Editorial: Biopharmaceuticals – discovery, development and manufacturing

Authors


Abstract

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This Special issue, Biopharmaceuticals – discovery, development and manufacturing is edited by Alois Jungbauer and Klaus Graumann and includes articles on various aspects of the development of biopharmaceuticals. Topics covered include the importance of antigen presentation in creating and selecting binding molecules, G-protein-coupled receptors as drug targets, and continuous downstream processing.

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Biopharmaceuticals have clearly revolutionized modern medicine. Prominent examples are growth factors and insulin in the 1980s as well as recombinant antibodies and more complex proteins in the 1990s and recent years. Bringing a biopharmaceutical product from discovery to the market takes enormous investments in time and money with many hurdles along the way. One of the biggest challenges facing the industry is the large number of drug candidates that fail to become licensed drugs. This problem is further exacerbated when drug candidats fail late in the development process. It is therefore important to address not only the issues related to safety and efficacy, but also issues related to production and further improvements of the therapeutic, as early as possible in biopharmaceutical drug discovery and development [1].

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Drug discovery and production are highly interlinked, because the main product attributes need to be defined early on. This Special issue on biopharmaceuticals covers several areas relevant to discovery, development and manufacturing of biopharmaceuticals. Ebersbach and Geisse discuss the importance of the antigen presentation in creating and selecting binding molecules [2]. By ensuring basic homogeneity and functionality of antigens used in immunizations and screenings unpleasant surprises can be avoided later in development. Antibody engineering and optimization has progressed rapidly in the past decade. The review by Vincent and Zurini [3] focuses on recent developments in this exciting field. For instance, a large variety of antibody-derived molecules are under clinical investigation, only a few, mainly Fc-fusions or antibody fragments, have been licensed so far. We are confident that more sophisticated and targeted constructs will reach the market soon and will be beneficial for patients in the future.

Safety and efficacy ... but also issues related to production, need to be addressed as early as possible in the development of a biopharmaceutical.

The majority of drug targets belong to a family of proteins known as the G-protein-coupled receptors (GPCRs). A valuable contribution of biotechnology to drug discovery is therefore the expression of GPCRs or construction of cell systems with co-expressed receptors, as reviewed by McNeely et al. [4]. GPCRs regulate cell communication and thus play an important role in physiology and pathophysiology.

The majority of biopharmaceuticals are glycoproteins. The biological functions of distinct glycans and the impact on some biopharmaceuticals are well understood, and it is known that they are essential for pharmacokinetics, i.e. half-life, and pharmacodynamic properties, i.e. drug potency. The biological functions of other glycans, however, are less clear. Therefore, the understanding of qualitative and quantitative glycan compositions by new analytical tools – reviewed by Lingg et al. [5] – is highly important.

Finally, biopharmaceuticals are often used for the treatment of chronic diseases. This requires the administration of a protein over a long period of time, sometimes even lifelong. Thus, the (potential) immunogenicity of a product is one of the major concerns for biopharmaceuticals, be it new innovative formats, biosimilars, or products of a significantly changed manufacturing process. Hence, it is highly important to develop methodologies to study immunogenicity in vitro and to create predictive tools for, e.g. choosing the right development candidates. Van Beers and Bardor review the latest progress in this field [6].

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Once all of these hurdles are overcome the compound has to be produced in an economic way, otherwise society cannot benefit from the advance in technology. A prime example of an improved production technology is shown by Godawat et al. [7]. They report the implementation of counter-current loading in continuous downstream processing of a biopharmaceutical (for those interested in continuous downstream processing, see also the interview with Konstantin Konstantinov [8]). Conventional batch chromatography is limited because the bed capacity cannot be fully used without losing material. Already in 1988 Arve and Liapis [9] developed a concept to fully load the column bed until saturation, while the breakthrough is loaded onto a second one, which is based on an even older idea on counter-current operation [10]. After saturation is reached the column is washed and eluted similar to batch operation, while the second column is loaded. The group at Genzyme has now brought this idea into practice [7]. We congratulate them for pioneering this brilliant idea. We believe that counter-current loading may be a door-opener for continuous manufacturing of biopharmaceuticals.

We hope you enjoy reading this Special issue.

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Prof. Alois Jungbauer, University of Natural Resources and Life Sciences, Vienna, Austria

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Dr. Klaus Graumann, Sandoz GmbH, Kundl, Austria

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