Simplification of Buffer Formulation and Improvement of Buffer Control with In-Line Conditioning (IC)

Carredano, Enrique; Nordberg, Roger; Westin, Susanne; Busson, Karolina; Karlsson, Tomas M.; Blank, Torbjörn S.; Sandegren, Henrik; Jagschies, Günter

doi:10.1016/b978-0-08-100623-8.00027-x

Cited by 9 publications

(10 citation statements)

References 4 publications

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“…By operating at the lower limits of our miniaturized 3D developed device (19 × 9 × 5 cm), we could theoretically supply continuous on‐demand fresh medium for a 15 L perfusion bioreactor with a working volume of 10 L operating at 1 VVD. In addition, we believe that a nonintegrated stand‐alone version of our developed system similar to already existing automated buffer preparation units could also substantially contribute to the reduction of preparation and storage costs of cell culture media (Carredano et al, 2018 ; Gibson et al, 2019 ). The trend of outsourcing media and buffer preparation increased in the last decade, and we believe that an on‐demand reconstitution directly from solids would position itself on the biotherapeutic manufacturing and supplier of process materials side and by that reduce the logistical pressure (Langer, 2016 ).…”

Section: Resultsmentioning

confidence: 99%

“…Undoubtedly, CDM differ significantly in their powder characteristics and flow behavior from buffer species commonly used in the biopharmaceutical industry simply due to their more complex formulations and manufacturing (Fike et al, 2001 ; Salazar, Bleifuß, et al, 2016 ). In contrast, most used buffers in the biopharmaceutical industry, are consisting of a few salts (Carredano et al, 2018 ). For that reason, we had to adapt our device for the differences in powder flow behavior by redesigning the geometrical shape, power translation, and screw design (Figure 2 ; Jenike, 1964 ; McGlinchey, 2009 ).…”

Section: Resultsmentioning

confidence: 99%

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Media on‐demand: Continuous reconstitution of a chemically defined media directly from solids

Komuczki

Dutra

Gstöttner

et al. 2021

Biotech & Bioengineering

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Chemically defined media are reconstituted batchwise and stored in hold tanks until use. To avoid large hold tanks and batchwise production of media, we developed continuous on‐demand reconstitutions directly from solids consisting of a hopper and a screw conveyor capable of feeding dry powdered media with the required precision ±5% at low dosing rates of 0.171 g min−1. A commercially available dry powdered cell culture medium was continuously fed over a duration of 12 h into a mixer which was connected to a UV‐cell for monitoring and the media were compared to a batchwise production. A comparable amino acid, carbohydrate, and osmolality profile to a batchwise reconstitution could be obtained. Cell cultivation showed comparable performance of batch and continuous reconstitution for two CHO cell lines producing the antibodies adalimumab and trastuzumab on a small and benchtop scale. In‐depth analysis of the produced antibodies showed the same glycosylation pattern, other posttranslational profiles such as methionine oxidation and deamidation compared to batchwise reconstitution. Therefore, we conclude a continuous reconstitution of the medium results in the same quality of the product. A continuous on‐demand media reconstitution will impact the supply chain and significantly reduce the floor space necessary for preparation and storage.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Media on‐demand: Continuous reconstitution of a chemically defined media directly from solids

Komuczki

Dutra

Gstöttner

et al. 2021

Biotech & Bioengineering

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“…The proposed approach satisfactorily tracks the biomass profile with controller capable to maintain relevant growth conditions [42]. Feedback control loops such as flow feedback, pH feedback, or a combination of both have been applied for buffer preparation in inline conditioning and have shown significant potential [43,44]. For complex systems, PID control strategy has been modified as a nonlinear gain in sequence with a linear PID.…”

Section: Proportional Integral/proportional Integral Derivative (Pi/pid) Controlmentioning

confidence: 99%

Bioprocess Control: Current Progress and Future Perspectives

Rathore

Mishra

Nikita

et al. 2021

Life

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Typical bioprocess comprises of different unit operations wherein a near optimal environment is required for cells to grow, divide, and synthesize the desired product. However, bioprocess control caters to unique challenges that arise due to non-linearity, variability, and complexity of biotech processes. This article presents a review of modern control strategies employed in bioprocessing. Conventional control strategies (open loop, closed loop) along with modern control schemes such as fuzzy logic, model predictive control, adaptive control and neural network-based control are illustrated, and their effectiveness is highlighted. Furthermore, it is elucidated that bioprocess control is more than just automation, and includes aspects such as system architecture, software applications, hardware, and interfaces, all of which are optimized and compiled as per demand. This needs to be accomplished while keeping process requirement, production cost, market value of product, regulatory constraints, and data acquisition requirements in our purview. This article aims to offer an overview of the current best practices in bioprocess control, monitoring, and automation.

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“…In-line conditioning (ILC) or In-line formulation (ILF) may provide a better solution management option, providing over 20× concentration factor for many solutions (Carredano et al, 2018). ILC does not simply dilute a solution with water, but mixes acid, base, concentrated untitrated buffer, and salt with water to achieve the correct solution composition.…”

Section: Solution Management Strategymentioning

confidence: 99%

A common framework for integrated and continuous biomanufacturing

Coffman¹,

Brower

Connell-Crowley

et al. 2021

Biotech & Bioengineering

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There is a growing application of integrated and continuous bioprocessing (ICB) for manufacturing recombinant protein therapeutics produced from mammalian cells. At first glance, the newly evolved ICB has created a vast diversity of platforms. A closer inspection reveals convergent evolution: nearly all of the major ICB methods have a common framework that could allow manufacturing across a global ecosystem of manufacturers using simple, yet effective, equipment designs. The framework is capable of supporting the manufacturing of most major biopharmaceutical ICB and legacy processes without major changes in the regulatory license. This article reviews the ICB that are being used, or are soon to be used, in a GMP manufacturing setting for recombinant protein production from mammalian cells. The adaptation of the various ICB modes to the common ICB framework will be discussed, along with the pros and cons of such adaptation. The equipment used in the common framework is generally described. This review is presented in sufficient detail to enable discussions of IBC implementation strategy in biopharmaceutical companies and contract manufacturers, and to provide a road map for vendors equipment design. An example plant built on the common framework will be discussed. The flexibility of the plant is demonstrated with batches as small as 0.5 kg or as large as 500 kg. The yearly output of the plant is as much as 8 tons.

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Simplification of Buffer Formulation and Improvement of Buffer Control with In-Line Conditioning (IC)

Cited by 9 publications

References 4 publications

Media on‐demand: Continuous reconstitution of a chemically defined media directly from solids

Media on‐demand: Continuous reconstitution of a chemically defined media directly from solids

Bioprocess Control: Current Progress and Future Perspectives

A common framework for integrated and continuous biomanufacturing

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