STERILITY

One of the major quality comparative characteristics of different bioreactors is the ability to secure sterile fermentations. These requirements are determined to a great extent by the bioreactor's construction and the surface treatment quality. All the further regarded non-sterility risk factors are mainly connected with securing of hermetic sealing at different stages of the process and surface treatment quality. The most characteristic possible non-sterility risk factors from the viewpoint of the construction are as follows:

1. Mixer's stuffing-boxes, sealing of the sensors' and other devices' inserting ports

   One of the most typical pathways of penetrating infectious diseases is the mixer's stuffing-boxes. It is not always easy to secure the effective sealing and unhindered rotation of the drive. Apart from this, the regular servicing of the driver's stuffing-box should be secured to avoid the accumulation of infection there. To prevent the stuffing-box connected problems, bioreactor drives are constructed on the principle of magnetic drives. In this case, the torque is transferred with the help of the magnetic field. As a result, the bioreactor vessel can be fully sealed.

   As regards the sensors and other devices (supply of the titrated and feeded up components, sampling, chemostate realisation, etc.), port sealing should be taken into account, so that the ports could be sealed with the force of the operator's hand, and so that the sealing properties would not change as a result of the sterilisation temperature.

2. "Pockets", unevennesses and other bottle-necks for the accumulation of infection inside the bioreactor vessel.

   Inside the bioreactor, infection can be accumulated in places of irregularities and unevennesses. In such places, infectious microorganisms can "hide themselves". Therefore, the bottom inside the reactor should be rounded off, there should not be acute angles, and the surfaces should be polished.

3. "Unreasoned" sampling, procedure and construction

   When sampling, the emergence of steam or flame and other conditions should be predicted, so that, after the termination of the sample spurt, the infection "would not manage" to get into the fermentation solution.

4. Filtration of the inlet and outlet air flows.

   Air should be supplied into the bioreactor through the corresponding porosity air filter so that to hold up the possible infection source. The inlet air flow can be also passed through the pipes, which are being heated. Thereby, by the thermal action, an attempt is made to combat the possible infection at least partially.

5. Maintenance of overpressure.

   It is important to maintain the overpressure (0.2-0.5 bar) in the bioreactor's upper space (i.e. between the fermentation solution and the bioreactor jacket) to ensure the protection against the income of infection. The infection income through the outlet air line is hampered by using the outlet air filter.

6. Even and effective heat transfer.

   It is necessary to secure the sterilisation temperature, where possible, by the even energy consumption, and heating would be even. If the heating inside the bioreactor is not even, there can be a risk that there will be zones inside the vessel with insufficient sterilisation temperature.

Apart from this, during the sterilisation process, the sensors, devices, connections and other units should not loose their properties. It means that only sterilisable sensors (i.e. those which do not change their properties after the effect of sterilisation) and rubber or other materials, whose working temperature does not exceed 150°C should be used in sealing.