Traditionally, cell-based vaccine production is performed using stainless steel bioreactors that require extensive cleaning procedures. Because disposable bioreactor systems have no need for cleaning and validation, they can significantly reduce start-up times for good manufacturing practice (GMP) manufacturing of cell-based vaccines ( 1 ). Although they are susceptible to a broad range of viruses, Vero cells were recently successfully used for industrial-scale influenza vaccine production ( 2 , 3 , 4 ). However, these adherent cells can proliferate only when provided with a suitable surface on which to grow. Scale-up of such cells is challenging because of the required detachment and reattachment of cells during passaging. The aim of this study is to present a process for scaling up adherent Vero cells for influenza propagation using single-use WAVE Bioreactor systems. Microcarrier Cultivation Vero cells were cultivated on Cytodex microcarriers in Cellbag™ bioreactors using WAVE Bioreactor 20/50 (10-L cu...
Picture the scene: You head to the boardroom for a meeting with a vendor who promises to optimize your company’s fluid-handling processes. “Sustainability,” he says, enshrined in the spotlight of an overhead projector, “is at the heart of today’s agenda.” You slump into your chair. Sustainability is key to your business, yet efforts to bottle this elusive ideal have so far cost more than they’ve saved. “How can a sustainable bioprocess container solution enhance my business?” you ask. “It’s about fusing business sustainability with a bioprocess containment strategy,” he explains. “This enhances efficiencies and public perceptions. It also reduces environmental impacts, whilst increasing long-term shareholder value.” You regain your posture, intrigued to hear more. The presentation begins. Slide 1: Business Sustainability What do we mean by business sustainability? Does it simply refer to your bank balance? Business sustainability encompasses that and a whole lot more. It is felt across every aspect of you...
End oxygen limitations when growing Escherichia coli, Streptomyces, Pichia, Aspergillus, and other high-demand aerobes in shake flasks. Many bioprocesses rely on aerobic growth and protein expression, yet traditional orbital shakers do not provide adequate oxygen. Cultures become oxygen limited. The RAMbio incubator solves this problem by providing active headspace refreshment using low-frequency acoustic energy that aerates standard shake flasks. Why Use the RAMbio? The increased dissolved oxygen provided by the RAMbio may benefit aerobic microbial cultures by RAMbio vs. Orbital Shakers Batch growth and protein production characteristics of E. coli K12 expressing green fluorescent protein (GFP) was evaluated using standard shake flasks in the RAMbio. For comparison, an orbital shaker at 400 rpm with a 0.75-inch orbit was also tested. Cells were grown at 37 °C in rich medium. RAMbio Improves Growth and Productivity: The RAMbio significantly improved culture productivity and kinetics relative to the o...
Catalent is your strategic partner for biologic drug development success. We create smart, tailored solutions with our novel SMARTag™ antibody–drug conjugation (ADC) technology, our market-leading GPEx ® cell line expression system, expanded biomanufacturing capabilities, and integrated development services to help you get better products to market faster. New SMARTag ADC Technology for Development of Optimized Antibody–Drug Conjugates — Superior Technology for Treatments in Development: Catalent has entered into an exclusive license and comarketing agreement with Redwood Bioscience to offer customers SMARTag advanced site-specific conjugation technology and linker–toxin combinations to develop optimized antibody–drug conjugates. SMARTag technology is a proprietary approach to help develop improved antibody–drug conjugates. It allows for very precise conjugation and optimal release of the therapeutic agent, providing advantages over existing technologies with precise site-specific drug placement and enh...
Production of biologics — whether for clinical development or large-scale manufacturing campaigns intended to be converted to final drug product — often involves frozen storage. It provides manufacturing process flexibility while enabling long-term product stability. Products are frozen and stored using a number of technologies: stainless-steel vessels, bottles, carboys, and disposable bags. Although single-use freezing bags are a common choice for storing biologics, challenges with durability persist. Single-use bags intended for freezing and storage are often made with films using ethylene-vinyl acetate (EVA) and/or low-density polyethylene (LDPE) polymers, with product routinely blast-frozen and stored to −30 °C in a cold-storage warehouse. During freezing and transport, the bags will typically experience temperatures well below −30 °C ranging from −50 °C to −80 °C. Under these conditions, the bags have to endure a wide range of stresses (film brittleness, volume expansion, and so on) that impact integ...
