Recent development and application of membrane chromatography

Chen, Jing; Yu, Bing; Cong, Hailin; Shen, Youqing

doi:10.1007/s00216-022-04325-8

Cited by 26 publications

(13 citation statements)

References 133 publications

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“…Also anticipated are future developments in alternative purification technologies to UF/DF, including preparative chromatography (HIC, IEX, and SEC) and membrane adsorbers. Membrane chromatography is a powerful alternative/complement to resin-based column chromatography for the purification of biomolecules, but has seen limited utilization to date for ADCs . Likewise, the use of activated charcoals or other adsorbents to remove small-molecule impurities is routine in small-molecule drug substance synthesis .…”

Section: Survey Results and Discussionmentioning

confidence: 99%

Strategies for UF/DF-Based Impurity Removal in the Post-conjugation Purification of Antibody–Drug Conjugates

Fernandez‐Cerezo

Holstein

Thirumalairajan

et al. 2023

Org. Process Res. Dev.

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Antibody–drug conjugates (ADCs) are increasingly prevalent as investigational and marketed treatments for a variety of cancers and other diseases. The structures of most ADCs comprise a small-molecule component (the drug-linker) chemically conjugated to a monoclonal antibody, and this hybrid construct presents a number of challenges for Chemistry, Manufacturing, and Controls (CMC) development. A Small Molecule Considerations for ADC Development Working Group (WG) has been established within the IQ Consortium to serve as a forum for biopharmaceutical industry companies to discuss development strategies for ADCs, with a focus on the drug-linker portion. The preceding paper from the WG presented results from a benchmarking survey of IQ member companies on a number of topics relating to drug-linker development. One of the key findings was that ultrafiltration/diafiltration (UF/DF) is used by all responding companies for purification of the ADC following the conjugation step and is a critical operation for control of small-molecule impurities in the ADC drug substance. UF/DF is well established in monoclonal antibody processing, but to date, there are relatively few literature reports detailing its application to ADCs. To help address this gap, this manuscript presents results and analysis from a more focused survey of IQ member companies on the application of UF/DF for post-conjugation purification of ADCs. Insight is provided into practical considerations such as common operating parameters, relative efficiency of removal of different types of impurities, technical challenges, and application of emerging technologies. In addition, recommendations are offered on where to start when developing a UF/DF process for a new ADC. The overall goals are to provide an overview of current industry practices for UF/DF purification of ADCs and to spur further communication and innovation in this area.

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Section: Survey Results and Discussionmentioning

confidence: 99%

Strategies for UF/DF-Based Impurity Removal in the Post-conjugation Purification of Antibody–Drug Conjugates

Fernandez‐Cerezo

Holstein

Thirumalairajan

et al. 2023

Org. Process Res. Dev.

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“…Bioprocess innovation is driven by generating more products in less time and less space with the goal of alleviating the price of therapeutics, both in terms of speed‐to‐clinic and minimizing the costs of the process itself (Erickson et al, 2021; O'Mara et al, 2023; Schwellenbach et al, 2016; Shukla et al, 2017; Sommerfeld & Strube, 2005). Single‐use, column‐free technologies have emerged as viable alternatives to multiuse columns that require cleaning validation and laborious column packing (Chen et al, 2023; Zhang et al, 2021). Especially suited for multiproduct facilities, single‐use, column‐free technologies enable quick turnaround from process to process and seamless scale‐up and scale‐out for each process.…”

Section: Introductionmentioning

confidence: 99%

“…Large, yet soluble, nanoscale particulates in feed streams present a greater likelihood of fouling issues for convective flow devices compared to legacy diffusion‐based separations (Burden et al, 2012). In the case of an agarose functionalized bead, large particulates flow outside of the bead and cannot diffuse to the binding sites inside the resin (Chen et al, 2023). In a convective fiber setting, large particulates will interact with the absorbent material, where fouling can become a problem if the particulates are not reduced in the loading pool.…”

