Periodic Reporting for period 2 - ETERNAL (Boosting the reduction of the environmental impact of pharmaceutical products throughout their entire life cycle.)
Reporting period: 2024-03-01 to 2025-08-31
ETERNAL promotes sustainable pharmaceutical development through full life cycle approaches, assessing environmental risks of APIs, residues, and by-products. Its case studies demonstrate how green manufacturing reduces environmental impacts, offering practical guidance to industry and regulators.
Objective 1: Launch a cocreation lab for industry-research-compliance codesign
Scoping sessions between R&D teams and pharma hosts of six case studies continued. Specifications, industry needs, KPIs, and regulatory requirements were defined to guide TRL3-4 developments and TRL5-6 scale-up of ETERNAL innovations in green chemistry, mechanochemistry, and digitalization.
Objective 2: Reduce solvent use and increase green solvents
Solvent reduction was achieved via continuous technologies and new synthesis routes, with validation ongoing in MyB, RJF, and QS case studies. A reduction of 20–40% is expected. Greener solvents (e.g. ethyl lactate, ionic liquids) are being applied, aiming for full substitution in some cases.
Objective 3: Optimize solvent recycle/recovery for carcinogenic impurities
Linked to WP1/WP3 and case studies of AZ and Angelini Pharma. Membrane and other technologies were applied for solvent swaps and purification, reducing energy use. Recycled isobutyl increased by 15–25%, and up to 90% in AstraZeneca’s case.
Objective 4: Apply mechanochemistry (HME) in pharmaceutical production
Angelini Pharma applied Hot Melt Extrusion for immediate/modified release formulations (ADS/CSD). Validation is based on product quality comparison with batch processes.
Objective 5: Develop eco-efficient purification/capture routes using biobased products
WP1/WP3 activities with JRF, Angelini Pharma, AZ, and QS focused on enzymatic degradation of waste molecules and capture of nitrosamines, metals, and APIs using natural sorbents like chitosan. Validation of intermediate/final products is ongoing.
Objective 6: Develop digital workflow, PAT, and Digital Twin solutions
Efforts focus on FAIR data transfer and scalable method development. A versatile PAT and ML platform supports Quality-by-Design and Green-by-Design. A Holonics-based Digital Twin framework is being developed for process optimization and dynamic control, validated in ETERNAL case studies.
Objective 7: Scale up innovations in 6 industrial pilots
Green chemistry, mechanochemistry, and continuous process innovations were scaled at pharma sites:
Objective 8: Assess regulatory implications and ensure compliance
ASPHALION leads the regulatory strategy aligned with EU legislation, Clinical Trials Regulation, and EMA guidelines. It supports compliant-by-design development and engages with ETERNAL stakeholders in progress meetings.
Objective 9: Generate scientific knowledge on environmental fate and ecotoxicology of pharmaceuticals
WP4 activities by UKCEH and UAVR include ERA and LCA assessments, gap analysis of the regulatory landscape, and development of spatially explicit risk maps for pharmaceutical mixtures and metabolites.
Objective 10: Catalyse behavioural change and social innovation
Engage industry decision-makers (20 EOIs) and educate consumers on safe medicine disposal via a pilot infographic campaign. A stakeholder group meets annually to exchange relevant pharma sector information.
Objective 1: Launch a cocreation lab for industry-research-compliance codesign
Scoping sessions between R&D teams and pharma hosts of six case studies continued. Specifications, industry needs, KPIs, and regulatory requirements were defined to guide TRL3-4 developments and TRL5-6 scale-up of ETERNAL innovations in green chemistry, mechanochemistry, and digitalization.
Objective 2: Reduce solvent use and increase green solvents
Solvent reduction was achieved via continuous technologies and new synthesis routes, with validation ongoing in MyB, RJF, and QS case studies. A reduction of 20–40% is expected. Greener solvents (e.g. ethyl lactate, ionic liquids) are being applied, aiming for full substitution in some cases.
Objective 3: Optimize solvent recycle/recovery for carcinogenic impurities
Linked to WP1/WP3 and case studies of AZ and Angelini Pharma. Membrane and other technologies were applied for solvent swaps and purification, reducing energy use. Recycled isobutyl increased by 15–25%, and up to 90% in AstraZeneca’s case.
