This week’s headlines include: WHO moves to roll out first malaria vaccine in Africa, FDA describes plans to expand remote regulatory assessments, An abundance of CAR-Ts: $37B cell therapy cancer market can’t support ‘congested’ pipeline, report says, New York reports 1st US polio case in nearly a decade, Pfizer starts mid-stage trial for vaccine against Omicron subvariant, Editas notches milestones for sickle cell disease therapy as FDA lifts partial clinical hold, and The FDA needs to get ready to evaluate synthetic cells, the next generation of therapeutics.

Podcasts:

Check out our podcast channel. We have over 50 great podcasts covering drug discovery, stem cell culture, upstream and downstream biomanufacturing and more! Click below to download from iTunes or Google play:

In Case You Missed It, Recent Articles on Cell Culture Dish and Downstream Column:

CGT leaders bluebird bio, BMS and Janssen share industry predictions for the decade to help you reinforce your go-to-market strategy

Despite the novelty of the CGT space, it’s already sending shockwaves through pharma. But getting into the mind of industry trailblazers can be a hard task for those trying to assemble an infallible launch strategy…

Accelerating cell and gene therapy development using custom media solutions early in process development

In this podcast, we spoke with Dr. Brad Taylor from Nucleus Biologics and Randy Jacinto from Cytiva about the benefits of using a custom media for cell and gene therapy process development. Topics included current development challenges, increases in the number of cell and gene therapies in clinical trials, and employing custom cell culture media solutions to address these issues…

Achieve unparalleled structural elucidation and sensitivity with the ZenoTOF 7600 system from SCIEX

Liquid chromatography with tandem mass spectrometry (LC-MS/MS) is one of the most versatile and high-performance analytical tools for the detection, characterization and quantification of biotherapeutic molecules and vaccines. However, emerging modalities require new analytical methodologies to enable in-depth characterization and mitigate potential risks early in the development process. In addition, the increasing potency of next-generation biologics drives the need for more sensitive assays for bioanalysis studies. Uncovering new perspectives for molecules, which might have even been previously undetectable, requires overcoming the specificity and sensitivity limitations of current LC-MS/MS technologies. In response to these needs, SCIEX has launched the ZenoTOF 7600 system. This accurate mass, quadrupole time-of-flight (QTOF) system can improve compound identification in protein, oligonucleotide, metabolite and lipid analyses, and it can help scientists uncover new insights and drive decision making processes faster. In addition to offering collision-induced dissociation (CID), the instrument offers a new tunable fragmentation technology based on electrons. The tunable electron activated dissociation (EAD) technology tackles the elucidation of challenging molecules across all charge states, allowing for new depths in the characterization of molecules…

The potential of cord blood is endless – Cell therapy developers need to tap into it

Many people look at umbilical cord blood as medical waste after a baby’s birth. I see it as a stem cell source with endless potential for changing—and saving—lives. And for cell and gene therapy developers, it is a cellular source material they should not shy away from using. I have seen firsthand the potential cord blood holds. I spent nearly 20 years as a physician scientist at the University of Minnesota treating pediatric patients who had leukemia. Many of these patients needed an allogeneic hematopoietic stem cell transplant (HSCT)—also known as a blood stem cell transplant—to treat their disease…

Optimizing Process Development Early – A critical factor in successful viral vector scale up and large scale manufacture

In this podcast, I spoke with John Ketz and Denis Kole about viral vector production, including current manufacturing challenges, navigating the road to commercialization, and successful scale up strategies…

Flexible single-use mixers are key to achieving a next level mixing experience and reducing delivery lead times

In this podcast we spoke with Klaus Kienle, Global Product Manager for the Mixing portfolio at Pall Corporation about the latest mixing technologies including single-use solutions, the need for increased flexibility, and a more standard vendor agnostic approach…

