Single-use Bioreactors Research Articles

CFD based mass transfer modeling of a single use bioreactor for production of monoclonal antibody biotherapeutics

In this study, Euler-Euler coupled computational fluid dynamics (CFD), species transport and population balance model (PBM) simulations have been used to model multiphase hydrodynamics and mass (O2) transfer in a single use bioreactor (SUB) for mAb production. In simulations, drag was estimated by Schiller-Neuman equations. O2(g) local volume fraction was estimated via species transport model (STM). The PBM equations were solved using quadrature method of moments (QMOM) to get bubble size distribution (BSD) and thereby the Sauter mean diameter,d32. Also, the mean diameter over surface (d21) and De Brouckere mean (d43) were estimated for calculation of the BSD. The mass transfer coefficient (kLa) was predicted using species transport model (STM) and Higbie’s penetration theory. The experimental estimation of kLa was performed via simplified dynamic pressure method. Total stress (τ) and energy dissipation rate (ε) were estimated as 34.17 Pa and 1.352 m2.s−3, respectively. Calculations of the d32, d21 and d43 indicate that the BSD becomes more dispersed with increase in agitation speed at all aeration rates. Further, the kLa values of STM were within 0.47% to 4.21% of experimental data. In summary, with error between 4 and 10%, the proposed approach offers better visualization of O2 transport mechanism across gas–liquid interface than conventional approaches.

Development of a Biodegradable Microcarrier for the Cultivation of Human Adipose Stem Cells (hASCs) with a Defined Xeno- and Serum-Free Medium

Stirred single-use bioreactors in combination with microcarriers (MCs) have established themselves as a technology that has the potential to meet the demands of current and future cell therapeutic markets. However, most of the published processes have been performed using fetal bovine serum (FBS) containing cell culture medium and non-biocompatible MCs. This approach has two significant drawbacks: firstly, the inevitable potential risks associated with the use of FBS for clinical applications; secondly, non-biocompatible MCs have to be removed from the cell suspension before implantation, requiring a step that causes loss of viable cells and adds further costs and complications. This study aimed to develop a new platform based on a chemically defined xeno- and serum-free cell culture medium and biodegradable MC that can support the growth of human adipose stem cells (hASCs) while still preserving their undifferentiated status. A specific combination of components and manufacturing parameters resulted in a MC prototype, called “BR44”, which delivered the desired functionality. MC BR44 allows the hASCs to stick to its surface and grow in a chemically defined xeno- and serum-free medium (UrSuppe). Although the cells’ expansion rate was not as high as with a commercial non-biodegradable standard MC, those cultured on BR44 maintained a better undifferentiated status in both static and dynamic conditions than those cultured on traditional 2D surfaces.

Biography of PharmaceuticalBioprocesses

The use of spectroscopic sensors for bioprocess monitoring is a powerful tool within the process analytical technology (PAT) initiative of the US Food and Drug Administration. Spectroscopic sensors enable the simultaneous real-time bioprocess monitoring of various critical process parameters including biological, chemical, and physical variables during the entire biotechnological production process. Approximately 30 ago, when modern biotechnology provided biological like Nobelmedaled monoclonal antibodies and more for the first time this innovative technology boosted pharm a’s pipeline of drug candidates. However, the low-hanging fruits were early gathered and another disruptive innovation is not in sight. What is often described as the so-called innovation gap gets even worse when looking at the remaining patent terms of the drugs on the market. It becomes shorter and shorter and it is foreseeable that the pipeline of new NCE patents will not balance the loss. On the other hand, this development pushes the market for generics, which in the USA, is believed to exceed $81.5 billion with an impressive projected annual growth rate of approximately 10% for 2011–2013. Consequently, the valuation of big pharm companies is falling in an alarming way. According to Burrell& Company, the 17 most relevant players are valued at only $1 trillion today, compared with $1.6 trillion in 2000. Single-use bioreactors are commonly used in the biopharmaceutical industry today; however, they are mostly limited to mammalian cell culture processes. For microbial processes, concepts including the CELL-tainer® technology provide comparable oxygen mass transfer such as in stirred tank reactors. this type of single-use bioreactor is applicable in biopharmaceutical processes, and also in a seed train for bulk chemicals production such as amino acid production. It is expected that single-use technologies will be applied ever more frequently in microbial-fed batch cultivation processes in combination with improved monitoring and control. Bioprocess and biocatalyst IP developed for small-volume/high value pharmaceutical production will therefore find another even bigger market in bulk volume/ lower value processes. Therefore, today’s financing climate for R&D targeting production processes is very different to the early days of biopharmaceuticals. For example, the development of genome sequencing has been financed at first by pharmaceutical industry investors and related industries. Later, such technologies were used by the chemical industry in their desire for modern biotechnological processes, without ever contributing to the basic cost of development. The controversy over intellectual property rights for pharmaceuticals and access to antiretroviral therapies in developing countries has been the subject of much public debate recently. This article provides a broader context for the debate. It first reviews characteristics of the developing country market for pharmaceuticals, including small markets, distinct disease environments and weak health care and regulatory systems. Pharmaceutical use is sometimes suboptimal due to pricing above marginal cost and positive treatment externalities for infectious diseases; sometimes too great due to the failure of consumers to take into account externalities from drug resistance; and sometimes simply inappropriate due to information asymmetries between health care providers and their patients. Drug procurement is often inefficient and corrupt, and inappropriate regulation can hinder access. In addition, health care workers are politically powerful relative to patients. Developed countries and international organizations could encourage differential pricing, allow more favourable tax treatment of appropriate drug donations, and encourage R&D and Pharmaceuticals and the Developing World 87 facilitate access to new products by committing in advance to purchase products needed in developing countries if and when they are developed.

