Prioritisation and Risk Evaluation of Medicines in the EnviRonment

Informations projet

PREMIER

N° de convention de subvention: 875508

DOI

10.3030/875508

Date de signature de la CE 24 Juin 2020

Date de début 1 Septembre 2020

Date de fin 31 Août 2026

Financé au titre de

• SOCIETAL CHALLENGES - Health, demographic change and well-being

Coût total

€ 10 904 029,62

Contribution de l’UE

€ 4 549 999,65

Coordonné par

STICHTING RADBOUD UNIVERSITEIT
Netherlands

CORDIS fournit des liens vers les livrables publics et les publications des projets HORIZON.

Les liens vers les livrables et les publications des projets du 7e PC, ainsi que les liens vers certains types de résultats spécifiques tels que les jeux de données et les logiciels, sont récupérés dynamiquement sur OpenAIRE .

Livrables

Documents, reports (14)

API prioritisation and selection for iterative assessment (D1.2.1)

This report describes the selection process of approximately 15 APIs that will be tested in WP1.3 because of a lack of data to conclude on the potential for environmental risk. This includes a description of the original API list considered, the decision tree(s) used for prioritisation, the prioritisation results, the criteria used for API selection, and the ultimate results of the selection process.

Determine bioavailability, metabolism and biological effects of MPA in fish (D2.2.5)

Uptake will be measured using rainbow trout gill cell assay; bioavailability will be quantified via blood plasma protein binding measurements in trout and fathead minnow; metabolism will be measured using trout hepatocyte assay; developmental toxicity will be measured using the ZEDTA assay; immunotoxicity will be measured using transgenic zebrafish to track B and T cells, neutrophils and macrophages.

Report on stakeholder questions and requirements and work plan for further guidance development (D4.1.1)

Report on the stakeholder questions and requirements, as identified during interviews and web-based questionnaire, the results of the workshop, the identified possible guidance products and the work plan for further guidance development.

A report describing the feasibility of greener drug design (D4.2.4)

Consensus document that determines whether greener drug design is feasible and how it can be realised if the potential exists.

Report summarising drug discovery and development process and key attributes of tools/models (D4.2.1)

Report highlighting a clear understanding where environmental hazard and risk are currently considered in the drug development process and where future potential exists for earlier integration of these considerations together with the attributes required for environmental screening tools/ models.

Evaluation of fish gill uptake and hepatic clearance for 10-20 APIs, including feasibility of the OECD 319b test or organ-chips for prediction of in vivo hepatic clearance of APIs in fish (D2.3.1)

Assessment of the API uptake (bioavailability) and clearance of selected APIs in a primary 3D rainbow trout gill cell culture assay system and an analyses on the hepatic clearance of selected APIs through the use of (i) a primary 3D rainbow trout liver cell culture assay and (ii) a rainbow trout subcellular S9 fraction.

List of approximately 10 APIs selected for MoA-driven testing in WP1.3 (D1.1.2)

This report describes the selection process of approximately 10 APIs that will be tested in WP1.3 because of a lack of ecotoxicity data on their specific Mode of Action. This includes a description of how the universe of APIs was compiled, the decision tree(s), the prioritisation results, the criteria used for API selection and the final results.

Mechanistic understanding on the potential for targeted pharmacological responses to mediate chronic effect outcomes from the application of transgenic zebrafish models (D2.3.3)

Physiological/functional outcomes for selected APIs with specific pharmacological target activation prioritised in WP2.2 will be investigated using transgenic reporter zebrafish. The resulting data will be made available for use in the iterative assessment in WP1.2.

Project communication plan and initial toolset

A plan for dissemination that includes the communication objectives, target audiences, activities to be carried out and tools that will support their implementation, with connections among these components. It will also include an initial set of communication materials.

Initial Data and Knowledge Management plan (D3.3.2)

Outline for the PREMIER data and knowledge management policy.

Guidance for first set of selected stakeholder questions and requirements (D4.1.2)

A first guidance document based on the main priorities identified in D4.1.1.

Machine-learning based models for estimating sorption in sludge, sediment, soil and sorbents used in treatment (D2.1.2)

Report describing the generalized model for estimating sorption behaviour in sludge, soil, sediment and sorbents used in treatment processes.

Evaluation of the risk for bio-accumulation of APIs in fish via irreversible inhibition of hepatic CYPs (D2.3.2)

The ability of selected APIs to irreversibly inhibit CYP enzyme activity will be quantified (IC50 shift) using rainbow trout RT-S9 and well-plate technologies.

Summary report describing fundamental drug design principles and their environmental significance (D4.2.2)

onsensus document that describes industry-wide principles used to design safe and efficacious medicines.

Other (3)

Inventory of APIs on the European market together with important ecotox, phys/chem and consumption data (D1.1.1)

All known APIs in use in Europe have been entered into the PREMIER database in collaboration with WP3.1. Additionally, data on name(s), CAS-No, IUPAC International Chemical Identifier (InChI), ATC classification, therapeutic plasma concentration, defined daily doses, usage, therapeutic MoA, physico-chemical properties and ecotoxicity, as far as available at this point in time, have been added to the PREMIER database.

PREMIER ERA database architecture agreed and established (D3.1.1)

An initial structure of the database will be agreed between partners to capture APIs authorised for use in Europe and facilitate the upload of existing environmental data.

Integration of existing GLP study data from industry partners and EPAR data (D3.1.3)

Existing GLP study data from industry partners and EPAR data from the EMA website will be uploaded using agreed templates and used to populate the PREMIER database. The templates will be designed specifically for each study so that they enable summary reports to be generated that meet the need of the wider stakeholder community.