Mustang Membrane Technology for AAV Empty and Full Capsid Separation

Interest in Adeno-Associated Virus (AAV) purification approaches have been increasing with recent AAV based gene therapy regulatory approvals. Purification approaches that have been developed for monoclonal antibodies and other recombinant proteins have been modified for the purification of viruses. However, as the demand for gene therapy increases, so does the need for the industry to create a fit-for-purpose purification solution. Resins, which are a mainstay of protein purification, can’t fully address virus purification because of diffusion limitation: The pores are often so small that they exclude viruses, limiting the binding capacity and requiring longer residence times. This, in turn, means operating at lower flow rates and increasing processing times…

Single-Use in Biotech – Addressing Opportunities and Challenges

Over the past decade, the growth and adoption of single-use technologies in biomanufacturing has been steep and sustained. What began primarily with single use bioreactors has expanded to include single-use components from early upstream processes through downstream and into commercial manufacturing. As of 2018, single-use systems were being used for about 85% of preclinical and clinical biomanufacturing and are increasingly being incorporated into commercial manufacturing¹. The benefits of single-use technologies have been well documented and include risk mitigation, increased efficiency, reduced personnel requirements, less validation time, and customizable solutions. The technology has also been found to reduce utility and water costs for cleaning and sterilization, as well as lower batch changeover time. This is particularly important for facilities that run smaller manufacturing lots, with several different products or are looking to maximize facility flexibility…

Full Adeno Associated Virus (AAV) Capsid Enrichment Using Mustang® Q Membrane

Adeno-associated virus (AAV) vectors are becoming increasingly important gene delivery platforms for the development of gene therapies for several reasons. They are relatively safe with low immunogenicity, and demonstrate high gene transfer efficiency and stable long-term expression in both dividing and quiescent cells. As well, a number of AAV serotypes exist that differ in their tissue tropism, or the types of cells they infect, making AAV a very useful system for transducing specific cell types. Typically, AAV production occurs within a packaging cell line, such as HEK293T cells, where plasmid containing the gene of interest (GOI) are assembled into a protein capsid shell. A current challenge in manufacturing is that the encapsidation efficiency for AAV is highly variable, which produces a heterogeneous mixture of AAV particles that contain the GOI (full) and particles without any genome (empty) or with fragmented, non-functional DNA (partial). Because only the full AAV capsids can exert a therapeutic effect in vivo, the other capsids are viewed as a process impurity and removing them is a necessary step in downstream purification process to achieve a consistent drug product. Existing methods to purify full AAV capsids like analytical ultracentrifugation (AUC) are effective yet have limitations in throughput and cost for a manufacturing environment, which has driven the development of more scalable methodologies for AAV purification…

Single-use Mixers – Ensuring the Customization, Scalability and Supply Required for Success

In this podcast, we talked with Dennis Hodgson and Phil Sanders from Agilitech about the benefits of single-use mixers, dealing with supply chain concerns, ensuring scalability, and tailoring a mixer to meet specific process needs…

Report:

A recent white paper, Osmolality monitoring for UF/DF and CEX capture of mAbs from mammalian cell cultures, published in collaboration with Advanced Instruments examined how osmolality can be used within downstream processing as an additional critical process parameter.

The goal of the study was to understand the impact of monitoring osmolality during an Ultrafiltration/Diafiltration (UF/DF) step prior to CEX capture of the monoclonal antibody Rituximab. The process of UF/DF in downstream workflows is essential within the production of biological therapeutics, such as monoclonal antibodies, proteins (e.g. hormones) and nucleic acids. The UF/DF steps can be undertaken separately or in combination to prepare the target molecule, including sample cleanup, purification, concentration, buffer exchange, and desalting. Since both pH and conductivity are both standard metrics used in downstream process analytics, they were used as a base to then build a model around osmolality measurements within the process of UF/DF.

Download the full white paper here: Osmolality monitoring for UF/DF and CEX capture of mAbs from mammalian cell cultures

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