through: (1) conducting a thorough literature review; (2) broad engagement of healthcare sector stakeholders, including industry, academia, NGOs, policy makers, GPs, patients, etc.; (3) execution of a stakeholder survey; (4) expert interviews; and (5) roundtable discussions with sustainability professionals in the field. Upon identifying the bottlenecks in current practices, four recommendations and key action points were determined: (1) the integration of the complete healthcare pathway within system boundaries; (2) the establishment of life cycle databases for pharmaceuticals and supplied resources; (3) the integration of LCA calculations directly into Enterprise Resource Planning (ERP) systems to work with primary data as much as possible; and, (4) the need to further harmonize developments in the field. The authors provide suggested actions to address the recommendations and propose this work as guidance to steer further research and developments in academia, industry and policy environments in order to serve and support decision making processes.