Single-Use VS Stainless-Steel Bioreactors for Biopharma

 
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Biopharmaceutical production equipment and technology are rapidly evolving to meet the industry’s ever-changing manufacturing, regulatory, and process engineering needs. These shifts include improvements in productivity, overall capacity, flexibility, and automation. Simultaneously, manufacturers keep in mind that facility complexity, start-up cost, maintenance expenses, and size must all be kept in balance to maintain competitive margins and pricing. Bioreactor technology is also changing to meet these new demands.

 

Initially, as with most equipment for biopharma manufacturing, bioreactors were stainless-steel. They were also typically large, holding sizable quantities of culture that produced only small amounts of product. Until recently, this was just the way things were done. Within the past decade, however, an industry-wide shift to single-use technology has caught up with bioreactors.

 

When choosing a bioreactor, most manufacturers take a variety of elements under consideration. What cell types are being cultured? Does the bioreactor need to produce mixed suspensions or adherent cell lines? Is the manufacturing facility large, with a limited number of products, or does it need to be smaller with more flexibility? How are novel therapeutic approaches that require special care for specific cell types represented by engineering? How much automation does the facility need now, and how much automation is anticipated in the future? 

 

The answers to all of these questions will vary by application and product line, but the industry overall sees a shift (over 85% adoption) to single-use equipment. Specific advantages to making this change are the same as the advantages represented by single-use technology across the board:

● Increased product line integrity, decreased cross-product contamination risks.

● Reduced cleaning and down-time during changeovers

● Lower facility set-up cost and timeline to implementation

● Smaller manufacturing footprint

● Long-term cost savings with regards to maintenance, upkeep, and downtime

● Improved facility flexibility and adaptability

 

Rising implementation of single-use systems (sometimes referred to as SUS or SUB) can be seen as a function of improved overall manufacturing processes. More than a decade ago, the production of as little as 100kg/year of a monoclonal antibody, for example, might have necessitated the use of several large stainless-steel bioreactors and equivalently sized equipment. However, with innovations in these and similar processes, the same or higher quantities can be produced with much smaller single-use bioreactors at a lower cost and a quicker turn-around time.

 

The flexibility these single-use systems provide is also vital for the rapidly evolving nature of the industry. Rather than spending time and money setting up a system that may only work for a limited number of product runs, single-use equipment allows for constant re-imagining of the manufacturing process. This often leads to cost savings and an enhanced ability to keep up with changing regulatory demands.

 

Still, not all manufacturers are on board with switching to single-use systems. Main concerns around single-use bioreactors are derived from the same questions asked earlier, including:

● Issues with bag breakage and loss of product

● Leaching of material into the manufacturing stream

● Cost of disposable replacements

● Compatibility with process fluids

● Production volume

 

These factors are heavily determined by cell culture and product requirements. For example, single-use bioreactors are currently limited to use with mammalian cells. Stainless-steel systems also have much larger capacities. Multiple single-use systems can be organized to run in parallel and produce products at prices and quantities that are still competitive. However, some of the most extensive facilities using stainless-steel equipment, if engineered correctly, can make the same quantities of products at a lower cost.

 

Some specific types of biopharma manufacturing, like microbial bioprocessing, have also not converted to single-use systems. These processes typically require equipment that can accommodate higher temperatures, a more comprehensive range of pressures, and increased mixing capacity than what single-use equipment currently offers.

 

Legacy manufacturers still using stainless-steel equipment and seeing acceptable profit margins are not likely to shift to single-use technologies without a significant reason to do so. Some, however, are starting to introduce single-use bioreactors alongside their stainless-steel counterparts. This solution provides the best of both worlds for these manufacturers, enhancing flexibility and decreasing maintenance costs while maintaining the high production volumes they have relied on.

 

Studies comparing single-use and stainless-steel bioreactors provide strong evidence for this mentality. Across the board, the products created and those products’ quality are comparable between the two equipment types. Therefore, both systems can typically be used interchangeably on an as-needed basis without the requirement for intensive testing.

Learn more about how Liquidyne Process Technologies can help support your process manufacturing needs by contacting us today! 

