University of Limerick, Ireland research could reduce time required to bring new medicines to market

Researchers at the University of Limerick in Ireland have developed a new modeling approach to pharmaceutical manufacturing that could reduce the time required to bring medicines to market.

Professor Gavin Walker at the University of Limerick’s Bernal Institute has had a world’s first paper published in applying molecular engineering methodologies to continuous pharmaceutical manufacturing.

The study addresses a significant public health issue of reducing the time required to bring new medicines to market for the benefit of patients and society.

The pharmaceutical industry has recently been increasing research in continuous manufacturing techniques to decrease the manufacturing costs of medical products, making them more affordable and getting them to more consumers more rapidly at a reduced carbon and environmental footprint.

The UL research emphasizes the increasing significance of combining process engineering, modeling, and data science to better understand processes at a molecular scale for the optimization of pharmaceutical manufacturing.

Professor Gavin Walker, Bernal Chair of Pharmaceutical Powder Engineering and project lead, explained that: “This contribution offers a ‘proof of concept’ to make it achievable to model specific co-crystals at a molecular scale within a continuous pharmaceutical manufacturing process.

“Molecular interactions can be altered to optimize drug properties and this process can be crucial to the performance of a dosage form which links to the preparation of the safe delivery of the content of the drug product for the ultimate benefits of patients and society.

“There is huge value in improving the productivity of the drug development process. This study expands on possibilities that exist for future development of progressing towards more supportive mechanisms in the pharmaceutical manufacturing space, improving processing and reducing time to market for new medicine,” he added.

The study was led by Professor Walker and funded through CONFIRM, the SFI Research Centre for Smart Manufacturing, and SSPC, the SFI Research Centre for Pharmaceuticals, which are both based at UL, and European funding through the MSCA ‘Process’ Co-Fund.

Professor Walker said of the research: “It will aid the current pharmaceutical development processes of exhaustive empirical experimentation, in that time and cost can be reduced through this more controlled and targeted approach via Smart Manufacturing techniques.

“The paper represents a significant bridge by adapting mathematical modeling developed in the discrete manufacturing sector into effective techniques for improving continuous manufacturing within the pharma-biopharma sector.

“This is critical to achieving UN Sustainable Development grand challenges in good health and wellbeing, as well as ensuring healthy lives and promoting well-being for all ages, optimizing biopharma processing and reducing time to market for new medicines,” he added.

Speaking about the research output, SSPC Director, Professor Damien Thompson, said: “The paper represents a significant deployment of data-driven molecular modeling for improving continuous manufacturing within the pharma-biopharma sector. It is great to see such impact from collaborative work bridging two SFI research centers hosted at the University of Limerick.”

Dr. Niall Keely, CONFIRM Strategic Research Manager, added: “The research presented in this paper highlights the significant impact of combining multiple sciences and engineering disciplines to advance knowledge of processes at the molecular level that ultimately can lead to benefits at the industrial scale and improved business processes such as faster time-to-market of products.”

UK researchers run supercomputer simulations that show limiting global warming to 1.5°C would reduce risks to humans by up to 85%

New research led by the University of East Anglia (UEA) Norwich, England quantifies the benefits of limiting global warming to 1.5°C and identifies the hotspot regions for climate change risk in the future.

The study calculates reductions in human exposure to a series of risks - water scarcity and heat stress, vector-borne diseases, coastal and river flooding - that would result from limiting global warming to 1.5°C rather than 2°C or 3.66°C. Effects on agricultural yields and the economy are also included.

Researchers from the UK, including scientists from UEA and the University of Bristol, and from PBL Netherlands Environmental Assessment Agency, find that the risks are reduced by 10-44% globally if warming is reduced to 1.5°C rather than 2°C.

Currently, insufficient climate policy has been implemented globally to limit warming to 2°C, so the team also made a comparison with risks that would occur with higher levels of global warming.

Risks will be greater if global warming is greater. The risks at 3.66°C warmings are reduced by 26–74% if instead warming is kept to only 2°C. They are reduced even further, by 32–85%, if warming can be limited to just 1.5°C. The ranges are wide because the percentage depends on which of the indicators, for example, human exposure to drought or flooding, are being considered.

The findings, published today in the journal Climatic Change, suggest that in percentage terms, the avoided risk is highest for river flooding, drought, and heat stress. Still, in absolute terms, the risk reduction is most significant for drought.

The authors also identify West Africa, India, and North America as regions where the risks caused by climate change are projected to increase the most with 1.5°C or 2°C of average global warming by 2100.

The study follows the Intergovernmental Panel on Climate Change (IPCC) Sixth Assessment Report, which finds that global net-zero CO2 emissions must be reached in the early 2050s to limit warming to 1.5°C with no or limited overshoot, and around the early 2070s to limit warming to 2°C.

