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Exclusive Life Science Feature validation process. "You really cannot learn anything about your reactors until they are installed," says Ciambrone. That conclusion led Shire to a unique proposition for its bioreactor vendor, Xcellerex. To prove that the solution could solve Shire's speed concerns, the pharma company wanted Xcellerex to provide a place where meaningful work could be done on the reactors by Shire staff along with technical support from Xcellerex. The resulting idea became known as the Atlas "Sandbox" Process Line Mockup, which eliminated a number of costly errors and inefficiencies from the finished process line. For example, during tests with Shire at larger scales (1,000L, 2,000L) and long periods of time, it was discovered that the mixing at 2000L was inadequate. Some design changes were needed, including a more robust impeller bearing for the bottom-mount agitator to provide adequate mixing. Had this deficiency not been detected in advance, the bioreactor would not have functioned properly — resulting in costly delays to getting the plant up and running. According to Ciambrone, once Shire and Xcellerex began generating data together in the Sandbox, it became obvious there would need to be some design changes to the bioreactors before the WHAT YOU NEED TO KNOW IF THINKING ABOUT ADOPTING SINGLE-USE "Everyone who sells disposable reactors will tell you your capital cost will be a lot less," says Shire's Bill Ciambrone. "You don't have to CIP (clean in place) or SIP (steam in place). You can do SUS in a closet without the air handling." According to the Ciambrone, EVP of global technical operations, when Shire completed the design for Project Atlas, it found going with SUS did save some of the capital costs. "But it was not as dramatic as people would have liked you to believe," he informs. "Operating expenses go down in some areas but go up in others because consumables are not cheap." Ciambrone advises to be sure to take this into account when considering capacity expansion of traditional (i.e. stainless-steel) versus SUS. For example, with a traditional plant, once the piping is in place, it is a sunk cost with some variable operating and maintenance costs. However, with SUS you will be purchasing a greater number of consumables (e.g piping, tubing, bags) every time you use an SUS bioreactor, which will increase your variable operating costs. "The real economic savings which appealed to us were the speed with which we could get the plant up and running by taking advantage of the Sandbox (see main article for explanation) and being able to do some qualification on the bioreactors before they were installed." Something else you need to consider, which Ciambrone admits he did not have full visibility into until the plant was up and running, is the physical aspects of operating and moving around large totes and collection bags (bigger than the reactors themselves). He advises to be sure to take these factors into consideration when considering the adoption of SUS, as well as planning for adequate space for storing the various disposable consumables you will be using. 22 LifeScienceLeader.com December 2013 company could take delivery. Furthermore, this testing environment gave the two companies experience with making a lot of sterile connections because the Sandbox was not ISO 7 or ISO 8 certified. In addition, the Sandbox familiarized operators with the systems long before they went live at the plant and facilitated the start of early, offsite commissioning and qualification (C&Q;) and SOP development. Being able to create the Sandbox was the clincher for Ciambrone to choose SUS for the Atlas Project. But when you are boldly going where no one has gone before, you need to gain buy-in not only from your internal team but from regulatory agencies as well. DON'T FEAR FAILURE — HATE IT Ciambrone reports directly to the president of the company. So, he only had to convince one person above him once he decided to build an SUS plant. However, the process of gaining buy-in from Shire employees below him, especially those intimately involved and actually helping to make the decision, proved to be a bit more difficult. "It was a matter of freeing them from the fear of failure," he explains. Ciambrone's approach to removing the fear of failure first involved communicating that he, and only he, would be accountable for the decision to build an SUS plant if things didn't go well. "If you stop people from thinking their heads will be on the chopping block, you create excitement," he affirms. In addition, he pointed out that the company not only had the opportunity to do something very different, but also that there were good reasons supporting the decision (e.g. lower costs [as compared to a stainless-steel facility], faster setup time, and the flexibility to change the plant for manufacturing other products in the future). "We cannot let fear push us in another direction, especially if we have a contingency plan," he explains. Having a contingency plan was another key to gaining buy-in from the team. Though the original plan required speccing for SUS, the Shire team also specced a hard-pipe solution. This allowed Ciambrone to communicate that if things didn't go according to plan, the company could still remediate back to a hard-pipe solution with minimal business impact. "It was a matter of letting people know there were a lot of good technical and business reasons to do it this way, but fear of failure wasn't one of them." Ciambrone's corollary to fear of failure is, "You have to hate failure. This makes you plan more and do everything you can so you don't fail." He says fear of failure leads to bad decision making and less risk taking. "Too many people, when setting out on a risky endeavor, feel they have an easy out and are quick to place blame on the decision as being the reason for failure. I utterly reject that," he states. "The decision and risk didn't cause you to fail. It was the fear of failure." Ciambrone ascribes to recognizing and understanding the risks a decision entails, and to plan accordingly. Just as Shire employees needed to be alleviated of the fear of failure, regulatory agencies needed a thorough understanding to