April 15, 2012 (Vol. 32, No. 8)
Sue Pearson Ph.D. Freelance Writer GEN
Flexibility and Cost Effectiveness Increasingly Essential in Modern-Day Production Facilities
The world’s population is getting older and is requiring more effective, often biological-based treatments for endemic diseases such as diabetes and rheumatoid arthritis. “In emerging markets, governments are looking to vaccinate or treat diseases in larger numbers of their population. Many of the big pharmas don’t have blockbusters in their pipeline anymore; now it’s all about producing smaller quantities of a greater variety of targeted vaccines, biologicals, and biosimilars,” explained Scott Ripley, marketing leader EMEA, GE Healthcare Life Sciences.
These trends will drive the demand for greater access to biologicals and vaccines, which will put the emphasis on being flexible and cost-effective to ensure biomanufacturing facilities are working at full capacity.
To drive down manufacturing costs, pharmas need to operate flexible facilities to maximize facility utilization while minimizing the risks associated with multiproduct manufacturing at various stages of clinical development and licensed production.
“In today’s market, facility utilization is key. If you’re not sweating your asset and only making one or two batches of a biological per year, then the cost of goods of that product is going to be very high,” Ripley said. “For many CMOs, for example, every day they don’t use their bioprocessing facilities costs them up to $2 million per day in lost revenues.”
Using traditional stainless steel bioreactors and fixed chromatography and filter systems, it can take anywhere from two to seven years to design and build a plant for specific large-scale production of a monoclonal or vaccine. This is a major gamble because if the product fails at Phase III, manufacturers can be left with a plant they find difficult to reconfigure.
One solution to this capacity and flexibility conundrum is to implement single-use biomanufacturing technology that can be swapped around to adapt to different production campaigns. Single-use bioreactors, for example, are established technology that can increase operational efficiency by reducing change over time. With single-use bioreactors there is no need for cleaning in place and cleaning validation steps, or steam sterilization and cool-down time before a bioreactor can be used.
“Cleaning and sterilizing are not value-added steps in biomanufacturing, so it’s desirable that they are kept to a minimum or removed to improve efficiency,” explained Neil Ross, marketing manager—bioprocess EMEA, GE Healthcare Life Sciences. “The proof is in the application, and there are many examples of biologicals in clinical-stage manufacture being produced quicker than if a traditional stainless steel route was implemented.”
Single-use technology has developed rapidly in the past five years, and it is now possible to implement an end-to-end process from cell to biological using an entirely disposable set-up.
GE Healthcare’s ReadytoProcess™ platform now offers around 250 different types of configurations that scientists could put together for their manufacturing.
“ReadyToProcess is a bit like Lego—you take what you need to get your process up and running and put it all together,” said Jonathan Royce, bioprocess marketing program manager.
“Our complete ReadyToProcess factory in a box is made possible by the use of ReadyMate™ disposable aseptic connectors,” Ross added. “These don’t come as either male or female connectors, which is unique, and they come in a range of sizes for scalable operation. They can be operated at pressures up to 5 bar and the pressure drop can be as low as 0.2 bar at flow rates as high as 6,000 L/hr.”
Barriers to Use
If single-use biomanufacturing facilities are to continue replacing traditional fixed plants, there are a number of technical, environmental, and logistical hurdles to overcome. Currently, many single-use biomanufacturing facilities do not have the capacity for large-scale production of biologicals or vaccines.
“The scale that single-use technologies are being operated at is increasing all the time,” Ross noted. Cell culture used to be a bottleneck; now 2,000 L bioreactors are available. Flow rates through disposable assemblies used to be an issue due to the dimensions of aseptic connectors that were previously available, but this has been addressed now. One of the current issues is the pump capacity available in a single-use format, but even here technologies are becoming available that allow for flow rates up to 400 L/min for running microfiltration and ultrafiltration applications.”
Another obstacle that requires a shift in perceptions and more research is the environmental impact of implementing a single-use biomanufacturing facility. To date, a life cycle assessment (LCA) comparing energy demand and global warming potential of stainless steel and single-use bioreactors carried out by GE Healthcare in conjunction with Biopharm Services showed that at a range of production scales single-use bioreactors utilize up to 43% less energy.
“Using disposable bioreactors is not like eating off paper plates every night because the amount of energy and water you’d use to clean a plate is negligible,” Royce commented. “However, when you’re talking about cleaning a bioreactor, the amount of energy to produce the steam to clean it and the amount of water you not only use to clean it but also produce as effluent is much greater then even we’d realized.
“This is why we were pleasantly surprised to see single-use bioreactors actually scored better than their stainless steel counterparts on all 18 environmental factors we evaluated.” This is good news for bioprocess scientists, and the LCA referenced in this article makes similar comparisons of energy demands of an end-to-end single-use process.
Additionally, companies that want to implement a single-use biomanufacturing facility may have difficulty sourcing all of the component parts. This may hold up production runs.
“Pharma and biotech companies are looking to the suppliers of single-use products to ensure each component is delivered on time, are traceable by RFID tagging, are fully validated, and all the leachable and extractable data of each plastic is supplied, too,” Ross said. This shifts the onus onto vendors to ensure their supply chains and logistics are really up to scratch, and this level of reliance requires a real shift in mindset for bioprocess scientists.”
With future trends in the biopharma industry such as generating monoclonal antibodies that are more potent and the rise of personalized medicine allowing smaller patient populations to be effectively treated, large-scale production of monoclonal antibodies may become less necessary. If this is the case, single-use end-to-end biomanufacturing facilities could become a much more popular manufacturing model in the next decade.