 

Continuous Manufacturing Challenges the Pharmaceutical Industry to Improve

 
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Technology innovation often causes a domino effect, regardless of which industry is experiencing process improvement and change. Updates in one area highlight the flaws in other aspects, pushing engineers to develop new solutions to old problems. Biopharmaceutical manufacturing is no exception to this rule. With advances in automation, single-use equipment, and an increased expectation for flexibility, process engineers have begun to examine the wisdom of traditional batch manufacturing.

In the past, batch manufacturing has been the gold standard for the pharmaceutical industry. Despite the rapid adoption of continuous manufacturing in other sectors, biopharma has stubbornly clung to a batch mentality. Often, what this means for the production process, is that biologics and other products are created in a stepwise manner. Once one step, or batch, is completed, the next starts. This can cause a bottleneck and corresponding delay in the time it takes to produce biologics from start to finish. Sometimes these delays are short (hours), but sometimes these delays take days or even weeks, potentially harming product integrity.

Estimates indicate that this manufacturing technique could be costing the pharmaceutical industry around $50 billion each year. In the current economic climate, this number is staggering and demands serious attention. But what alternatives do pharmaceutical manufacturing companies have? And what challenges face manufacturers who move away from batching?

Continuous manufacturing is the growing trend that is on pace to replace batching. As the name implies, this technique requires constant momentum, moving biologics, and ingredients directly from one step of manufacturing to the next. When continuous manufacturing is done well, no hold or wait time, and operations run 24/7 to produce products. It begins with raw materials and stops only when the endpoint of the process is reached. Because of this, there is rarely a need to shut down equipment, reducing time to completion, costs, and improving quality control. Continuous manufacturing promises drug production in as little as a day, compared to the exaggerated timeline associated with batch manufacturing.

Implementing and utilizing continuous manufacturing is not without challenges, however. There are broad industry concerns regarding the material robustness of parts in terms of equipment, especially replaceable elements (like pump hoses) over time. With the shift to single-use technology, this issue is at the forefront for some manufacturers because single-use equipment largely relies on these replaceable parts to function. Additionally, continuous manufacturing requires facilities to step up operations in almost every way. Continuous manufacturing necessitates more sensors with high accuracy, integration of equipment with these sensors to enable automation, and a more robust supply chain to handle the constant demand associated with consistent manufacturing efforts. Many technologies are being developed to meet these needs but may require more work before they are robust enough to displace their batch counterparts. These issues add up to a potentially large price tag associated with going batch-less.

Another issue worth considering is the difficulty in tracking product integrity in a continuous manufacturing system. With batches, it’s easy to track down the step where a product was compromised and issue a recall, if necessary, based on that step. Without batches, recalls rely heavily on sensors and automation to identify contamination.

The FDA and many manufacturers believe that technology is at a place to overcome these challenges, however. And with good reason – the advantages of continuous manufacturing are substantial when done correctly.

Some estimates suggest that continuous manufacturing could reduce workforce, product deviation, and manufacturing footprint by greater than fifty percent. Continuous manufacturing facilities also use around forty percent less power and have a quicker setup and scale-up time frame. Overall, switching to continuous processes may improve efficiency, manufacturing robustness, and enhance quality control while reducing waste and cost inputs. These systems are also more flexible, becoming a vital feature of the market’s most competitive manufacturing facilities.

To capture these advantages, choosing the right equipment is essential. Pumps, for example, vary in reliability over time depending on type and hose quality. Peristaltic pumps tend to experience rapid hose wear, but advances in hose material reduce some of these concerns, as with the GORE® STA-PURE® Pump Tubing, Series PCS. This tubing shows reduced failures even after 90 days of continuous operation. Quaternary diaphragm pumps by Quattroflow eliminate the concern around tube wear entirely by introducing a gentle, pulsing flow enabled by differential pressure in each of the chambers rather than active mechanical forcing of product through the pump.

Single-use technologies may also be better suited for continuous manufacturing processes in general, as their longevity is equal to the task. These equipment types reduce downtime between production runs, which is critical in maintaining flexibility if a facility anticipates sequential continuous manufacturing of more than one product type.

Like Liquidyne, who can help to choose the equipment best suited for specific production needs, identifying a distributor is important when considering a switch from batch manufacturing to continuous.