Although single-use bioreactors are widely applied in the biopharmaceutical industry, microbial cultivation in them is restricted due to limitations in oxygen mass transfer, mixing, and heat transfer. The CELL-tainer™ single-use bioreactor makes use of an innovative principle applying a two-dimensional (2D) rocking motion, thus providing excellent mass transfer, making this single-use reactor very suitable for microbial cultivation at different scales. With a simple pillow-shaped bag without moving parts, the technology is robust and leads to cost savings compared with other single-use or classical glass or stirred bioreactors. Mass Transfer In a CELL-tainer single-use bioreactor, a pillow-shaped bag is positioned in a tray. The movement of this tray is in two directions: a vertical rocking motion combined with a horizontal translation. This combination of movement results in oxygen mass transfer coefficients, k L a > 300 (h −1 ) both at 12L and 120L scales (working volumes). The oxygen mass transfer co...
Setting its sights on the benefits to the customer, Eppendorf has steadily expanded its proven bioprocess technology portfolio since 2007. With the integration of New Brunswick™ and DASGIP ® , Eppendorf combines its own expertise with the know-how of these renowned suppliers of bioreactors to set new benchmarks. For industrial and research users, this translates into sophisticated bioprocess software and hardware solutions from a single source that covers the full range from miniature bioreactor systems for R&D to production-scale, sterilize-in-place systems. The combination of proven glass, disposable, and stainless steel bioreactor technology with intuitive, easy-to-use, precise process control and comprehensive software solutions for effective benchtop process development is defined as quality by design (QbD). DoE with Minibioreactors With the DASbox ® system, Eppendorf offers a flexible solution that supports bioprocess development activities using four, eight, 12, or more minibioreactors in parallel...
This application note describes the cultivation of Chinese hamster ovary (CHO) suspension cells in the Finesse SmartGlass vessel bioreactor with a maximum working volume of 2.0 L. Using chemically defined minimal media, cell densities of up to 7.44 × 10 6 cells/mL were achieved. Recombinant secreted embryonic alkaline phosphatase (SEAP) expression was induced by medium exchange and temperature shift. Maximum SEAP activities of up to 63 U/mL were reached. A novel stirred glass bioreactor suitable for cell culture applications at benchtop scale was designed by Finesse Solutions, Inc. With a maximum working volume of 2.0 L, this bioreactor is controlled by the Finesse G3Lab controller. Introduction The present study focuses on the cultivation of CHO suspension cells in fed-batch mode using chemically defined minimal culture media and SEAP expression, which is induced by medium exchange and temperature shift. The bioreactor was agitated by a combination of a modified Rushton turbine and a three-bladed segmen...
One of the major bottlenecks in the production of biopharmaceuticals is the efficient expression of therapeutic proteins in microbial or mammalian cells. The Escherichia coli pAVEway™ expression system described here has been developed to ensure high product titers and efficient scale up to GMP manufacture while minimizing many common issues seen in other expression systems, such as “leaky” expression (expression of recombinant protein in the absence of inducer). How It Works The use of a number of powerful E. coli RNA polymerase promoters — such as T7A3, λpL, and tac — opens up a large host range in comparison with the popular T7 system that is limited to hosts carrying the λDE3 prophage. Control over basal expression is provided by the use of perfectly palindromic lac operator sequences (Figure 1). This high level of control is extremely important in large-scale (≥5 L) fermentations because it allows high biomass accumulation prior to induction, which can be helpful when expressing proteins that...
When planning a modern 750-L fermentation plant including a cross-flow unit, the GEA Diessel company was looking for the best available measurement technology suited for its customer requirements. Attention turned to the new intelligent Arc sensors from Hamilton. After testing the Arc system, the plant engineer and GEA’s customer were convinced of the advantages of the new technology, deciding to use the Arc system in the fermentation plant. GEA Diessel and Hamilton were able to supply an accurate and innovative solution to the customer. Requirements Efficiency, compact construction, reliability and precise process controls — these are the requirements for the new GEA. Diessel Company Fermentation Plant: Process stability and the necessary measurement equipment for the entire plant were especially important for the customer. In using the modern Hamilton Arc sensors, a suitable solution is established. Intelligent measurement data processing and robust, high-quality signals directly from the sensor head a...
