US 12,448,659 B2
Method in bioprocess purification system
Key Hyckenberg, Uppsala (SE); Helena Skoglar, Uppsala (SE); Gunnar Malmquist, Uppsala (SE); Mikael Carlsten, Uppsala (SE); Roger Lundqvist, Uppsala (SE); Dan Andersson, Uppsala (SE); Linda Mathiasson, Uppsala (SE); Lars Mattsson, Uppsala (SE); Sara Sendabo, Uppsala (SE); and Mikael Berg, Uppsala (SE)
Assigned to Cytiva Sweden AB, Uppsala (SE)
Appl. No. 17/253,067
Filed by Cytiva Sweden AB, Uppsala (SE)
PCT Filed Jul. 1, 2019, PCT No. PCT/EP2019/067643
§ 371(c)(1), (2) Date Dec. 16, 2020,
PCT Pub. No. WO2020/002713, PCT Pub. Date Jan. 2, 2020.
Claims priority of application No. 1810772 (GB), filed on Jun. 29, 2018.
Prior Publication US 2021/0269888 A1, Sep. 2, 2021
Int. Cl. C12Q 3/00 (2006.01); C12M 1/00 (2006.01); C12M 1/34 (2006.01); C12M 1/36 (2006.01)
CPC C12Q 3/00 (2013.01) [C12M 29/10 (2013.01); C12M 41/12 (2013.01); C12M 41/42 (2013.01); C12M 41/48 (2013.01); C12M 47/12 (2013.01)] 6 Claims
 
1. A method for controlling a bioprocess purification system comprising a continuous cell culture process in a bioreactor comprising cells capable of expressing a target product and a downstream purification process arranged downstream the continuous cell culture process and being configured for purification of harvest fluid from the continuous cell culture process to purify the target product from said harvest fluid, the method comprising:
a) withdrawing harvest fluid from the continuous cell culture process;
b) at least partly purifying the target product from the harvest fluid in the downstream purification process;
c) detecting at least one quality attribute indicative of characteristics of the at least partly purified target product;
d) identifying correlations between the at least one quality attribute measured in the downstream purification process and parameters to control the continuous cell culture process in the bioreactor; and
e) controlling the continuous cell culture process to meet desired characteristics based on the identified correlations; whereby the target characteristics are within a pre-determined range; and wherein the downstream purification process comprises:
i) a hold step comprising collecting a pre-determined volume or a pre-determined mass of the target product from the harvest fluid, whereby step ii) below starts when the pre-determined volume value is reached, or when the pre-determined mass is reached;
ii) a capture step comprising a continuous chromatography process or a semi-continuous chromatography process;
iii) a viral inactivation step comprising performing batch mode chromatography to filter the target product based on volume, time, temperature, and pH;
iv) a polishing step comprising a straight through processing (STP) with a connected batch step or continuous chromatography with a continuous load step, or a combination thereof; and
v) a delivery step comprising for subjecting the target product to an ultra-filtration step, prior to continuous or batch delivery of the target product, to further filter the target product based on pH, conductivity, absorbance, volume, and pressure.