Reduce Common Process Challenges – Biopharmaceutical Hose & Hose Assembly Maintenance

 
biopharmaceutical hose & hose assembly maintenance

Hoses are a crucial part of most biopharmaceutical and many other manufacturing processes. Moving fluids and products from one stage to another often involves transfer through a system reliant on pumps and pump hoses. As with all equipment involved in the manufacturing process, understanding when to change and to maintain hoses can decrease the risk of hose failure and help control costs.>/p>

In general, the best maintenance practice is either predictive or preventative. Predictive maintenance strategies are custom schedules that are developed based on equipment risk profiles and tailored maintenance needs. These are often designed based on failure analysis but can sometimes be provided by the hose supplier or manufacturer, depending on the application. Preventative maintenance involves sticking to pre-determined schedules, typically set by the equipment manufacturer. Both predictive and preventive plans can maximize productivity and reliability while maintaining safety standards, reducing cost, and decreasing contamination risks to both the product directly and the facility in general.

Maintenance isn’t always the controlling factor affecting hose life, however. Careful consideration needs to be taken when choosing the correct hose and adjusting maintenance schedules based on other contributing elements.

For example, single-use hoses may need to be changed out more frequently as the batch or product types alternate. Since these hoses are designed to be sterile upon installation and discarded after use, their maintenance schedule can be significantly different than other hoses. In biopharma applications, single-use hoses are quickly becoming the norm for a variety of liquid transfer processes. A supplier like Liquidyne can work with the manufacturing facility to source, select, and pre-cut single-use hoses to minimize downtime during a changeover.

For all hoses, single or multi-use, maintenance frequency also depends on choosing the correct hose for the application in the first place and performing the right pump and hose set up.

In biopharma manufacturing, chemical and material compatibility are crucial, as some materials may leach or react chemically with certain substances. PTFE hose liners react with fluorine, chlorine trifloride, and molten alkali metals. This hose type should not be used in processes involving these materials. Additionally, when PTFE lined hoses are used to transport chlorine or bromine, diffusion becomes a concern. Once the chemicals have diffused through the hose, they combine with moisture in the atmosphere and cause severe corrosion. Corroflon hoses are a better choice for these kinds of applications. The technicalities around hose compatibility can be intimidating. When in doubt, the best course of action is consulting with the supplier or manufacturer directly for a recommendation.

Physical setup is also essential to hose life. Hoses should be cut and fit correctly for the application. End fittings must be appropriately connected to mating parts, and hoses should not be set up in a way that causes kinking, torsion, external corrosion, or frequent abrasion. Although each of these set up errors might not cause a failure immediately, they compromise the hose’s integrity over time and result in more frequent maintenance and replacement.

During use, hoses should also be handled with as much care as possible. Stretching or crushing a hose can damage the hose’s overall lifespan, even for a short period. If it is necessary to insert an object into the hose, for cleaning or other purposes, it is essential that the inserted object does not have any sharp edges or burs that could damage the interior surface. For cyclical applications where gasses and fluids are passed through the hose during temperature and/or pressure changes, more frequent maintenance and change will be required, regardless of the hose material. All hose types fail quickly under these circumstances, and manufacturers should plan maintenance schedules accordingly.

If hoses are chosen, set up, and used correctly, manufacturers typically provide a maintenance plan based on expected wear and tear. For Aflex Hose, they recommend a visual inspection once per month. These inspections should check for visible leaks, bubbles caused by internal leaks on rubber-lined hoses, and any change in physical characteristics that could indicate hose damage or imminent failure. Every six months, Aflex Hose recommends a more robust inspection. However, they offer this inspection to Aflex customers, and a supplier like Liquidyne can help coordinate with the manufacturer on both predictive and preventative maintenance best practices.

