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Most biopharmaceuticals are produced as sterile parenteral preparations, requiring very strict production conditions. In addition, liquid formulations face stability challenges which is why currently around half of all biologics are freeze dried for preservation. The environmental impact of the fill and finish processes to produce a freeze dried biopharmaceutical (infliximab) was evaluated from two perspectives: (i) considering only process-specific needs and (ii) calculating the overall site needs. An Exergetic Life Cycle Assessment was conducted using both a bottom-up and top-down approach. The process-specific and overall site needs are 6.5 and 39.6 MJex/vial, respectively. These results reveal that 84% of the cumulative exergy entering the manufacturing plant is non-process-specific. Electricity consumption is the highest footprint driver (86%), dominated by the Heating, Ventilation and Air Conditioning (HVAC) system running during non-production hours and/or supporting non-production related areas. If resource efficiency is pursued, the focal target might need to shift towards non-process-specific needs which are not essential for the product functionality/quality (e.g. full HVAC regime during non-production hours). It should be kept in mind that Good Manufacturing Practices conditions always have to be maintained. Currently performed energy saving measures addressing HVAC systems could potentially reduce the overall site needs calculated in this study by up to 16.5 MJex/vial.

BACKGROUND: Although the biopharmaceutical market grows rapidly, the environmental impacts of biopharmaceutical manufacturing have been hardly evaluated. The aim of the study is to comprehensively assess the environmental sustainability of a biologically‐produced active pharmaceutical ingredient (API) manufacturing process. For this purpose, an exergy analysis and an (exergetic) life cycle assessment were performed using primary (foreground system) and modeled data (background system). Infliximab, a monoclonal antibody, was considered. RESULTS: The fermentation and its raw materials' supply chain was determined to have the highest environmental impact, since the culture media requires chemicals and complex compounds such as animal‐derived materials (ADMs). The total impact per 100 mg of API produced ranged between 18.6 and 101.8 MJₑₓ and 2.0–3.1 kg CO₂‐eq, mainly as a function of the ADMs' source. A comparison of infliximab and ustekinumab, a biopharmaceutical produced without ADMs, showed that eliminating these materials can reduce the cumulative resource consumption of monoclonal antibody manufacturing by up to 7.5 times. The fermentation is the process taking the longest and the heating, ventilation and air conditioning system which support fermentation areas consumes approximately 75% of all plant electricity use. CONCLUSIONS: Culture media nutrients and cleanroom requirements are driving factors in the environmental impact of biological API manufacturing. Obtaining more precise data of the bioprocesses behind these nutrients' supply chain is crucial to corroborating this study's results. © 2019 Society of Chemical Industry

Life Cycle Assessment typically focuses on the footprint of products and services, expressed on three Areas of Protection (AoP): Human Health, Ecosystems and Resources. While the handprint is often expressed qualitatively, quantified handprints have recently been compared directly to the footprint concerning one AoP: Human Health. We propose to take this one step further by simultaneously comparing the quantified handprint and footprint on all AoPs through normalization and weighting of the results towards a single score. We discuss two example cases of a pharmaceutical treatment: mebendazole to treat soil-transmitted helminthiases and paliperidone palmitate to treat schizophrenia. Each time, treatment is compared to 'no treatment'. The footprint of health care is compared to the handprint of improved patient health. The handprint and footprint were normalized separately. To include sensitivity in the normalization step we applied four sets of external normalization factors for both handprint (Global Burden of Disease) and footprint (ReCiPe and PROSUITE). At the weighting step we applied 26 sets of panel weighting factors from three sources. We propose the Relative Sustainability Benefit Rate (RSBR) as a new metric to quantify the relative difference in combined handprint and footprint single score between two alternatives. When only considering the footprint, the first case study is associated with an increased single score burden of treatment compared to 'no treatment', while in the second case study treatment reduces the single score burden by 41.1% compared to 'no treatment'. Also including the handprint provided new insights for the first case study, now showing a decrease of 56.4% in single score burden for treatment compared to 'no treatment'. For the second case study the reduction of single score burden was confirmed as the handprint burden was also decreased because of treatment by 9.9%, reinforcing the findings.

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.

The nutritional value of food and its environmental impact have received considerable attention, however an assessment of environmental sustainability of catered meals is lacking. We therefore assessed the nutritional value and resource consumption of a specific catered meal, pork tenderloin with potato croquettes, carrots and mushroom sauce (‘Canteen Pork’). The outcomes are compared with that of an identical meal cooked at home (‘Home’), for which ‘Low’ and ‘High’ scoring hypothetical alternatives were defined (e.g. whether or not frying oil as a waste product was reprocessed or recycled), as well as with that of a vegetarian alternative: Quorn™. The resource consumption impact is assessed from cradle-to-disposal, expressed as the Cumulative Exergy Extraction from the Natural Environment (CEENE). Exergy is the amount of useful energy. The CEENE approach accounts for all resource types and is unique since it considers the deprived natural net primary production (expressed in exergy) as the impact for human land occupation, highly relevant for crop and thus food production. The food production, processing and packaging stage accounts for the largest amount of resource consumption compared to food preparation and waste management. The ‘Home Pork High’ scenario has the highest resource consumption at 83 MJex meal−1. ‘Home Pork Low’, ‘Home Quorn™ High’, ‘Canteen Pork’, ‘Home Quorn™ Low’ and ‘Canteen Quorn’ have a 15, 18, 26, 32 and 40% lower resource consumption compared to ‘Home Pork High’, respectively. For all scenarios, biomass resources contribute 52–64% of the total CEENE, mainly through land occupation. The nutritional analysis, via nutritional density scoring (the higher the better), resulted in a score of 18.1 and 31.2 for the ‘Home Quorn Low’ and ‘High’, 10.4 and 23.4 for the ‘Home Pork High’ and ‘Low’ scenario and 17.0 and 27.3 for the ‘Canteen Pork’ and ‘Canteen Quorn™’, respectively. To conclude, the vegetarian meal scores best on both attributes, however, this effect diminishes considerably if one considers outcomes per energy or protein amount. With regards to catered vs home cooked meals, resource consumption is lower in canteen prepared meals than in the case of the home-cooked meal. However, the nutritional value can be lower or higher depending on consumer behaviour, namely the extent of the use, type and application of butter is key in altering this result.