Chemically Defined, Xeno-Free Expansion of Human Mesenchymal Stem Cells (hMSCs) on Benchtop-Scale Using a Stirred Single-Use Bioreactor.

In recent years, the use of hMSCs, which may be isolated from adipose tissue among others, for the treatment of diseases has increased significantly. The cell quantities required for such therapeutic approaches, between 1012 and 1013, have thus far been predominantly produced using commercially available multi-tray systems, such as the Cell Factory (Thermo Fisher Scientific) or HYPERStack (Corning), which can be purchased with up to 40 layers. However, the handling of these planar multilayer systems is difficult, and process monitoring opportunities remain limited. Here, automated stirred single-use bioreactors provide a viable alternative to the time-consuming multiplication of cells using such planar systems, while still managing to achieve the desired clinically relevant quantities. In these stirred single-use systems, adherent cells are predominantly cultivated in suspension up to pilot scale using carrier materials, also referred to as microcarriers (MCs).This chapter describes the steps which need to be realized to guarantee successful hMSC expansion within a stirred single-use bioreactor (Eppendorf's BioBLU® 0.3c) operated using MCs under serum- and xeno-free conditions at benchtop scale. The cultivations were performed using an immortalized human adipose-derived mesenchymal stem cell (hASC) line, hence referred to as hASC52telo, and a new chemically defined, xeno-free medium, hence referred to as the UrSuppe formulation. Spinner flask cultivations were performed under comparable process conditions.

Spectroscopy integration to miniature bioreactors and large scale production bioreactors-Increasing current capabilities and model transfer.

Spectroscopy techniques are being implemented within the biopharmaceutical industry due to their non-destructive ability to measure multiple analytes simultaneously, however, minimal work has been applied focussing on their application at small scale. Miniature bioreactor systems are being applied across the industry for cell line development as they offer a high-throughput solution for screening and process optimization. The application of small volume, high-throughput, automated analyses to miniature bioreactors has the potential to significantly augment the type and quality of data from these systems and enhance alignment with large-scale bioreactors. Here, we present an evaluation of 1. a prototype that fully integrates spectroscopy to a miniature bioreactor system (ambr®15, Sartorius Stedim Biotech) enabling automated Raman spectra acquisition, 2. In 50 L single-use bioreactor bag (SUB) prototype with an integrated spectral window. OPLS models were developed demonstrating good accuracy for multiple analytes at both scales. Furthermore, the 50 L SUB prototype enabled on-line monitoring without the need for sterilization of the probe prior to use and minimal light interference was observed. We also demonstrate the ability to build robust models due to induced changes that are hard and costly to perform at large scale and the potential of transferring these models across the scales. The implementation of this technology enables integration of spectroscopy at the small scale for better process understanding and generation of robust models over a large design space while facilitating model transfer throughout the scales enabling continuity throughout process development and utilization and transfer of ever-increasing data generation from development to manufacturing.