Properly selected and adequately maintained hoses will enable efficient, effective, safe, and contamination-free transfer of materials for biopharma and other manufacturing from start to finish. The rules for hose maintenance aren’t very different than general maintenance best practices: choose the right tool for the application, ensure proper use and installation, follow the manufacturer’s suggestion for inspection and replacement. For any additional concerns, Liquidyne is available to consult and design custom solutions for specific applications, from choosing the correct hose to providing a reliable supply chain for all future hose and hose assembly needs.

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

Single-Use VS Stainless-Steel Bioreactors for Biopharma

 
bioreactor-stainless-vs-single-use

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

 
continuous-manufacturing-biopharmacetucal-pharmaceutical

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

 
From-fear-to -innovation-process-engineering-for-biopharma

“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! 

Why Preventive Maintenance (PM) is Critical for Pharmaceutical Manufacturing

 
preventative-maintenance-pharmaceutical-manufacturing

Reliable pharmaceutical manufacturing begins with dedicated equipment. A well-maintained facility with functional machinery is, obviously, more productive than a poorly maintained facility with frequent machine failure. Equipment malfunction can lead to issues like batch contamination, safety concerns, and decreased overall site functionality. Despite this clear connection, many manufacturers struggle to develop and keep up with a maintenance strategy that works for all equipment types within the facility.

There are three* major approaches to maintenance, predictive, preventive, and corrective:

PredictivePreventiveCorrective
ApproachUses root-cause analysis and advanced tools to stay ahead of facility maintenance needsUses manuals and manufacturer recommendations to set best practices and maintenance expectationsRelies on real-time problem solving and periodic maintenance to correct facility issues as-needed basis.
SchedulingCustom, predictive schedules are developed based on equipment criticality, and specific maintenance needs (often created based on failure analysis)Schedules are pre-determined by either set periods or specific equipment maintenance guidelinesUses a standard program for all equipment, if any maintenance is scheduled ahead of time (often monthly or quarterly, regardless of failure analysis)
Major equipment failureAims to avoid significant equipment issues by proactively addressing issues before they escalate or create problems with other, connected pieces of equipmentAims to prevent significant equipment issues by proactively addressing issues before they escalate or develop problems with other, related articles of equipmentCorrects problems with equipment as these problems arise, frequently on an emergency or “fire-drill” basis, which can result in compounding process deficiencies
CostFacilitates predictable, lower maintenance costs by streamlining processes, allocating labor, and reducing downtimeIf the established schedule works as intended, preventative plans can also result in predictable, lower maintenance costs by simplifying processes, allocating labor, and reducing downtimeUnpredictable, high maintenance costs and increased downtime which is often compounded by multiple system failures as a result of a critical malfunction

*While predictive maintenance plans technically fall under the umbrella of preventative maintenance, they have been separated here to highlight the essential efficiency gains available with a predictive approach

Relying on predictive or, at least, preventive care is crucial for any company looking to maximize productivity and reliability while improving safety, reducing cost, and remaining competitive. Once a facility has decided to utilize preventative maintenance as a strategy, implementation becomes a key concern. What is the right tool for the job? What will track maintenance reliably without creating more work for supervisors or general laborers?

The best solution is to use a computerized maintenance management system (CMMS). These programs replace the combination of spreadsheets and equipment manuals that have traditionally been utilized to keep up with equipment needs. A good CMMS should be accessible on any device and extremely user friendly. Additionally, geolocation, compatibility with other “smart” systems in the facility, and analytical tools to continuously adapt the maintenance schedule based on actual equipment failures are essential features.

When getting set up with a CMMS, the facility will need to identify key performance indicators (KPIs) to use as a basis for measuring failures and improving maintenance schedules. Analysis should be done to determine the common causes of these failures. Historical data on required interventions and equipment life-cycle should also be collected and taken into consideration.

Because all facilities utilize a unique set of technologies, there is no one-size-fits-all preventive or predictive maintenance strategy. However, a successful program will reduce equipment downtime and improve operations and reliability at every stage of the manufacturing process.

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