Review
Engineering, Chemical
Xing Yang, Andrea Merenda, Riyadh AL-Attabi, Ludovic F. Dumee, Xiwang Zhang, San H. Thang, Hung Pham, Lingxue Kong
Summary: Membrane chromatography is considered a potential solution for downstream processing in protein purification. Despite limited commercial adoption in large-scale production, significant progress has been made. However, robust evaluation of its performance is still needed, and the disconnection between academic and commercial efforts should be addressed.
JOURNAL OF MEMBRANE SCIENCE
(2022)
Article
Engineering, Chemical
Lukas Gerstweiler, Jingxiu Bi, Anton P. J. Middelberg
Summary: Continuous production offers higher productivity and better quality compared to traditional batch-wise approaches, but has not yet fully guided biomanufacturing industry to the 21st century advanced manufacturing status. Despite advancements in upstream processing, the lack of development in continuous processing for downstream operations remains a hindrance to modernization and process system integration. Hopeful advances in continuous chromatographic purification and other unit operations are on the horizon, signaling a turning point in process intensification research.
CHEMICAL ENGINEERING SCIENCE
(2021)
Article
Biotechnology & Applied Microbiology
Ryan R. Davis, Fletcher Suber, Ian Heller, Boxuan Yang, Juan Martinez
Summary: Improving productivity and decreasing costs for biotherapeutic agents is a key driver in the biologics manufacturing industry. Advances in upstream processes have outpaced downstream operations, particularly in monoclonal antibody purification. Utilizing cellulose nanofibers with a protein A ligand in continuous chromatography can greatly increase productivity and reduce costs.
JOURNAL OF BIOTECHNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Sabrina Yang, Ryszard Braczkowski, Shih-Hsun Chen, Ricarda Busse, Yudhi Li, Louis Fabri, Innocent Berbelle Bekard
Summary: The evaluation of the Sartobind (R) Rapid A affinity membrane showed that it is a scalable alternative to traditional Protein A resin chromatography for the isolation and purification of monoclonal antibodies (mAbs) from harvested cell culture media.
Review
Biochemistry & Molecular Biology
Allan Matte
Summary: Despite the development of new therapies, therapeutic monoclonal antibodies remain a significant biologics product with a high market value. The use of single-use technologies in process development and manufacturing has led to a paradigm shift in antibody production. Early-stage assessment of lead antibodies is crucial for minimizing development risks and identifying molecules suitable for manufacturing. Statistical and mechanistic modeling approaches are increasingly used in downstream process development to gain a deeper understanding of chromatographic unit operations. Continuous and semi-continuous downstream processes are being explored as alternatives to batch processes due to the widespread adoption of perfusion processes. Process analytical technologies play a key role in real-time quality assessment of antibody products as part of the Quality by Design paradigm. Computational prediction and modeling approaches are expected to continue advancing and being utilized due to their cost-effectiveness and efficiency compared to experimental studies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Chemistry, Applied
Solmaz Hajizadeh
Summary: The demand for efficient separation and purification methods has led to the development of new techniques and materials, such as composite cryogels. These composite cryogels can directly purify targets from particulate-containing fluids and offer higher binding capacities, improved selectivity, and enhanced overall performance compared to conventional chromatographic columns.
REACTIVE & FUNCTIONAL POLYMERS
(2023)
Article
Engineering, Chemical
Christopher J. Yehl, Andrew L. Zydney
Summary: This study explores a novel approach for protein separations based on High Performance Countercurrent Membrane Purification (HPCMP), demonstrating the feasibility of achieving high selectivity and over 98% yield of proteins without significant pressure-driven flow. The results suggest the potential of utilizing HPCMP for high resolution separations in the preparation of biopharmaceuticals and natural protein products.
JOURNAL OF MEMBRANE SCIENCE
(2021)
Review
Biochemical Research Methods
Sathish Nadar, Gary Shooter, Balaji Somasundaram, Evan Shave, Kym Baker, Linda H. L. Lua
Summary: The article reviews the application of membrane-based technologies in the bioprocessing of monoclonal antibodies, focusing on the recent progress towards developing intensified end-to-end bioprocesses and the critical role membrane technology will play in achieving this goal. Membrane technologies show promise in fulfilling industry needs due to their operational flexibility and ease of implementation, especially as the industry moves towards continuous operations and single use processes.