Objective 4: Apply mechanochemistry (HME) in pharmaceutical production
Angelini Pharma applied Hot Melt Extrusion for immediate/modified release formulations (ADS/CSD). Validation is based on product quality comparison with batch processes.
Objective 5: Develop eco-efficient purification/capture routes using biobased products
WP1/WP3 activities with JRF, Angelini Pharma, AZ, and QS focused on enzymatic degradation of waste molecules and capture of nitrosamines, metals, and APIs using natural sorbents like chitosan. Validation of intermediate/final products is ongoing.
Objective 6: Develop digital workflow, PAT, and Digital Twin solutions
Efforts focus on FAIR data transfer and scalable method development. A versatile PAT and ML platform supports Quality-by-Design and Green-by-Design. A Holonics-based Digital Twin framework is being developed for process optimization and dynamic control, validated in ETERNAL case studies.
Objective 7: Scale up innovations in 6 industrial pilots
Green chemistry, mechanochemistry, and continuous process innovations were scaled at pharma sites:
Objective 8: Assess regulatory implications and ensure compliance
ASPHALION leads the regulatory strategy aligned with EU legislation, Clinical Trials Regulation, and EMA guidelines. It supports compliant-by-design development and engages with ETERNAL stakeholders in progress meetings.
Objective 9: Generate scientific knowledge on environmental fate and ecotoxicology of pharmaceuticals
WP4 activities by UKCEH and UAVR include ERA and LCA assessments, gap analysis of the regulatory landscape, and development of spatially explicit risk maps for pharmaceutical mixtures and metabolites.
Objective 10: Catalyse behavioural change and social innovation
Engage industry decision-makers (20 EOIs) and educate consumers on safe medicine disposal via a pilot infographic campaign. A stakeholder group meets annually to exchange relevant pharma sector information.
WP1 assessed the feasibility of case studies at lab scale (TRL 3–4) and defined requirements for scale-up in WP3 (TRL 5–6). Work progressed smoothly, with initial validation and dissemination activities launched.
WP3 is scaling the six case studies into pilots, including risk assessments. A co-creation lab fosters collaboration among ETERNAL partners, with quarterly reviews and shared learnings. All pilots are on track, and results are being disseminated. A pre-LCA sustainability method and a lipid nanoparticle measurement protocol (Case Study 3) are being standardized via CEN workshops.
WP4 focuses on environmental risk assessment of pharmaceuticals, including current products and ETERNAL innovations. Progress includes experimental studies, data analysis, and modeling, aligned with pharmaceutical legislation. Comparative risk assessments for ETERNAL case studies have begun.
WP5 drives external communication, result dissemination, and behavioral change. Four “Change Lab” initiatives were launched for industry, regulators, healthcare, and the public. Gendered innovation is also being addressed through data collection and analysis.
WP6 ensures project coordination and impact, led by AIMPLAS. Two key changes occurred: Cristina Padeanu replaced Jiannis Kougoulis as Project Officer, and Carlos Fernández took over technical leadership. The consortium remains stable, with regular meetings and all deliverables submitted on time.
WP3 is scaling the six case studies into pilots, including risk assessments. A co-creation lab fosters collaboration among ETERNAL partners, with quarterly reviews and shared learnings. All pilots are on track, and results are being disseminated. A pre-LCA sustainability method and a lipid nanoparticle measurement protocol (Case Study 3) are being standardized via CEN workshops.
WP4 focuses on environmental risk assessment of pharmaceuticals, including current products and ETERNAL innovations. Progress includes experimental studies, data analysis, and modeling, aligned with pharmaceutical legislation. Comparative risk assessments for ETERNAL case studies have begun.
WP5 drives external communication, result dissemination, and behavioral change. Four “Change Lab” initiatives were launched for industry, regulators, healthcare, and the public. Gendered innovation is also being addressed through data collection and analysis.
WP6 ensures project coordination and impact, led by AIMPLAS. Two key changes occurred: Cristina Padeanu replaced Jiannis Kougoulis as Project Officer, and Carlos Fernández took over technical leadership. The consortium remains stable, with regular meetings and all deliverables submitted on time.
At this moment of the project, no result have been achieved.