A Proven, Cost-Effective, Single-Use Powder Transfer Solution

By Scott Patterson, ILC Dover

Single-use transfer technology has been used in biopharma manufacturing for nearly two decades. However, until recently, upstream powder-handling processes haven’t received the attention they need for improvement. Now, the industry is seeing a need for a better way to bring powders to the hydration process and begin upstream biologic manufacturing. That’s where EZ BioPac comes in.

Single-Use Technology Cost Reduction Model

The benefits of EZ BioPac can be tied directly to costs and savings and can be found when the value differential of a disposable bag vs. a stainless steel vessel are examined. Acquiring, implementing, and validating stainless steel equipment can become very expensive, totaling in the millions of dollars. Often, specialized equipment is required for cleaning and sterilization, adding to the cost of investment and making it significantly more expensive, with much more complicated user processes, than a single-use transfer bag.

Finding ways to reduce capital expenditures (CapEx) can result in millions of dollars in cost savings for biologics manufacturers. One popular method in biologics manufacturing is the ballroom strategy, where the manufacturing space is a wide-open room with utility connections placed in strategic areas. However, in this strategy, the processes are configurable by bringing in single-use products. EZ BioPac can be part of the ballroom concept since additional equipment, such as bin lifters, are not needed. Dramatic savings in CapEx are also found in a greatly reduced implementation timeline of these items in the ballroom strategy. The bottom line: facilities are ready for qualification and manufacturing much quicker when using single-use vs. stainless steel process equipment.

Once CapEx savings are established, cost of ownership savings using EZ BioPac can be reviewed. The main source of cost savings comes from the virtual elimination of cleaning and validation processes. Another level of savings comes from not needing utilities to generate large amounts of energy for processes like water for injection (WFI) during clean-in-place (CIP). Cleaning and disinfecting stainless steel vessels also do not provide the same level of contamination mitigation as a single-use product. Despite validated cleaning and sterilization processes, contamination can still occur. Single-use bags are used once and thrown away, mitigating any risk of contamination during powder transfer.

Additional benefits can be found in increased production speeds provided by the EZ BioPac. Media can be prepared on an as-needed basis using the EZ BioPac. When using stainless steel bins, many bins need to be filled with media ready for use. Bins can also be held up in wash cycles or on hold to go through validation procedures. This can create significant delays in production. And imagine the reduced plant space when you do not need bins at all!

Single-use powder transfer bags are also helping in plant design and reducing a facility’s footprint. When using a single-use powder transfer system, storage and dispensing rooms can be eliminated and/or repurposed. And because this space can be eliminated from the plant, other costs — total cost of the facility and its real estate, heating, cooling, electricity consumption, plumbing, water usage, etc. — can be reduced, resulting in dollars saved. Rarely is a plant designed, built, and used for the exact purpose it was intended. Plants can take up to seven years from concept to use. In that time, market dynamics, sales forecasts, manufacturing needs, and biological approval requirements all change. Investing in expensive, stainless steel equipment is not only costly, but it also may be rendered inefficient by market needs and requirements in the future.

As biopharma manufacturing has evolved, single-use powder transfer bags have proven their value over traditional bulk handling methods — stainless steel drums and bins. Single-use transfer solutions offer a better way to address ingredient discharge, product retention, product and cross contamination, filling, and transport. Despite single-use powder transfer bags having shown their worth over traditional methods, there is still room for improvement in addressing these major concerns. The EZ BioPac delivers solutions to all of them. Here’s how.

How Does The EZ BioPac Work?

EZ BioPac is a two-port bag with a large opening on top that operators use for filling and a closed neck with a tri-clamp at the bottom for discharge. The top port can be filled much more quickly than their single-port counterparts, and the bags are able to be discharged quickly through use of the bottom port and clamp. Every other single-use powder transfer bag on the market is two-dimensional — two sheets of plastic welded together at seams, similar to a sandwich bag, never taking a round shape. EZ BioPac uses a cylindrical top section without seams and a 3-D conical bottom section designed to maximize flow. Three-dimensionally constructed bags have a proper angle of repose, allowing powder to flow out of them quickly and smoothly. The construction of most two-dimensional bags generally doesn’t include angle of repose as a design characteristic.

