Side‐by‐side comparability of batch and continuous downstream for the production of monoclonal antibodies

Abstract

Continuous processing is the future production method for monoclonal antibodies (mAbs). A fully continuous, fully automated downstream process based on disposable equipment was developed and implemented inside the MoBiDiK pilot plant. However, a study evaluating the comparability between batch and continuous processing based on product quality attributes was not conducted before. The work presented fills this gap comparing both process modes experimentally by purifying the same harvest material (side‐by‐side comparability). Samples were drawn at different time points and positions in the process for batch and continuous mode. Product quality attributes, product‐related impurities, as well as process‐related impurities were determined. The resulting polished material was processed to drug substance and further evaluated regarding storage stability and degradation behavior. The in‐process control data from the continuous process showed the high degree of accuracy in providing relevant process parameters such as pH, conductivity, and protein concentration during the entire process duration. Minor differences between batch and continuous samples are expected as different processing conditions are unavoidable due to the different nature of batch and continuous processing. All tests revealed no significant differences in the intermediates and comparability in the drug substance between the samples of both process modes. The stability study of the final product also showed no differences in the stability profile during storage and forced degradation. Finally, online data analysis is presented as a powerful tool for online‐monitoring of chromatography columns during continuous processing.

Analysis of filtration behavior using integrated column chromatography followed by virus filtration

“…As protein was pushed out from the column by the equilibration buffer wash (50 ml), the protein concentration decreased and the filtration pressure also gradually decreased. For the total collected volume of (David et al, 2020) achieved HCP reduction from about 100 ppm to about 10 ppm with HCP LRV around 1. The load capacity on the CEX column was 22 mg/ml-resin and that of the AEX membrane was less than 470 mg/ml-membrane with a flow rate of 0.5 membrane-volume/min.…”

The Emergency Response Capacity of Plant-Based Biopharmaceutical Manufacturing-What It Is and What It Could Be

“…Although infiltration is typically a discontinuous process requiring stainless-steel equipment due to the vacuum that must be applied to plants submerged in the bacterial suspension, most other steps in the production of PMPs can be designed for continuous operation, incorporating single-use equipment and thus complying with the proposed concept for biofacilities of the future (Klutz et al, 2015). Accordingly, continuous harvesting and extraction can be carried out using appropriate equipment such as screw presses (Buyel and Fischer, 2015), whereas continuous filtration and chromatography can take advantage of the same equipment successfully used with microbial and mammalian cell cultures (David et al, 2020). Therefore, plant-based production platforms can benefit from the same >4-fold increase in space-time yield (e.g., measured in g L −1 d −1 or g m −2 d −1 ) that can be achieved by continuous processing with conventional cell-based systems (Arnold et al, 2019).…”

Pilot‐scale demonstration of an end‐to‐end integrated and continuous biomanufacturing process

“…Several significant advances in enabling technologies for integrated and continuous bioprocessing (ICB) have been reported in the last few years (Farid, 2019; Godawat et al, 2012; Jungbauer, 2019; Mothes et al, 2016; Orozco et al, 2017; Pollock et al, 2013; Rucker‐Pezzini et al, 2018). In particular, the integration of a production bioreactor with one or more continuous chromatography steps and low pH virus inactivation has reached a stage of technical maturity that several companies are moving to clinical and commercial manufacturing with these hybrid ICB systems (Brower et al, 2019; David et al, 2020; Hewig, 2019; Orozco et al, 2019; Otes et al, 2020; Shields, 2019; Shultz, 2019). This transition has been supported by several economic analyses that demonstrated the value of a hybrid continuous process (Pollock et al, 2017; Walther et al, 2015).…”