Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - iConsensus (Integrated control and sensing platform for biopharmaceutical cultivation process high-throughput development and production)

Teaser

1. What is the problem/issue being addressed?Biopharmaceuticals are large molecules, most often proteins, used for therapy, e.g. antibodies. In contrast to small molecule drugs generated by organic synthesis, the biopharmaceuticals are produced using cells in well-regulated...

Summary

1. What is the problem/issue being addressed?
Biopharmaceuticals are large molecules, most often proteins, used for therapy, e.g. antibodies. In contrast to small molecule drugs generated by organic synthesis, the biopharmaceuticals are produced using cells in well-regulated processes (\'bioprocess\') in bioreactor.

Today health technology is highly profitable but spending the highest percentage of its revenues on R&D. The development of a new drug costs about 1 billion dollars and takes ≥ 10 years. Reducing cost and time for the development of the manufacturing process represent very large savings and is essential to be first to market.

The worldwide community of bioprocessing is in quest for more rational tools to understand, predict and optimize the industrial biopharmaceutical manufacturing processes under development. To ensure the patient safety, these drug proteins are produced under very strict rules by the manufacturers and closely monitored by the Health Authorities.

2. Why is it important for society?
iConsensus aims to bring a disruptive new technology platform in mammalian-cell based production of biopharmaceuticals. It can be expected to reduce the time and costs for the process development and lead to a better manufacturing control. This improvement influences the time-to-market. Adding on for the biopharmaceutical European industry competiveness advantage, higher consistency, efficacy and robustness will be achieved. All these factors will generate reduced cost, failure and risk for product shortage.

The project clearly supports European Innovation, competiveness and industrial leadership while giving tools to improve the European well-being and societal challenges.

3. What are the overall objectives?
A cell culture used for the production of a biopharmaceutical is a complex mixture of components. Monitoring all the medium components (≥ 70) could provide a better knowledge of the process however it is a very large task. All these components can have an effect on the process performance, the purification process or on the product quality, which is the reason why monitoring all these compounds is advantageous.

To address the issues listed above, iConsensus will provide innovative analytical, hardware, software and high-throughput (HTP) solutions for the development, monitoring and control of mammalian cell cultivation process producing biopharmaceuticals. iConsensus will develop an analytical platform with on-line/at-line sensors and detection methods measuring multiple factors in the cell culture and the produced therapeutic protein with monoclonal antibody taken as one of the models. Under advanced data management, the analytical platform will be integrated in new micro-bioreactors for HTP screening on one hand and in classical stirred tank vessel bioreactors on the other hand. Based on the analytical information, feedback control will be applied. Implementation in GMP production of the sensing and control tools will be a major goal.

Work performed

High-throughput microbioreactors (MBR)
In iConsensus, novel microbioreactors for mammalian cell culture development are created. During the first reporting period, the work within WP 2 was focused on defining the user requirement specifications for the microbioreactor system. Designing and characterization of the reactor’s geometry was started.

CE chip platform
This work focuses on developing methods based on capillary electrophoresis (CE) to measure different components in the culture and to transfer these methods into miniaturization into chip format. During this first year the work within WP3 has been focused on establishment of Analytical Target Profiles, development of CE methods for amino acids and sugars, transfer of CE methods from conventional CE instruments to CE chip setups.

Optical on-line sensors
Several sensors based on optical properties are used or created in the project. User requirement specifications for the different sensor elements were drafted. pH, oxygen and CO2 sensors in various form factors were integrated into different bioreactors of the partners.

Spectrometry and chemometry support
Ideally, the information of components in the culture could be provided by on-line probes immersed in the bioreactor. For this, probes based on different physical principles have been suggested such as Raman, infrared or fluorescence. These probes provide a spectral information, which has to be deciphered by chemometric approaches. A spectral database was created with spectra from the EFPIA members, preliminary general trends about the prediction quality were assessed and data transformation was developed to encounter for different probe used.

Holographic methods
Iprasense has developed a new concept for the quantification of the cell concentration based on holographic image. The evaluation of holographic imaging technology supplied by Iprasense was carried out at GSK. The results obtained in comparing holographic imaging and the commercial instrument Vicell as reference indicate very close correlation (<10% error) with multiple processes.

Affinity-based microfluidics
The purpose of this work is develop new methods in lab-on-a-chip format. The team of Russom at KTH have developed a multiplexed bead-based microfluidic device to perform four immunoassays targeting four different analytes on a single sample. Sandwich immunoassay or competitive immunoassay formats were evaluated and a very low limit of detection could be achieved.

Analysis of glycosylation
PAIABio has developed a technology based on interaction with lectin, molecules with high affinity to glycans. GSK evaluated the glycan assay from PAIABio on three assets with multiple samples. Optimal denaturation conditions were identified to improve the detection method for two of the three assets.

Total integration and data management, MID
In iConsensus, an integrated analytical system is created, \'At-line integrated analytical system\' or \'ALIAS\'. The focus of WP7 for the first year was the determination of the architecture and functionalities of the integrated system of iConsensus together with the set up of the monitoring information database (MID). The decision for the functionalities of ALIAS and the MID were realized.

Final results

iConsensus aims at developing a new platform for real time analysis of the components.
Nowadays, the development of cultivation processes uses empirical methods supported by statistics, and high-throughput, where only very few parameters are easily quantified, leading to suboptimal outcome. When more efforts are put on the analytical technology, this requires enormous resources and time. To address this, iConsensus brings solutions by far pioneer, with no equivalent product today, with real-time solutions and advanced MBR. Besides the importance of the use of innovative tools in development it is also crucial to have reliable, fast and qualified analytical tools for commercial manufacturing processes. Data and knowledge gained during development should be usable in a straight line in the final manufacturing process. The possibility to use the same analytical tools throughout the development and life cycle management of a process/product will be highly beneficial for the control and robustness of the final manufacturing process (Process Analytical tools, Design Space).
The impacts are given above in Section 2. Why is it important for society?

Website & more info

More info: https://www.iconsensus.eu.