By Trish Meek, Thermo Fisher Scientific, Dr. Jonathan Wingfield, AstraZeneca, and Roger Clark, AstraZeneca
The Assay Sciences Group (ASG) at AstraZeneca’s Alderley Park, United Kingdom, has centralized biochemical screening operations, servicing more than 80 internal customers. Prior to centralization, the time from decision to test a sample until the data was made available for further analysis differed on a project-by-project basis, but typically this could have taken up to one month, and (sometimes unnecessary) repeat-testing was commonplace. “If we can turn data around faster and test across multiple targets, we should help prevent the progression of inappropriate chemical series, while identifying unexpected leads — ultimately accelerating the research on promising compounds,” explains Roger Clark, senior scientist, CIRA Bioscience at AstraZeneca. The solution included centralization of biochemical screening (with the expansion of this to cellular screening at a later date). In doing so, a central LIMS (laboratory information management system [Thermo Scientific Nautilus]) was deployed.
Investigating A Change
AstraZeneca is heavily involved in the research, development, manufacturing, and marketing of prescription pharmaceuticals. The company has more than 12,000 research and development employees across eight countries. The ASG in AstraZeneca Cancer Bioscience, which encompasses both biochemical and cellular aspects of drug-discovery projects, has more than 80 internal customers, including scientists based in several different countries, each independently requesting work. ASG must handle every aspect of these requests, from compound order to tracking/processing and data analysis.
In 2005, a UK-based team began exploring the idea of centralizing its biochemical screening operations. The Biochemical Screening Team (BST), which forms part of the ASG, has been delivering all routine screening data to Cancer Bioscience at AstraZeneca’s Alderley Park site since mid-2006. Moving away from the traditional project-centric lead-identification strategy, the BST is effectively offering a pool of assays spanning all current cancer projects. As such, customers to the service, who include both bioscientists and chemists, are able to create their own selectivity panels from the assays offered. This approach has many advantages in terms of efficiency and effectiveness; however, it also brings with it a fresh set of challenges, not least of which is information management.
Building on the concept of centralized biochemical screening, the department has expanded to centralize cellular screening as well. While the challenges within the cellular environment are subtly different from those in the biochemical area, the high-level process of screening is the same, and therefore a common infrastructure can support the needs of both areas.
The Challenge: A Decentralized Approach
The decentralized approach to biochemical screening was identified as a major hindrance to productivity. As one person manually ordered and tested samples before following these through to results, they could reasonably manage just a few targets at a time. AstraZeneca wanted to increase its average productivity levels of 2.5 assays per full-time equivalent (FTE), while also reducing the time taken to get to the results stage in order to speed up their ability to make decisions around whether or not to continue research on a particular chemical series.
The BST began to explore centralization of biochemical screening operations to service more than 50 bioscientists and chemists operating mainly in Alderley Park but also in R&D centers across three other AstraZeneca sites globally. Previously managed at a local laboratory level, the effort to harmonize disparate processes to record, track, and manage a growing number of requests for compound screening was identified as a potential bottleneck in the centralization process.
A 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 data. However, this approach raises the challenges of implementing an efficient information management system. As the BST does not operate in a project-centric manner, anyone within the team could be generating data for any of the assays; this means that all information must be instantly accessible via a common IS (information systems) interface.
Under the traditional project-centric lead-identification strategy, the time from decision to test a sample until the data was made available for further analysis could have been anywhere up to a month, and repeat testing was commonplace. The team needed a system that could coordinate global requests to BST, create automated workflows, and standardize screening, ultimately accelerating the quality and overall process.
A More Flexible, Faster Solution
“Centralization of screening activities post HTS enables us to be more flexible about our use of resources, allowing a rapid response to changing business demands,” says Dr. Jonathan Wingfield, team leader BST. “Furthermore, it provides for best practices to be employed across assay delivery because the number of different teams generating data is reduced; therefore, consistency is increased.”