The need for a rapid turn-around in quantity (and the loss of technicians in many laboratories) has created a trend toward single-use vessels. Their advantages include no time lost in cleaning or sterilization (especially for bench-scale, autoclavable systems), no chance of inhibition or cross-contamination due to poor cleaning, and no need for cleaning and sterilisation facilities in a crowded laboratory. For production-scale steel bioreactors, fully automated clean-in-place (CIP) and sterilization-in-place (SIP) has been possible for decades. By contrast, bench-scale systems required considerable downtime for disassembly, cleaning, reassembly, autoclaving, and cooling before use — with no guarantee that each step was carried out correctly and reproducibly. An innovation from INFORS HT brings the advantages of CIP/SIP to bench-scale bioreactors, offering a true alternative to single-use systems for microbial applications. The LabCIP provides user-configurable recipes for cleaning, sterilization, and rins...
Researchers have turned to Chinese hamster ovary (CHO)–based transient gene expression (TGE) as an alternative to CHO stable cell line production for early stage antibody development. Despite advances in transfection methods and culture optimization, most CHO-based TGE systems produce antibody titers (low mg/L) that are insufficient for full use in biotherapeutic development pipelines. MaxCyte electroporation is a universal, transient transfection platform with unmatched quality, flexibility, and scalability and the capacity to transfect up to 2 × 10 11 cells in under 30 minutes. CHO transfection efficiencies and viabilities of >90% generate antibody titers over 400 mg/L within two weeks of transfection and can exceed 1 gram/L with optimization. MaxCyte electroporation can simultaneously create high-yield, stable CHO cell lines (>3 g/L productivity) in six to eight weeks using a simple selection protocol, thereby streamlining scale up to clinical-grade biomanufacturing. MaxCyte Electroporation Outperform...
Disposable Clamps Qosina offers slide clamps, pinch clamps, and roller clamps in an assortment of sizes, colors, and styles. In stock and available for immediate delivery, these disposable clamps are available to fit tubing dimensions ranging from 0.06 inch OD to 0.75 inch OD. Material selection consists of polyacetal, polypropylene, polycarbonate, ABS, PVC, and many more to meet your needs. In addition, Qosina also carries clamps in a variety of sizes, styles, color, and materials, including closure clamps, catheter clamps, flow control clamps, hose clamps, towel clamps, and non-reopening clamps. Anti-Slip Boot Qosina is pleased to announce the addition of an anti-slip boot (#51599) to its extensive line of stock components. The new anti-slip boot helps prevent luer fittings from slipping apart and works with most standard luer fittings. Made from medical-grade silicone and applicable for autoclave, gamma, and EtO sterilizing, the anti-slip boot measures 11/32 inch ID × ½ inch OD × ¾ inch (0.343 inch × 0...
For more than 65 years, Kerry’s Sheffield brand has earned its reputation for reliability and excellence in serving the biotech, pharmaceutical, and nutrition markets. We deliver innovative, animal-component– free supplements to help customers increase cell proliferation, extend cell viability, and increase target protein production. Every day we expand our capabilities to meet the changing needs of the biotech market by providing the industry’s most innovative and extensive biotechnologies, including complete supplement systems, hydrolyzed proteins, recombinant proteins, and yeast extracts. We have the vast global resources and technical platform to deliver consistent, high-quality products backed by unparalleled service, technical support, and formulation customization capabilities. Sheffield rInsulin ACF Tertiary Animal-Component–Free To meet the challenging needs of the market, Sheffield introduced Sheffield rInsulin ACF as a tertiary ACF, or animal-component–free in the third degree, supplement for i...
In the manufacture of biopharmaceuticals, single-use technologies are now employed throughout the workflow — from buffer and media preparation to bioreactor cultures for vaccines and biotherapeutics production as well as in the storage of those intermediates and bulk biologics. This diversity of applications adds to the difficulty in establishing appropriate testing and requirement specifications, as well as qualification and validation approaches. The integrity and performance of single-use systems depends primarily on the characteristics of the film, the largest component (and product contact surface area) of any flexible container system. Thermo Fisher Scientific employs a three component science- and risk-based approach to characterizing single-use film addressing: The expansion of single-use systems into drug discovery, process development, and manufacturing have exposed those systems to a growing and diverse number of cell systems used in bioprocessing. Recently, the impact of an ultra-low concentra...
