Cell Line Development

Development of a Plant-Made Pharmaceutical Production Platform

Since the late 1980s, studies have shown that plants can manufacture functional transgenic pharmaceutical compounds. Advantages attributed to plant-made pharmaceutical (PMP) approaches are compelling, and PMP production continues to attract interest from investors and the biopharmaceutical industry (Table 1). Proposed PMP benefits include proven scalability, high production capacity, limited exposure to human or animal pathogens, lower capital expenditures (CapEx), and decreased operating costs. Those putative advantages have proven to be significant business forces driving continued investor support for PMP ventures.…

Limited Analytical Technologies Are Inhibiting Industry Growth

    Progress in the development of bioprocessing-related assays and analytical instrumentation has not kept up with industry demands. The industry wants analytical technologies (especially for single use) to help improve productivity, optimize and monitor processes, provide real-time product quality control, and characterize biosimilars. These trends are reflected in our recent survey data. Over 30% of biopharmaceutical manufacturers and contract manufacturing organizations (CMOs) have expressed demands for improved assays and analytical equipment (1). BioPlan Associates’ eighth annual survey of biopharmaceutical…

Localized Surface Plasmon Resonance for Bioprocess Development, Monitoring, and Validation

    Academic laboratories have embraced localized surface plasmon resonance (LSPR) as the “new wave” of label-free technology (1). This technique is based on the ability of colloidal metal nanoparticles or nanostructured metallic films to absorb light in a narrow wavelength range. Metal nanostructures “sense” changes occurring at their surfaces by shifting the frequency of the light they absorb or reflect. As a consequence, a basic LSPR system requires only optical fibers, a source of white light, and a detector…

An Update on Cell-Based Technologies

    It’s always exciting to find out where the next meeting of the European Society for Animal Cell Technology will be. This venerable conference happens somewhere in Europe every other year. Recent sites have included Dublin, Ireland (2009); Dresden, Germany (2007); Harrogate, England (2005); Granada, Spain (2003); and Tylösand, Sweden (2001). This May, the gathering of animal cell culture scientists and engineers will convene in the palatial setting of the historic Hofburg Congress Center, formerly the Hapsburgs’ imperial residence…

Implementation of Single-Use Technology in Biopharmaceutical Manufacturing

    The increasing application of single-use components and systems in bioprocessing represents one of the most significant changes in biopharmaceutical manufacturing in recent times. Driven by various factors such as improved efficiency, flexibility, and economics, this trend also presents specific challenges to end users. In one industry review by Langer, extractables and leachable compounds from disposable components were considered by end users to be a major area of potential concern regarding safety, efficacy, and stability of the pharmaceutical product…

Putting It All into Perspective

    As part of The Automation Partnership’s “20 Years of Automated Cell Culture” series, science writer Sue Pearson interviewed Dr. John Birch, the chief scientific officer of biopharmaceuticals for Lonza Custom Manufacturing APIS based in Slough, UK. Birch has been with that company since 1996, Before that, he held senior technical positions at Tate and Lyle, GD Searle, and Celltech. Birch has a PhD in microbiology from London University, where he also spent a period lecturing before moving into…

Sequence Variant Analysis Using Peptide Mapping By LC–MS/MS

    Monoclonal antibodies are usually expressed in mammalian cell lines and are produced in several variants known as isoforms (1,–2). Microheterogeneity can result from posttranslational and enzymatic modifications as well as those caused by processing, alteration, storage, and incorrect translation of the target protein (1,3). Common sources of heterogeneity include Fc glycosylation, partial carboxypeptidase processing of heavy-chain (HC) C-terminal lysine residues (4), deamidation or isomerization (5), Fc methionine oxidation, hinge-region fragmentation (6), aggregation, and sequence variants. Sequence variants are…

Demonstrated Performance of a Disposable Bioreactor with an Anchorage-Dependent Cell Line

    Increased adoption of disposable storage vessels and mixing systems for biopharmaceutical manufacturing operations has provided economic and efficiency benefits to a number of life-science companies. Single-use technologies have reduced validation requirements, shortened turnaround times, eliminated cleaning regimes, increased the speed of set-up procedures, and facilitated the development of flexible manufacturing platforms. Many biomanufacturers have sought to extend those benefits into the field of cell culture by using disposable bioreactors. Here we describe work undertaken to develop and demonstrate…

Polymers and Additives Used in Fabrication of Disposable Bioprocess Equipment

The materials used to fabricate single-use processing equipment for biopharmaceutical manufacturing are usually polymers, such as plastic or elastomers (rubber), rather than the traditional metal or glass. Polymers offer more versatility because they are light-weight, flexible, and much more durable than their traditional counterparts. Plastic and rubber are also disposable, so issues associated with cleaning and its validation can be avoided. Additives can also be incorporated into polymers to give them clarity rivaling that of glass or to add color…

Isolation of Novel High-Osmolarity Resistant CHO DG44 Cells After Suspension of DNA Mismatch Repair

    Recent technological advances in cell line and bioprocess development have driven significant improvements in product titers and enabled scientists to accelerate product development timelines (1). Despite those successes, many limitations in developing cell lines for biotherapeutics remain. One example in fed-batch cultures is an apparent paradox: when cell growth is inhibited by high osmolarity after multiple additions of concentrated nutrients intended to enhance cell growth and protein production. Generation of novel host cells to overcome specific bottlenecks found…