It takes huge amounts of time and money to develop and produce life-saving biopharmaceutical medications, so anything that can make their production systems more flexible, scalable and quicker to implement can save equally huge amounts of these valuable resources. This is why GE Healthcare Life Sciences 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, GE Healthcare. "It's estimated that by 2022, biopharmaceuticals will make up about 30% of the prescription drug market."
Seaver presented a keynote address at the Rockwell Automation Process Solutions User Group (PSUG) meeting, held in the run-up to Automation Fair 2019 this week at McCormick Place in Chicago.
Time and market pressures
In general, 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."
Speed = savings
Seaver reported that GE Healthcare'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."
Augmented by automation
GE Healthcare'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 GE Healthcare adopted Rockwell Automation's PlantPAx 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.
GE Healthcare'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 GE Healthcare 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% increases in production throughput, availability and production employee efficiency, as well as 5-30% decreases in energy use, scrap material, batch release time, maintenance, and downtime investigations.
To integrate these gains even more firmly, Seaver reported the GE Healthcare 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.