Upstream Processing

Reducing Timelines in Early Process Development – Using a Multiparametric Clone-Selection and Feed-Optimization Strategy

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The market for biopharmaceutical products remains highly attractive to small biotechnology companies and big pharmaceutical corporations alike (1). Most leading market products are made using recombinant technology (2). Pressures are continually increasing on process development groups to reduce development costs and timelines for taking new clinical products forward from product research bench scale into initial clinical evaluation studies. For many years a recognized critical bottleneck in development of products from mammalian cell lines was selection and isolation of stable, high-producing…

November 10, 2014

Polymer Resins: Building Blocks for Single-Use Bioreactor Components

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Single-use manufacturing equipment for the production of certain biological compounds (e.g., recombinant proteins from mammalian cell cultures) makes good sense. Such equipment reduces water and energy use, decreases the need for equipment sterilization and waste treatment, and optimizes space in a manufacturing facility. But consider the plastic resins used to construct the disposable parts of such equipment. In BPI’s April 2014 issue, Tony Kingsbury discussed the fundamentals of how plastics are made. In this second installment of BPI’s series on…

October 16, 2014

Increase Protein Yield through Optimization of Suspension CHO Transient Transfection

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This webcast features: Laura Juckem, PhD, R&D Group Leader, Mirus Bio High efficiency transient transfections of suspension CHO cells enable researchers to bridge upstream and downstream processes and provide confidence that recombinant protein will have the same properties throughout the drug discovery pipeline. To address this need, Mirus Bio has developed the TransIT-PRO® Transfection Kit to maximize plasmid DNA delivery and therefore recombinant protein yield. There are several important parameters to consider during transient transfection including: (1) growth media compatibility,…

October 2, 2014

Automated Mini Bioreactor Technology for Microbial and Mammalian Cell Culture: Flexible Strategy to Optimize Early Process Development of Biologics and Vaccines

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The use of mammalian and microbial cells in the production of biologics and vaccines is well established, and the majority of the top 10 drugs are now manufactured in this way. There is a significant and growing pipeline of new biologics (1), which in combination with increased pressure on cost reduction and generic competition from biosimilars (2), means that many biopharmaceutical companies are looking for ways to improve productivity in their development laboratories to ensure that upstream processes are efficient…

September 23, 2014

Single-Use, Stirred-Tank Bioreactors: Efficient Tools for Process Development and Characterization

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During the past decade, single-use bioreactors have become widely accepted as an alternative to conventional stainless steel or glass bioreactors for clinical manufacturing and process development. In the biopharmaceutical industry, glass bioreactors are used mainly for process development and optimization, but also scale-down models for process characterization. So it is of significant importance that such vessels replicate the design of production-scale bioreactors for both reusable and single-use applications. Stirred-tank bioreactors with 2-L, 5-L, and 10-L working volumes have proven to…

September 23, 2014

Superior Scalability of Single-Use Bioreactors

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During the past several years, single-use bioreactors have been gradually established in modern biopharmaceutical processes (1, 2). This adoption is directly linked to their unique ability to enhance flexibility and reduce investment and operational costs. Furthermore, production output can be increased, and time to market is shortened (3). Today a wide variety of single-use bioreactors exists for the cultivation of mammalian and insect cells (4), whereas only limited solutions are available for microbial cultures (5). Typically, processes are established and…

September 23, 2014

Integrated Optical Single-Use Sensors: Moving Toward a True Single-Use Factory for Biologics and Vaccine Production

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Through the past decade, single-use bioreactors for culturing mammalian and insect cells have been widely adopted in preclinical, clinical, and production-scale biopharmaceutical facilities (1, 2). With such bioreactors in operation, monitoring and control of process parameters is vital for ensuring critical quality attributes (CQAs) of biologicals or vaccines are met for production of a safe product. Traditionally, bag-based and bench-top vessels have been fitted with conventional pH and dissolved oxygen (DO) probes similar to those used in stainless steel or…

September 23, 2014

Consistently Superior Cell Growth: Achieved with New Polyethylene Film Formulation

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During the past decade, single-use bioprocessing bags and bioreactors have gained a significant foothold in the biopharmaceutical industry because they offer a number of advantages over traditional stainless steel equipment, especially for clinical production, multiproduct facilities, and emerging economies. At the same time, some companies are concerned that plastic materials might release potentially toxic substances that could affect cell growth and product titers (1). In a worst-case scenario, they could even compromise drug safety when a company uses disposable bags…

September 23, 2014

Development and Qualification of a Scalable, Disposable Bioreactor for GMP-Compliant Cell Culture

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During the development of single-use, stirred-tank bioreactors (e.g., BIOSTAT STR bioreactors), different phases can be distinguished (Figure 1). First, a clear definition of the intended application and all related requirements should be captured in a user requirement specification (URS). Based on that, the single-use bioreactor design phase and the material selection phase are initiated, both closely linked to each other. During the proof-of-concept phase, relevant component- and product-based tests are established and realized to ensure URS compliance. Finally, the qualification…

September 23, 2014

Verification of New Flexsafe STR Single-Use Bioreactor Bags: Using a CHO Fed-Batch Monoclonal Antibody Production Process at 1,000-L Scale

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In the past decade, single-use bioreactors have gained wide acceptance for biomanufacturing. The biopharmaceutical industry is increasingly interested in performing modern production processes in single-use facilities. That trend is driven by the time and cost benefits of single-use technologies, as well as the enhanced manufacturing flexibility they offer (1). With single-use bioreactors increasingly used in late-phase clinical trials and commercial production, their quality, reliability, and assurance of supply becomes more critical. Many industry experts consider process control of film and…

September 23, 2014