Publications

Peer reviewed articles (11)

GREENER Pharmaceuticals for More Sustainable Healthcare

Auteurs: Caroline T. A. Moermond, Neele Puhlmann, A. Ross Brown, Stewart F. Owen, Jim Ryan, Jason Snape, Bastiaan J. Venhuis, and Klaus Kümmerer
Publié dans: Environmental Science and Technology Letters, Numéro 23288930, 2022, ISSN 2328-8930
Éditeur: ACS (American Chemical Society) Publications
DOI: 10.1021/acs.estlett.2c00446

Defining the data gap: what do we know about environmental exposure, hazards and risks of pharmaceuticals in the European aquatic environment?

Auteurs: F.D. Spilsbury, P.A. Inostroza, P. Svedberg, C. Cannata, A.M.J. Ragas, T. Backhaus
Publié dans: Water Research, 2023, Page(s) 121002, ISSN 0043-1354
Éditeur: Elsevier BV
DOI: 10.1016/j.watres.2023.121002

Systematic Handling of Environmental Fate Data for Model Development─Illustrated for the Case of Biodegradation Half-Life Data

Auteurs: Jasmin Hafner, Kathrin Fenner, and Andreas Scheidegger
Publié dans: Environmental Science & Technology Letters, 2023, ISSN 0000-0000
Éditeur: Environmental Science & Technology Letters
DOI: 10.1021/acs.estlett.3c00526

Many human pharmaceuticals are weak inhibitors of the cytochrome P450 system in rainbow trout (Oncorhynchus mykiss) liver S9 fractions

Auteurs: Tea Pihlaja, Timo Oksanen, Netta Vinkvist, Tiina Sikanen
Publié dans: Frontiers in Toxicology, Numéro 6, 2024, ISSN 2673-3080
Éditeur: Frontiers in Toxicology
DOI: 10.3389/ftox.2024.1406942

Prioritisation of data-poor pharmaceuticals for empirical testing and environmental risk assessment

Auteurs: Cristiana Cannata, Thomas Backhaus, Irene Bramke, Maria Caraman, Anna Lombardo, Rhys Whomsley, Caroline T.A. Moermond, Ad M.J. Ragas
Publié dans: Environment International, Numéro 183, 2024, Page(s) 108379, ISSN 0160-4120
Éditeur: Pergamon Press Ltd.
DOI: 10.1016/j.envint.2023.108379

Combining predictive and analytical methods to elucidate pharmaceutical biotransformation in activated sludge

Auteurs: Leo Trostel, Claudia Coll, Kathrin Fenner, and Jasmin Hafner
Publié dans: Environmental Science: Processes & Impacts, 2023, ISSN 0000-0000
Éditeur: Environmental Science: Processes & Impacts
DOI: 10.1039/d3em00161j

Design of greener drugs: aligning parameters in pharmaceutical R&D and drivers for environmental impact

Auteurs: Rodrigo Vidaurre, Irene Bramke, Neele Puhlmann, Stewart F. Owen, Daniela Angst, Caroline Moermond, Bastiaan Venhuis, Anna Lombardo, Klaus Kümmerer, Tiina Sikanen, Jim Ryan, Andreas Häner, Gemma Janer, Silvio Roggo, Alison Nimrod Perkins
Publié dans: Drug Discovery Today, Numéro 29, 2024, Page(s) 104022, ISSN 1359-6446
Éditeur: Elsevier BV
DOI: 10.1016/j.drudis.2024.104022

Minimizing Experimental Testing on Fish for Legacy Pharmaceuticals

Auteurs: Anja Coors, A. Ross Brown, Samual K Maynard, Alison Nimrod Perkins, Stewart Owen, Charles R Tyler
Publié dans: ACS publications, 2023, ISSN 0000-0000
Éditeur: American Chemical Society
DOI: 10.1021/acs.est.2c07222

Designing greener active pharmaceutical ingredients: Insights from pharmaceutical industry into drug discovery and development

Auteurs: Neele Puhlmann, Rodrigo Vidaurre, Klaus Kümmerer
Publié dans: European Journal of Pharmaceutical Sciences, Numéro Volume 192, 1 January 2024, 106614, 2023, ISSN 0928-0987
Éditeur: Elsevier BV
DOI: 10.1016/j.ejps.2023.106614

A Generalized Physiologically Based Kinetic Model for Fish for Environmental Risk Assessment of Pharmaceuticals

Auteurs: Jiaqi Wang, Tom M. Nolte, Stewart F. Owen, Rémy Beaudouin, A. Jan Hendriks, and Ad M.J. Ragas
Publié dans: Environmental Science & Technology, Numéro 0013936X, 2022, ISSN 0013-936X
Éditeur: American Chemical Society
DOI: 10.1021/acs.est.1c08068

The VERA software: Implementation of the acute fish toxicity endpoint and its application to pharmaceutical compounds

Auteurs: Erika Colombo, Edoardo Luca Viganò, Giuseppa Raitano, Anna Lombardo, Alberto Manganaro, Alessio Sommovigo, Emilio Benfenati
Publié dans: Chemosphere, Numéro 358, 2024, Page(s) 142232, ISSN 0045-6535
Éditeur: Pergamon Press Ltd.
DOI: 10.1016/j.chemosphere.2024.142232

Other (1)

Factors Determining the Susceptibility of Fish to Effects of Human Pharmaceuticals

Auteurs: Chrisna Matthee, Andrew Ross Brown, Anke Lange, and Charles R. Tyler
Publié dans: Environmental Science & Technology, 2023
Éditeur: ACS Publications
DOI: 10.1021/acs.est.2c09576