Periodic Reporting for period 1 - ENVIROMED (Next generation toolbox for greener pharmaceuticals design & manufacturing towards reduced environmental impact)
Reporting period: 2022-06-01 to 2023-11-30
Pharmaceuticals have undoubtably made our world a better place, ensuring longer and healthier lives. However, pharmaceuticals and their active metabolites are rapidly emerging environmental toxicants. It is thus critical that we fully understand, and mitigate where necessary, the environmental impact resulting from their production, use and disposal.
In this direction, ENVIROMED addresses two aspects of the environmental impact of pharmaceuticals, a) impact of the processes in manufacturing the compound, and b) impact of the compound itself, during its lifecycle. The project narrows the knowledge gap when it comes to the effect of pharmaceutical compounds and their derivatives in the environment, as it enables the better understanding of the environmental impact of such compounds, throughout their lifecycle. It aims to offer - via extensive monitoring campaigns and scientific studies - information regarding occurrence of pharmaceuticals in the environment, their persistence, environmental fate, and toxicity (via in-vitro & in-vivo models), as well as application of in-silico methods to provide information about the basic risk management and fate prediction in the environment. Brief ideas about toxicity endpoints, available ecotoxicity databases, and expert systems employed for rapid toxicity predictions of ecotoxicity of pharmaceuticals will also be taken into account, in order to have a comprehensive approach to pharmaceuticals' Life Cycle Assessment (LCA). Moreover, the project aims at developing a set of technologies that enable greener and overall, more efficient pharmaceuticals production, which include: a) Green-by-design in-silico drug development; b) Novel sensing to allow reduction of rinsing chemicals and cycles; c) a robust Continuous Biomanufacturing line (CBM), which makes use of AI-enabled process optimisation and prediction, using data assimilation based on chemical sensing and energy disaggregation/monitoring.
In this direction, ENVIROMED addresses two aspects of the environmental impact of pharmaceuticals, a) impact of the processes in manufacturing the compound, and b) impact of the compound itself, during its lifecycle. The project narrows the knowledge gap when it comes to the effect of pharmaceutical compounds and their derivatives in the environment, as it enables the better understanding of the environmental impact of such compounds, throughout their lifecycle. It aims to offer - via extensive monitoring campaigns and scientific studies - information regarding occurrence of pharmaceuticals in the environment, their persistence, environmental fate, and toxicity (via in-vitro & in-vivo models), as well as application of in-silico methods to provide information about the basic risk management and fate prediction in the environment. Brief ideas about toxicity endpoints, available ecotoxicity databases, and expert systems employed for rapid toxicity predictions of ecotoxicity of pharmaceuticals will also be taken into account, in order to have a comprehensive approach to pharmaceuticals' Life Cycle Assessment (LCA). Moreover, the project aims at developing a set of technologies that enable greener and overall, more efficient pharmaceuticals production, which include: a) Green-by-design in-silico drug development; b) Novel sensing to allow reduction of rinsing chemicals and cycles; c) a robust Continuous Biomanufacturing line (CBM), which makes use of AI-enabled process optimisation and prediction, using data assimilation based on chemical sensing and energy disaggregation/monitoring.
The activities and main achievements on a technical and scientific level during the first reporting period are summarised below:
A literature review explored sustainable and green production methods in pharmaceutical manufacturing, focusing on metrics, technology, and wastewater treatment.
Digital tools for green biomanufacturing were identified, focusing on continuous processes and real-time monitoring.
The ecotoxicity studies and the environmental monitoring campaigns have been designed.
The metrics that will be used to estimate the Key Performance Indicators for the assessment of the environmental impact of pharmaceuticals during their full life cycle have been defined.
The system requirements specifications of the three monitoring devices (Wastewater Spectroscopic Analyser, Liquid Monitoring Analyser, and Surface Inspection Analyser) and of the custom mid-IR laser sources have been defined.
A digitalisation technology roadmap for continuous biomanufacturing has been prepared.
A digital twin has been launched successfully and can be used for optimisation of feeds and for optimum process control.
An explainable Artificial Intelligence module for interpretation to identify the on-line/in-line components directly affecting biomass has been defined.
The development of AI algorithms for energy demand forecasting and energy consumption optimization has started.
ML algorithms have been trained to recognize potential ecotoxic outcomes in the context of the development of a multimodal platform towards early green drug discovery.
The development of custom mid-IR laser sources, the Wastewater Spectroscopic Analyser, the Liquid Monitoring Analyser, and the Surface Inspection Analyser has started.
Data have been collected from different sources regarding the presence of pharmaceuticals in the environment and the most abundant and potentially harmful ones have been identified.
A large dataset of compounds with known ecotoxicity was constructed and various ML algorithms were applied, resulting in an accurate and scalable model for predicting fish toxicity.
