Automatisering/ robotisering av antistoffproduksjon

The project aim is to use robotics together with artificial intelligence for the production of antibodies in order to improve the working conditions, avoid contamination, and to ensure the highest possible quality of each production volume. Antibodies are large molecules that are produced naturally by the cells in our immune system. In the health industry, antibodies are used, among other things, for medicines and in vaccines. Industrial production of antibodies in laboratories still takes place in cells, and it is important to ensure that the cells environment is well maintained. The cells are grown in bottles called bioreactors. To thrive, the cells need nutrients (medium), the right temperature, and the right amounts of O2 and CO2. The cells must be fed and "replaced" regularly, by "replaced" it is meant that the medium is eventually filled with waste products and must be replaced. The bottles look like rectangular drinking bottles, and are divided into two chambers, where antibodies are collected in one chamber and can be harvested, and the medium with waste substances is collected in the other chamber and can be changed and refilled. When the cells thrive, they will produce good amounts of antibody. When living cells are used to make antibodies, it is called biological production. Biological production is a very complicated production method and requires a lot of the operators who do the actual production work. In order to relieve our operators, we want software and robots to take over parts of the work tasks, such as feeding and shifting, harvesting of antibodies, and parts of the large amount of measurements and logging that is a requirement from the authorities when working with diagnostics or medicines. Antibody production also takes place in clean rooms, where the requirements for hygiene are extremely strict. Our biggest source of contamination is actually the people who stay inside the clean room. In cases where large amounts of antibody would be needed in a short time, for example in the event of an urgent need for vaccines or medicines, robots can work around the clock, every day and thus ensure that the need is met without creating extreme working conditions for the employees. The work in 2021 has included the following focus areas: Development of new automated sensor technology The development of real time sensors was continued with the aim of measuring the glucose concentration in the harvest fluid. It turned out that the preliminary results from MEDPROT could not be reproduced with samples from different cell lines due to variation in other media components. It has therefore been decided to test other sensor options. Furthermore, the project has tested camera technology to measure pH changes in the media and turbidity. In the sub-project for software integration and data capture from the process, the various workstations needed to automate the processes with CL1000 flasks have been established. Furthermore, a lot of work has been done around developing new process diagrams, as the automation using robots provides completely new possibilities and solutions. In the sub-project for the setup of pilot plants, experiments have been initiated to optimize the harvesting process. Experiment is performed to assess the impact of skipping the centrifuge step, the need for external medium heating and the effect of a non-humid environment. The first setup of the room where the process will take place (AUTOBOT) is made to determine the size of the robot arm and the location of racks, refrigerators, stations and analysis equipment inside the controlled space. For the CL1000 flask handling it has been decided to use a Universal robot. We are now working with design solutions in collaboration with several external actors.

Produksjon av antistoff-baserte medisiner utføres i dag i renrom, hvor mennesker håndterer produksjonsprosessen. Her utgjør mennesket den største risikofaktoren, både fordi man bringer med seg mulig forurensning, og fordi man kan gjøre manuelle feil. Dette stiller store krav til hygiene, er tidkrevende og gir utfordringer på kvalitet, pris og arbeidsmiljø. Manuelle prosesser kan gi uønsket variasjon i sluttprodukt samtidig som det stilles stadig økende krav til kvalitetskontroll. Vi vil utvikle teknologi som kan benyttes til småskala produksjon i celledyrkningsflasker og i større bioreaktorer. Helt konkret vil vi sette opp et nytt, fullt ut automatisert og robotisert pilotanlegg, for småskala produksjon i celledyrkningsflasker (CL1000). I pilotanlegget med mange parallelle produksjoner vil det være minimalt behov for inngripen av operatører. Prosjektet vil bli utført i samarbeid med partnere som har ekspertise innen prosess-sensorteknologi, automatisering og robotisering, deriblant SINTEF Manufacturing. Prosjektet vil være et strategisk veivalg for bedriften hvor vi vil initiere oppbygging av biofarmasøytisk produksjon i Norge med fremtidsrettede nye metoder. Dette vil gi grunnlag for økt konkurransedyktighet ved salg av biofarmasøytiske produkter og tjenester i et internasjonalt marked, og kan bidra til mange fremtidige arbeidsplasser. Kortfattet har vi som mål å oppnå sikrere og mer effektiv produksjonsprosess og bedre dokumentasjon, redusert sannsynlighet for kontaminering, redusert sannsynlighet for menneskelige feil og forsinkelser i produksjon, forbedret arbeidsmiljø, kostnadsbesparelser og bedre konkurransedyktighet.