The term Single Use in the biopharmaceutical field refers to the products that can be that can be used only one time, It is also known as disposable that are usually made from plastics therefore after these products are used , they are being discarded.
The innovation of Single use technology were first invented and circulated in 1978 in form of disposable capsules and a variety of filters for the purpose of eradicating the risk of contamination that had become a problem to the manufacturers of biopharmaceuticals, however up to now this problem still requires high level of attention in monitoring the manufacturing processes. The use of single use technology has efficiently improved its operational by minimising the need for sterilization practices between the batches. (Dieter elbl, 2012)
Implementation of disposables:
Disposables are being manufactured in order to serve the same purpose the way the stainless steel counterparts provided according to their specific characteristics. The performance of the disposable, its costs and the security of supply chain must put into consideration when minimising the risk of using disposable.
In terms of disposable development and their use in commercial manufacturing system, they are considered to be still in their infancy, in other words, the disposable establishment in various areas of biopharmaceutical production are still lacing the long term studies, reference and standards that would be normally associated with a mature technology. Currently no supplier is able to provide all available technologies and majority of products have not been standardised. However numerous suppliers provide a broad range of products and technologies with different development stages.
The diversity of disposable and its importance in bio manufacturing applications were initially used only in research and development, but there applications are now gradually used in commercial manufacturing operations especially in producing hybrid facilities, incorporating disposable devices, buffer, media and bulk products through mixing system and disposable bioreactors for filtration, chromatography and filling.
Currently there are limiting to the use of disposable system due to chemical, biological and physical properties shown by the polymer material in contact with process fluids and the intermediates or final product. (Regine Eibl, 2011)
In past years, disposables and Single Use Technologies have turned out to be popular and now it is possible to make a small amount of drug products with Single Use Technologies that might be useful for clinical testing.
Single use technology is currently the leading field of development within bio manufacturing companies, this has enabled most of bioprocessing industries to focus into Single use technology contributions as this has benefited the production of all categories of biopharmaceuticals.
Many Companies have advanced in new Single Use technologies used in both processing of upstream and downstream forms of biopharmaceutical production. The Single Use Technology field involves different types of systems for upstream processing, and the example of this is the disposable bioreactors, membrane adsorbers this has been successfully applied in purifying DNA, media bags, bioprocess containers, disposable mixers, and samplers. On the other hand, single use technology has expanded in downstream processing area through making various products such as disposable filter cartridges, depth filters, tangential flow filters, tubing, and connectors.
Before single use technology were introduced, facilities such as buffer, and medial preparation had to be available for material to be used throughout the workflow of bio manufacturing but currently, this has led to the production of small portion of drug that are used in preclinical and clinical testing.
The single use systems has been strategically accepted by the most of biotechnology to be part of producing an effective product with heathy and efficient processes. These technological benefits has offered and demanded the biotech industry disposable schemes into new processes. Numerous developments for upstream processing in single use are now clarified and accessible for example cell culture development, how to prepare media, aseptic technique sampling, aseptic connection, and filtering the depth.
Another important area for the growth of single use technologies is microbial fermentation. Initially the problem was to provide sufficient quantity transfer needed for fermentation and also to handle the heat created by microbial cultures but the Modern single use microbial fermenters are restricted to the 50 liter scale, therefore lack of higher mass fermenters for the manufacturing of biopharmaceuticals on the clinical scale could be the big problem.
There has been an increase in the disposable technology users in terms of supplying disposable goods and this has significantly reduced the risk of handling critical process operations. Although the majority of disposable processes are still inadequate to cell culture and vaccine processes. Most of the integrated disposable systems are used for mixing buffers and media, holding media and product intermediates. (Stok, 2010)
In considering advanced unit operations, the most developed systems available for cell culture are the bioreactors. Some of the available options includes temperature, pH and aeration control, mixing, fed batch capabilities, aseptic sampling and aseptic harvest. Most of these systems are designed with electronic batch records. However the floor space footprints, disposable portions, validation, hardware and custom preferences differ in their price and availability. Most systems are capable in cell culture capabilities.
The Single use technology has hold a huge potential in reducing development cycles and time to market for new bio therapeutics for example antibodies and human vaccines. The applications potential in the vaccine production, has led to the use of small volumes, production of batch, requirements of flexible production and the risk of cross contamination. These areas has been achieved by single use technologies. (stephan, 2012)
The Single-use bioprocessing equipment in upstream single use bioprocess has developed the technology within short period of time. Disposable devices and all its components have rapidly created market positions and new technology that continue to prosper. However in biopharmaceutical manufacturing, single use mechanisms and systems are now providing different advantages over reusable systems. In order to move to a single use method, various factors has to be considered and in a recent study of bio manufacturers, the risk of leachable materials entering drug products were at high rate. (W.G, 2003)
The stainless technologies does not necessarily need to be replaced, but the benefits of combining Single Use systems into system operations can be only attained by producing either a full conversion to plastic solutions or suitable combination of Single Use and stainless technologies. Manufacturers can strongly maintain process flexibility and improve competence with limited conversion to Single Use technologies. For example the cell culture processes combining Single Use bioreactor technology with traditional stainless reactors and final fill operations integrating Single Use systems with traditional vial filling equipment.
At the moment, Single Use technology can be used in a variety of stages as well as unit systems in bio processing manufacturing although some unit operations have limitations because of present capital installed and lack of technologies available in Single Use technology formats.
The demand for single use technologies has led to various benefits such as reduced costs, minimizing the risk of product contamination, and has improved flexibility in multi-product facilities. Modern bio manufacturing developments have taken the demand for single use to a new level.
