Drug production can require substantial amounts of energy, solvents and raw materials, while also generating waste streams that are expensive to manage. Environmental impacts can continue after medicines leave the factory, as active pharmaceutical ingredients and metabolites may persist in wastewater and ecosystems.
The four-year ETERNAL project examined whether manufacturers could reduce some of those impacts without sacrificing product quality, safety or efficacy. Coordinated by AIMPLAS and funded through Horizon Europe, the initiative brought together 16 organizations to evaluate technologies including continuous manufacturing, membrane separations, biotechnology, digital twins and environmental risk assessment.
The results offer pharmaceutical manufacturers a mixed picture. Several technologies have progressed toward pilot-scale testing and established industrial processes. Others remain earlier-stage concepts whose technical performance may be promising but whose cost, validation requirements and commercial scalability still need to be demonstrated.
Some of ETERNAL’s clearest near-term opportunities involve changes to processes manufacturers already use.
Angelini Pharma tested twin-screw granulation for solid-dose medicines as an alternative to conventional batch production. Pharmaceutical batch manufacturing can involve several processing stages, multiple pieces of equipment and controlled manufacturing spaces that require considerable energy to operate.
The continuous approach combines portions of that production sequence into a smaller processing train.
In project testing, Angelini used twin-screw processing to manufacture granules for immediate-release tablets while eliminating water addition and certain energy-intensive steps. Development progressed from laboratory testing to an 18-millimeter pilot extruder.
The project has not, however, published a percentage reduction in operating cost, cycle time or energy use for the process. That leaves an important question for manufacturers evaluating the technology. Eliminating processing steps does not necessarily result in proportional cost savings once equipment utilization, quality controls, validation and capital investment are considered.
Across ETERNAL’s broader work on continuous production and synthesis, European Commission reporting cited expected solvent reductions of roughly 20% to 40%, with several processes still undergoing validation.
The potential benefit is not limited to solvent use. Continuous manufacturing may allow manufacturers to replace stop-and-start batch production with more consistent processing, potentially reducing equipment footprints and simplifying operations.
ETERNAL has not published a project-wide figure showing increased hourly or annual production capacity, however. For now, the stronger business argument is based on process simplification, lower material consumption and potentially smaller manufacturing footprints rather than a documented increase in throughput.
Membrane technology produced another set of results with potential operational implications.
AstraZeneca evaluated organic solvent nanofiltration, or OSN, as an alternative to relying entirely on distillation during solvent exchanges. Distillation can be one of the more energy-intensive steps in pharmaceutical synthesis because it requires substantial thermal energy.
The ETERNAL work tested commercially available membranes during synthesis of AZD4625, a drug candidate studied for KRAS G12C-positive tumors.
Rather than eliminating distillation, the researchers examined a hybrid system in which membranes perform part of the separation before the remaining material is processed conventionally. The approach reduced energy demand, solvent waste and associated carbon emissions.
Across relevant ETERNAL work, solvent recycling improvements were reported at approximately 15% to 25%. Recycling reached as high as 90% in one AstraZeneca case.
The public project results do not provide a corresponding cost saving per batch, and the company continued pilot-scale optimization rather than presenting membrane separation as a universal replacement for conventional solvent exchange.
A second AstraZeneca application may provide a clearer commercial incentive.
Researchers used OSN to recover a homogeneous palladium catalyst, allowing the catalyst and ligand to be reused rather than discarded after a single process cycle.
Published results reported catalyst rejection of approximately 98.6% during the first cycle and 96.3% by the fifth. The recovered catalyst and ligand were reused five times while conversion remained above 90%. ETERNAL’s final reporting also cited recovery of 98% of the pharmaceutical product in the catalyst-recovery process.
For manufacturers, recovering a high-value catalyst creates a more direct connection between environmental performance and production economics. Lower waste volumes may reduce disposal requirements, while repeated catalyst reuse can reduce purchases of expensive precious metals.
The economics will still depend on factors including catalyst loading, membrane life, solvent recovery rates and metal prices. Researchers also observed some decline in catalyst rejection during repeated use.
Even with those limitations, catalyst recovery represents one of the project’s more tangible examples of a sustainability measure that could potentially generate a measurable operating return.
Some ETERNAL technologies remain further from routine pharmaceutical production. Reig Jofre paired continuous manufacturing of liposomes and DNA-loaded lipid nanoparticles with digital-twin modeling that could reduce physical experiments, material use and development time. Other teams explored modified fermentation organisms and continuous rapamycin production to reduce by-products and simplify purification. Industrial validation remains incomplete, and these approaches carry different commercialization risks from improvements being tested in established manufacturing processes.
Beyond the equipment, ETERNAL helped develop Green Pharma Cluster policy recommendations and assessment tools encouraging companies to consider environmental and social impacts alongside economics and technical performance across the pharmaceutical life cycle.
For manufacturers, the strongest business cases may come where environmental and operational benefits overlap: fewer processing steps, lower energy demand, reduced solvent purchases and recovery of valuable catalysts. Benefits measured primarily through avoided emissions may require different investment criteria, particularly when process changes bring substantial validation requirements.
The larger question remains whether these improvements consistently lower validated production costs at commercial scale. Technical demonstrations can show that greener processes work. Adoption will depend on whether they also deliver the productivity, reliability and return on investment needed to justify changing highly controlled manufacturing systems.
