Advances in technology have brought innovative equipment to the forefront of the biopharmaceutical industry, where drug companies now have the opportunity to integrate their production processes with the capabilities of “smart” manufacturing. In this paradigm shift, the potential for a digital transformation becomes reality, as the ability to collect and monitor data using automation marries with the possibilities of what we can achieve in an information-driven future ― improved safety and quality, optimized performance, and increased compliance.
Traditional monolithic automation systems driving a top-down approach to integration are not palatable to mid-sized companies unable or not ready to make a major investment in something not often seen as a necessity, especially as the industry trends toward more diverse product types and flexible manufacturing strategies. These factors have led many to delay investments in automation, which creates cost and time challenges when trying to integrate disparate systems into one unified platform later.
In its continuous effort to solve customer problems with flexible automation solutions, Cytiva is offering the reliability of its single-use technology equipped with Rockwell Automation’s scalable distributed control system (DCS), PlantPAx®. The seamless functionality of these solutions together empowers you to capture the benefits of collecting and sharing data while simultaneously creating a connected enterprise that grows with the pace of your business.
Automation integration for the future of biopharma
Data has been a fundamental component of drug development and manufacturing since the industry began. This vital information has historically been collected and managed using manual methods that are laborious and prone to error, which not only presents substantial risks to your product’s safety and quality but also significantly slows its path to commercialization. However, the arrival of modern technologies, such as single-use sensors and probes, has significantly advanced the role of data in today’s biopharmaceutical industry, making efficient data collection and storage critical. Compounding this is a new generation of novel drugs manufactured in lower volumes, increasing the need for operational efficiency in order to reduce the overall cost of bringing a drug to market.
The digitization of biomanufacturing operations using automated solutions can help control the firehose of data and unlock valuable insights about your development processes and manufacturing cycles, enable real-time decision-making, and improve compliance. Yet, implementing equipment-level automation where each unit operation has its own control system and user interface can lead to other issues later. “Multiple process steps that are individually automated on ‘islands of automation’ used to work for the industry, but now we have to collect data from these systems in a way that proves to the regulators that you have control of your processes and facility,” says Tim Wortley, senior product manager, Bioprocess Industrial Automation at Cytiva. “Rather than walking around collecting data on a USB drive, you must figure out a way to centralize data collection and system administration and control, which is a key step toward making a digital transformation. Unfortunately, the initial design of a manufacturing line is often based only on the process requirements, with automation becoming an afterthought. This makes it incredibly difficult and time-consuming to integrate later when you want these islands to communicate with each other and exchange critical batch data.”
Larger, monolithic distributed control systems that can help achieve this and have widespread use across the industry require a considerable investment. For mid-sized companies pursuing promising treatments that are still in clinical trials, using the devil you know may be too big of a step to take at this point in your journey and understandably so. However, your company’s evolution to digital maturity does not necessitate a costly, top-down approach with one of these systems but can instead take place in stages, as outlined in the BioPhorum Operations Group’s Digital Plant Maturity Model (DPMM). The DPMM is part of the organization’s Technology Roadmap and outlines “the stages of maturity from simple paper-based plants through to the fully automated and integrated ‘adaptive plant’ of the future.”1 One of the overarching goals of the DPMM is to help not only assess your digital maturity but also progress you to where you want to eventually be.
Intended to facilitate this evolution is a collaboration between Cytiva and Rockwell Automation, which pairs equipment and expertise from a trusted global provider of technologies and services with a modern and scalable DCS built by leaders in system automation and integration. This stepwise approach to digital maturity gives you the freedom to transform your automation capabilities at the pace your business grows.
PlantPAx® DCS: scalability and consistency in your digital transformation
In 2019, nearly half of 483 warning letters issued to drug companies in the U.S. contained a data integrity component.2 Stringent regulatory expectations are anticipated to increase, as the FDA considers data to be the backbone of cGMP compliance, further emphasizing the importance of data integrity and traceability. Automation, which has been utilized to improve quality and data control in other manufacturing industries for decades, is finally making its impact and value known in biopharmaceutical facilities and processes. Yet, hesitation across the industry to implement it continues to hold back its adoption. Modular automation systems have become a viable alternative to costly DCSs, especially as the focus on smaller patient populations calls on flexible facilities that can accommodate different manufacturing demands and business models. Even so, these systems can lead to other issues if a company implements multi-vendor solutions without a long-term vision for how they will stay connected later as they evolve. This is where Cytiva equipment with PlantPAx® DCS stands to make a difference.