Rapid Lentiviral Vector Producer Cell Line Generation Using a Single DNA Construct

Stable suspension producer cell lines for the production of vesicular stomatitis virus envelope glycoprotein (VSVg)-pseudotyped lentiviral vectors represent an attractive alternative to current widely used production methods based on transient transfection of adherent 293T cells with multiple plasmids. We report here a method to rapidly generate such producer cell lines from 293T cells by stable transfection of a single DNA construct encoding all lentiviral vector components. The resulting suspension cell lines yield titers as high as can be achieved with transient transfection, can be readily scaled up in single-use stirred-tank bioreactors, and are genetically and functionally stable in extended cell culture. By removing the requirement for efficient transient transfection during upstream processing of lentiviral vectors and switching to an inherently scalable suspension cell culture format, we believe that this approach will result in significantly higher batch yields than are possible with current manufacturing processes and enable better patient access to medicines based on lentiviral vectors.

Mesenchymal stromal cells maintain the major quality attributes when expanded in different bioreactor systems

Mesenchymal Stromal Cells (MSCs) are being targeted for diverse cell-therapies applications. The MSC expansion in bioreactor is necessary to achieve the cell number required for clinical applications in accordance with cGMP guidelines. Since the culture conditions may influence the post-expansion MSC outcomes, in this work, human Umbilical Cord Matrix derived Mesenchymal Stromal Cells (hUCM-MSCs) were evaluated during and after expansion using CultiSpher-S® microcarrier with different bioreactor hydrodynamics: the single-use Wave-Induced Motion Bioreactor (WIMB) with a modified cellbag design proposed by our laboratory, and the conventional spinner flask. WIMB cultures showed longer cell culture times and lower cell yields than spinner flask culture, positioning the WIMB as a less suitable bioreactor than conventional stirred-based systems for high-yield MSC expansion bioprocess. Regarding cell biological functions, hUCM-MSCs harvested from the CultiSpher-S®/WIMB and the CultiSpher-S®/spinner kept determining major MSC molecular and biological characteristics according to immunophenotyping and multilineage differentiation assays. Moreover, biological processes were not regulated differently when hUCM-MSCs were cultivated in WIMB or spinner flask, indicating that post-expansion hUCM-MSCs characteristics are similar in both bioreactor systems.

Scalable Generation of Mature Cerebellar Organoids from Human Pluripotent Stem Cells and Characterization by Immunostaining.

The cerebellum plays a critical role in the maintenance of balance and motor coordination, and a functional defect in different cerebellar neurons can trigger cerebellar dysfunction. Most of the current knowledge about disease-related neuronal phenotypes is based on postmortem tissues, which makes understanding of disease progression and development difficult. Animal models and immortalized cell lines have also been used as models for neurodegenerative disorders. However, they do not fully recapitulate human disease. Human induced pluripotent stem cells (iPSCs) have great potential for disease modeling and provide a valuable source for regenerative approaches. In recent years, the generation of cerebral organoids from patient-derived iPSCs improved the prospects for neurodegenerative disease modeling. However, protocols that produce large numbers of organoids and a high yield of mature neurons in 3D culture systems are lacking. The protocol presented is a new approach for reproducible and scalable generation of human iPSC-derived organoids under chemically-defined conditions using scalable single-use bioreactors, in which organoids acquire cerebellar identity. The generated organoids are characterized by the expression of specific markers at both mRNA and protein level. The analysis of specific groups of proteins allows the detection of different cerebellar cell populations, whose localization is important for the evaluation of organoid structure. Organoid cryosectioning and further immunostaining of organoid slices are used to evaluate the presence of specific cerebellar cell populations and their spatial organization.

Development of a scale-up strategy for Chinese hamster ovary cell culture processes using the kL a ratio as a direct indicator of gas stripping conditions.

Herein, we described a scale-up strategy focused on the dissolved carbon dioxide concentration (dCO2 ) during fed-batch cultivation of Chinese hamster ovary cells. A fed-batch culture process for a 2000-L scale stainless steel (SS) bioreactor was scaled-up from similarly shaped 200-L scale bioreactors based on power input per unit volume (P/V). However, during the 2000-L fed-batch culture, the dCO2 was higher compared with the 200-L scale bioreactor. Therefore, we developed an alternative approach by evaluating the kL a values of O2 (kL a[O2 ]) and CO2 [kL a(CO2 )] in the SS bioreactors as a scale-up factor for dCO2 reduction. The kL a ratios [kL a(CO2 )/kL a(O2 )] were different between the 200-L and 2000-L bioreactors under the same P/V condition. When the agitation conditions were changed, the kL a ratio of the 2000-L scale bioreactor became similar and the P/V value become smaller compared with those of the 200-L SS bioreactor. The dCO2 trends in fed-batch cultures performed in 2000-L scale bioreactors under the modified agitation conditions were similar to the control. This kL a ratio method was used for process development in single-use bioreactors (SUBs) with shapes different from those of the SS bioreactor. The kL a ratios for the SUBs were evaluated and conditions that provided kL a ratios similar to the 200-L scale SS bioreactors were determined. The cell culture performance and product quality at the end of the cultivation process were comparable for all tested SUBs. Therefore, we concluded that the kL a ratio is a powerful scale-up factor useful to control dCO2 during fed-batch cultures.