Learn more about how Liquidyne Process Technologies can help support your process manufacturing needs by contacting us today! 

 

 

From Fear to Innovation, Process Engineering for Biopharma

 
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“Innovation” is one of the most prevalent buzzwords that companies across all industries use to describe themselves and their company culture. From mission statements to brand and positioning, Biopharmaceutical companies are no exception to this rule. When the curtain is pulled back, however, there are critical areas in which the biopharma industry has been slow to innovate and where it must change to thrive moving forward. Of crucial importance is the resistance to innovation and improvement seen in manufacturing process engineering. The industry seems to be hamstrung by the fear of progress and the lack of desire to embrace the digital, agile, and demanding future. Continued resistance to these types of changes will inevitably lead to increased costs, lower profit, and loss of business opportunities in the worst-case scenario. 

With all this at stake, it’s essential to understand why this internal conflict exists. Historically, more traditional industries like biopharmaceutical manufacturing are slower to adopt new processes and digitization. Often, these kinds of changes can be seen as more risk than they are worth. The mentality is something like, “if it’s not broken, don’t fix it.” The trouble with this thinking is that it ignores the problem, waiting until the damage has been done to make a move.

Strict cost controls are one of the factors contributing to innovation paralysis. Biopharmaceutical manufacturers are primarily concerned with creating a quality product within a specified timeframe. They are less concerned with the process efficiencies or manufacturing costs unless an apparent problem arises with product profitability. Why risk making a change that might do more harm than good? While this is an understandable position (difference equals risk, after all), it doesn’t allow for growth and improvement in areas where process engineering can thrive. 

Another issue is found in the lack of desire to embrace new technology. Advances in digital have happened rapidly in the last several years, leaving some biopharma manufacturers in the dust or with digital whiplash. Many manufacturers are still bogged down by paper and spreadsheet-based analytics and tools. These manual processes are less accurate and more prone to error than data collected using sensors and other digital means. Disconnected data sources can also lead to what’s known as data silos – disparate sources of information that cannot be easily compared, contrasted, and analyzed to identify relevant trends and specific places for improvement.  

Socially created information silos often mirror these digital data silos. In many biopharmaceutical manufacturing companies, there is not enough cross-department communication. These conversations between R&D chemists and process engineers are vital for sparking informed innovation to existing processes. From start to finish, a full understanding of what is required for accurate, efficient manufacturing of products must become a standard part of the system to construct positive changes within the industry. 

If biopharma manufacturers can overcome these hurdles and step into what’s been termed “Pharma 4.0,” there are significant advantages available.

For example, enhanced flexibility will mean that manufacturers will be able to take advantage of innovative technologies more quickly. Advances in cell and gene therapies, among others, and new FDA guidelines require manufacturers to pivot and adapt more rapidly than ever before. A facility that can’t handle a variety of products or which can’t adhere to the strict quality standards the industry is held to will likely see an increase in cost and an eventual loss of customers to competitors better suited to meet these demands. On the other hand, a facility that is comfortable with innovation will be able to continuously improve product development, save costs, and remain highly competitive. This has been seen frequently through the ways companies have approached the COVID 19 crisis – companies that adapt, evolve and demonstrate agility have experienced more profitability and stability during times of economic uncertainty.

According to research, digitizing just the supply chain portion of manufacturing can boost revenue by close to 10% and result in a similar increase in market valuation. Cost savings like these are available in almost every aspect of biopharma manufacturing as processes are improved, and data are moved to a more Internet of Things (IoT) friendly approach. Companies that invested in these upgraded, digital solutions tend to benefit from better inventory management, enhanced fulfillment processes, lessened data issues, increased productivity, and generally improved relationships with customers and vendors.

Overall the message seems clear – the industry must step out of its way and embrace change and innovation if manufacturers want to keep up with modern demands.

Learn more about how Liquidyne Process Technologies can help support your process manufacturing needs by contacting us today! 

Could COVID Be A Positive Catalyst for Biopharma Innovation?

