Designing & Implementing Single-Use Solutions in Biopharmaceuticals

Three unique examples of single-use solutions that saved time and money and enabled growth.

By Rob Jewett, President, Terracon Corporation

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As companies in the biopharmaceutical industry increasingly look to single-use technology to cut costs and increase manufacturing efficiencies, they seek proven ideas and solutions that meet their unique needs. Often product engineers and their teams are faced with options that compromise their specific requirements. For the three single-use stories included in this article, the engineering teams achieved custom, reliable solutions designed to their specifications.

Every application is unique, of course, but the three cases described here demonstrate that product and engineering teams design and implement the best solutions, avoiding surprises, delays, functional compromises, and cost overruns when they engage early with a partner who specializes in custom solutions using innovation, creativity, strong engineering capabilities, and extensive experience.

An off-the-shelf solution was not an option for any of the following single-use applications. Their teams sought practical, reliable solutions that they could count on—to scale up to commercial production, to replace stainless steel tanks that were failing, and to launch a full product line of single-use mixers filling a market void. In all cases, Terracon Corporation was the partner to design and engineer the custom solutions that enabled each company to achieve its goals. Terracon, which is largely known for its high-quality, non-metallic tanks and vessels, offers single-use solutions as a natural extension of its capabilities to design tanks and mixing solutions, and incorporate the aseptic fittings and accessories required for complete, reliable, and pragmatic solutions.

With Limited Budget, Start-up Biotech Company Implements Scalable Single-Use System
When biopharmaceutical manufacturers implement single-use (or disposable) technologies, they gain a number of advantages that are not possible when stainless steel components are used. One of the key ones, of course, is cost-savings.

Companies can now build far less expensive production facilities using single-use systems than was previously possible using expensive stainless steel components. This is particularly advantageous for small labs or companies that have completed the research and development stage of product development and want to begin commercial production. They can now launch products and compete in the marketplace without the capital investment that was once required for entry into the industry.

Recently, a Massachusetts-based biotech research and development firm was preparing to bring a new product to market. The company needed to build an affordable production operation that would enable it to start off producing small quantities of its product and then scale as demand increased.

The company integrated Terracon Corporation into the design process to develop the cost-effective production environment to meet both its short- and long-term needs. From the early design phase, the Terracon team assisted by providing insight and ideas to finalize the design, and develop and implement the total solution.

As is the case with most biopharmaceutical operations, it was critical that the production facility provide aseptic conditions both for the mixing process, as well as transitions in order to adhere to current good manufacturing practice (cGMP) regulations. Knowing this was a critical requirement, the biopharma company completed a cost-benefit analysis to evaluate pursuing a single-use solution versus establishing a production environment that would include cleaning and validating the equipment. Confirming single use was the desired alternative as it would be more economical and faster, the teams moved forward on designing the various components for the production environment.

The production facility includes a single-use mixing system comprised of a dozen 20L custom-configured plastic tanks, disposable mixing bags, enclosed agitation, and aseptic withdrawal lines—all of which work to maintain manufacturing purity. During the prototyping phase, Terracon designed multiple versions of the mixing tanks to help finalize the design. Rapid revisions were possible by working with poly materials as the Terracon team could easily incorporate changes during the design cycles.

The final production system includes mixing tanks using low-sheer mixers and re-usable covers that provide the necessary sanitary transition protecting the tank's contents from any contamination risks. Dip tubes were added to the covers, as well, enabling the company to draw samples at critical intervals. Each tank also includes a non-shedding seal around a rotating disposable shaft to prevent contaminants from entering the vessels.

In the end, single-use technology decreased the initial investment required to build the facility, while increasing the flexibility of the overall manufacturing environment. The company can now easily and cost-effectively scale-up operations when demand for its product increases by simply incorporating bigger plastic tanks—up to 200L— and adding larger mixing impellers. The agitation system and other components of the plant will remain unchanged.

With Terracon’s help, this start-up company was able to quickly go from manual bench-top processing to small-scale automated mixing in single-use vessels for initial commercialization—no small feat.

‘Uh Oh’ Moment Leads Company to Disposable Mixing Tanks
When the health care division of a multi-national organization that manufactures clinical diagnostic equipment went into production with a fleet of 600L stainless steel process tanks for one of its pharmaceutical products, the company quickly realized that a material was creating batch to batch contamination. When the company installed stainless steel vessels, it had intended to reuse them, but discovered that the cleaning process was ineffective, which rendered the vessels unusable for repeated manufacturing.

Given the expense of stainless steel tanks, discarding the tanks after each use was not a feasible option. A less expensive alternative had to be found. The company turned to Terracon and, in just four weeks, they came up with a solution: custom-configured cone bottom plastic tanks that met all of the manufacturer’s requirements and saved the company thousands of dollars a year. The company now orders 5-10 of these systems several times each quarter.

To design the solution, the Terracon team met with the production team to detail manufacturing requirements in order to design an alternative solution using 600L plastic tanks and the appropriate fittings and configurations.

