Upstream Processing

T-Cell Suspension Culture in a 24-Well Microbioreactor

Cell therapy promises revolutionary new therapeutic treatments for cancer and other serious diseases and injuries. For example, T-cell therapy response rates of >50% and durable complete response rates of 20% have been reported in patients with metastatic melanoma who had failed other therapies (1). In another example, sustained remissions of up to a year were achieved among a small group of advanced chronic lymphocytic leukemia patients upon treatment with autologous T-cells expressing an anti-CD19 chimeric antigen receptor (2). Numerous other…

A Risk-Based Life-Cycle Approach to Implementing Disposables for Facility Flexibility

Plastic-based, single-use, disposables has been prevalent in biotech/pharmaceutical manufacturing processes for decades. Examples of such technologies include filters, gaskets, tubing, sampling bags, carboys, and ultrafiltration/diafiltration (UF/DF) capsules. In recent years, single-use technology has made great leaps in broadening the range of options and applications available. Disposable bioprocess containers are now widely used for applications such as media/buffer preparation and storage, bioreactors and cell culture operations, in-process intermediate containers for manufacturing operations, final drug substance/product containers, and so on. Customized solutions…

Drug Products for Biological Medicines

Traditionally, the CaSSS CMC Strategy Forum meetings have provided a scientific focus on the development of biotech drug substances and their manufacture and characterization, leaving the development of drug product formulation and filling, understanding primary containers, and considering novel delivery systems somewhat out of scope. Over recent years, however, the importance of investing more science and technology into drug product development has become evident as different product types, higher protein concentrations, and doses and requirements for improved delivery of biological…

The Influence of Polymer Processing on Extractables and Leachables

Polymers provide a unique set of material properties, including toughness, chemical resistance, versatility, and low cost for both multiple-use and single-use bioprocessing systems. Polymer materials are manufactured as fittings and tubing for research and development (R&D) laboratories, as containers for bulk chemical and biological storage, as filters and separation technologies for downstream processing, and as containers and bottles for drug substance storage. These components and systems are helping drug companies improve their manufacturing flexibility, reduce their operating costs and capital…

Advances in Sensor Technology Improve Biopharmaceutical Development

Today’s biomanufacturing operations require constant management of biopharmaceutical process attributes throughout process development and production. Continuous online measurements of pH, dissolved oxygen (DO), oxidation–reduction potential (ORP), and conductivity (Figure 1) allow real-time industrial process monitoring and adjustment. These functions are crucial to process improvement studies and accurate, reliable manufacturing of high-quality products. Figure 1: () “In the pharmaceutical industry, it is extremely valuable to see how an attribute changes with time and correlate that change with parts of the process,”…

Single-Use Technology and Modular Construction

To enable broad, global access to life-saving biopharmaceutical products, our industry is facing significant pressure to reduce the overall cost of manufacturing and enable local manufacturing where possible. Combined with growing markets outside the United States and Europe and development of high-titer, high-yield processes, that pressure has led to a shift in the industry’s approach to facility design and construction. Today’s biopharmaceutical production facilities must be flexible, cost effective, and readily constructed with minimal capital investment and construction timelines. As…

A Short History of Cell Culture Media and the Use of Insulin

A surprising history of cell culture media and the use of insulin, outlining the basic developments behind growing mammalian cells.

It will take you on a journey from the late 1800 where organ tissues were kept in balanced salt solutions -BSS- and later PBS, until the early 50’s synthetic media, over chick embryo extract and Eagle’s Minimal Essential Medium (MEM) or its modification by Dulbecco (DMEM). Finally describing insulin mimicking growth factors.

Gram Scale Antibody Production Using CHO Cell Transient Gene Expression (TGE) via Flow Electroporation

MaxCyte flow electroporation provides a universal means of fully scalable, highly efficient CHO-based TGE for the rapid production of gram to multi-gram level s of antibodies without the need for specialized reagents, expression vectors, or engineered CHO cell lines. In this technical note, we present data demonstrating the reproducibility, scalability, and antibody production capabilities of MaxCyte electroporation. Secreted antibody titers routinely exceed 400 mg/L and can exceed 1gram/L following optimization, thereby enabling multi-gram antibody production from a single, CHO cell transfection. In addition, we present data showing the use of MaxCyte electroporation for the rapid generation of high-yield stable CHO cell lines to bridge the gap between early and late stage antibody development activities.

Has Your Current LIMS Implementation Been a Nightmare?

Because current traditional LIMS have not delivered on their promise, many organizations are still searching for solutions to optimize their laboratory operations. For those engaged in deploying traditional LIMS, frequent sleep-disturbing issues include poor flexibility and configurability, expensive and time-consuming customization, difficulties extending and upgrading systems, poor usability, lack of modular functionality, poor service/support, problems integrating with existing instrumentation/IT systems and extra time and resources required to meet critical qualification/compliance requirements. Learn how you can avoid the top 5 LIMS nightmares and rest easier with today’s next-generation process and execution-centric LIMS.

Stress-Induced Antibody Aggregates

Biomanufacturing of monoclonal antibodies (MAb) involves a number of unit operations, including cell culture in a bioreactor followed by chromatography and filtration. Purification is intended to remove impurities, such as protein aggregates, but some such operations may actually generate protein aggregation (1). Table 1 summarizes potential sources of aggregate formation during biomanufacturing processes. Aggregates are multimers of native, partially denatured, or fully denatured proteins. Their presence in biological formulations can trigger detrimental immunogenic responses upon administration (2). Moreover, aggregates can…