 
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The COVID pandemic has caused upheaval in almost every industry and has impacted individuals and businesses in dramatic ways. Most of what is in the news regarding this virus’s effect has been appropriately gloomy, given the cost to human life and society as a whole. What has been historically accurate of crises, though, is that they eventually drive innovation. The biopharmaceutical manufacturing industry, which has struggled to adopt process engineering changes without significant external motivation, stands to benefit tremendously from the pressure that COVID has applied to the market.

COVID 19 Biopharma Innovation

As with the race for a polio vaccine in the early 1950s, the surge in research and development related to COVID has caused a corresponding increase in collaboration. This is a return to what’s seen by some as the true “nature of science.” Rarely, if ever, do scientific discoveries happen in a vacuum. The fact that the industry has been attempting to do without collaboration has slowed innovation and thus stagnated creativity. It’s crucial that scientists and engineers, at all levels, can work together to spark change and solve problems. With any luck, this culture of collaboration will become the new normal.

Investment into biopharma initiatives has also been on the rise since the start of the pandemic, with billions of dollars pouring into COVID related research and development projects. This could imply an uptick in the value placed on these types of efforts and the stability of the biopharma manufacturing industry. Regardless of whether this trend continues after COVID’s resolution, the money invested will help facilitate improvements that will have a ripple effect for years to come.

Perhaps most importantly, though, COVID seems to be providing many manufacturers with the push needed to overcome some of the hurdles traditionally associated with making changes to process engineering and facility design. Cost, reliability, bureaucracy, and perceived risk have stopped some companies from pursuing these changes. However, in this more demanding market climate, improvements that were seen as a “nice to have” are rapidly becoming a “need to have” if manufacturers want to survive and, eventually, thrive. The overarching goal of these types of advancements, which is in alignment with industry trends before COVID became a global issue, is the industry’s need for more flexible solutions, including:

  • Smaller, decentralized facilities
  • Modular, single-use equipment
  • Improved automation
  • Enhanced supply chain management

Smaller, decentralized facilities: with the need for rapid development, production, and deployment of biopharma products, more companies embrace a less centralized approach to product manufacturing. The challenges associated with these facilities include the need for standardized training and enhanced company-wide communication. It’s also crucial to choose simple, low start-up-cost equipment to avoid extra expenses. This has caused a steady shift from stainless steel equipment to less permanent, less expensive solutions. These smaller facilities provide an advantage as they can quickly pivot to accommodate changing supply demands and production needs.

Modular, single-use equipment: single-use technology, including pumps, have been increasingly prevalent within biopharma manufacturing for the last several years. The main selling points for single-use equipment include lower cost of maintenance, quicker changeover, and more reliable product integrity. For example, the Quattroflow single-use quaternary diaphragm pump virtually eliminates cross-contamination when used correctly, and components can be switched over in as little as 30 seconds per pump. Depending on the use case, there are a variety of single-use solutions available. Having a dependable supplier who can offer guidance can be an important starting place for companies looking to make the switch.

Improved automation: to maintain production quality and enhance overall facility reliability, biopharma has been pressured for years to ride the Internet of Things (IoT) wave. Sensors, data collection, and feedback loops provide greater insight into every step of the manufacturing process. Pumps with this kind of automation are increasingly available for various uses and often can be customized depending on the application.

Enhanced supply chain management: a recent study of biopharma executives showed that unreliable supply chains are the main concern for many manufacturers. COVID revealed, for many companies, inherent instability within their inventory management and procurement systems. Automation and data-driven solutions for inventory are available and can provide facilities with improved optics and greater control over critical manufacturing inputs. Implementing these solutions may help avoid similar issues in the future. As facilities switch to single-use equipment, having a supplier who can consistently ensure demand is met is also essential. Building that relationship ahead of a crisis is ideal, but many suppliers are eager to earn trust during this tumultuous time.

Overall, there is hope on the horizon for biopharmaceutical manufacturing in a post-COVID world. If the industry chooses to see this crisis as a chance to adapt and grow, it is probable that innovations will be made in leaps and bounds. These improvements will likely have a positive, long-lasting effect on increasing productivity, maintaining quality, and enhancing profitability for manufacturers of all sizes.

Learn more about how Liquidyne Process Technologies can help support your process manufacturing needs by contacting us today!