Microspectroscopic investigation of the membrane clogging during the sterile filtration of the growth media for mammalian cell culture

Cao, Xiaolin; Loussaert, James A.; Wen, Zai‐Qing

doi:10.1016/j.jpba.2015.11.014

Cited by 8 publications

(3 citation statements)

References 18 publications

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“…After dissociating in solution, these ions can form small concentrations of ionic phosphates (Cao, Stimpfl, Wen, Frank & Hunter, ). During HTST treatments, elevated temperatures in excess of 100°C can drive these ionic phosphates and other inorganic salts out of solution (Cao, Loussaert & Wen, ; Cao et al, ; Floris, Curtin, Kaisermayer, Lindeberg & Bones, ; Pohlscheidt et al, ). Consequently, lot‐to‐lot variabilities of trace metal content are accentuated after the precipitating solids are removed from the solution.…”

Section: Vendor and Batch/lot Variability Of Metal Content In Culturementioning

confidence: 99%

“…Consequently, lot‐to‐lot variabilities of trace metal content are accentuated after the precipitating solids are removed from the solution. In addition, precipitating salts have also shown to cause membrane fouling, which can further lead to ineffective media processing and compromise batch sterility as well (Cao et al, ; Pohlscheidt et al, ).…”

Section: Vendor and Batch/lot Variability Of Metal Content In Culturementioning

confidence: 99%

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Consequences of trace metal variability and supplementation on Chinese hamster ovary (CHO) cell culture performance: A review of key mechanisms and considerations

Graham

Bhatia

Yoon

2019

Biotech & Bioengineering

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Trace metals are supplied to chemically-defined media (CDM) for optimal Chinese hamster ovary (CHO) cell culture performance during the production of monoclonal antibodies and other therapeutic proteins. However, lot-to-lot and vendor-to-vendor variability in raw materials consequently leads to an imbalance of trace metals that are supplied to CDM. This imbalance can yield detrimental effects rooted in several primary mechanisms and pathways including oxidative stress, apoptosis, lactate accumulation, and unfavorable glycan synthesis. Recent research endeavors involve supplying zinc, copper, and manganese to CDM in excess to further maximize culture productivity and product quality. These treatments significantly impact critical quality attributes and furthermore highlight the degree to which trace metal availability can affect CHO cell culture performance. This review highlights the role of trace metal variability, supplementation, and interplay on key cellular mechanisms responsible for overall culture performance and the production and quality of therapeutic proteins. K E Y W O R D SCHO cell culture performance, raw material variability, therapeutic proteins, trace metal deficiency, trace metal supplementation, trace metals

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Section: Vendor and Batch/lot Variability Of Metal Content In Culturementioning

confidence: 99%

Section: Vendor and Batch/lot Variability Of Metal Content In Culturementioning

confidence: 99%

Consequences of trace metal variability and supplementation on Chinese hamster ovary (CHO) cell culture performance: A review of key mechanisms and considerations

Graham

Bhatia

Yoon

2019

Biotech & Bioengineering

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“…Medium optimization is a balance between planning and chemistry, as these highly productive cell lines often have high cell‐specific nutrient demands and so modern cell culture media systems must deliver those nutrients while keeping solubility limitations in mind. High pH, which is required to dissolve amino acids like tyrosine for example, can cause subvisible precipitation of metal salts among other critical medium components which may only be detectable after obstructing sterile filters (Cao et al, 2016; de Chialvo et al, 1984). Medium formulations are generally developed on a small scale for evaluation in micro‐scale or bench‐scale bioreactors, and scale‐up can introduce new challenges as scale‐dependent differences in temperature profile and mix time may impact the amount of precipitate formed in a preparation.…”

Section: Introductionmentioning

confidence: 99%

Investigating trace metal precipitation in highly concentrated cell culture media with Pourbaix diagrams

Brantley

Moore

Grinnell

et al. 2021

Biotech & Bioengineering

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Commercial production of therapeutic proteins using mammalian cells requires complex process solutions, and consistency of these process solutions is critical to maintaining product titer and quality between batches. Inconsistencies between process solutions prepared at bench and commercial scale may be due to differences in mixing time, temperature, and pH which can lead to precipitation and subsequent removal via filtration of critical solution components such as trace metals. Pourbaix diagrams provide a useful tool to model the solubility of trace metals and were applied to troubleshoot the scale‐up of nutrient feed preparation after inconsistencies in product titer were observed between bench‐ and manufacturing‐scale batches. Pourbaix diagrams modeled the solubility of key metals in solution at various stages of the nutrient feed preparation and identified copper precipitation as the likely root cause of inconsistent medium stability at commercial scale. Copper precipitation increased proportionally with temperature in bench‐scale preparations of nutrient feed and temperature was identified as the root cause of copper precipitation at the commercial scale. Additionally, cell culture copper titration studies performed in bench‐scale bioreactors linked copper‐deficient mammalian cell culture to inconsistent titers at the commercial scale. Pourbaix diagrams can predict when trace metals are at risk of precipitating and can be used to mitigate risk during the scale‐up of complex medium preparations.

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Potato hierarchical clustering and doneness degree determination by near-infrared (NIR) and attenuated total reflectance mid-infrared (ATR-MIR) spectroscopy

Bakalis

Sun

2019

Food Measure

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Microspectroscopic investigation of the membrane clogging during the sterile filtration of the growth media for mammalian cell culture

Cited by 8 publications

References 18 publications

Consequences of trace metal variability and supplementation on Chinese hamster ovary (CHO) cell culture performance: A review of key mechanisms and considerations

Consequences of trace metal variability and supplementation on Chinese hamster ovary (CHO) cell culture performance: A review of key mechanisms and considerations

Investigating trace metal precipitation in highly concentrated cell culture media with Pourbaix diagrams

Potato hierarchical clustering and doneness degree determination by near-infrared (NIR) and attenuated total reflectance mid-infrared (ATR-MIR) spectroscopy

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