The superior discharge flow of the EZ BioPac also maintains the integrity of powders being charged into a heated tank. If you don't have a very fast flow, the powder can start to change into a solid. For instance, glucose — a common ingredient in biologic media — will quickly become sticky and will eventually become solid because of the slow flow rate. This can result in a shutdown of operations to clean nozzles, tanks, and other components in contact with the glucose that are covered in a hard, sugary, candy-like substance.

EZ BioPac has undergone additional studies showing a very low, 0.04 percent, retention rate of powder. This is key to precision weighing, a critical area of producing biologics. In traditional single-use bags, because of the seams, powder can be trapped as the two sheets of film collapse against each other. This creates much higher retention rates of powder, up to 100 grams or more, and this changes how the feeding of the media occurs and the efficacy of the biologic being produced.

EZ BioPac’s 3-D construction makes it easier to fill the bag. Its larger, round opening for product filling allows powders to be added to the transfer solution quickly and efficiently. It also allows operators to add and remove powder as necessary to achieve precise weights.

Because EZ BioPac attains a superior discharge flow, manual labor is reduced. Internal studies have concluded that using the EZ BioPac will result in a 71 percent reduction in labor for the filling process compared to a single port bag. From this, setup time, filling time and accuracy, and post cleaning processes are all improved.

EZ BioPac is composed of ArmorFlex — a blend of linear low-density polyethylene and low-density polyethylene — that promotes minimal product retention and quick discharge. This blend provides superior strength for assuring the strength of the EZ BioPac.

ArmorFlex also contains an anti-static additive in a mono-layer film that significantly reduces the risk of static buildup that could impede the discharge of powders. Typical powders will rub against plastic film and develop a static charge. ArmorFlex is static-dissipative: as static charge begins to develop, that charge dissipates rather than building a charge and jumping from the product to a person or equipment and slowing discharge flow.

ArmorFlex’s linear low-density polyethylene construction gives the product strength, which helps improve the transport of powders within the plant. Just as a consumer doesn’t want a garbage bag to break in their kitchen, biologics manufacturers don’t want their powder-transfer bags to break in their facilities. When powders escape the bag and enter the environment, they can stimulate bacteria growth and contamination. Further, a powder bag break requires a shutdown and extensive cleaning and sanitation, slowing operations. Using this high-strength material in the EZ BioPac virtually eliminates failures. Another layer of preventing powders from becoming airborne and causing contamination during filling and transport is EZ BioPac’s secure closed connection.

Closed Powder Transfer To Reduce Contamination Issues

Even though biopharma operators generally work with nontoxic powders, powders can become airborne in open handling, and transfers using traditional methods can create contamination. Single-use powder transfer bags create a closed discharging powder environment, which significantly reduces contamination risk. However, not all single-use powder bags are created equally, especially in terms of reducing potential contamination.

The EZ BioPac’s 3-D construction, rather than being derived from liquid-handling bags, is designed specifically for handling powders. Essentially, the design is a round bag with a large, round opening. This opening reduces spills and overflows that contribute to contamination. It also helps keep powder in the bag rather than allowing it to disperse into the air and settle in the cleanroom. This leads to fewer wipe-downs of the bag and its environment and reduces contamination risk. Once filling is complete, EZ BioPac is clamped shut, keeping all powder in place. Additionally, the two-port design eliminates the potential for contamination better than single-port bags because there is less manipulation of the bag.