In order to streamline the operation of lead identification / lead optimization (LI/LO) within CIRA, AstraZeneca centralized its post-HTS biochemical screening along with the associated data management infrastructure to ensure a consistent platform of communication and delivery of data. Sharing information across the team and department can be complex, but it is essential to the concept of centralization. A common IS interface was deployed across the BST (and later expanded to the wider Assay Sciences Group) — the Thermo Scientific Nautilus LIMS.
The ASG implementation of Nautilus allows AZ to “cherry-pick” samples to fulfill requests from customers, a process that breaks into two workflows. First is the process of managing the multiple requests for sample testing and tracking all virtual samples as they progress to the point of assay. The second part includes tracking all physical samples through the laboratory, allowing assignment to each request. In helping to coordinate this, the LIMS provides the framework, which allows the screening service to be delivered in a centralized setting — greatly enhancing collaboration and efficiency with a view to speeding up the discovery process.
ASG was able to meet its requirements for a LIMS by configuration of the standard system, coupled with bespoke extensions. AZ built an interface between Nautilus and their corporate database so that sample information could be easily transferred into the LIMS through manual or automated scanning of a bar code (on either tube, rack, or Microtitre plate). Once in the system, Nautilus’ workflow functionality provides the testing instructions for each sample.
In addition to tracking samples, ASG also used the LIMS as a central repository for all 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. Running several different assays with various components in each, it is essential to keep an up-to-date inventory (otherwise efficiency gains made from centralization could be lost due to lack of available reagents). The cellular screening area brings 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.
Nautilus is now deployed for cell as well as enzyme screens with Assay Sciences, moving ASG toward a consistent platform for workflow management. While the challenges within the cellular environment are subtly different from those in the biochemical area, the high-level process of screening is the same, and therefore the existing infrastructure has been exploited.
“Fundamental to improving any process is the ability to capture metrics on key performance indicators,” explains Clark. “Using a LIMS to help manage the workflow means that all information with regard 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 demonstrates to our management an immediate and tangible benefit from our investment in LIMS.”
A 180% Efficiency Gain
Within six months of deployment, BST realized a 180% efficiency gain in its laboratory through the centralized screening process. The laboratory now achieves approximately 7 assays per FTE, up from 2.5 prior to centralizing the screening process. Currently, ASG handles more than 20 cellular and more than 30 biochemical assays on a regular basis. This means an average of 12,000 samples per month goes through these assays, but this figure has peaked at more than 30,000.
Streamlining the centralized approach through the use of LIMS, BST is now able to achieve a current average turnaround of seven days from initial request to upload of data — a substantial improvement from the 16.5-day average when the centralized system was first implemented. This timeline takes into account order and delivery times for compounds from AZ’s central store, as well as processing within the BST laboratory.
BST’s centralized service has the added advantage of allowing customers to test simultaneously against several biological targets, with minimal compound usage. Since the team now turns the data around faster and can test across multiple targets, the chemists get their answers more quickly, thereby accelerating research on promising compounds.
To effectively centralize any operation, it is necessary to centralize knowledge, and the most effective way to do this in a laboratory environment is via a LIMS. The benefit of selecting a configurable off-the-shelf (COTS) LIMS solution is the ability for that system to grow with and adapt to emerging business needs. Any LIMS selected will require some degree of local configuration, coupling vendor knowledge with the particular laboratory process. The degree of customization required for any COTS LIMS will clearly depend upon the complexity of the process in question, and within AZ, the decision was taken early on to appoint an internal LIMS project manager with intimate knowledge of the laboratory process, along with some IT experience. This enabled AZ to deliver much of the bespoke requirements to its system, without greatly extending the deployment timeline.
Within ASG at AZ, the LIMS has become the information hub, providing the framework to allow delivery of screening in a centralized setting. It not only tracks samples and coordinates test information, but also acts as a central repository for all the ancillary information associated with screening. This facilitates sharing of information across the department and enables generation of accurate productivity metrics. Ultimately, the goal of centralization is to increase efficiency in the LI/LO phase of drug-discovery (and consequently drive down the “make-test” cycle time).