Bioreactors

Raman Spectrometric PAT Models: Successful Transfer from Minibioreactors to Larger-Scale, Stirred-Tank Bioreactors

Spectroscopic sensors are powerful tools for bioprocess monitoring within the process analytical technology (PAT) initiative of the US Food and Drug Administration (FDA). The PAT framework includes process understanding based on scientific background with the aim of monitoring and controlling critical process parameters (CPPs) that influence critical quality attributes (CQAs) of final biological products. The driving force for PAT implementation is a need to realize consistent product quality, process intensification, and real-time manufacturing control (1, 2). Using real-time spectroscopic measurements…

Analytical Tools for Improving Up- and Downstream AAV Process Development

During a May 2022 Ask the Expert presentation, Ivana Petrović Koshmak (head of upstream process development at BIA Separations, part of Sartorius) highlighted the gene- therapy industry’s need for fast, reliable analytics that work with both up- and downstream samples. High-performance liquid chromatography (HPLC) methods can fulfill that need, but process development (PD) scientists would need to account for the complexity of bioreactor samples to make such methods feasible for end-to-end analytics. Koshmak described a novel instrument that is designed…

Hardware, Software, and Wetware: 20 Years of Advancements in Biopharmaceutical Production, Part 1

The past couple of decades have witnessed significant advances in upstream bioprocess technologies and approaches. Since its establishment, BPI has been a facilitator of discussion in both print and professional conferences, as well as in webcasts and news online. To mark the 20th anniversary of the publication, we surveyed articles published over the past two decades and found hundreds that highlight significant advances in both emerging and established themes in biopharmaceutical production: • “hardware” and assets (e.g., analytical instrumentation, bioreactors,…

eBook: Factors Affecting Scalability of Cell Therapies

The number of cell and gene therapies in different phases of development is increasing. The industry currently needs to increase commercial good manufacturing practice (GMP) capacity to keep up with current and future demands. Cell and gene therapy scale-up from clinical to commercial capacity levels can reduce cost of goods and thus price per dose.  An optimized bioprocess facilitates scale-up from hundreds (clinical scale) to thousands of doses (commercial scale). Different approaches for increasing scale can be taken. For example,…

Pressure Vessels for Biomanufacturing: Basic Considerations for Cleaning and Process Compatibility

Pressure vessels are enclosed containers used to contain liquids, vapors, and gases at pressures that are significantly higher or lower than the ambient pressure of their surroundings. Equipment such as bioreactors, holding tanks, mixing tanks, separators, and heat exchangers all are examples of pressure vessels. As such, they form an integral part of biopharmaceutical manufacturing. Apart from pressure containment itself, a key challenge in building pressure vessels is making them meet the high purity and cleanability requirements of bioprocessing. As…

High-Yield Production of rAd26-S for Sputnik V Vaccine Component I: An Optimized Process in a Scalable Shaken Bioreactor

The recent outbreak of the severe acute respiratory syndrome coronavirus (SARS-CoV-2) led to the development of different vaccine approaches worldwide to prevent the coronavirus disease 2019. The first registered vaccine on the market was the Sputnik V product based on two recombinant adenoviral vectors (Ad5 and Ad26). The product has received approval in 70 countries by several national and regional regulatory authorities, meanwhile. Though the availability of SARS-CoV-2 vaccines in most developed countries is not an issue any longer, other…

Strategizing Scale-Up and Scale-Out for Cell Therapy Production

When considering strategies for expanding the number of cells being grown to support cell therapy development, companies often focus on decisions regarding scale-up and scale-out: increasing capacity either by using larger vessels to increase production volume or by implementing more units of the same vessel, respectively. Complete workflows often involve both. Figure 1 shows an example of scaling out from one to multiple cell culture flasks of the same dimension before transitioning to a larger format. Scale-out can be straightforward…

Ask the Expert: Facilitating Process Development Using a Microfluidic Perfusion Bioreactor

Suitable scale-down perfusion systems generally have been unavailable for process development (PD) activities. Some commercially available systems require daily media exchanges. No such system performs in a way that accurately represents large-scale perfusion, and none maintains sufficiently high cell densities. Kevin Lee (cofounder of Erbi Biosystems) joined BPI on 4 May 2021 to explain how his company’s Breez bioreactor system integrates all the functions of a stirred-tank reactor (STR) into a compact format that can facilitate PD, enabling one person…

High-Yield AAV Viral Vector Production in Corning Ascent Fixed-Bed Reactor System

Gene therapies hold great promise for one-time treatments that alleviate or cure certain genetic conditions. Recombinant adenoassociated viral (AAV) and lentiviral vectors have emerged as leading gene delivery methods for in vivo and ex vivo gene therapies, respectively. With more than 500 gene therapy clinical trials underway, the industry needs scalable, cost-efficient viral vector manufacturing. To address those needs, Corning developed the Ascent fixed-bed bioreactor system for scalable, high-density, adherent cell culture, including high-yield viral vector manufacturing. The Ascent fixed-bed…

eBook: Bioreactor Sensors —
Inside the Dynamics of Cell Culture

Cell culture monitoring can fall into something like a “black box” conundrum. Efforts to measure key parameters such as pH, glucose, and even cell density require sampling and removal of the contents from a bioreactor. But that procedure can expose both a process and an operator to contamination risks. Emerging bioreactor sensors are designed to address some of those challenges, but the rapid adoption of single-use technologies and the rise of perfusion cell culture have presented obstacles to their implementation.…