Section: Introductionmentioning

confidence: 99%

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Fiber chromatographic enabled process intensification increases monoclonal antibody product yield

Anderson,

Seto,

Chau

et al. 2023

Biotech & Bioengineering

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The most straightforward method to increase monoclonal antibody (mAb) product yield is to complete the purification process in less steps. Here, three different fiber chromatographic devices were implemented using a holistic approach to intensify the mAb purification process and increase yield. Fiber protein A (proA) chromatography was first investigated, but traditional depth filtration was not sufficient in reducing the contaminant load as the fiber proA device prematurely fouled. Further experimentation revealed that chromatin aggregates were the most likely reason for the fiber fouling. To reduce levels of chromatin aggregates, a chromatographic clarification device (CCD) was incorporated into the process, resulting in single‐stage clarification of harvested cell culture fluid and reduction of DNA levels. The CCD clarified pool was then successfully processed through the fiber proA device, fully realizing the productivity gains that the fiber technology offers. After the proA and viral inactivation neutralization (VIN) hold step, the purification process was further intensified using a novel single‐use fiber‐based polishing anion exchange (AEX) material that is capable of binding both soluble and insoluble contaminants. The three‐stage fiber chromatographic purification process was compared to a legacy five‐step process of dual‐stage depth filtration, bead‐based proA chromatography, post‐VIN depth filtration, and bead‐based AEX chromatography. The overall yield from the five‐step process was 60%, while the fiber chromatographic‐enabled intensified process had an overall yield of 70%. The impurity clearance of DNA and host cell protein (HCP) for both processes were within the regulatory specification (<100 ppm HCP, <1 ppb DNA). For the harvest of a 2000 L cell culture, the intensified process is expected to increase productivity by 2.5‐fold at clarification, 50‐fold at the proA step, and 1.6‐fold in polishing. Relative to the legacy process, the intensified process would reduce buffer use by 1088 L and decrease overall process product mass intensity by 12.6%.

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“…In this area, membrane chromatography can be used for purification of e.g. biological macromolecules and is an efficient alternative to traditional column chromatography 25 . One of the challenges with cellulose is its insolubility in water and other common organic and inorganic solvents.…”

Section: Introductionmentioning

confidence: 99%

Direct ink writing of high-resolution cellulose structures

Rezaei,

Carlsson,

Hedin Dahlstrom

et al. 2023

Sci Rep

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Abstract3D printing is envisioned to play an important role in the production of membranes for e.g., water purification and bio-separation applications due to the prospect of creating new and cleverly designed structures. Among different 3D printing techniques, direct ink writing offers the opportunity to print a wide variety of materials with high-detail resolution. There is a range of parameters that need to be optimized in order to develop robust printing techniques at that scale. In this study, cellulose acetate (CA), which is a biocompatible material, has been used as an ink. In order to examine the printability and the possibility of printing features as small as a few µm, nozzles with different diameters and inks with varying amounts and molecular weights of CA were investigated. Findings in this study indicate that, depending on the wetting on the underlaying structure, the nozzle's internal and external diameter affects the detail resolution of the printed structure. Different inks result in different widths of printed strands and generally a higher amount and higher molecular weights of CA results in higher detail resolution. However, too high amount of CA and molecular weight will increase the clogging risk in the nozzle. In this study, the internal size of the nozzle was 3 µm, and by selecting a suitable ink, it was possible to print strands down to 1 µm size and 6 µm inter-strand distance in the air, bridging supports with limited sagging. Furthermore, wall structures consisting of 300 layers, corresponding to about 300 µm in total height, were successfully printed.

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Recent development and application of membrane chromatography

Cited by 26 publications

References 133 publications

Strategies for UF/DF-Based Impurity Removal in the Post-conjugation Purification of Antibody–Drug Conjugates

Strategies for UF/DF-Based Impurity Removal in the Post-conjugation Purification of Antibody–Drug Conjugates

Fiber chromatographic enabled process intensification increases monoclonal antibody product yield

Direct ink writing of high-resolution cellulose structures

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