Assessment of Pall's Xpansion® bioreactor for the production of mesenchymal stromal cells for therapeutic use

Background & Aim Mesenchymal Stromal Cells (MSCs) are involved in several clinical trials in the field of Advanced Therapeutic Medicinal Products (ATMPs) for their properties and therapeutic potential. However, the production of MSCs is currently done in multi-plates culture chambers (CellSTACK, Corning) that only allow the production of a limited number of cells and it's time consuming. This therefore represents a constraint, especially for allogeneic uses. Now, the major challenge is to increase this production capacity. The use of a bioreactor would overcome this problem. The Xpansion® bioreactor (Pall) is composed of a controller and single-use bioreactors. Similar in concept to CellSTACK, the Xpansion bioreactors are composed of stacked cell culture plates that are sold in four variations: 10, 50, 100, and 200. Although the plastic of the bioreactor plates is identical to those of the CellSTACK, the feasibility and equivalence of quality and expansion of the MSCs produced using the Xpansion bioreactor had to be demonstrated. Methods, Results & Conclusion Preliminary tests were carried out on the smallest model of the Xpansion bioreactor product line: The XP10 (10 culture plates). All experiments were performed in parallel with a CellSTACK manipulation. The tests were performed using MSCs at passage 0 (from bone marrow or adipose tissue) or raw materials. Quantitative and qualitative tests were carried out at the end of the culture. From raw material or MSCs, cell densities obtained after 6 days of culture are equivalent in both the Xpansion bioreactor and CellSTACK, demonstrating similar cell growth. The average cell expansion rates in the Xpansion (XP10) bioreactor and CellSTACK are 24.39 times and 21.69 times (n=3), respectively. The flow cytometry analysis showed that the phenotype and viability of the MSCs from the bioreactor were not altered by this culture method. Preliminary tests on the Xpansion bioreactor have demonstrated the feasibility of MSCs cell expansion without affecting the quality of the finished product compared to the current method in CellSTACK. In addition, using a bioreactor allows the production of cells in large quantities by managing only one culture chamber while reducing the risk of contamination and operation time. Additionally, using a bioreactor improves monitoring of culture parameters and scalability. Manufacturing MSCs in this bioreactor would make the graft of a larger number of patients from the same initial collection possible.

Perfusion enables increased lentivirus production using the iCELLis® bioreactor system

Background & Aim Historically, there have been no manufacturers using Good Manufacturing Practices (GMP) to produce lentivirus in Canada, which has hampered gene therapy and CAR-T clinical programs in the country. The Ottawa Hospital recently developed a lentivirus manufacturing process using adherent cells in a flatware culture system, and used this process to produce sufficient amounts of clinical-grade lentivirus in a GMP manner for the Canadian CLIC-1901 CD19-CAR T Phase I/II clinical trial. While our previously established lentivirus manufacturing process used a flatware culture system, we plan to develop a larger-scale production process for clinical-grade lentivirus using the iCELLis bioreactor system. The iCELLis bioreactor system provides a large surface area for adherent cell growth, has a small physical footprint, and recently emerged as the leading scalable, single-use bioreactor technology for clinical manufacturing of viral vectors and vaccines. Methods, Results & Conclusion Our initial estimates suggest we could produce lentiviral vectors for approximately 2000 clinical doses for CAR-T cell therapy applications in a full-scale iCELLis 500+ bioreactor system; however, observed experimental titers in the first several iCELLis Nano batches were low. We hypothesized that this low titer was due to product instability in the bioreactor for long exposure times, and therefore implement a perfusion-based feeding system to remove product form the bioreactor for storage at more stable conditions. In this poster, we demonstrate that this perfusion strategy successfully resulted in bioreactor titers greater than the legacy flatware process for n=4 batches.

