Thermo Fisher Scientific Sails into astra Zeneca with nautilus lims Roger Clark, Senior Scientist, Cancer & Infection Department, AstraZeneca, discusses biochemical screening and the impact of Nautilus. Please describe your role, working environment and the biochemical screening team. Prior to implementing a LIMS, what business challenges (productivity, quality, etc.) were you facing? he Biochemical Screening Team (BST) is a new concept for Cancer Bioscience at AstraZeneca and forms part of the Assay Sciences Group. Moving away from the traditional project-centric lead identification strategy, BST is effectively offering a pool of assays spanning all current projects. As such, customers to the service, both bioscientists and chemists, are free to create their own selectivity panels from any or all of the assays offered. This centralized approach to post HTS (High Throughput Screening) has many advantages in terms of efficiency and effectiveness, making smarter use of the group’s human resource and better use of the data generated. However, it also brings with it a fresh set of challenges, not the least of which is information management. My role in the setup of BST was to define and deliver the IS infrastructure which would enable the team to meet its challenging targets. The timeline for delivery of a working system was four months from initial start-up. The constant drive for efficiency gains within pharmaceutical R&D required us to look differently at the way resources were deployed. The question to answer was: “How can we achieve rapid generation of high quality decision-making data without compromising quality?” Secondary screening within the pharmaceutical industry has traditionally been carried out within project teams, in many cases both biochemical and cellular screening being conducted by the same bioscience resource which was aligned solely to an individual project. Centralization of all screening activities post HTS enables us to be more flexible about our use of resources, allowing a rapid response to changing business demands. Furthermore, it provides for “best practice” to be employed across assay delivery because the number of different teams generating data is reduced; therefore consistency is increased. T What types of samples and tests are you processing? The laboratory processes compounds from AstraZeneca’s collection, testing them against any or all of the biochemical assays currently running. We have the capability to process dry samples, solublizing to a desired concentration in diluents before plating. However, the majority of processing is derived from liquid stocks. Testing from liquids allows the team to source the samples from our compound management group in a timely fashion, thus enabling a faster turn-around of data. We utilize acoustic dispensing technology in order to build assay plates in low nanoliter volumes. This approach has many advantages including speed, low compound usage and reduced carry-over liability (as nanoliter volumes mean that diluent concentrations can be kept very high). 30 FUTURE PHARMACEUTICALS Please describe this application and talk about how Nautilus LIMS addressed some of your issues? What is Thermo Scientific Nautilus LIMS’ primary function and how many samples are tested per year? Nautilus LIMS is fundamental to the process of centralized biochemical screening within our team. We process around 10,000 samples per month, originating on a daily basis from over 60 customers globally. In any given week the team will run assays against 20 to 30 different biochemical targets. As we do not operate in a project-centric manner, anyone within the team could potentially be generating data for any of the assays; this means that all information must be instantly accessible via a common IS interface. In our setting, the primary function of Nautilus LIMS is “cherry-picking” samples to fulfill requests from customers. This DRIVING THE INDUSTRY FORWARD drug discovery breaks down into two discreet but related workflows. Firstly, the system manages the multiple requests for sample testing, tracking the status of virtual samples as they progress to the point of assay. Secondly, the system enables tracking of all physical samples through the lab, allowing us to pick the most relevant example for assignment to each customer request. How does Nautilus LIMS allow you to manage your workflow effectively? Nautilus LIMS allows us to capture requests for work from our global customers and keep those same customers automatically updated as the status of their individual requests changes. The system also acts as a central repository for all of the ancillary data associated with biochemical screening, capturing everything from reagent stock levels and supplier information, to the exact time requests were made or samples were assayed. Sharing information across the team and the department can be a complex task, but is essential to the concept of centralization. Nautilus now provides the core framework to allow the screening service to be delivered in this setting. How has Nautilus LIMS improved laboratory productivity in terms of time, throughput and money? What other benefits have you experienced? Prior to centralization, each FTE (Full Time Equivalent) involved in biochemical screening was delivering against 2.5 assays. BST now achieves over seven assays per FTE which is a 180 percent efficiency gain. We have the added advantage of allowing customers to test simultaneously against several biological targets, with minimal compound usage. Fundamental to improving the efficiency of any process is the ability to capture metrics on key performance indicators. Using a LIMS to help manage our workflow means that all information with regards to the process is accessible to various database reporting tools. Generating real-time statistics on the team’s productivity not only allows us to identify bottlenecks and remedy them, but also enables our management to see an immediate and tangible benefit from their investment in LIMS. How are you using the LIMS in terms of database, workflow and functionality? Nautilus LIMS comes with a generic database structure including such tables as “Plate,” “Sample” and “Aliquot.” With guidance from Thermo Fisher, we were able to map our laboratory process onto this structure, creating a “data dictionary” to relate entities in our real-world workflow to the virtual entities described in the LIMS. This means that the Nautilus LIMS workflow is almost an exact mirror of our actual laboratory process. For example, if we move a sample from one plate to another or use an amount of reagent, an operator must perform the same transaction within Nautilus LIMS. Please discuss your experience with Thermo Fisher Scientific for this project so far. Key to the successful implementation of Nautilus LIMS within BST was the provision of an experienced Thermo Fisher consultant. While we knew exactly what we wanted from a system at the outset of this project, we obviously did not have the knowledge to configure the product to our particular process. The extremely challenging timelines applied to our LIMS implementation meant that the learning curve from both our own perspective and that of Thermo Fisher was very steep. The consultant was able to assess the timelines involved and tailor training on Nautilus in order to bring me up to speed with the fundamentals within a matter of days. What does the future hold for Nautilus LIMS in terms of new developments and advancements? Since the initial implementation of the system, it has needed to evolve in order to take advantage of advances in liquid-handling technology. I have no doubt that the system will need to evolve further as new technologies and therefore different liquid-handling equipment is implemented within the laboratory. The benefit of selecting a highly configurable solution such as Nautilus LIMS, is the ability for the system to grow with and adapt to emerging business needs. Building on the concept of centralized biochemical screening, the department is expanding to centralize cellular screening as well. This area brings with it a host of new challenges, however the existing IS infrastructure should be compatible with these new workflows, as at the highest level the process remains the same: requests and compounds in, data and knowledge out. Is there anything else that you would like to add? I would suggest that anyone wishing to follow our example of a speedy and successful LIMS implementation should assign an internal LIMS project manager who has intimate knowledge of the laboratory process and some IT experience. We have been able to further streamline and adapt our workflow, both in reality and within the LIMS, since the initial implementation. This was only possible due to the in-house knowledge gained while working closely with the Thermo Fisher consultant. FP Roger Clark has a BSc in Cell Biology from The University of Manchester and is a Senior Scientist within the Cancer & Infection Department at AstraZeneca. Over the past eight years Roger has worked in the fields of high throughput screening, secondary screening and laboratory automation. He is an experienced programmer and has been involved in the implementation of many custom IT solutions to the Bioscience community at AstraZeneca. www.futurepharmaus.com FUTURE PHARMACEUTICALS 31