Biointelligent Production Sensor to Measure Viral Activity

Project Information

BioProS

Grant agreement ID: 101070120

DOI

10.3030/101070120

EC signature date 23 June 2022

Start date 1 July 2022

End date 30 June 2026

Funded under

• Digital, Industry and Space

Total cost

€ 6 317 693,50

EU contribution

€ 6 317 693,50

Coordinated by

FRAUNHOFER GESELLSCHAFT ZUR FORDERUNG DER ANGEWANDTEN FORSCHUNG EV
Germany

Periodic Reporting for period 2 - BioProS (Biointelligent Production Sensor to Measure Viral Activity)

Reporting period: 2024-01-01 to 2025-06-30

Summary of the context and overall objectives of the project

Healthcare systems worldwide are facing increasing cost pressures due to the influx of new therapeutic modalities. In contrast to traditional treatments such as small molecules or protein-based biomolecules, next-generation therapeutics include a variety of biological molecules ranging from viruses to genetically modified eukaryotic cells. This increase poses major challenges for the development of sustainable and resilient production processes. Viruses have long been used for the production of vaccines, but their importance is increasing in various biopharmaceutical sectors. However, the production of viruses and virus-like particles for clinical use requires complicated, multi-stage processes with strict safety requirements. The production of viral vectors is still prone to errors and there is insufficient capacity to meet commercial demand. To overcome these challenges, decentralised and flexible production units with streamlined quality control mechanisms are essential.
Our goal is to revolutionise virus bioproduction and quality control with a continuous real-time biohybrid sensor technology. The BioProS sensor concept combines optical sensor technology with cell-based measurement principles and uses biofunctionalised sensor surfaces for the specific detection of analytes. This platform technology can be adapted to different analytes, which promotes its usefulness in different industries and production environments. Such technological advances require pan-European and interdisciplinary collaboration between stakeholders to promote the development of biointelligent systems. This paradigm shift, recognised worldwide as a strategic area, offers enormous opportunities for innovation. The BioProS sensor is an example of European manufacturing excellence and demonstrates the integration of technical, informational and biological components - a concept known as biointelligence. Furthermore, this approach meets the emerging requirements for flexible and sustainable manufacturing, especially for small and decentralised processes.

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

The BioProS project aims to achieve the following objectives:
1. Develop a bio-intelligent sensor platform using living cells for multiparametric analyses.
2. Create a miniaturized detection platform measuring virus particle activity in almost real-time.
3. Establish new manufacturing concepts, supply chain, and validation methods for bio-intelligent systems.
4. Develop technology implementation concepts for end-user production sites, enabling rapid adoption in various industries and regulatory approval.
5. Apply AI and digital twin concepts for online quality control and predictive process control.
6. Assess technology life cycle and sustainability impact.

The project is organized into four interconnected action lines:
1. Create a cell-based sensing mechanism for measuring viral activity.
2. Develop sensor hardware and manufacturing processes.
3. Incorporate digital aspects, including AI and digital twins.
4. Address sustainability aspects and perform ecological impact assessments.

Efficiency in implementing action line 1 is maximized by developing components independently and integrating them at a higher technical level with solutions from action line 2. This workflow provides early sensor data for action line 3. Action line 4 focuses on developing sustainable bio-intelligent technologies and conducting ecological impact assessments.

The biosensor development consists of two parts:
Part I involves an automated evaluation platform for handling cell-based biosensors. This platform establishes the measurement principle for viral infectivity and conducts multiparametric analyses, enabling faster process development. The generic design allows its use for other bio-integrated sensor technologies.
The biosensor chip in Part II detects a broad range of virus infection events throughout the production process. Manufactured via 3D bioprinting, the chip is sensitive at each timestamp, considering parameters from the evaluation platform in Part I.

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)

The implementation of our sensor system in biomanufacturing processes, especially for personalized therapies like cell and gene therapies, addresses the challenge of extensive testing, a bottleneck in efficient process control. As personalized therapies increase, our sensor system is crucial for faster product release, improved process flows, and reduced testing efforts. This not only accelerates the production process but also meets the high demand for viral vector production. The benefits include enhanced yield, improved batch quality, and reduced production costs, ultimately making therapies more affordable.
The use of biological elements in manufacturing aligns with sustainability goals. Biosensing principles enhance manufacturing processes, ensuring higher product quality at reasonable costs. The biointelligent sensor concept aids in critical decisions, prevents bioprocess failures, and mitigates financial losses.
Enabling decentralized production settings and reducing manufacturing costs increases production capacity, strengthening the pharmaceutical and biotech industries in Europe. This is particularly important as the European cell and gene therapy landscape, dominated by SMEs, seeks independence from international supply chains. Direct supply of viral vectors accelerates clinical phases, shortening the time to market for new therapeutics.
Investing early in key enabling technologies supports Europe's open strategic autonomy by maintaining first-mover advantages. Bio-intelligent manufacturing ensures accessibility to diverse therapeutics, keeping healthcare costs affordable.
Global competition and sustainability requirements drive the evolution of European manufacturing. Traditional industries must adapt to avoid environmental damage and societal rejections. Our bio-intelligent manufacturing strategy aligns with the United Nations' Sustainable Development Goals and the EU Green Deal, promoting circular economy, sustainability, and climate neutrality.
This unique approach aims to establish new production ecosystems, transforming industries across Europe. Biological capabilities bring about significant changes in economies and societies. Bio-digital convergence, often linked to healthcare, expands the impact of our sensor platform to various industries. Real-time data collection ensures targeted process control, virus-free end-products, and interoperability with Industry 4.0 standards, making bio-intelligent manufacturing in Europe a broader movement.

Biointelligent Production Sensor to Measure Viral Activity (Source: Fraunhofer IPA)