VACCINE MANUFACTURING: FASTER, MORE EFFICIENT & FLEXIBLE

A new generation of vaccine manufacturing is rising

We offer an interdisciplinary, proactive, user-centered and holistic approach for pharmaceutical manufacturing engineering. We apply state of the art automation and robotics, with a focus on service and competence, while redesigning pharmaceutical processes. Our goal is to have a deep understanding of our client’s processes and supply chains in order to enable the next generation pharmaceutical production facility.

With inactivated vaccines, the pathogen must be rendered non-infectious without changing the antigen structure. The most common approach to date is the inactivation through toxic chemicals. KyooBe is using, in a new and innovative approach, electron beams for pathogen inactivation instead. This increases time-efficiency, quality, and reproducibility of vaccine manufacturing.

The approach

Inactivation by low energy electron irradiation

With inactivated vaccines, the pathogen must be rendered non-infectious without changing the antigen structure. The most common approach to date is inactivation through toxic chemicals. However, the Fraunhofer Research Institute is using, in a new and innovative approach, electron beams instead. This increases time-efficiency and reproducibility.

We inactivate the pathogens through low-energy-electron irradiation (LEEI) to damage the nucleic acid inside the pathogen and to keep the surface/antigen structure of the pathogens as intact as possible.

Here, LEEI is presented as an alternative inactivation method for pathogens in liquids. We show that LEEI efficiently inactivates different bacteria, eukaryotic parasites, as well as viruses, and maintains their antigenicity.

Based upon a unique combination of expertise from immunology and engineering a robust, safe, and scalable technical solution was developed to establish LEEI as a promising alternative for vaccine manufacturing.

As irradiation technology, LEEI outlines a strong dose-absorbance dependency. The patented liquid role module guarantees optimal dose impact on irradiated pathogenes for vaccine formulation.

The advantages & benefits

Faster, more efficient and flexible

Pathogens are commonly inactivated using chemicals such as formaldehyde or Beta-Propiolacton. This is time-consuming and creates toxic waste. The chemicals also damage structural integrity of the antigenic proteins in turn leading to lower levels of immunity in patients.

The weaknesses of chemical inactivation are compensated for by repeated booster vaccinations, increased amounts of infectious starting material, and efficacy enhancers, such as adjuvants.

This results in enormous costs and the social acceptance of many vaccines can be severely hampered by the fear of side effects. In addition, because of the limitations of formaldehyde inactivation processes against various pathogens, no vaccines have been developed for certain infections.

With LEEI the inactivation of the pathogens can be realized faster and without toxic substances while preserving the antigenic surfaces.

Eye-catching illustration of the LEEI technology platform by Fraunhofer IZI scientist Lea Bayer from Thomas Grunwald’s Lab.

At a glance: comparison of the disadvantages of chemical processes with the advantages of LEEI

The technology

The patented technology in detail

The system consists of two parts: the liquid-coated rolling system and the irradiation chamber.
A maximum of 0.15 mm thin liquid film with a pathogen solution is created using the patented roll-system.
This liquid roll-system is pushed into the irradiation chamber.
The liquid film is irradiated with low energy electrons inside the chamber.
The inactivated liquid is drawn off at the end of the roll.

The components

Irradiation chamber
Low energy electron irradiation source
Liquid roll-system
Rotating roll
Thin liquid film
Squeegee
Peristaltic pump
Pathogens solution
Inactivated solution

The benefits of the technology

continuous system
cooled process
safety sensors in place
applicable to different pathogens e.g. viruses, bacteria

Check out INACTIVATE’s product data sheet here

Next generation of pharmaceutical manufacturing technologies | KyooBe Tech GmbH

The research prototype

The 300 keV irradiation chamber “ELLI 300” – assembled at Fraunhofer IZI‘s BSL-2 lab – already enables the automated process in a prototype and research assembly.

The development of the automated process module makes this technology easily scalable and ready for use in the pharmaceutical industry. Larger quantities of liquid can be treated, and the safe handling of biologically active liquids complies with industry-requirements.

The LEEI can be used in non-GLP laboratories, good manufacturing practice (GMP)- or high biosafety level (BSL)-environments, as only minor shielding is necessary.

The application of the technology is not limited to the field of vaccine production; Sterilization of biologicals or other liquid biological materials is also possible.

Part 1: Liquid roll-system

Production of an ultra-thin liquid film
Continuous system and production
Safety sensors in place
Cooled Process

Part 2: Irradiation chamber

Minimal shielding required
Usable in non-GMP and GMP environment
Suitable for integration into biological production processes
Exact irradiation conditions

Picture of the irradiation chamber, Fraunhofer IZI

The creation of a very thin liquid film is one of the technical challenges, but more importantly, it opens a completely new business field.

In addition, the corresponding radiation doses must be determined for each type of pathogen.

In order to transform LEEI into a process for industrial-scale vaccine manufacturing, developments of such solutions for a multi-liter-scale LEEI-based inactivation procedure are currently ongoing.

The scientists are offering the opportunity to use this new technology in various areas of biotechnology, pharmaceutical manufacturing, and research in conjunction with its partners.

Downsizing the machine

For use in industrial vaccine production plant dimensions will shrink to the size of a refrigerator. The continuous module can currently produce four litres of vaccine per hour.

However, it will take at least another two to four years before the first vaccines produced with electron beams enter the clinical trials.

Studies on pathogens

Irradiation experiments to determine the dose required for inactivation

Irradiation experiments were conducted to determine the doses required for the inactivation of various pathogens.

Furthermore, it was examined whether the surface structure of the inactivated pathogens remained intact.

To determine the antigen conservation after inactivation, treated and untreated pathogens were immobilized on plates and ELISA experiments using a polyclonal serum from previously infected mice were performed.

The procedure for a new vaccine processing is as follows:

First, the irradiation dose for the inactivation of the pathogen is determined. Then the pathogen-containing liquid is implemented on the machine. In the last step, the process is optimized and the exact setting for the automated process is made.

An overview of existing developments were presented at DCVNM Conference: More, pdf

More data coming soon.

Publications

Research by the Fraunhofer Institutes
Four Fraunhofer institutes bundle their expertises : The IZI provided proof of concept, which means that it demonstrated that the process worked as desired. The researchers at the IZI also carried out vaccination studies. The colleagues at the IGB demonstrated that their nucleic acids were destroyed after the radiation and that the germs were rendered harmless. The FEP contributed to the radiation technology and participated in the construction of the prototype, which is located at the IZI in Leipzig. The IPA brought expertise in automation and focused on the requirements of the pharmaceutical manufacturers.

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