Biomanufacturers are looking for technologies that can make their production systems more flexible and efficient – single use technology can help
The advancements in single-use and mobile technology have made biopharmaceutical production more flexible and profitable. Antibodies, proteins, vaccines, cell therapy, and gene therapy are all examples of molecules that can benefit from being manufactured in fully single-use, end to end processes.
Single-use systems help to lower overall operating costs by reducing the time required to perform cleaning and cleaning validation – decreasing analytical quality control costs and improving facility utilization time. They also allow manufacturers to more easily and quickly change over from one product to another, or from one batch to another batch.
Given the significant costs involved when developing and producing biopharmaceutical mediations, biomanufacturers are looking for technologies that can make their production systems more flexible, scalable and quicker to implement.
As a result, single use technologies have evolved to become a mainstream approach for achieving productivity. From single-use bioreactors and disposable chromatography columns, to complete single-use workflows and biomanufacturing facilities, Cytiva has been at the forefront of single-use innovation.
Streamlining process control and automation
Cytiva has been partnering with Rockwell Automation to streamline the process controls and automation of its bioreactors, FlexFactory production lines, and shipping container-based, clean-room units it operates worldwide.
"Biotechnologies and biopharmaceutical processes affect all of our lives—from removing lactose from milk to improving bread and cheese to creating flu vaccines, pregnancy tests and diabetic therapies. We're also using them to develop a protein that can help fight lung cancer by making cancer cells a target, which allows the body's natural white cells to attack those cancer cells, while leaving regular lung tissue unharmed," said Kevin Seaver, general manager, Bioprocess Automation and Bioprocess Digital, Cytiva. "It's estimated that by 2022, biopharmaceuticals will make up about 30 percent of the prescription drug market."
Both upstream and downstream manufacturing processes benefit from single-use systems, particularly when manufacturers are producing buffer solutions or cell-culture media. Furthermore, bioprocessing applications include large-molecule and small-molecule processes. So, while traditional medicines like Prozac are compounded from molecules with less than 60 atoms, biopharmaceuticals like insulin have molecules with hundreds of atoms, monoclonal antibodies have more than 10,000 atoms, and flu vaccines have more than 100,000. This complexity makes development and upstream and downstream production of these newer biopharmaceuticals increasingly complex and costly.
"Because of these expenses, there are efforts to develop 'bio-similar' medicines that cost less. Plus, when patents expire, other manufacturers start producing them," explained Seaver. "Other drivers of change in the biopharmaceutical market include personalized medicine, localized manufacturing, and other new technologies."
Seaver added that the industry is challenged by downward price pressures, time-to-market pressures, and adapting quickly to changing market demands. "For example, cellular therapies have only been available for four or five years, and now gene therapies are quickly emerging," he explained. "However, because it can take seven years and $1.2 billion to $1.7 billion to develop a new drug, pharmaceutical manufacturers need to build their plants four or five years ahead of time. Consequently, if we can implement a single-use bioprocess facility in just one year or 18 months, it allows our biopharmaceutical manufacturers to put off decisions to go into production, which can save money and time, and avoid a lot of frustration."
Collaboration yields benefits
Seaver reported that Cytiva's 30-year partnership with Rockwell Automation has already yielded many benefits, but their latest collaboration on optimizing the bioreactors in its FlexFactory lines, which can be deployed in its KUBio prefabricated shipping-container clean rooms, have even more potential benefits.
"When we run a typical 2,000-liter bioreactor, there can be 300 pipes, lines and connection that must be made every time we run a batch," explained Seaver. "Developing an application like this can start small with one type of process control, but it may need an entirely different, more expensive type of control when we scale up. We needed a better, more consistent way to scale up, and this is another reason why we're partnering with Rockwell Automation."
Seaver added the pharmaceutical industry wastes about $50 billion per year in inefficient manufacturing, and so biopharmaceutical players are trying to unlock isolated data that can't be accessed, reduce the substantial time spend on gathering and cleaning data, and at the same time protect against cybersecurity probes, intrusions and attacks.
"One FlexFactory generates about one terabyte of data per day," said Seaver. "So we also need to waste less of that data, and do more with it."
Choosing the right technologies
Cytiva's strategy for addressing these multiple challenges in its biopharmaceutical application is called "Figurate," and it includes taking advantage of automation, flexibility, efficiency and confidence. Seaver added that automation's benefits for bioprocesses include:
- Optimized uptime due to system redundancy;
- Reduced maintenance and training by using a common framework;
- Yield optimization with centralized data trending and alarming; and,
- Reduced regulatory exposure with GAMP-proven and CFR-compliant designs.
"Whenever we heat, agitate, add air or otherwise process these $1-2 million batches, we need redundant servers and redundant power that can swap over if one system fails," added Seaver. "These solutions also help with achieving common training and reducing our regulatory exposure.”
To develop and put its Figurate program in place, Seaver reported that Cytiva adopted Rockwell Automation's PlantPAx process system & software and GE's Unicorn software to automate its bioprocess equipment; made their data available by integrating it with applicable manufacturing execution system (MES) applications and electronic batch records (EBR); and also provided it to cloud-computing services.
Cytiva's FlexFactory lines include its media and buffer preparation, cell culture production, harvesting, purification, viral clearance, sterile filtration and bulk formulation processes. All of these can be combined in modular KUBio clean-room shipping containers, and Cytiva presently has 63 of these modular production facilities running worldwide.
"We're able to deliver a FlexFactory inside a KUBio in one year to 18 months because we can do all testing, electronics, pre-verification and pre-validation, and have these units ready to go," said Seaver. "This allows our manufacturers to adjust deployment as needed."
Seaver added that benefits from its Figurate program also include 10-20 percent increases in production throughput, availability and production employee efficiency, as well as 5-30 percent decreases in energy use, scrap material, batch release time, maintenance, and downtime investigations.
To integrate these gains even more firmly, Seaver reported the Cytiva is also working with Rockwell Automation and PTC to create augmented reality (AR) versions of these tools. For example, its operators can use AR image capture, display and manipulate images that show pH, dissolved oxygen, carbon dioxide, control cabinet performance and other crucial parameters more quickly. PTC Chalk software even allows operators and supervisor to mark up images to point out details that need to be addressed.
Staying ahead of the innovation curve
Billy Sisk, Life Sciences Industry Manager EMEA, Rockwell Automation, explains that there’s been a large increase in the level of complexity in the biopharma manufacturing industry.
Rockwell Automation has developed solutions for the single-use market to help increase the speed to market for end users, reduce risk and increase regulatory compliance. We do this through our technology.
In a typical single-use environment, everything is built around EtherNet/IP. We adopted EtherNet/IP as part of the single-use solution because it allows for equipment mobility and the addition of new and different equipment.
AR can be a game-changer for biopharmaceutical companies that not only enhances workforce management, but also improves quality, yield and time-to-market.
In fact, more companies are beginning to use AR to support operator-driven activities. New advancements in AR and artificial intelligence (AI) can guide operators through a sequence of tasks and then verify that the correct connections were made – all from a handheld device.
Furthermore, that verification can be stored in the electronic batch record (EBR) – along with supporting pictorial or video documentation.