PlantPAx® DCS is Rockwell Automation’s standardized, open, and modular architecture providing efficient and consistent predictable batch processing that supports the reuse of code, recipes, phases, and logic without the need for top-down integration. It is a common infrastructure that simplifies connectivity and maintenance, allowing the flexibility of integration into complex single-unit applications up to an enterprise-wide platform. And while Cytiva offers a wide range of industry-leading equipment, we understand you do not want to be locked into one supplier or one way to assemble your manufacturing line. The open architecture of the PlantPAx® system means you can seamlessly integrate other vendors’ equipment along with Cytiva’s. “What we want to do is offer mid-sized biopharma companies the opportunity to take smaller steps toward automation because we understand the end game,” says Wortley. “Setting the stones down to create a path toward that is the beginning of creating an efficient and robust manufacturing line that doesn’t require millions of dollars to establish, nor do you have to throw it all out in a few years if you want to expand. We’re building these things with our customers in mind because we want you to grow, and we want to grow with you.”
Detailed production information in electronic batch records helps regulatory authorities confirm proper handling of raw materials and consistency and repeatability during processing. Once that information is in one place for analysis, you can use it to identify opportunities for improvement, such as reducing batch cycle time and inconsistencies. You can also apply analytical tools to improve yield and quality. “When you think about how that adds up over time, a modern DCS like PlantPAx® offers a considerable return on investment,” explains Dave Rapini, business manager at Rockwell Automation. Applying one control and information system across your process also facilitates training and operation on not just the technology itself but also the equipment to which it is connected. “There are many manual processes in the single-use space, such as when putting together a ballroom suite,” continues Rapini. “PlantPAx® can help guide operators with this using a step-by-step wizard, which ensures they are following all of the steps to correctly set up the equipment, further reducing human error.”
A one-stop shop for automation integration
Getting a product to market that is safe, effective, and of the highest quality is the primary goal of any drug manufacturer. Yet, we know doing so quickly is the competitive advantage you need in your journey to market. One of the many steps involved in designing and implementing an automated system is system verification. “Part of working with engineering firms that are often commissioned to implement customized automation solutions is creating user or product requirement specifications,” explains Wortley. “There is a long chain of custody for these documents, and review and approval can be an extensive process, especially when they are not familiar with the bioprocessing industry.” Combined with all other steps in the process, including waiting on that verification documentation package, can take years. Cytiva’s single-use equipment operating on the PlantPAx® automation platform is already designed and verified using GAMP5 methodology and is compliant with ISO 9001. “Some customization may be necessary to meet specific needs,” continues Wortley, “but a predefined and preverified system like ours is a one-stop shop that can take software development and verification off the critical path and reduce the time between purchase order and production runs down to 12 to 18 months.”
As you embrace a digital transformation, you reap the benefits of automation but also increase the risk of a security breach, threatening your highly sensitive and valuable intellectual property. Rockwell Automation has taken the necessary steps to ensure anyone using PlantPAx® DCS is protected at the highest level. “Manufacturers can take comfort in knowing that they can move to market quickly with the security protection of a system that is ISA/IEC 62433 cybersecurity certified,”3 says Rapini. “This standard for industrial automation and control systems, which no other automation vendor has in their reference architecture, reduces the risk of security vulnerabilities. And while the regulatory authorities do not require certification yet, we do not feel it is too far down the road.”
The inherent complexities of drug development and manufacturing means every decision we make can impact the quality and safety of a drug product. Closing the gap between science and manufacturing using real-time, data-driven decision-making not only increases confidence in your product but also offers the overall cost savings needed to get ahead of your competition. In a recent study by McKinsey and Company, it is estimated that the operational efficiencies achievable when leveraging advanced analytics is 15 to 30 percent of earnings before interest, taxes, depreciation, and amortization over five years and can be as high as 45 to 70 percent, given the impact of predictive modeling.4 Therefore, the decision to integrate automation may not be a matter of preference but rather a matter of not being left behind in the race to market. “Expectations about quality and optimization are going to continue to expand,” says Rapini. “As companies delay automation and, ultimately, their digital transformation, they are going to find themselves on the outside, looking in at a market that has changed rapidly. Will they be able to keep up?”
As we continue to roll out this offering from Cytiva and Rockwell Automation, look for more articles to guide you in your automation journey.
For more information about Cytiva single-use technology equipped with PlantPAx automation, visit www.cytivalifesciences.com.
- Unger, Barbara. (February 21, 2020). U.S. Sites Play Surprise Starring Role In FDA’s Drug GMP Warning Letter Report. Pharmaceutical Online.
- BioPhorum Operations Group. (February 2017). The Development of a Digital Plant Maturity Model to Aid Transformation in Biopharmaceutical Manufacturing.
- International Society of Automation. New ISA/IEC 62443 standard specifies security capabilities for control system components.
- Darino, Lucia, et. al. (January 2018). How pharma can accelerate business impact from advanced analytics. McKinsey & Company.