Single-Use Transfer Bag Selection Criteria

It’s important to look at the value that single-use powder transfer bags provide vs. their stainless steel counterparts. On average, standard single-use bags are a fraction of the cost of stainless steel powder handling containers, and the EZ BioPac is specifically designed for powder handling, unlike other single-use bags that are derived from liquid handling applications. Those rudimentary bags may seem like a low-cost solution, but you get what you pay for. EZ BioPac provides many improvements in efficiency and tangible benefits over single-use powder transfer bags. Biologics makers should look beyond the purchase price and review the entire value proposition EZ BioPac presents for a true cost analysis.

For operators on the fence in their buying process, EZ BioPac demonstrations are an excellent way to get hands-on experience with the product and the benefits, including cost savings, it provides. ILC Dover will visit potential client sites to provide hands-on demonstrations. In those visits, operators will see how EZ BioPac can make their work faster, easier, and more efficient, with improved accuracy.

Bag size is often a concern of operators, and EZ BioPac offers solutions to fit nearly every biologics manufacturer’s needs. EZ BioPac comes in 5-liter, 10-liter, 25-liter, 50-liter, 100-liter, and 140-liter capacities. However, there is no standardization in the market regarding connector sizes to reactors and hydration tanks. ILC Dover offers several sizes — 2-inch, 3-inch, 4-inch, and 8-inch — of connectors in both gasket and non-gasket varieties. The non-gasket tri-clamp connector eliminates another piece in powder handling that process operators are concerned about: connectors falling into the tank. Additionally, there is small time savings to be found from not using a gasket, but the risk of contamination is substantial.

ILC Dover’s wide variety of sizes for the EZ BioPac offers users distinct advantages. For instance, a competitor’s largest single-use powder transfer bag has a 40-liter capacity. Let’s say sodium chloride needs to be added to a process and requires 10 bags at 40-liter containers each to reach the batch size of 400 liters. EZ BioPac would only require four 100-liter bags to be filled, transferred, and discharged. Each time an operator fills, transports, connects, and discharges a powder container, it is a time-consuming endeavor filled with risk of contamination. Reducing the number of powder transfer bags required benefits both efficiency and product and operator safety.

A growing number of biologics manufacturers are purchasing the EZ BioPac from the suppliers of media and buffer powders. Historically, powders were purchased in bulk and were placed in a dispensing room for weigh out into a powder transfer bag or a stainless steel bin. However, this paradigm shift now allows purchase of pre-weighed EZ BioPacs from companies, completely eliminating this dispensing step.

EZ BioPac is the only single-use container and transfer system designed specifically for powders. Its unique 3-D design offers numerous advantages over traditional, single-use transfer bags and stainless steel containers. Biologics manufacturers looking to improve efficiency, hasten filling speeds, and reduce waste and contamination, while bolstering their bottom line, would be remiss in not exploring how EZ BioPac can help their business.

About The Author

Scott Patterson is a subject matter expert for containment of pharmaceutical manufacturing processes as well as powder handling in upstream biopharmaceutical manufacturing. He has been supporting the global marketplace with ILC Dover for the past 14 years and has a total of 21 years of experience in the life sciences market. He has led innovative advancements using single-use products to demonstrate the performance capabilities and value proposition. With a mechanical engineering education at Youngstown State University, he is now starting year 41 of experience in a wide range of markets, including plastics, pulp and paper, packaging, and inspection equipment.

About ILC Dover

Innovators at our core, we develop engineered solutions for our customers’ complex problems.

Recognized globally for our flexible containment solutions, ILC Dover serves customers in a diverse range of industries, including pharmaceutical and biopharmaceutical manufacturing, personal care, food and beverage, chemical, aerospace, healthcare, and government agencies. At ILC Dover, quality is a culture, not a measurement. Our customers will tell you that we cater to their every need and that we’re highly innovative, responsive, dedicated, and competitive. We have been innovating since 1947. ILC Dover’s visionary solutions improve efficiency, safeguard workers and product, and prevent disasters – proof that we are on the front line of business excellence.

Engineering evolution beyond boundaries.