Single–Use Technology for Downstream Processing
Despite the fact that the increasing deployment of single-use systems in upstream processing has led to the development of similar systems for downstream processing, the latter are not as significant a factor as the
The basic downstream processing steps used in the production of biopharmaceutical products include conventional filtration and chromatographic techniques as well as recent developments – such as functional filtration/absorption and mixed-mode technologies. The term mixed-mode refers to a multiple retention mechanism, which forms the basis for interactions between the target and the sorbent. In contrast, the filling process for the formulated end product in biopharmaceutical production normally involves conventional fluid transfer with or without final lyophilisation.
From the available set of basic operations, the most suitable methods for product isolation and purification are selected and combined to form a sequence. The sequence and quality of the methods chosen varies depending on the properties and quality requirements of the product, which needs to be purified.
Upstream Processes: How to Apply Single–Use Technology
In upstream processing, single-use technologies offer a number of advantages compared to conventional reusable systems, such as – lower investment costs, shorter development and implementation times, reduced qualification and maintenance effort and increased flexibility. Nevertheless, there is more work to be done in downstream processing. Disposable mixers with capacities up to 1,000 litres and disposable versions of conventional microfiltration (0.1/0.2 μm) and depth filtration systems have already established a foothold, but ultrafiltration remains a bottleneck.
Chromatographic systems are a different story altogether. The cost of chromatography gels offsets the advantages of pre-packaged, ready-to-use columns (i.e., greater flexibility and a reduction in the time and effort involved). Currently, disposable chromatographic systems are not an attractive option for processes that involve frequent harvesting and purification in columns, which have a long service life.
Lack of Alternatives to Affinity Chromatography Great Impediment for Single–Use Technology
At this moment, efforts are underway to develop single-use technologies that enhance process performance and reduce cost. One such notable example is the use of mixedmode sorbents and sequential chromatography. The objective is to reduce chromatography media consumption by developing new protein capture selectivity and increasing utilisation efficiency.
The slow rate of progress in chromatography has led to the development of alternative purification techniques. Functional filtration using membrane adsorbers combines the advantages of single-use filtration and functional surfaces, particularly those with ion exchanger and affinity properties. They are designed right from the outset as single-use systems. Nevertheless, according to Detlef Eisenkrätzer, Roche, the lack of low-cost alternatives to reusable affinity chromatography columns is one of the greatest impediments to the deployment of single-use technologies.
Detection of Process Variables – Technology Depends on Available Instrumentation
In terms of process monitoring and automation functionality, single-use systems are not yet fully on a par with competing systems. They are supplied with in situ and ex situ sensors. In situ sensors, which come into
contact with the culture medium, must be sterilisable. Ex situ sensors are based on non-invasive optical technology, where sensors collect data through transparent windows, or conventional sensors placed in a sample flow outside the sterile barrier do not require sterilisation.
A number of systems are available for detecting process variables such as pressure, temperature and to some extent pH and pO2, so detection of these variables is not a problem. However, the selection of instrumentation for analysis of other process parameters is limited to systems offered by suppliers for integration into their own product. In effect this means that the selection of the single use system supplier determines what analysis instrumentation will be available.
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