The integrated single use solutions are currently address user supplies by offering extreme flexibility to changing process needs, this makes it easier for bio manufacturers to embrace single-use technologies. There are several factors that have contributed to the development of single use technologies, and these includes the strong development in the demand for monoclonal antibodies, about 8,500 kg in production currently and an estimated growth rate of 16% through 2014.
In addition, increased inspection by the FDA has transformed into stricter safety regulations with which bio manufacturers must fulfill. At the same time, companies are focusing at the problem of sustainability and how it can affect developments and profitability.
Single-use manufacturing
The market for single use technologies has increased. According to current survey conducted by an industry group of single-use manufacturers and end-users called Bioprocess International on behalf of BPSA shows that the leading market producer for transferring to single-use technologies is due to the eradication of cleaning and sterilization cycles. The survey also aimed at lowering costs, accumulative production speed and enable flexibility, and to reduce contamination risks as factors stimulating the market growth.
Lower manufacturing costs
Single use technology enables the companies to lower its costs mainly in the elimination of costly stainless steel equipment during installation and cleaning. If single use technologies is to be Compared with stainless steel for 1 g/l cell titers, the manufacturer are able to save approximately 50% in the amount of goods cost including repaid capital, labour, water, utilities and other plant infrastructure necessities. As the amount of titers increase, companies are able to produce additional product with lesser volume bioreactors, which are predominantly well suited for single-use practices.
Considering the environmental footprint of a stainless steel based bioprocessing facility compared to one based on disposables, a study that was conducted in 2008.the study discovered that single use processes required: 87% less water; 21% less labour; 38% less space; 29% less energy to run. (andre siclair, 2008)
Enhanced speed and flexibility
Single use technologies, were first adopted by the Contract manufacturers because they found it successful to turn around the manufacturing operations quickly their main objective was to obtain a complete manufacturing atmosphere that will enhance the process efficiently and flexible. They realized that Single-use system allow companies to obtain a high level of flexibility to enable the manufacturer to increase multiple drugs in single manufacturing suite. This is more beneficial when drugs are still in clinical trials and companies are able to create quick process changes to accommodate a range of drugs in a collection.
Safety
On the issue of safety, in single use equipment can be pre-sterilised before are used by the supplier, this means that it is possible to eliminate any classified surroundings around the manufacturing process. This helps manufacturer to eliminate the risk of cross contamination hence reducing the costs as well as material waste.
A Need for integration
Despite their numerous advantages, single use technologies has the problem of building a wide range process step and putting up single use products together. Therefore the manufacturer offers solutions about the benefits of disposable technologies and make their acceptance easier for direct use. Therefore it is easy to use single use solutions features, filtration validation devices and documentation and technical support.
Reduced costs and Compressed production time,
A single use solution should be designed to help the disposable flow paths that will facilitate set up and reduce the space. This reduces time that might be used by the stuff during the preparation, set up, and its cost. These integrations should be elevated for a dedication application, therefore the single use components eradicate the need for post cleaning, and all of these structures allow bio manufacturers to enable them to concentrate on work, quality and service to customers.
Flexibility:
The single use solution should be intended for extreme operational flexibility, this enable the users to implement new processes faster. This feature mainly suits the changing process of contract manufacturers. Flexible hardware platforms should be accessible and movable, in order accommodate a variety of processes.
Safety and efficiency:
Single use technology tend to minimize contamination, keeps the error to the minimum, the system does not dependent on skill and reliability. This single use system is aimed at lowering costs, and sustain productivity of staff efficiently and also reducing material costs of waste. They also prevent process deviations that can be a substantial factor over cost problems.
Future directions for single-use technologies
In the near future, single use systems are likely to be improved as a main element of the biopharmaceutical manufacturing process. It is evident that this has happened already with disposable filters and tubing, and buffer and media storage bags, has slowed its market growth to less than 10%. However other forms of disposable technologies are still being developed and yet to be established and advancing from innovative developments. This will help to create more different end user choices. Therefore, although single use systems are discovering the important mainstream applications in bioprocess practices with new production trains presently they are starting to employ these structures, more research is needed to improve the diversity for unit operations to completely embrace the disposables campaign. (Abhinav A Shukla, 2013)
Conclusion
Single use technologies that began as an inventive alternative to fixed equipment for the production of biopharmaceutical products, they have now become turned out into a strong competitive technology for several areas of the manufacturing and processing chain.
Companies have resorted to single use technologies because they prefer more flexibility with different batch sizes, it has also led to faster processing times and highly effective unit operations. Integrated single use solutions facilitates faster implementation and enhanced safety, this shortens development and production time. This is aimed at meeting the requirements of contract manufacturers, such integrated single-use solutions saves time and money and creates a peace of mind.
The growing pressure on capital and working costs, the threat of product cross-contamination and the cleaning validation costs all pushes manufacturers away from traditional fixed equipment and gives credit to the crucial advantages of disposable practices for intensifying network of production facilities. The development of single use production systems are aimed at reducing biopharmaceutical manufacturing costs hence supporting the promotion of biosimilars, enabling clinical entry for a broader range of innovative products and an increase of bio manufacturing activities faster to markets for those products that are manufactured in these facilities. According to those factors, single use technologies have the potential to considerably modify the biopharmaceutical landscape in the coming future.
Numerous innovations recently have enabled the implementation of integrated manufacturing facilities based completely on single use technologies. However, more improvement is required to improve the number of suppliers, more platforms, and the increase in the capacity of single use bioreactors, and the addition of biosensor systems for non-invasive process control. But all in all it is expected that all these areas will develop significantly in the years to come, this will bring the disposable technologies to the lead of biopharmaceutical manufacturing in both clinical and commercial production settings.
The figure above shows the closed design of integrated single use solutions that minimizes the risks of operator error and contamination, making the quality of user processes less dependent on operator skill and reliability
Bibliography
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