• Corpus ID: 53003706

White Paper on Continuous Bioprocessing

  title={White Paper on Continuous Bioprocessing},
  author={Charles L Cooney and Konstantin B. Konstantinov},
There is a growing interest in realizing the benefits of continuous processing in biologics manufacturing, which is reflected by the significant number of industrial and academic researchers who are actively involved in the development of continuous bioprocessing systems. These efforts are further encouraged by guidance expressed in recent FDA conference presentations. The advantages of continuous manufacturing include steady state operation, consistent product quality, reduced equipment size… 

Current state of the art in continuous bioprocessing

This review focusses on the current state of the art of continuous downstream processing, highlighting the key advantages over traditional batch manufacturing, and allows the identification of scenarios where continuous downstreamprocessing may be critical for commercial manufacturing success.

Continuous Capture of mAbs—Points to Consider and Case Studies

White paper on high‐throughput process development for integrated continuous biomanufacturing

The major gaps in HTPD are illustrated and the major needs and possible solutions to achieve an end-to-end Integrated Continuous Biomanufacturing are discussed, as discussed in the context of the 2019 ICB Conference.

Economic Analysis of Batch and Continuous Biopharmaceutical Antibody Production: a Review

This paper provides a review of the work that has been published in the literature on computational process design and economic analysis methods on continuous biopharmaceutical antibody production and its comparison with a conventional batch process.

Throughput Optimization of Continuous Biopharmaceutical Manufacturing Facilities

A novel mathematical algorithm is introduced to determine the most optimal equipment scheduling configuration that maximizes the mass output for a facility producing a single product.

Continuous Manufacturing in Pharmaceutical Process Development and Manufacturing.

The pharmaceutical industry has found new applications for the use of continuous processing for the manufacture of new therapies currently in development, driven by cost reduction, decreased development cycles, access to new chemistries not practical in batch, improved safety, flexible manufacturing platforms, and improved product quality assurance.

Single pass diafiltration integrated into a fully continuous mAb purification process

This work illustrates the feasibility of incorporating a single pass diafiltration step into an end‐to‐end continuous protein purification process and several critical design aspects were incorporated to minimize system complexity and reduce the buffer volume requirements.

Continuous Manufacturing of Recombinant Therapeutic Proteins: Upstream and Downstream Technologies.

This review first discusses approaches for continuous cell culture, with a focus on perfusion-enabling cell separation technologies including gravitational, centrifugal, and acoustic settling, as well as filtration-based techniques.

Continuous counter‐current chromatography for capture and polishing steps in biopharmaceutical production

Different continuous multi‐column chromatography processes are discussed, associated with increased productivity per cycle and decreased buffer consumption, whereas the typical purity‐yield trade‐off of classical batch chromatography can be surmounted by continuous processes for polishing applications.



Practical Use of Continuous Processing in Developing and Scaling Up Laboratory Processes

This review discusses the advantages of continuous processing for thermochemical rearrangements, immobilized catalysts, and microwave, photochemical, electrochemical, and sonochemical processes, and how these can be performed using equipment readily available for the laboratory and pilot plant.

Integrated continuous production of recombinant therapeutic proteins

The first successful demonstration of the integration of a perfusion bioreactor and a four‐column periodic counter‐current chromatography system for the continuous capture of candidate protein therapeutics is reported, demonstrating the potential of integrated continuous bioprocessing as a universal platform for the manufacture of various kinds of therapeutic proteins.

Continuous annular chromatography: General characterization and application for the isolation of recombinant protein drugs.

The potential of CAC for industrial application is demonstrated by continuous isolation of rFVIII from cell culture supernatant in pilot scale, where thirty-fold concentration can be achieved at 94% yield, while purity is increased 3-5-fold.

Characterization of a recombinant antibody produced in the course of a high yield fed‐batch process

To gauge the effect of extended culture lifetime on product quality, biochemical characteristics of MAb isolated from different time points in the fed‐batch culture were determined and it was revealed that MAb produced later in the culture contained greater percentages of truncated N‐acetylglucosamine and highmannose N‐glycans.

Continuous Countercurrent Tangential Chromatography for Monoclonal Antibody Purification

A continuous countercurrent tangential chromatography system in which the resin flows sequentially through a series of static mixers and hollow fiber membrane modules to accomplish the binding, washing, elution, stripping, and equilibration steps in continuous operation with true countercurrent staging is tested.

Effects of cell culture conditions on antibody N‐linked glycosylation—what affects high mannose 5 glycoform

Unusually high levels of the mannose‐5 (Man5) glycoform were observed during the early development of a therapeutic antibody produced from a Chinese hamster ovary cell line, model cell line A, and it has been hypothesized that specific enzyme activity in the glycosylation pathway could have been altered in this fed‐batch process.

Very High Density of Chinese Hamster Ovary Cells in Perfusion by Alternating Tangential Flow or Tangential Flow Filtration in WAVE Bioreactor™—Part II: Applications for Antibody Production and Cryopreservation

A high cell density perfusion process of monoclonal antibody (MAb) producing Chinese hamster ovary (CHO) cells was developed in disposable WAVE Bioreactor™ using external hollow fiber filter as cell separation device and cell resuscitation was very successful, showing that this system was a reliable process for cell bank manufacturing.