Method for continuous virus inactivation

Abstract

The invention provides a method for continuous virus inactivation. The product stream is segmented by introducing a separating medium which is immiscible with the product stream and the segmented product stream is transported into a reactor 1 as detention segment under virus-inactivating conditions for the required detention time.

Claims

1. Method for continuous virus inactivation of a product stream that is to be inactivated in a reactor 1 having a low hydraulic diameter of 0.01 mm to 6 mm, preferably optionally 0.5 mm to 3 mm, comprising: a. Provision of the product stream that is to be inactivated, b. Setting the virus-inactivating conditions, c. Introducing a separating medium that is immiscible with the product stream into the product stream to segment it, d. Feed and passage through of the segmented product stream from c) under virus-inactivating conditions in a detention segment formed by the reactor 1, e. Outflow from the detention segment.

2. Method according to claim 1, wherein, in a), the pH of the product stream is set to 4, provided that the pH of the material that is to be inactivated does not already have the required pH.

3. Method according to claim 1, wherein the solution that is to be inactivated is a solution of macromolecules, optionally a protein or peptide solution, optionally an antibody solution.

4. (canceled)

5. Method according to claim 1, wherein, in f), the separating medium is separated off continuously.

Description

[0056] FIG. 1 shows a parabolic flow profile of the tube with laminar throughflow (top: longitudinal section of the tube). Lines of equal velocity in the direction of flow in the tube with laminar throughflow (bottom: cross section of the tube).

[0057] a=Tube wall

[0058] b=Axial direction of the tube in the direction of flow

[0059] c=Radial direction

[0060] d=Lines of equal flow velocity in the direction of flow.

[0061] FIG. 2 shows the principle of segmentation.

[0062] FIG. 3 shows alternative means for pulsed introduction of the separating agent connected to the tubular reactor.

[0063] FIG. 4 shows a flow chart of the virus inactivation with subsequent adaptation of the pH, wherein the device for virus inactivation is shown only schematically.

[0064] FIG. 5 shows a square frame for coiling the reactor tube.

[0065] FIG. 6 shows a plurality of frames mounted on a stand.

EXAMPLE 1

[0066] For the experimental studies, a flexible tube internal diameter of 1.6 mm was selected. The tubular reactor was wound onto frames having the following dimensionsframe diameter of 63 mm; outer edge length of the frame 195 mm. The frame was fabricated in accordance with FIG. 5, and mounted on a stand according to FIG. 6.

[0067] In each case 11 coils having a minimum separation were carried out per arm. The flexible tube length used per frame is in proportion to the frame diameter with the assumption of constant number of coils per arm.

[0068] In this case, the exit of the upper frame was connected to the entry of the frame beneath it in such a manner that the flexible tube coiling of the frame ran from top to bottom. Alternatively, it is also possible for the flow to flow from bottom to top or in the horizontal.

[0069] A volumetric flow rate of around 3 ml/min flowed through the test plant.

[0070] The experiments for detention time measurement in the device for continuous virus inactivation were carried out using a UV measurement at the outlet of the system. The tracer substance used was a vitamin B12 solution having a concentration of 0.25 g/l, since vitamin B12 absorbs UV light at a wavelength of 280 nm and therefore is suitable as an indicator.

[0071] First, the device was purged with distilled water. At time point k, at the inlet of the virus inactivation the system was switched over to the tracer solution and the recording of the measurement signal of the UV sensor was started (consequently a step function of the tracer solution was applied to the system). When the UV signal at the outlet of the system corresponded to the UV signal of the tracer solution, the experiments could be terminated, since the system, from this time point, was completely filled with tracer solution and therefore the response of the system to the step function was completely recorded.

[0072] The work which led to this application was funded under financial aid agreement Bio.NRW: MoBiDiKModular bioproductiondisposable and continuous in the scope of the European Fund for Regional Development (EFRD).