A Novel Application of Granulation Technology to Improve Physical Properties and Biological Performance of Powdered Serum-Free Culture Media

Jayme, David W.; Fike, Richard M.; Radominski, R.; Dadey, Barbara; Hassett, R.; Cady, David

doi:10.1007/978-94-017-0728-2_28

Cited by 10 publications

(10 citation statements)

References 3 publications

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“…As a result, the large-scale batch blend uniformity, impurities, chemical compatibility, and/or heat sensitivity during the milling process were deemed to be the source of variation as detected by NIR spectra. During large scale manufacturing of powder raw materials, limitations to conventional milling processes, and the importance of performance qualification have been reported Jayme et al, 2001;Radominski et al, 2001). These limitations include: difficulty in achieving homogeneous distribution of minute formulation components; potential crosscontamination associated with dust generation, and lengthy and incomplete processes of powder solubilization and dissolution .…”

Section: Resultsmentioning

confidence: 99%

“…Uniformity of milling and blending during manufacturing of large batches of media could be a source of variation due to loss of micronutrients and inconsistency of content levels. These problems during milling process can be caused by chemical incompatibility or heat sensitivity of milling groups Jayme et al, 2001;Radominski et al, 2001). Further, changes in raw material sourcing may occur due to constraints in availability, increase in requirements due to change in scale, changes to equipment and/or manufacturing procedures, new regulations (USP/EP), cost, and/or as outcome of supplier audits.…”

Section: Introductionmentioning

confidence: 99%

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Application of near‐infrared (NIR) spectroscopy for screening of raw materials used in the cell culture medium for the production of a recombinant therapeutic protein

Kirdar

Chen

Weidner

et al. 2009

Biotechnology Progress

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Control of raw materials based on an understanding of their impact on product attributes has been identified as a key aspect of developing a control strategy in the Quality by Design (QbD) paradigm. This article presents a case study involving use of a combined approach of Near-infrared (NIR) spectroscopy and Multivariate Data Analysis (MVDA) for screening of lots of basal medium powders based on their impact on process performance and product attributes. These lots had identical composition as per the supplier and were manufactured at different scales using an identical process. The NIR/MVDA analysis, combined with further investigation at the supplier site, concluded that grouping of medium components during the milling and blending process varied with the scale of production and media type. As a result, uniformity of blending, impurity levels, chemical compatibility, and/or heat sensitivity during the milling process for batches of large-scale media powder were deemed to be the source of variation as detected by NIR spectra. This variability in the raw materials was enough to cause unacceptably large variability in the performance of the cell culture step and impact the attributes of the resulting product. A combined NIR/MVDA approach made it possible to finger print the raw materials and distinguish between good and poor performing media lots.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Application of near‐infrared (NIR) spectroscopy for screening of raw materials used in the cell culture medium for the production of a recombinant therapeutic protein

Kirdar

Chen

Weidner

et al. 2009

Biotechnology Progress

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“…These results thus indicate that compaction of CHO210 and Feed210 does not impact its performance in cell culture, further suggesting no change to media composition. Studies have been carried out to investigate the influence of processing of CCM on cell culture [13,15,16]. Granulation of cell culture media by fluid bed granulation did not influence the expression of recombinant protein or virus titer when tested with multiple cell lines [15].…”

Section: Cell Culture Characterization Of Compacted Ccmmentioning

confidence: 99%

“…Studies have been carried out to investigate the influence of processing of CCM on cell culture [13,15,16]. Granulation of cell culture media by fluid bed granulation did not influence the expression of recombinant protein or virus titer when tested with multiple cell lines [15]. Fluid bed granulation of cyclodextrin with lipids was found to be an efficient delivery method for cholesterol and other fatty acids to cell lines sensitive to these ingredients [16].…”

Section: Cell Culture Characterization Of Compacted Ccmmentioning

confidence: 99%

Compaction of chemically defined cell culture media increases its dissolution rate through an increase of solvent accessible surface area

et al. 2016

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Cultivation of mammalian cells for the generation of therapeutics requires the use of cell culture media which is a defined mixture of nutrients including carbohydrates, amino acids, lipids, vitamins, and inorganic salts. Its composition influences the cell density, yield, and quality of the molecule expressed. These chemically defined cell culture media are manufactured as powders since they offer advantages of storage, handling and stability. To prevent de-mixing of the powders and maintain homogeneity, these powders are milled down to small particle size ranges. However, this small particle size allows for inter-particle forces to impact powder flow properties, and decreases the surface area available to dissolution. Hence a method is required that improves these powder parameters, without altering their composition. A deeper understanding of the dissolution mechanism of multicomponent mixtures like cell culture media is also needed. Here, cell culture media granules, generated from homogeneous powders by roller compaction are evaluated. The granulation process did not alter the composition of the media and properties of solutions generated thereof. The analysis and comparison of the dissolution profile of powder and compacted media enabled the calculation of the actual surface area available to dissolution. The improvement in granule dissolution can be attributed to dispersion and disintegration of the granules on wetting increasing available surface area. Decrease in inter-particle forces in granules also improves flow-ability properties. Surface character and pores on the granules further augments the improvement in dissolution.

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“…Evaluation of these data reveals a correlation between raw material type and product attributes. Limitations to conventional milling processes that are used to manufacture powder raw materials have been known to include potential cross-contamination associated with dust generation; lengthy and incomplete processes of powder solubilization and dissolution; need to isolate ''sensitive'' constituents from the basal formulation and to add them separately to the hydrated powder; difficulty in achieving homogeneous distribution of minute formulation components; and need for postformulation pH and osmolality adjustment Jayme et al, 2002;Radominski et al, 2001). These observations supported our findings that the root case of process underperformance was the combination of largescale media and high pCO 2 conditions in the large-scale Figure 2.…”

Section: Designmentioning

confidence: 99%

Process analytical technology (PAT) for biopharmaceutical products: Part II. Concepts and applications

Read¹,

Shah²,

Riley³

et al. 2009

Biotech & Bioengineering

145

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Implementing real-time product quality control meets one or both of the key goals outlined in FDA's PAT guidance: "variability is managed by the process" and "product quality attributes can be accurately and reliably predicted over the design space established for materials used, process parameters, manufacturing, environmental, and other conditions." The first part of the paper presented an overview of PAT concepts and applications in the areas of upstream and downstream processing. In this second part, we present principles and case studies to illustrate implementation of PAT for drug product manufacturing, rapid microbiology, and chemometrics. We further present our thoughts on how PAT will be applied to biotech processes going forward. The role of PAT as an enabling component of the Quality by Design framework is highlighted. Integration of PAT with the principles stated in the ICH Q8, Q9, and Q10 guidance documents is also discussed.

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A Novel Application of Granulation Technology to Improve Physical Properties and Biological Performance of Powdered Serum-Free Culture Media

Cited by 10 publications

References 3 publications

Application of near‐infrared (NIR) spectroscopy for screening of raw materials used in the cell culture medium for the production of a recombinant therapeutic protein

Application of near‐infrared (NIR) spectroscopy for screening of raw materials used in the cell culture medium for the production of a recombinant therapeutic protein

Compaction of chemically defined cell culture media increases its dissolution rate through an increase of solvent accessible surface area

Process analytical technology (PAT) for biopharmaceutical products: Part II. Concepts and applications

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