Parker domnick hunter’s HarvestClear™ Filtration System is a complete, out-of-the-box filtration system that provides automated clarification of small-scale bioreactor outputs while maximizing filtration performance. The HarvestClear™ System allows for walk-away cell-culture harvest, reducing hands-on time and increasing operator safety without filter blockage. Summary The clarification of batch and fed-batch bioreactor systems can pose a practical challenge to biopharmaceutical manufacturers because of high cell densities in cell culture process streams. The HarvestClear™ Filtration System provides an easy solution for clarifying 1–20 L of high-density fermentation batches of Chinese hamster ovary (CHO) cells. Introduction When correctly sized and controlled, single-use normal-flow filtration (NFF) systems can provide biopharmaceutical manufacturers with high-quality, fast, and cost-effective clarification of discovery and development-scale bioreactors. This offers an alternative to traditional time-cons...
Background Tryptic soy broth (TSB) is a general-purpose medium used for cultivating numerous microorganisms including Serratia marcescens, a Gram-negative rod commonly found in water and involved in pharmaceutical contaminations ( 1, 2 ). This study examines the growth characteristics and bacterial retention of S. marcescens (ATCC #14756) in five types of TSB: EMD TSB (type 1), EMD Irradiated TSB (type 2), EMD Non-Animal Origin TSB (type 3), EMD Non-Animal Origin Irradiated TSB (type 4), and Competitor A TSB (type 5). Materials and Methods To compare the growth characteristics of S. marcescens, standardized cultures were prepared in each TSB and incubated at 30 °C. OD 600 and titer measurements were taken at 0, 2, 4, 6, 8, 20, 24 and 28 hours. S. marcescens cells (24 ± 0.5 h) were imaged using a FEI Corporation Quanta 200F field-emission scanning electron microscope, and ≤100 cells were measured with Image Pro Plus v7.0 using a calibrated measuring standard. To assess the effect of different TSB ...
Eshmuno ® CPX resin is a new strong cation exchanger developed using EMD Millipore’s tentacle technology to provide high binding capacity, resolution, and target yield. For process improvement purposes, this resin was applied for capture of rhFGF18, a fibroblast growth factor (expressed in Escherichia coli ) in phase 2 clinical development for restoring damaged cartilage surface in osteoarthritis. Early purification work used Resin A at low load (12.3 mg target/mL CV) and moderate flow rate (180 cm/h = 6.7 min residence time, RT). For direct comparison, the Eshmuno ® CPX resin was first tested under the same conditions as Resin A. With both resins, rhFGF18 was obtained with high purity and yield (>96%). Process Improvements Eshmuno ® CPX resin has great potential for process improvements because it can be operated at increased flow rates and high loadings. This resin can be used at RTs as short as 2.4 min at <3 bar net pressure (for a packed bed of 20 × 20 cm and standard process buffers). For low-tit...
A platform approach for MAb purification is desirable as it saves both time and money in process development. GE Healthcare Life Sciences’ MAb toolbox employs protein A chromatography media (resins) as well as a wide range of options for polishing purification steps. One of these options is Capto adhere ImpRes, a cost-effective and flexible multimodal anion exchange chromatography medium designed for high-resolution polishing of MAbs. The medium allows operation in either bind-elute (B/E) or flow-through (FT) modes. Here we describe a workflow for method development of a polishing step for a MAb in B/E mode using Capto adhere ImpRes. Screening for Optimal Binding Conditions The influence of pH and NaCl concentration on static binding capacity and dynamic binding capacity of Capto adhere ImpRes was determined in PreDictor™ 96-well filter plates and by design of experiment (DoE) in Tricorn™ 5/50 columns, respectively. The results show that the highest binding capacities were obtained at high pH and low salt...
The vaccine manufacturing industry is continuously seeking more flexible and time-saving solutions for a quicker response to pandemic outbreaks ( 1 , 2 ). For influenza, vaccine is traditionally produced in fertilized hen eggs and purified in fixed steel equipment. Here we describe the scale-up of a downstream purification process of cell-based influenza virus, from a 10 L cell culture to the purification from a 50 L culture using ReadyToProcess single-use technology. Single-use technology reduces the need for time-consuming device preparations, such as cleaning and cleaning validation, and minimizes the risk for cross-contamination, all essential parameters in traditional vaccine manufacturing. Virus Purification Influenza virus was propagated in Vero cells grown on microcarriers ( 3 ). Virus particles were subsequently purified using robust and scalable single-use filtration and chromatography techniques. In the laboratory-scale experiment, standard equipment was used for the downstream purification of...
