Downstream Development

Site-Specific Characterization of Glycosylation on Protein Drugs

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A large proportion of biotherapeutic products are glycoproteins. These include erythropoietin and other cytokines, antibodies, glycosyltransferases, and glycosidases, which together generate billions of dollars in sales worldwide. Such drugs are inherently complex. As new treatments emerge and biosimilars are evaluated, the need to better understand their molecular structures is more acute than ever. Therapeutic glycoproteins are typically produced as recombinant products in cell culture systems. Glycosylation is of major importance during development of these drugs because their glycan chains markedly…

June 1, 2014

Enabling Greater Process Control and Higher Protein Titers: Advances in Downstream Single-Use Technologies

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Downstream protein purification (the stage in which a protein is isolated and purified) is one of the last steps in biotherapeutic manufacturing. Single-use technologies are an increasingly popular choice for both upstream and downstream bioprocessing because they offer significant benefits over traditional multiuse manufacturing systems. Single-use technologies also provide an array of logistical benefits, including reduced costs, minimized risk of cross-contamination, and improved operational efficiency (1). Challenges remain, however, in designing a complete, streamlined, single-use process for downstream protein purification.…

June 1, 2014

Development of a Single-Use Filling Needle

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Single-use components such as tubing, connectors, and filters have been widely used for many decades in bioprocess unit operations. Users have been able to identify and quantify the specific benefits of single-use over cleanable systems. In more recent years, many other process components have been designed for disposability such as bioreactors, mixers, and chromatography and ultrafiltration systems. Those and other advances have made it possible to incorporate multicomponent, presterilized manifolds into both existing and new processes, realizing benefits such as…

May 1, 2014

Accelerating Purification Process Development of an Early Phase MAb with High-Throughput Automation

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    Monoclonal antibodies (MAbs) are the fastest growing segment in the biopharmaceutical industry because they are potentially efficacious in the treatment of diseases such as cancer and autoimmune disorders (1,2). With steadily increasing demand for efficient and affordable therapies, speed to clinic/market is important, and biopharmaceutical companies push multiple drugs into development each year to ensure business sustainability (3,4,5,6). Downstream purification process development for therapeutic MAbs is a critical step on their path to reach clinical trials and beyond…

March 1, 2014

Single-Use Bioreactors and Microcarriers

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Cell-based therapies hold promise for treating many acute and chronic diseases (1). Optimism surrounding that therapeutic potential has driven the initiation of multiple clinical trials in pursuit of such treatments. Procedures for preparing these therapeutic agents begin with selective isolation of cells from desired tissues. That is followed by ex vivo expansion of cells of desired phenotype and functionality. Once expanded to acceptable levels, cells are stored to preserve their viability during transportation to treatment facilities. The final step in…

March 1, 2014

Enabling Technologies

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Many technological advancements in recent years have enabled companies to shorten time to market, to better understand their manufacturing processes, and to characterize their products well. In BPI’s December 2013 issue (pages 47–50), I reported on the first half of an informal reader survey about those technologies, with commentary from some survey participants and others. This month concludes with my examination of analytical, formulation/fill–finish, and facilities technologies. Analytical Technologies After writing several installments of our new “BPI Lab” series this…

February 1, 2014

Innovation in Biopharmaceutical Manufacture

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The following is a report from a workshop on innovation in biopharmaceutical manufacturing held at the Annual bioProcessUK Conference in Bristol on 29 November 2012. The aim of the workshop was to access the experience of practitioners in the United Kingdom so as to understand better the challenges and opportunities for innovation in this sector. The workshop addressed the drivers that influence the implementation of process improvements and novel technologies in biopharmaceutical manufacture from the perspective of both manufacturers and…

January 1, 2014

Emerging Challenges to Protein A

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Protein A affinity chromatography has been a target for replacement since its commercial debut, mainly because of its high acquisition cost. The technique became established despite the cost because it was born into an industrial culture that favored speed to market over manufacturing economy (1). Vendors have since strengthened protein A’s position with incremental but worthy improvements such as higher capacity, lower ligand leaching, and modest tolerance of NaOH. Collateral improvements in polishing technologies, such as the high throughput and…

October 1, 2013

Keeping New Technologies Coming

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The biomanufacturing industry is heavily invested in improvements in productivity and efficiency, and innovation is a critical component to ensuring gains in these areas. Yet that is not always the case. Suppliers and innovators in this market face greater challenges, and much longer product evaluation cycles than in other segments, for example the information technology or semiconductor industries. In the highly regulated biomanufacturing environment, changing any aspect of a process can potentially necessitate additional regulatory submissions to the US Food…

June 1, 2013

Comparability Protocols for Biotechnological Products

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Comparability has become a routine exercise throughout the life cycle of biotechnological products. According to ICH Q5E, a comparability exercise should provide analytical evidence that a product has highly similar quality attributes before and after manufacturing process changes, with no adverse impact on safety or efficacy, including immunogenicity (1). Any doubt about data from such studies could translate into unforeseen pharmacological or nonclinical studies — or worse, clinical studies. Selection of analytical methods and acceptance criteria that will be applied…

June 1, 2013