Pall Xpansion® Bioreactor Supports Progenitor Cell Growth to >1 Million cells/cm2 and Proper Cell Differentiation

Background & Aim With the recent increase in early phase cell therapy clinical trials, there is a need for a manufacturing platform which can be implemented in research labs and easily scaled up to expedite process development studies, pre-clinical testing, and large-scale expansion of adherent human cells. Although various platforms such as traditional flatware and stirred tank bioreactors with microcarriers exist and have been well characterized, traditional flatware often does not allow for tight control of the cellular environment and is not scalable. Pall's Xpansion single-use bioreactor offers a tightly-controlled, scalable manufacturing platform for cell therapy applications, allowing for expedited process development, pre-clinical testing and large scale, high-density expansion of progenitor cells while maintaining their differentiation capacity. Methods, Results & Conclusion We have previously demonstrated efficient expansion of both epithelial cells (Vero, HEK293), human mesenchymal stem/stromal cells (hMSC), and progenitor cells in the Xpansion single-use bioreactor. Here we extend the progenitor cell findings by successfully expanding a proprietary progenitor cell to extremely high cell densities (> 1 million cells/cm2) reproducibly for 8 batches. In summary, all batches resulted in 1) cell expansion to > 1 million cells/cm2 and equivalent cell densities to the traditional flatware process control; 2) equivalent differentiation to a more mature cell fate as indicated by expression of key cell surface markers; and 3) self-assembly into characteristic three-dimensional structures.

Surface termination, crystal size, and bonding-site density effects on diamond biosensing surfaces

Diamond's properties, such as chemical stability and low biofouling rates, make it an ideal material for developing more adequate biosensing technology for single-use bioreactors. We propose a simplistic approach to covalently functionalizing diamond and evaluating the effects of different variables on the sensitivity of the bioactive surface. We hypothesize that by maximizing sensitivity, we can maximize the signal-to-noise ratio of the biosignal. Three different methods of achieving an oxygenated surface on diamond with varying crystal sizes is investigated to see which results in the most active biointerface. Surface termination species were confirmed post‑oxygenation with X-ray Photoelectron Spectroscopy. The diamond was then functionalized with a biotinylated monolayer, which was treated with gold-conjugated streptavidin to quantify the available bonding sites. After complete biofunctionalization, detection sensitivity of IL-8 and antibody density were assessed with ELISA and electrochemical impedance spectroscopy for quantification of sites with functional antibodies. The contradicting correlations between diamond morphology and percentage of CO bonds lead us to conclude that the effectiveness of oxygen-termination method is independent of diamond morphology. Through quantifying bonding sites, it was found that both the number of available sites and active sites increased with increasing crystal size. This result is suspected to be directly correlated to the hybridization of the diamond-carbon material in that functional species prefer sp3 carbon over sp2. Therefore, a diamond film with the largest possible crystals is predicted to have a higher detection sensitivity in biosensing applications.

Beyond heuristics: CFD-based novel multiparameter scale-up for geometrically disparate bioreactors demonstrated at industrial 2kL-10kL scales.

The timely delivery of the most up-to-date medicines and drug products is essential for patients throughout the world. Successful scaling of the bioreactors used within the biopharmaceutical industry plays a large part in the quality and time to market of these products. Scale and topology differences between vessels add a large degree of complication and uncertainty within the scaling process. Currently, this approach is primarily achieved through extensive experimentation and facile empirical correlations, which can be costly and time consuming while providing limited information. The work undertaken in the current study demonstrates a more robust and complete approach using computational fluid dynamics (CFD) to provide potent multiparameter scalability, which only requires geometric and material properties before a comprehensive and detailed solution can be generated. The CFD model output parameters that can be applied in the scale-up include mass transfer rates, mixing times, shear rates, gas hold-up values, and bubble residence times. The authors examined three bioreactors with variable geometries and were able to validate them based on single-phase and multiphase experiments. Furthermore, leveraging the resulting CFD output information enabled the authors to successfully scale-up from a known 2kL to a novel and disparate 5kL single-use bioreactor in the first attempted cell culture. This multiparameter scaling approach promises to ultimately lead to a reduction in the time to market providing patients with earlier access to the most groundbreaking medicines.

Mass transfer in a single-use angled-shaft aerated stirred bioreactor applicable for animal cell culture

The single-use stirred bioreactors are increasingly recognized as a viable alternative in animal cell culture due to the higher production capacity, increased flexibility, prevention of cross contamination, reduction of the cleaning cost, and shortened downtime. In this paper, the effects of the impeller speed, the volumetric gas flow rate, and the impeller type on the volumetric gas-liquid mass transfer coefficient in a single-use unbaffled angled-shaft bioreactor applicable for the animal cell culture were analyzed and compared with those attained for the baffled vertical-shaft bioreactors. The volumetric gas-liquid mass transfer coefficient (KLa) was experimentally determined by the simplified dynamic pressure method. The lowest P/V values as well as the highest KLa values were achieved for an unbaffled angled-shaft bioreactor. It was found that the Rushton impeller was the most efficient impeller in term of mass transfer for this bioreactor. An empirical correlation for the mass transfer coefficient was also developed.