LEWA developed its first pulseless pump for liquid chromatography in the late 1970s and delivered its first chromatography system in the early 1980s. LEWA is the leader in supplying pumps used for pilot and industrial HPLC, SMB, and LPLC chromatography worldwide. A customer came to us several years ago requesting a low-pressure liquid chromatography system with a flow range of 20–2,200 L/h. They also wanted the ability to achieve linear gradient from 1 to 99%. We designed and built the system, and it is now in a validated process. This was a very challenging task. Upon completion, this question was asked: “Is there a better way?” The Intellidrive technology is the answer. LEWA has now integrated this technology into chromatography skids. The LEWA EcoPrime brings wide dynamic flow range, low-pulsation flow, and accuracy to modern chromatography as unique features. We have combined state-of-the-art functionalities into one unit: It can be a buffer dilution skid, or directly connected to a column to be a chr...
Current downstream processing strategies for recombinant proteins often require multiple chromatographic steps, which may lead to poor overall product yields. Product purification can be especially difficult when a target protein displays reduced stability, has isoforms or misprocessed variants, or needs to be purified from a complex mixture containing a high level of impurities. Through highly specific antibody–antigen based interactions, affinity chromatography brings significant technical advantage to these protein purification challenges. Developed to tackle such challenges, CaptureSelect™ technology is based on chromatography matrices functionalized with highly specific, camelid-derived but yeast-expressed, single-domain antibodies. With a single peptide chain of ~110 amino acids (MW 12–15 kDa) comprising a single monomeric variable domain of a camelid heavy-chain–only antibody (VHH) (Figure 1), these fragments are significantly smaller and more stable than conventional antibodies. These properties o...
Protein A chromatography is still the preferred capture step in monoclonal antibody (MAb) production because of its high selectivity and robustness, although cation-exchange (CEX) or multimode chromatography techniques are claimed as alternatives. KANEKA KanCapA increases the value of protein A affinity chromatography for MAb production. Kaneka’s unique combination of a proprietary-designed alkaline stable protein A ligand and a highly cross-linked cellulose base matrix meets customer requirements for improved performance, high binding capacity, alkaline and chemical stability for cleaning in place (CIP), mild acidic elution pH, limited nonspecific binding, and scalability with good pressure flow characteristics. KANEKA KanCapA is therefore a powerful tool for improving your MAb purification platform. Dedicated Design of Protein Aligand The elution profile of a Protein A column is a critical factor at industrial scale. For example, the VH3 subfamily of MAbs requires lower elution pH than other MAb types d...
Sartobind ® STIC Pico and Sartobind ® STIC Nano are the smallest scalable representatives of the Sartobind ® STIC membrane adsorber family. STIC is a salt-tolerant anion-exchange membrane effective at removing contaminants in buffers containing up to 200 mM NaCl, saving time and reducing costs by avoiding buffer changes. The small size and high throughput of these capsules make them perfect for use on automated chromatography systems such as the popular ÄKTA ® series offered by GE Biosciences. Although both Pico and Nano capsules are designed for high flow rates, the array of valves, pumps, monitors and the flow restrictor found in a typical flow path for gel chromatography can cause unacceptable pressures at their designed flow rates. Although a lower flow rate will reduce pressure in the system, this does not take advantage of the rapid processing offered by Sartobind ® membrane adsorbers. A method designed to maintain ideal conditions without generating excessive pressure is described below, along...
TOYOPEARL GigaCap Q-650S high capacity, high resolution anion-exchange resin for process scale applications was recently introduced by Tosoh Corporation. This resin, with dynamic binding capacities (DBCs) approaching 190 g/L for bovine serum albumin (BSA), is the newest member of the TOYOPEARL ® product line. TOYOPEARL GigaCap Q-650S maintains the high capacity of our popular TOYOPEARL GigaCap Q-650M, and the 35 µm particle size provides high resolution for improved separation of process impurities and aggregates. Introduction The purification of oligonucleotides using anion exchange chromatography has traditionally fallen to resins such as TSKgel ® SuperQ-5PW (20) that offer high resolution and selectivity in conjunction with excellent mechanical stability at very high column pressures. TOYOPEARL GigaCap Q-650S resin offers a low pressure alternative to oligonucleotide purification while preserving the selectivity, resolution, and yields of those higher pressure processes. TOYOPEARL and TSKgel products...
