Biomanufacturing Single-Use Technologies in Biomanufacturing
The benefits of single-use technologies include cost savings, reduced risk of product contamination, and increased flexibility in multi-product facilities. Current biomanufacturing trends have brought the demand for single-use to a new level.
Today, integrated single-use solutions address user requirements by offering maximum adaptability to changing process needs, making it easier for biomanufacturers to adopt single-use technologies.
A number of factors have contributed to the movement to single-use technologies, including strong growth in the demand for monoclonal antibodies, with approximately 8,000 kg in production today and an anticipated growth rate of 15% through 2014. Sales of other biotechnology products, including recombinant proteins and vaccines, are expected to grow 9% in the same period. Protein titers are also increasing significantly. In the past, companies used titers in the 0.5 to 1 g/l range; today, new processes are commercialized in the 2–5 g/l range and will likely near 10 g/l in the not-too-distant future. Companies are reporting well over a five-fold increase in titers in their commercial processes and higher values in pre-commercial processes, requiring even smaller bioreactors. Personalized medicine is another trend impacting the industry, with the growing market for niche products driving the need for smaller drug quantities.
Contract manufacturers are also expanding their markets, according to a 2009 June report from “High Tech Business Decisions”, with 2009 revenues projected at $ 2.6 billion. As contract manufacturers continually strive to improve and optimize their processes, they are demanding faster turnaround times to help improve speed to the clinic or market.
In addition, increased scrutiny by the FDA has translated into stricter safety regulations with which biomanufacturers must comply. At the same time, companies are looking at the issue of sustainability and how it can affect processes and profitability.
In response to these and other factors affecting the biotechnology industry, it’s not surprising that companies want to lower their cost of goods, improve process efficiency, gain operational flexibility and upgrade their facilities. These goals lead naturally to the use of single-use technologies.
The market for single-use technologies is growing. In a recent survey by Bioprocess International on behalf of BPSA (Bio-Process Systems Alliance, an industry group of single-use manufacturers and end-users), the biggest market driver for switching to single-use technologies is the elimination of cleaning and sterilization cycles. The survey also lists lowering costs, increasing production speed and flexibility, and reducing contamination risks as factors spurring this market growth.
Lower manufacturing costs
By adopting single-use technologies, companies can lower the costs of turning a manufacturing operation around after campaigns by reducing or eliminating the need for expensive stainless steel equipment and the associated expenses of installation and cleaning.
Comparing single-use technologies with stainless steel for 1 g/l cell titers, a company can potentially realize savings of almost 50% in total cost of goods (including amortized capital, labor, consumables, water, utilities and other plant infrastructure requirements). As titers increase, companies can produce more product with smaller-volume bioreactors, which are particularly well-suited for single-use processes.
In terms of the environmental footprint of a stainless steel-based bioprocessing facility compared to one based on disposables, a 2008 study (“The Environmental Impact of Disposable Technologies”, Andrew Sinclair, Lindsay Leveen, Miriam Monge, Janice Lim, Stacey Cox, Biopharm International, November 2008) found that disposables required: 87% less water; 21% less labor (primarily by reducing CIP activities); 38% less space; 29% less energy to run.
These figures highlight the environmental impact of single-use technologies compared to steel, as noted by David Newman, Director, Sustainability of Millipore Corporation in the article “Environmental Considerations for Biomanufacturing Processes”, Industrie Pharma, February 2008.
Enhanced speed and flexibility
Contract manufacturers were among the earliest adopters of single-use technologies, because the ability to turn around manufacturing operations quickly is vital to their success. “Our goal is to have a complete manufacturing suite in place that will give us the flexibility to respond quickly and efficiently as our operational needs change,” says one manufacturer. Single-use processes allow companies to gain a high degree of flexibility to accommodate multiple drugs in one manufacturing suite. This is especially advantageous when drugs are in clinical trials and companies must make quick process switches to accommodate a variety of drugs in a portfolio.
Since single-use equipment can be pre-sterilized by the supplier prior to use, there is the potential elimination of classified environments from the manufacturing process. In addition, the reduced risk of cross-contamination helps companies avoid costly downtime and material waste.
The future is integration
Despite their multiple benefits, one downside of single-use technologies is the building of a complete process step and setting up individual disposable products together. In response, manufacturers are starting to offer “plug and play” solutions to more fully leverage the benefits of single-use technologies and make their adoption easier for immediate use. Ideally, complete, easy-to-use single-use solutions feature configurable pre-application tested assemblies, best-in-class filtration devices, validation packages and comprehensive documentation and technical support.
Compressed production time, reduced costs
A single-use solution should be ergonomically designed to hold integrated single-use flow paths for faster set-up and reduced space requirements. This will reduce the amount of time staff must spend on preparation, set-up, validation and documentation — along with the related costs.
Because integrated solutions should be optimized for a dedicated application, there is no need to stock, locate and assemble fitting components. In addition, the disposable components eliminate the need for post-cleaning, a step that can consume as much as one third of the total process time. All of these features enable biomanufacturers to free up capacity, enabling them to concentrate on work, quality and service to internal and external customers.
The integrated single-use solution should be designed for maximum operational flexibility, enabling users to implement new processes more quickly. This feature particularly suits the rapid process-changing of contract manufacturers. Modular hardware platforms should be scalable and movable, to accommodate a wide range of processes.
Safety and efficiency
The closed design of integrated single-use solutions minimizes the risks of operator error and contamination, making the quality of user processes less dependent on operator skill and reliability. As a result, integrated systems can help prevent costly downtime, maintain high staff productivity and prevent waste from driving up material costs. They can help prevent process deviations that can be a significant driver of cost overruns. Integrated solutions would be delivered validated and presterilized, facilitating compliance with safety regulations. “I can never find everything I need before a TFF run. With these systems, everything I need is readily available in one place,” expressed a single-use user.
Companies turn to single-use technologies because they want more flexibility with varied batch sizes, faster processing times and more efficient unit operations. Integrated single-use solutions enable even faster implementation and improved safety, thereby shortening development and manufacturing time. They are ideally suited to meet the requirements of contract manufacturers, including quick turnaround time. Such integrated single-use solutions free up time and money and provide peace of mind.