BIOTECHNOLOGY JOURNAL
(2021)
Article
Chemistry, Applied
Yiran Qu, Innocent Bekard, Ben Hunt, Jamie Black, Louis Fabri, Sally L. L. Gras, Sandra E. E. Kentish
Summary: Membrane adsorbers (MA) are a promising alternative to resin chromatography in protein separation due to their benefits in terms of residence time, pressure drop, scale-up, and cost-effectiveness. This review compares the application of commercially available MA and resin chromatography devices in purifying monoclonal antibodies and other proteins in the pharmaceutical and food industries. The evaluation shows that MA can achieve comparable or even better product quality than resin chromatography, and it can be more economical in terms of cost.
SEPARATION AND PURIFICATION REVIEWS
(2023)
Article
Immunology
Petra Steppert, Magdalena Mosor, Larissa Stanek, Daniel Burgstaller, Dieter Palmberger, Shirin Preinsperger, Patricia Pereira Aguilar, Matthias Mullner, Patrick Csar, Alois Jungbauer
Summary: The developed purification process efficiently captures small impurities and maintains virus infectivity through concentration and buffer exchange. The process demonstrates high flexibility and can be easily and quickly adapted to other vectors based on the measles virus vector platform.
Article
Computer Science, Interdisciplinary Applications
Federico Rischawy, Till Briskot, Nathalie Hopf, David Saleh, Gang Wang, Simon Kluters, Joey Studts, Juergen Hubbuch
Summary: Mechanistic modeling was used to describe the entire downstream process of a Fab fragment, with various models connected to predict online and offline data and accommodate input process parameter variations at large manufacturing scale.
COMPUTERS & CHEMICAL ENGINEERING
(2023)
Article
Medicine, General & Internal
Juan Carlos Cordova, Sheng Sun, Jeffrey Bos, Srinath Thirumalairajan, Sanjeevani Ghone, Miyako Hirai, Ricarda A. Busse, Julia S. v. der Hardt, Ian Schwartz, Jieyu Zhou
Summary: Membrane chromatography, specifically utilizing Sartobind(R) S and Phenyl membranes, is used to remove aggregates and excess payload in ADC downstream processing. This approach effectively improves the purity of ADCs by clearing unwanted species and increasing homogeneity of drug-to-antibody ratio (DAR).
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Biotechnology & Applied Microbiology
Fuminori Konoike, Masatoshi Taniguchi, Shuichi Yamamoto
Summary: A continuous downstream process for monoclonal antibodies was developed using periodic-counter current chromatography (PCCC) for capture, a batch reactor for low pH virus inactivation (VI), and flow-through chromatography (FTC) for polish. Different runs with varying feed rates and concentrations were performed, achieving good recovery and purity values. The process was found to be flexible and stable for feed fluctuations, requiring only a few surge or pool tanks in addition to the final product pool tank.
BIOTECHNOLOGY AND BIOENGINEERING
(2023)
Article
Biotechnology & Applied Microbiology
Fabian Schmitz, Thomas Kruse, Mirjana Minceva, Markus Kampmann
Summary: A flow-through process for monoclonal antibody purification has been developed using two different membrane adsorbers combined with single-pass tangential flow filtration. The process achieves continuous buffer exchange and efficient removal of DNA and host cell proteins. The selection of buffer conditions and the sequencing of membrane adsorbers were optimized to maximize mAb yield while minimizing DNA and HCP content. The integrated double flow-through process achieved superior throughput compared to the standard bind and elute mode.
BIOCHEMICAL ENGINEERING JOURNAL
(2023)
Review
Biotechnology & Applied Microbiology
Joseph Lavoie, Jinxin Fan, Behnam Pourdeyhimi, Cristiana Boi, Ruben G. Carbonell
Summary: Nonwoven membranes, as highly engineered fibrous materials, can be manufactured on a large scale and modified on their surfaces using various chemistries and ligands. They have great potential for the development of novel membranes with unique properties. This article summarizes the methods of manufacturing nonwoven fabrics, reviews the use of nonwoven fabric devices in membrane chromatography, and discusses the challenges to overcome for their application in downstream processing operations.
BIOTECHNOLOGY AND BIOENGINEERING
(2023)