Lead author Prof Rachel Warren, of the Tyndall Centre for Climate Change Research at UEA, said: “Our findings are important because the Paris Agreement target is to limit global warming to ‘well below 2°C and to ‘pursue efforts to limit it to 1.5°C. This means that decision-makers need to understand the benefits of aiming for the lower figure.

“In addition, at COP26 last year, the commitments made by countries in terms of greenhouse gas emission reductions are not sufficient to achieve the Paris goals. At present, current policies would result in average warming of 2.7°C, while the Nationally Determined Contributions for 2030 would limit warming to 2.1°C.

“While there are a number of planned additional actions to reduce emissions further, potentially limiting warming to 1.8°C in the most optimistic case, these still need to be delivered and further additional action is needed to limit warming to 1.5°C.”

For this study the researchers ran sophisticated supercomputer simulations of climate change risk, using a common set of climate change scenarios in which global temperatures rise by 2°C and separately by 1.5°C and 3.66°C. They then compared the results.

The findings include:

  • Overall, global population exposure to malaria and dengue fever is 10% lower if warming is constrained to 1.5°C rather than 2°C.
  • Population exposure to water scarcity is most evident in western India and the northern region of West Africa.
  • A continuous increase in global drought risk with global warming is estimated, with hundreds of millions of people additionally affected by drought at each, successively higher warming level.
  • By 2100 if we do not adapt, global warming of 1.5°C would place an additional 41-88 million people a year at risk from coastal flooding globally (associated with 0.24-0.56 m of sea-level rise), whereas an additional 45-95 million people a year would be at risk under global warming of 2°C (corresponding to 0.27-0.64 m of sea-level rise) in 2100.
  • Global economic impacts of climate change are 20% lower when warming is limited to 1.5°C rather than 2°C. The net value of damages is correspondingly reduced from 61 trillion US dollars to 39 trillion US dollars.

The study used 21 alternative climate models to simulate the regional patterns of climate change corresponding to 2°C warmings and 1.5°C warmings respectively. Previous research has used simpler models, a more limited range of climate models, or has covered different risk indicators.

‘Quantifying risks avoided by limiting global warming to 1.5 or 2 °C above pre‑industrial levels’, Rachel Warren et al, is published in Climatic Change on June 29.

Duke's modeling predicts habitat changes along the Atlantic coast may further fuel climate change

As rising sea levels cause marshes to move inland in six mid-Atlantic states, the coastal zone will not continue to serve as a carbon sink but release more carbon into the atmosphere, a new modeling study led by researchers at Duke University finds.

Earlier estimates focused on the potential for an expanded area of coastal marshes to capture more carbon, removing it from the atmosphere where it acts as a greenhouse gas in the form of carbon dioxide. But as coastal marshes invade low-lying forests and freshwater wetlands, the loss of trees and decomposition will release more carbon into the air than can be captured by the marshes, further contributing to global climate change.

The study was conducted in consultation with natural resource agencies in North Carolina, New York, New Jersey, Delaware, Maryland, and Virginia. Maps of predicted changes in coastal habitats and carbon due to sea-level rise were created to support coastal planning.

“This research and our conversations with the states raise lots of questions about options for managing coastal landscapes given these changes, and emphasizes the importance of reducing greenhouse gases and sea-level rise overall because that's the main driver of all of this,” said Katie Warnell, lead author of the study and a policy associate at Duke’s Nicholas Institute for Environmental Policy Solutions. “Carbon is one piece of the picture. There are many other reasons to keep marshes around, including coastal protection and nursery habitats for fisheries. We need to weigh all of these different factors in making decisions about managing our coastal habitats.”

The peer-reviewed, open-access study was published on June 23 in the journal PLOS Climate.

The modeling runs looked at land changes in coastal areas through the year 2104 in scenarios that predict intermediate sea level rise. In 16 out of the 19 runs of the model, inland marsh migration converted the land from a net carbon sink to a net carbon source.

“There might be some things that can be done to protect key areas from converting,” Warnell said. “In North Carolina, berms and pumps have been used to protect agricultural land and towns from sea level rise. While these are expensive, they might be worth it in certain areas.”

Another possible option, said Warnell, is preemptive forest harvest in vulnerable areas to prevent carbon from entering the atmosphere upon decomposition. As the sea level rises and causes saltwater to replace freshwater, trees in certain low-lying areas are dying and forming ominous-looking “ghost forests.” The tree deaths reduce carbon storage and emit carbon through decomposition.

“In this new study, Warnell and others have made initial estimates of the carbon costs associated with the drowning and salinization of coastal wetland ecosystems,” said Emily Bernhardt, a professor in Duke’s Nicholas School of the Environment who has extensively studied ghost forests in the eastern United States. “These early estimates suggest that habitat transitions caused by a sea-level rise across the Mid Atlantic coastal plain will shift coastal ecosystems from carbon sinks to carbon sources without thoughtful intervention.”