Periodic Reporting for period 2 - TransPharm (Transforming into a sustainable European pharmaceutical sector)
Periodo di rendicontazione: 2023-12-01 al 2025-05-31
Pharmaceuticals comprise a variety of compounds designed to guarantee safe and effective therapies. The active pharmaceutical ingredients (APIs) are those that deliver the beneficial health effects. The goal of the project is to develop greener methodologies for APIs that simultaneously reduce the environmental footprint and the dependence on third countries for API production. The TransPharm project delivers digital tools, also based on artificial intelligence, for the development of greener pharmaceutical products and APIs, as well as models to judge their impact. The result should lead to a more independent and competitive European pharmaceutical industry, which can ensure the timely delivery of green therapeutics in the future.
Starting from literature data bases, artificial intelligence methods are used to extract relevant data to predict important features of molecules which are of major importance for API’s. Several characteristics of the molecules are being predicted such as solubility, but also the biodegradability of compounds. This feature is crucial to develop greener pharmaceuticals that degrade more readily and more completely in the environment leading to better surface water quality. Further, much effort is being focused on developing more sustainable methods to prepare API’s. This involves methods to reduce the formation of hazardous residues, but attention is also paid to develop continuous flow and telescoped methods to reduce the footprint of the synthesis methods.
However, the footprint/handprint of the pharmaceutical sector is not only created by the production, also other aspects have to be accounted for which are less obvious, such as the impact of limited biodegradability, long term health benefits, local legal constraints, spatial distribution of environmental impact... Therefore, a holistic Life Cycle Assessment is being developed to evaluate the sustainability of pharmaceuticals. This assessment will take also into account the ecotoxicological profile which will be based on medium / high throughput research.
The project is performed in close collaboration with all stakeholders of the process in order to judge the drive and the economic viability to transition towards greening the pharmaceutical sector.
The TransPharm project aims at developing greener pharmaceutical production schemes which favours the production in Europe and to contribute to the logistic difficulties of the sector.
The pharmaceutical sector is coping with a number of important challenges at the moment. These challenges range from logistic problems to provide the required APIs to patients, over environmental issues related to residues in surface water and hazardous residues, leading to high development costs directing the API production to low-income countries. Also, the stimulation of the use of generic drugs by several national governments leads to a potential reduction of investments by major pharmaceutical companies. These concerns were also discussed with the project officer and EU representatives during the meeting of the sister projects in Brussels on December 10th, 2024.
The objective of the TransPharm project is to contribute to most of the above challenges by greening the pharmaceutical production and optimizing production methods in order to reduce the footprint of the pharmaceutical sector and to try to bring back some of the API production to Europe by stimulating more regional production. This should lead to a more secure supply and to a better situation for patients in Europe.
Starting from literature data bases, artificial intelligence methods are used to extract relevant data to predict important features of molecules which are of major importance for API’s. Several characteristics of the molecules are being predicted such as solubility, but also the biodegradability of compounds. This feature is crucial to develop greener pharmaceuticals that degrade more readily and more completely in the environment leading to better surface water quality. Further, much effort is being focused on developing more sustainable methods to prepare API’s. This involves methods to reduce the formation of hazardous residues, but attention is also paid to develop continuous flow and telescoped methods to reduce the footprint of the synthesis methods.
However, the footprint/handprint of the pharmaceutical sector is not only created by the production, also other aspects have to be accounted for which are less obvious, such as the impact of limited biodegradability, long term health benefits, local legal constraints, spatial distribution of environmental impact... Therefore, a holistic Life Cycle Assessment is being developed to evaluate the sustainability of pharmaceuticals. This assessment will take also into account the ecotoxicological profile which will be based on medium / high throughput research.
The project is performed in close collaboration with all stakeholders of the process in order to judge the drive and the economic viability to transition towards greening the pharmaceutical sector.
The TransPharm project aims at developing greener pharmaceutical production schemes which favours the production in Europe and to contribute to the logistic difficulties of the sector.
The pharmaceutical sector is coping with a number of important challenges at the moment. These challenges range from logistic problems to provide the required APIs to patients, over environmental issues related to residues in surface water and hazardous residues, leading to high development costs directing the API production to low-income countries. Also, the stimulation of the use of generic drugs by several national governments leads to a potential reduction of investments by major pharmaceutical companies. These concerns were also discussed with the project officer and EU representatives during the meeting of the sister projects in Brussels on December 10th, 2024.
The objective of the TransPharm project is to contribute to most of the above challenges by greening the pharmaceutical production and optimizing production methods in order to reduce the footprint of the pharmaceutical sector and to try to bring back some of the API production to Europe by stimulating more regional production. This should lead to a more secure supply and to a better situation for patients in Europe.
The research project started 36 months ago, and some groups had quite severe problems to recruit the required personnel due to the war on talent many universities and companies are struggling with. It illustrates the economic possibilities for highly educated Master students in the European area and the need to educate more young people in this area of research.
The different work packages progress very well, and promising results have been obtained. The use of artificial intelligence has resulted in the delivery of on-line tools to predict product features of pharmaceuticals and chemicals.
Important work has been realized in developing a miniaturized medium throughput system to test the biodegradability of very small amounts of new compounds.
A library of ciprofloxacin analogues has been designed and derivatives have been synthesized for a better biodegradability. The scale-up of 4 Cip-hemi derivatives for biodegradation testing has been realized.
Further, a recuperation method for Cyrene, the most important renewable solvent that can be used as a replacement for dimethylformamide, has been developed. Extraction performed at elevated temperature, in batch and in flow, led to high recuperation of the solvent.
Protocols to scan and interrogate literature data on flow processes have been developed and are almost fully finalized.
Further, important work has been performed to get a complete overview of the life cycle of API’s and the impacts on environment, economics and social life. Next to that, stakeholders have been interrogated and an overview of the interviews have been collated.
The development of training methods and educational material has been nearly finalised.
The different work packages progress very well, and promising results have been obtained. The use of artificial intelligence has resulted in the delivery of on-line tools to predict product features of pharmaceuticals and chemicals.
Important work has been realized in developing a miniaturized medium throughput system to test the biodegradability of very small amounts of new compounds.
A library of ciprofloxacin analogues has been designed and derivatives have been synthesized for a better biodegradability. The scale-up of 4 Cip-hemi derivatives for biodegradation testing has been realized.
Further, a recuperation method for Cyrene, the most important renewable solvent that can be used as a replacement for dimethylformamide, has been developed. Extraction performed at elevated temperature, in batch and in flow, led to high recuperation of the solvent.
Protocols to scan and interrogate literature data on flow processes have been developed and are almost fully finalized.
Further, important work has been performed to get a complete overview of the life cycle of API’s and the impacts on environment, economics and social life. Next to that, stakeholders have been interrogated and an overview of the interviews have been collated.
The development of training methods and educational material has been nearly finalised.
Because of the high complexity of the project, a few results beyond the state of the art have already been obtained. The Cyrene recuperation method has been established with reasonable to good yields. Further some very interesting results are obtained on the development of renewable building blocks and on the selective oxidation of alcohols to aldehydes. The most important and long-lasting aspect realized at the moment is the dissemination of the concept to a broad number of young people. More impact will be realized by the on-line training data.
Some hurdles have been detected in the concrete realization of innovative methods into the pharmaceutical industry. It was communication to the EU officials that the change for a greener method leads to an administrative burden and additional cost to the companies, if the company wants to change their synthesis.
Some hurdles have been detected in the concrete realization of innovative methods into the pharmaceutical industry. It was communication to the EU officials that the change for a greener method leads to an administrative burden and additional cost to the companies, if the company wants to change their synthesis.