The importance of proper aggregate removal during polishing of a monoclonal antibody (MAb) for therapeutic use is beyond controversy. Severe anaphylactic reactions have been described in the literature for the application of aggregated proteins as a drug byproduct. Traditionally, ion-exchange chromatography (IEX) or hydrophobic-interaction chromatography (HIC) are used to purify a structurally homogeneous product. In case those platforms do not satisfy the requirements for MAb polishing, advanced chromatography resins need to be considered. For instance, mixed-mode stationary phases such as TOYOPEARL MX-Trp-650M may pave the way for more challenging polishing applications. This application note intends to give you some insights into how you could start handling MAb polishing with the tryptophan immobilized ligand. Screening for the Appropriate Conditions for MAb Aggregate Removal Mixed-mode chromatography is one approach to combine the advantages of HIC and IEX. The number of potential ligands for mixed-m...
Cell therapy is offering a promising future in medical advances. Although multilayer trays are suitable for R&D and preclinical cell amplification, they cannot support large-scale industrial production. A successful transition from laboratory scale to an efficient and robust process based on good manufacturing practice (GMP) is key. The Integrity ® Xpansion™ multiplate bioreactors have been specifically designed to enable an easy transfer from existing multiple-tray stacks processes by offering the same cell growth environment on two-dimensional (2D) hydrophylized polystyrene (PS) plates in a fully closed system. To make the bioreactor compact, the headspace between each plate has been reduced to a minimum (1.3 mm). Gas transfer is made through a semipermeable silicone tubing mounted in the central column. A magnetic stirrer at the bottom of the bioreactor ensures a homogenized distribution of gas. Preserving the cell culture environment is critical as small variations in physicochemical parameters such ...
Ajinomoto Althea is a contract developer and manufacturer of biopharmaceutical and injectable products, with fully integrated product development and CGMP manufacturing expertise to support client projects from preclinical development through commercial supply. Each project program at Ajinomoto Althea is tailored to the specific needs of your product, allowing you to leverage our entire integrated manufacturing approach or just the parts you need. While realizing all the tangible benefits of consolidating your development and manufacturing steps, you’ll also have the confidence of knowing that your product is being championed by seasoned professionals who boast an impressive track record of more than 300 cell banks, 160 CGMP protein and plasmid DNA lots, and more than 1,800 CGMP fill– finish lots delivered to date. Biologics Manufacturing: Recombinant Protein & Plasmid Whether it is protein or plasmid production, Ajinomoto Althea’s experienced staff can take your microbially expressed product from cell ba...
Associates of Cape Cod, ® Inc. Contract Test Service (CTS) laboratory specializes in method developement, bacterial endotoxin testing (BET), and glucan contamination. With the most extensive experience of any endotoxin testing laboratory in the world, CTS is GMP compliant, ISO registered, and licensed by the US Drug Enforcement Agency (DEA) as a laboratory capable of handling all controlled drug substances except those included in Schedule I. Endotoxin testing can be performed in accordance with US Food and Drug Administration (FDA), United States Pharmacopeia (USP), European Pharmacopoeia (EP), and/or Japanese Pharmacopoeia (JP), depending on your specifications. In addition to routine testing, CTS has extensive expertise and the ability to customize endotoxin testing to individual client needs, develop methods for difficult samples and devices, transfer BET test methods, and design and produce custom depyrogenation controls for oven validations. CTS has experience with the following sample types : CTS...
Adherent cell processes for production of adenoviruses often involve 2D vessels that require many manual operations and large areas of cleanroom space, or microcarrier cultures that require complex cell transfer steps and a very high level of expertise. To maximize surface area within a compact space, Integrity ® iCELLis ® bioreactors contain macrocarriers trapped in a fixed-bed, providing ≤500 m 2 of 3D growth surface area in only 25 L of fixed-bed. The iCELLis technology can be used at small scales (iCELLis nano bioreactor, starting at 0.53 m 2 ) and large scales (iCELLis500 bioreactor, ≤500 m 2 growth surface) with straightforward process scale-up, easy single-use operation, and minimal space requirements. Transfer and Scale-Up of a HEK293 Cell Culture Process for Adenovirus Production An existing process using HEK293 cells for production of an adenovirus was first transferred from multitray systems to an iCELLis nanobioreactor (0.53m 2 ) by keeping equivalent cell culture parameters. Additional ex...