Upstream Processing

Better Cells for Better Health

Since its inception 35 years ago, the biennial meeting of the European Society for Animal Cell Technology (ESACT) has built on a tradition of combining basic science and applications into industrial biotechnology to become the international reference event in its subject matter. Every other year, this gathering of academics and industry professionals features a famously exciting social program and an extensive vendor/supplier exhibition specific to animal cell technology. ESACT meetings are much-anticipated international venues for information exchange, inspiration, networking, and…

Broadening the Baseline

When the editors of BPI asked us at BPSA to put together a content-rich article for the single-use supplement, we were happy to do so. Our challenge was how to bring in multiple viewpoints about the growing business of single-use that would be a “quick read” for the BPI audience. The answer: an expert colloquy (a “conversational exchange or topical dialogue”). Represented here are several of the most qualified industry spokespersons in single-use — all are members of BPSA and…

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

During the past decade, single-use bioreactors have become widely accepted for use in cell culture process development and clinical manufacturing. Their key benefits over stainless steel bioreactors are flexibility, cost, and time savings associated with the reduction of cross-contamination risks (1). Here, we describe our approach to development and qualification of the Biostat STR single-use, stirred-tank bioreactor. Unlike other stirred single-use bioreactors, it offers a similar design to that of well-established, conventional (stainless steel) stirred-tank bioreactors. Disposability of the single-use…

Amplifying the Possibilities

Polymerases are natural enzymes that are vital to nucleic acid synthesis: DNA polymerase for replication of deoxyribonucleic acid and RNA polymerase for replication of ribonucleic acid. Thus all living things make and use polymerases of their own. But in 1969, the University of Wisconsin’s Thomas D. Brock and Hudson Freeze identified a new species of extremophilic bacterium thriving at 160 °F (70 °C) in a hot spring in Yellowstone National Park. In time, heat-tolerant polymerase isolated from Thermus aquaticus (Taq)…

Single-Use Pumps Take Center Stage

The multibillion-dollar global biopharmaceutical industry is placing increased emphasis on development and manufacture of advanced biologics. Such products offer exciting potential for the development of drugs that could provide as-yet-unknown treatments for a wide array of diseases. One important goal is to commercialize biologic products as early as possible within the typical 20-year patent window. Patent submission must occur during drug development. Much work follows a patent filing, including further product development, toxicity checks, and clinical trials. Hopefully, US Food…

High-Yield Production of PASylated Human Growth Hormone Using Secretory E. coli Technology

Since the 1985 approval of the first recombinant human growth hormone (hGH, such as Protropin/somatrem human growth hormone from Genentech, now Roche), the number of clinical indications for therapy with hGH has steadily increased (1). That led to a highly successful drug with more than US$3 billion sales in 2011 (2). Even so, hGH shares a common problem with most other first-generation protein therapeutics: a very short plasma half-life of just about two hours in humans. Because such biologics are…

Implementing Disposable Sampling Devices for Fully Autoclaved Equipment

Sampling is used extensively to monitor both behavior and quality throughout biopharmaceutical processesing (1, 2). Methods must deliver representative samples and — more important — not compromise the integrity of a given unit operation or the process of which it is part. When microorganisms, animal cells, viruses, or nonfilterable materials are involved, sampling methods must not introduce contamination (see the “Regulatory Requirements” box). For successful sampling, three methods have been used routinely over the years: steam-in-place (SIP) valves; aseptic tube…

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…