Industrial bioseparation

Chapter 16 provides guidance relating to the choice of industrial bioseparation equipment that is available and the issues that must be taken into account when selecting a suitable system to meet both technical and economic objectives. 

The complexity of many industrial bioseparation equipment items means that the design and construction can be time consuming, particularly if process development is required to test the equipment on a typical product to see if it will work at the larger scale. It is not unusual to have 6 to 9 month delivery periods for this type of equipment, and even when delivered, it will be necessary to install, commission, and validate it. Therefore, the project program must recognize the long duration for introducing commercial bioseparation equipment. 

Research activity on drug delivery using mesoporous materials currently far exceeds that on nutrient delivery (Bernardos and Kourimska 2013). The widespread use of mesoporous silica as adsorbents for separating functional food ingredients has also been hindered by insufficient chemical stability under t5qDical food processing conditions (Brady et al. 2007). In the food industry, bioseparation media are typically cleaned and regenerated with sodium hydroxide solutions at 80 °C. This specific application area does not look compatible with mesoporous silicon. 

At present, the purification by chromatographic processes is the most powerful high-resolution bioseparation technique for many different products from the laboratory to the industrial scale. In this context, continuous simulated moving bed (SMB) systems are of increasing interest for the purification of pharmaceuticals or specialty chemicals (racemic mixtures, proteins, organic acids, etc.).This is particularly due to the typical advantages of SMB-systems, such as reduction of solvent consumption, increase in productivity and purity obtained as well as in investment costs in comparison to conventional batch elution chromatography [1]. 

ATPE of proteins/enzymes was reported several years ago [350] while only recently this concept has been developed as a pilot scale by Kula and coworkers [351]. We envisage that RME, despite the fact that industrial or pilot scale studies are not reported, has the potential to develop into a new bioseparation tool for biotechnology. 

Bioseparation processes make use of many separation techniques commonly used in the chemical process industries. However, bioseparations have distinct characteristics that are not common in the traditional separations of chemical processes. Some of the unique characteristics of bioseparation products can be listed as follows ... 

Affinity adsorption offers high selectivity in many bioseparations. However, the high cost of the resin is a major disadvantage and limits its industrial use. 

The economic feasibility of a bioreaction process clearly depends on the characteristics of the associated bioseparation process, especially in the usual case when the product is present at low concentration in a complex mixture. For example, the existence of an extremely efficient and low-cost separation process for a particular compound could significantly lower the final concentration of that compound required in the bioreactor to achieve a satisfactory overall process. After noting that special approaches and processes are needed for efficient recovery of small molecules (ethanol, amino acids, antibiotics, etc.) from the dilute aqueous product streams of current bioreactors, I shall discuss further only separations of proteins. These are the primary products of the new biotechnology industry, and their purification hinges on the special properties of these biological macromolecules. 

Bioseparations frequently entail separations of proteins and related materials from biological matrices.1 This book is planned to serve as a handbook of bioseparations, where the primary focus is separations of proteins however, separations of other materials of interest such as nucleic acids and oligonucleotides are also covered to assist the reader in tackling their particular bioseparation problems. Included in this text is a chapter on the separation of monoclonal antibodies, as these materials have found numerous uses in the biopharmaceutical industry. As a matter of fact, in the last few decades, monoclonal antibodies and recombinant antibodies have become one of the largest classes of proteins that have received FDA approval as therapeutics and diagnostics. 

The diversity of industries that involve bioseparations has led to the development of a wide range of techniques and unit operations for the efficient processing of biological materials. Chapter 16 is planned to aid the scientist or engineer in selecting a method of bioseparation that will be suited to the particular requirements of the process and the product at a commercial scale of operation. 

In moving from laboratory- or pilot-scale processing to full-scale manufacturing, it can be difficult to scale up certain types of bioseparation equipment easily for example, high g centrifuges are available as bench-mounted units (using test tubes), but an equivalent industrial machine with a similar g force is unlikely to be a cost-effective solution, even if it were possible to build a suitable unit. It would not be realistic to consider 10 or 100 identical units as a realistic alternative. Compromises are therefore required as a process is commercialized, to ensure that the process remains technically and economically feasible. 

In this section, the wide range of industries using bioseparation techniques are briefly reviewed. 

The competitive nature of the food and beverage industry and the need for continued improvements in cost-effective manufacturing have provided an impetus for companies to develop and use new bioseparation techniques at very large scales, for example, freeze-drying in coffee production and continuous centrifugation in brewing. 

The industries described are diverse but all require bioseparations at various scales. Although not all such manufacturing processes involve fermentation, it is possible to identify common types of bioseparations which are required at particular stages. 

In the industries using bioseparations described above, there is a great variation in terms of production scale and product quality between waste water treatment and pharmaceutical production. This will obviously affect the choice of equipment for the process, although in many cases the principle on which bioseparation is based will be common. For example, centrifuga-... 

Where small-scale bioseparations have been developed, particularly in the biopharmaceutical industry, there has been a tendency to retain laboratory type equipment even if this results in more labour and capital intensive processing. The reason for this is often to avoid the need for extended periods of process development work with new equipment designs, which might delay the launch of a product where competitors are not far behind. Manufacturers are also wary of adopting new bioseparation techniques for processes if there is any risk that regulators such as the U.S. Food and Drug Administration (FDA) will require more evidence that the equipment is fit for the purpose. This conservative tendency is understandable and may influence the choice of bioseparation equipment for pharmaceutical manufacturing in particular. 

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