How to Produce mAbs in a Cube-Shaped Stirred Single-Use Bioreactor at 200 L Scale.

Single-use bioreactors have increasingly been used in recent years, for both research and development as well as industrial production, especially in mammalian cell-based processes. Among the numerous single-use bioreactors available today, wave-mixed bags and stirred systems dominate. Wave-mixed single-use bioreactors are the system of choice for inoculum production, while stirred single-use bioreactors are most often preferred for antibody expression. For this reason, the present chapter describes protocols instructing the reader to use the wave-mixed BIOSTAT® RM 50 for cell expansion and to produce a monoclonal antibody (mAb) in Pall's Allegro™ STR 200 at pilot scale for the first time. All methods described are based on a Chinese hamster ovary (CHO) suspension cell line expressing a recombinant immunoglobulin G (IgG).

Orbitally Shaken Single-Use Bioreactor for Animal Cell Cultivation: Fed-Batch and Perfusion Mode.

Increasing the cultivation volume from small to large scale can be a rather complex and challenging process when the method of aeration and mixing is different between scales. Orbitally shaken bioreactors (OSBs) utilize the same hydrodynamic principles that define the success of smaller-scale cultures, which are developed on an orbitally shaken platform, and can simplify scale-up. Here we describe the basic working principles of scale-up in terms of the volumetric oxygen transfer coefficient (kLa) and mixing time and how to define these parameters experimentally. The scale-up process from an Erlenmeyer flask shaken on an orbital platform to an orbitally shaken single-use bioreactor (SB10-X, 12 L) is described in terms of both fed-batch and perfusion-based processes. The fed-batch process utilizes a recombinant variant of the mammalian cell line, Chinese hamster ovary (CHO), to express a biosimilar of a therapeutic monoclonal antibody. The perfusion-based process utilizes either an alternating tangential flow filtration (ATF) or a tangential flow filtration (TFF) system for cell retention to cultivate an avian cell line, AGE1.CR.pIX, for the propagation of influenza A virus, H1N1, in high cell density. Based on two example cell cultivations, processes outline the advantages that come with using an orbitally shaken bioreactor for scaling-up a process. The described methods are also applicable to other suspension cell lines.

Fujifilm boosts gene-therapy activity

Fujifilm will invest $120 million at its Diosynth Biotechnologies contract-services campus in College Station, Texas, with the addition of a 6,000 m2 building, including laboratories dedicated to gene-therapy research. The company will also expand current good manufacturing practice capacity at the site with eight single-use bioreactors ranging from 500 to 2,000 L. It has offered gene-therapy fill-and-finish services at College Station since early 2019.

CAR-T Cell Expansion in a Xuri Cell Expansion System W25.

Cell expansion is typically a long and labor-intensive step in CAR-T cell manufacture. The Xuri Cell Expansion System (CES) W25 semiautomates this step while functionally closing the process. Cells for autologous or allogeneic cell therapies are cultured inside a single-use Xuri Cellbag™ bioreactor. Wave-induced agitation, performed by a rocking Base Unit, transfers gas and mixes the culture. The integral UNICORN™ software allows customization of culture conditions and media perfusion schedules. Culture volumes can range from 300mL to 25L, making the Xuri CES W25 system suitable for both scale-up and scale-out manufacturing processes. CAR-T cell therapies have been successfully generated using the Xuri CES W25 system, which reduces manual labor compared with static culturing methods. This chapter details how to initiate a culture, install the Xuri CES W25, and install a 2L Cellbag bioreactor. Protocols on inoculation, monitoring, and sampling are also outlined in this chapter.

GSK invests $120 million in manufacturing

In another manufacturing investment, GlaxoSmithKline will spend $120 million to revamp and expand its facility in Upper Merion, Pennsylvania. GSK has shifted to using single-use bioreactors at the facility to produce experimental biologic therapies for cancer and other diseases. In August, GSK announced the opening of two continuous manufacturing facilities in Singapore. And in April, it announced a $100 million investment at its site in Hamilton, Montana, which produces parts of its shingles vaccine.