A fully integrated, animal-free, end-to-end modelling approach to oral drug product development

Project Information

InPharma

Grant agreement ID: 955756

DOI

10.3030/955756

Project closed

EC signature date 7 September 2020

Start date 1 January 2021

End date 31 December 2024

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 3 464 964,00

EU contribution

€ 3 464 964,00

Coordinated by

UNIVERSITY COLLEGE CORK - NATIONAL UNIVERSITY OF IRELAND, CORK
Ireland

Periodic Reporting for period 2 - InPharma (A fully integrated, animal-free, end-to-end modelling approach to oral drug product development)

Reporting period: 2023-01-01 to 2024-12-31

Summary of the context and overall objectives of the project

Oral medicines are preferred by patients worldwide due to ease of self-administration and overall higher patient compliance. Yet, the challenges around formulating molecules into medicines for oral administration have increased substantially over the last 30 years, mainly because most drugs coming through the drug discovery pipeline are too poorly soluble to be dissolved and efficiently absorbed from the gastrointestinal tract. Furthermore, due to the considerable challenges in formulating poorly soluble drugs for oral delivery, the number of animals used to screen oral absorption of formulation prototypes is increasing, despite the EU’s commitment to reducing animals in research.
In order to ensure a rich pipeline of new oral medicines for European patients and to avoid unnecessary animal testing in oral drug product development, a quantum leap is needed in identifying the optimal formulation design for a new drug candidate. The InPharma consortium aims to solve these important challenges through pioneering research focused on advancing an integrated, end-to-end, animal-free approach to formulating poorly soluble drugs for oral administration.
InPharma is the first European Industrial Doctorate (EID) that aims to eliminate animals from the development of oral drug formulations. The InPharma consortium brings together leading pharmaceutical scientists from six multi-national pharmaceutical companies, five world-class research institutions and eight partner organisations, from complementary technology and service providers (SMEs) to additional pharma and regulatory representatives to create a research network involving nine European countries.
The main research objectives in InPharma are to develop a fully integrated, end-to-end model-based approach to oral drug development, linking ‘big data’ available from drug profiling repositories with computational tools to predict oral formulation design, generating innovative physiologically relevant in vitro tools and adapting computational models to predict drug absorption from ‘enabling’ oral drug formulations in clinically relevant scenarios.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Thirteen Early Stage Researchers (ESRs) were recruited into the InPharma European Industrial Doctorate network to undertake industrially based PhD programmes. These programmes are broadly focused on developing a fully integrated, animal-free, end-to-end modelling approach to oral drug product development. Each ESR completed a unique intersectoral training plan, gaining experience in both industry and academia. As of March 2025, six ESRs have successfully been awarded PhDs, while the remaining seven are on track to submit their PhD theses in 2025. All ESRs received training in computational formulation design, bio-predictive in vitro testing, and physiologically based pharmacokinetic modelling, with specific training tailored to the individual needs of each ESR project. Additionally, all ESRs underwent a transferable skills training programme to build proficiency in essential research and industry disciplines, including professional skills and entrepreneurship, inspiring them to become trailblazers in industrial drug product development.

This research strategy is reflected in two research work packages (WPs), with key achievements in the project summarized as follows:

WP1 is dedicated to advancing computational tools for developing oral drug formulations. The two primary research objectives are: (1) Investigating novel mechanistic and data-driven algorithms to support the formulation design of poorly soluble drugs, and (2) Using these algorithms to select drug-excipient mixtures for optimal excipient selection for a given drug. Collectively, ESR research in WP1 has led to significant formulation innovations, enabled by diverse computational approaches. These achievements span multiple formulation platform technologies, including co-crystals (ESR1), solid dispersions (ESR6), deep eutectic solvents (ESR5), co-milling (ESR3), and lipid-based formulations (ESR2, ESR4). Various formulations have been thoroughly characterized on a physicochemical basis, successfully linking with WP2 for further biopharmaceutical analysis, including in vitro testing and physiologically based pharmacokinetic modelling.

WP2 focuses on developing animal-free assessment methods for predicting formulation performance in patients. This is achieved by developing in vitro methodologies that are bio-predictive of enabling formulations under clinically relevant conditions, as well as developing in silico models for predicting drug concentration profiles in patients after oral administration. Highlights of WP2 include progress in establishing the animal-free ‘rDCS approach’ to predicting formulation strategy (ESR7), novel in vitro methods for evaluating bio-enabled formulations (ESR8, ESR9, ESR11, ESR12 & ESR13), and advancing in silico approaches to replace allometric scaling from animal studies with virtual trials (ESR8, ESR10, ESR11 & ESR12).

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

To date, InPharma has published 30 peer-reviewed publications, with over 10 additional publications currently in draft. To maximize the impact of InPharma-related research, the consortium has arranged for a special 'InPharma' themed issue in the prestigius 'European Journal of Pharmaceutical Sciences' (Elsevier). This special issue remained open to collect scientific papers throughout the project's duration and has so far included 16 publications from InPharma.

The results achieved in InPharma have advanced innovation in computational pharmaceutics tools and established animal-free approaches for predicting oral formulation performance in patients. All ESRs have been actively involved in outreach, dissemination, and management activities. The network activities promoted the transfer of knowledge between academia and industry which will, in the medium to long term, significantly strengthen the advanced pharmaceutical development research in Europe

Collectively, the new technologies and tools developed by InPharma will support the pharmaceutical industry's need to accelerate 'molecule to market' timelines for oral medicines. The outcomes from InPharma also align with societal obligations to reduce animal testing in drug development. Ultimately, a key impact of InPharma will be the more efficient formulation design of oral medicines, faster market access timelines for new medicines with lower overall costs and fewer ethical challenges associated with animal testing.

The InPharma network at the third annual meeting held at the University of Southern Denmark in 2024

InPharma vision and project aims