The first phase of the ecotoxicity studies involving in vivo/ex vivo experiments was initiated.
A registry of pharmaceutical micropollutants was demonstrated to consortium partners and discussions / feedback exchange on potential expansions towards the definition of the final registry version have started.
The methodology, goal, and scope of the Life Cycle Assessment (LCA) have been defined and a detailed list including all the information that will be needed from involved partners to build a comprehensive Life Cycle Inventory has been prepared.
A literature review explored sustainable and green production methods in pharmaceutical manufacturing, focusing on metrics, technology, and wastewater treatment.
Digital tools for green biomanufacturing were identified, focusing on continuous processes and real-time monitoring.
The ecotoxicity studies and the environmental monitoring campaigns have been designed.
The metrics that will be used to estimate the Key Performance Indicators for the assessment of the environmental impact of pharmaceuticals during their full life cycle have been defined.
The system requirements specifications of the three monitoring devices (Wastewater Spectroscopic Analyser, Liquid Monitoring Analyser, and Surface Inspection Analyser) and of the custom mid-IR laser sources have been defined.
A digitalisation technology roadmap for continuous biomanufacturing has been prepared.
A digital twin has been launched successfully and can be used for optimisation of feeds and for optimum process control.
An explainable Artificial Intelligence module for interpretation to identify the on-line/in-line components directly affecting biomass has been defined.
The development of AI algorithms for energy demand forecasting and energy consumption optimization has started.
ML algorithms have been trained to recognize potential ecotoxic outcomes in the context of the development of a multimodal platform towards early green drug discovery.
The development of custom mid-IR laser sources, the Wastewater Spectroscopic Analyser, the Liquid Monitoring Analyser, and the Surface Inspection Analyser has started.
Data have been collected from different sources regarding the presence of pharmaceuticals in the environment and the most abundant and potentially harmful ones have been identified.
A large dataset of compounds with known ecotoxicity was constructed and various ML algorithms were applied, resulting in an accurate and scalable model for predicting fish toxicity.
The first phase of the ecotoxicity studies involving in vivo/ex vivo experiments was initiated.
A registry of pharmaceutical micropollutants was demonstrated to consortium partners and discussions / feedback exchange on potential expansions towards the definition of the final registry version have started.
The methodology, goal, and scope of the Life Cycle Assessment (LCA) have been defined and a detailed list including all the information that will be needed from involved partners to build a comprehensive Life Cycle Inventory has been prepared.
ENVIROMED aims at progressing well beyond the current state of the art in both technology and products. The key elements where the project pushes beyond the state of the art are as follows:
• Extensive literature review and preliminary studies to determine the core contaminants of interest
• Ecotoxicity in-silico, in-vitro & in-vivo models for determining toxicity of each compound
• Development of a registry on pharmaceutical compounds and of an in-depth LCA framework
• Laser-based spectroscopy for online monitoring of wastewater (effluents of clinical facilities, wastewater treatment plants input/output, pharmaceutical industries output, etc.) to accurately map concentration levels of pharmaceutical micropollutants
• Extensive monitoring campaigns (field studies), to better understand the severity of contamination at various stages of pharmaceutical lifecycle (production, use and disposal)
• A robust and efficient Continuous Biomanufacturing (CBM) line, overcoming the problems of batch production, using advanced sensing, AI/ML algorithms and digital twin models, for better prediction and control
• Novel in-silico drug design tools for “green-by-design” pharmaceuticals
• Spectroscopic techniques for continuous monitoring of manufacturing processes, and reduction of used chemicals
• Mid-infrared polarimetry for vessel inspection to reduce rinsing cycles and use of solvents & cleaning.
• Extensive literature review and preliminary studies to determine the core contaminants of interest
• Ecotoxicity in-silico, in-vitro & in-vivo models for determining toxicity of each compound
• Development of a registry on pharmaceutical compounds and of an in-depth LCA framework
• Laser-based spectroscopy for online monitoring of wastewater (effluents of clinical facilities, wastewater treatment plants input/output, pharmaceutical industries output, etc.) to accurately map concentration levels of pharmaceutical micropollutants
• Extensive monitoring campaigns (field studies), to better understand the severity of contamination at various stages of pharmaceutical lifecycle (production, use and disposal)
• A robust and efficient Continuous Biomanufacturing (CBM) line, overcoming the problems of batch production, using advanced sensing, AI/ML algorithms and digital twin models, for better prediction and control
• Novel in-silico drug design tools for “green-by-design” pharmaceuticals
• Spectroscopic techniques for continuous monitoring of manufacturing processes, and reduction of used chemicals
• Mid-infrared polarimetry for vessel inspection to reduce rinsing cycles and use of solvents & cleaning.