As it turns out, in the manufacturing process, materials would flow from a feeder to the tank; therefore, Terracon needed to configure the top of the tank to mate with the existing equipment. To solve the problem, the team developed an application-specific top collar with a 15-inch opening to allow ingredients to flow in, and mixers to be inserted. The team then welded the collar to the top dome of the tank. It should be noted that all of connections and fitting transitions comply with the ASME (American Society of Mechanical Engineers) BPE (BioProcessing Equipment)-2009 Standard.

In addition to integrating with the existing manufacturing process components, a critical requirement of the plastic tank system design was to conform to aseptic manufacturing practices. To ensure elimination of dead leg and to promote complete drainage, the original tank—molded with a 45-degree slope and a small 6- to 7-inch-diameter flat surface at the bottom—was modified to eliminate the flat, and continue the cone slope all the way to the bottom outlet port. The design achieves two important objectives: complete drainage and improved mixing efficiency. The solution also includes a sanitary outlet port that links up to a recirculation and dispensing loop through which the operator withdraws finished product.

The final aspect of the complete plastic tank solution was portability of the solution. To promote ease of movement and workplace safety, the tanks, weighing about 75 pounds each when empty, were equipped with handles on each side—an easy fix.

What started out as the need to replace stainless steel tanks that compromised aseptic manufacturing requirements turned into a manufacturing solution and a long-standing relationship that has identified and overcome more of the customer's processing challenges than originally defined, including aseptic transitioning with the feeder and mixers, improved ease of carrying and moving the tanks, and ports to enable in-process sampling while providing smooth-flowing full-drainage vessels as defined in the initial specification. The customer is pleased because the single-use system solved a serious problem in just four weeks, and the solution not only meets its specific manufacturing requirements, but delivered significant savings as well.

Single-Use Mixing Tank Product Line Brought to Market
One of the most expensive aspects of manufacturing operations has traditionally been the cleaning and validation process required by the U.S. Food and Drug Administration (FDA). When manufacturers need to change production from one batch to another batch or from one product to another product, everything needs to be completely cleaned and then validated. Moreover, the validation process requires these companies to undertake extensive and time-consuming documentation.

Single-use systems, of course, solve this problem—and when a global pharmaceutical equipment manufacturer identified a market opportunity for large-scale (up to 500L) single-use mixing capabilities, the company decided to team with Terracon Corporation to design and deliver a complete, state-of-the-art solution that would cut costs and speed production. Primary components of the single-use system would be 3-D mixing bags validated and certified to be clean and sterile and a cylindrical open-top cone bottom (COC) tank.

Initially, the two companies met weekly at Terracon’s facilities, detailing requirements and discussing ideas and potential solutions. The team tackled one problem at a time. One of the key challenges was how to place the heavy motor in a position to ensure it engages and aligns reliably with the internal mixing elements without tearing the mixing bag; the team solved this issue by developing a sturdy hinged platform that incorporates the motor and swings up and down in a precise fashion to maintain the integrity of the bag.

Another key requirement was to design a way for the operator to easily replace one single-use mixing bag with another without slowing the production process. They solved this problem by designing a hinged door in the tank sidewall to enable users to reach in to install bags. A transparent window in the door allows visual confirmation of mixing activity. A small cut-out at the bottom of the door also enables operators to access product for sampling. In addition, the carrier comprises custom accessories and features including flared legs to prevent tipping and a base with fully locking casters for mobility, security, and stability.

The custom tank supports a single-use bag, which is guaranteed to be clean and sterile, decreasing the risk of contamination. In addition, the new mixing system eliminates the downtime and labor cost that was once required for the cleaning and validation process—and provides complete regulatory compliance ensuring 100% reliability and repeatability.

Together, the two companies designed a highly innovative and cost-effective single-use mixing system. Furthermore, the global pharmaceutical equipment manufacturer was able to launch an extensive line of single-use mixing systems that solved significant challenges in the industry. The new solutions enable biomanufacturers to produce small batches of products while controlling their capital budgets because the systems reduce contamination risks, prompt faster and more efficient production, and avoid costly validation steps.

Innovative, Single-use Solutions for Today’s Biopharma and Biotech Market
As companies look to adopt single-use systems to gain a competitive edge in the market, they will quickly realize that there is a great benefit in engaging with the right partners to work with their product and engineering teams. Whether companies intend to transition from R&D to production, eliminate cross contamination, or bring a new single-use system to market, it is critical that they secure a partner who can design and deliver the kind of quality, integrated solutions that meet all their needs.

As the above examples highlight, custom solutions can deliver measurable bottom-line results—results that far outweigh the costs of going the 'custom' route. When custom means a solution that meets, oras in the above cases, exceeds expectations, teams will agree it was a wise business decision.

These three examples are proof positive that when companies in the biopharmaceutical market decide to produce a product using single-use technology, they can benefit by talking, right from the start, with experienced, innovative firms who can implement a solution that addresses all their requirements and enables them to achieve long-term market success.

About the Author
Rob Jewett is the president of Terracon Corporation. He has 30 years’ experience in water treatment and fluid monitoring, control, and containment. Terracon Corporation began manufacturing non-metallic fluid-management tanks, vessels and mixers in 1976 as a cost-saving alternative to stainless steel. Since then, Terracon has established a reputation for solving complex fluid management challenges with creative and cost-effective custom solutions. For more information about Terracon, visit its website.

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