Background Environmental impact assessments of pharmaceuticals typically consider only a part of the pharmaceutical supply chain, e.g. tablet formulation. While the environmental impact can be expressed in environmental Human Health burden due to resource use and emissions, the Human Health benefit of the pharmaceutical treatment of patients is currently not simultaneously taken into account. The study aims include a cradle-to-grave assessment of all Human Health impacts of the production, administration and disposal of two antipsychotics for the treatment of schizophrenia. This is complemented with the environmental impact of health care providers such as hospitals. The aim is to holistically quantify to what extent the environmental Human Health burden compares to the Human Health benefit associated with the treatment. Methods We applied an overall framework which included Life Cycle Assessment to model the environmental Human Health impacts of the pharmaceutical supply chain, administration and disposal of the drug and health care providers. To model the patient benefit, this was complemented with a Markov model with a 1-year time horizon. Three patient groups were modeled: medicine coverage of paliperidone palmitate for either one month (PP1M) or three months (PP3M) at a time, and compared to Treatment Interruption (TI) as a control group. Outcomes were quantified using Years of Life Lost (YLL), Years Lived with Disability (YLD) and Disability-Adjusted Life Years (DALY). Results The main environmental impacts were visits to the psychiatrist and psychiatric hospitals. The pharmaceutical supply chain had a limited impact. For 1000 patients for 1 year, PP1M and PP3M respectively avoided 0.38 and 0.49 environmental DALYs compared to TI. PP1M and PP3M further avoided 45.60 and 57.87 YLL and 23.31 and 29.91 YLD compared to TI. The main outcome was the sum of environmental DALYs, YLL and YLD, in which PP1M and PP3M respectively avoided 69.29 and 88.26 DALYs. Alternative analysis of Quality-Adjusted Life Years confirmed the results. Conclusions The overall environmental burden was lower for PP1M and PP3M treatment than Treatment Interruption because patients are kept more stable, which reduces the environmental burden due to hospitals. Moreover, the Human Health burden was outweighed by the Human Health benefit. Electronic supplementary material The online version of this article (10.1186/s12913-019-4247-2) contains supplementary material, which is available to authorized users.

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.

The formulation and scale-up of batch processes is one of the major challenges in the development of pharmaceutical dosage forms and at the same time a significant resource demanding process which is generally overlooked in environmental sustainability assessments. First, this paper proposes general trends in the experience curve of cumulative resource consumption of pharmaceutical tablet manufacturing of PREZISTA® 800 mg through wet granulation (WG) at four consecutive scales in both R&D and manufacturing environments (resp. WG1 = 1 kg/h, WG5 = 5 kg/h, WG30 = 30 kg/h and WG240 = 240 kg/h). Second, the authors aim at evaluating the environmental impact from a life cycle perspective of a daily consumption of PREZISTA® 2× 400 mg tablets versus the bioequivalent PREZISTA® 800 mg tablet which was launched to enhance patient compliance. Environmental sustainability assessment was conducted at three different system boundaries, which enables identification, localization and eventually reduction of burdens, in this case natural resource extraction. Exergy Analysis (EA) was used at process level (α) and plant level (β) while a cradle-to-gate Exergetic Life Cycle Assessment (ELCA) was conducted at the overall industrial level (γ) by means of the CEENE method (Cumulative Exergy Extraction from the Natural Environment). Life cycle stages taken into account are Active Pharmaceutical Ingredient (API) production, Drug Product (DP) production and Packaging. At process level (α), the total resource extraction for the manufacturing of one daily dose of PREZISTA® (800 mg tablet) amounted up to 0.44 MJex at the smallest scale (WG1) while this amount proved to be reduced by 58%, 79% and 83% at WG5, WG30 and WG240 respectively. Expanding the boundaries to the overall industrial level (γ) reveals that the main resource demand is at the production of the Active Pharmaceutical Ingredient (API), excipients, packaging materials and cleaning media used in DP production. At the largest scale (WG240) the use of cleaning media during DP production contributes considerably less to the total resource extraction. Overall, the effect of scale-up and learning on resource consumption during DP production showed to possess a power-law experience curve y = 2.40 * x−0.57 when shifting from WG1 (smallest lab scale) to WG240 (industrial manufacturing). Tablet dosage (2× 400 mg versus 1× 800 mg) did not significantly affect the absolute environmental burden. However, the relative contribution of resource categories did change due to the different production technology. It could be concluded that in meeting social and economic demands by launching the PREZISTA® 800 mg tablet, no trade-off in environmental burden occurred. On the long term, future research should strive to take into account R&D processes and all services related to pipeline activities taking place prior to market launch and eventually to allocate impacts to the final product.

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.