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Columns: March 01, 2015 (Vol. 35, No. 5)

Lab Data Systems for Biomanufacturing

New Levels of Integration Enable Dynamic Workflows and Accountability

  • Integration of (and interoperability between and among) the alphabet soup of LIMS, ELN, LES, SDMS, and supervisory packages has been the most significant trend in laboratory IT over the last half-dozen years. The goal is to automate the flow of data between instruments and systems that store, process, and execute laboratory workflows.

    “Managers select integrated information systems in biomanufacturing for the same reasons they choose them in other laboratories,” says Trish Meek, director of product strategy at Thermo Fisher. Supporting and maintaining all data in one system eliminates the need to retrofit or reprogram after purchase. “The system now rolls all data up to the sample record and ultimately up to production. This is even more important in biomanufacturing, which is a continuous process."

    The other big push behind laboratory informatics is the FDA’s emphasis on Quality by Design (QbD). “There’s a push for a quality culture that drives sustainable compliance within organizations,” adds Meek. “Human error, which information systems reduce, is still a prominent root cause of noncompliance.”

    Meek asserts that Thermo Fisher customers who express interest in laboratory information management systems (LIMSs), electronic laboratory notebooks (ELNs), and other integrated informatics packages do so because they want all information to flow into and be reported through one system.

    “They want the ease of use that laboratory executions provide, so they know with confidence that techs and scientists are following appropriate procedures,” Meek explains. “They want assurance that the right instruments are used, that they have been calibrated and maintained, and that nobody can execute tests without the right training.

    “But more important, they want the power of LIMSs to drive the overall laboratory process and essentially act in the role of ERP [enterprise resource planning] for the laboratory.”

  • Integration

    LIMSs fit best where the data is structured. ELNs and scientific data management systems (SDMSs) are used in research where the data is experiment-based and unstructured. But needs and capabilities are far from set in stone.

    For example, Abbott’s web-based laboratory information software, STARLIMS, incorporates SDMS and ELN functionality requiring no integration development. STARLIMS, says Abbot, is more of a laboratory execution system (LES) because it focuses on workflows and procedures rather than unstructured experimental data.

    As laboratory IT systems coalesce, vendors nevertheless provide support for specific workflow types.

    “Research laboratories seek ways to collect unstructured experimental data and then examine that data to find commonality in results that will allow them to identify novel drug entities and analogs,” observes Ray Stonecipher, director of commercial operations, informatics, at Abbott.

    By contrast, development laboratories create dosage systems for these drugs that provide maximum benefit and optimal shelf life. These laboratories also desire systems that allow them to create recipes and small batches, and to test these batches for stability and product performance. Abbott offers an application within STARLIMS specifically designed for testing new recipes and capturing results.

    During manufacturing, users define a product and laboratories focus on optimizing yield, quality, and efficiency. Yet as Stonecipher notes, “it is additionally important to meet regulatory requirements.” A best-in-class, manufacturing-worthy LIMS will cover compliance for stability testing, instrument calibration, analyst certification, and other critical tasks.

    Top IT packages also enable laboratories to manage method execution by linking executable procedures to ELNs. The software then guides analysts through the procedure, capturing intermediate data and directly associating it with whatever step in the procedure is relevant. This kind of functionality is fundamental to LESs.

    “[By combining] these elements with full audit trails and electronic signatures, laboratories can meet regulatory requirements,” asserts Stonecipher.

    As laboratories increasingly flee paper-based systems, the integration of LIMS capabilities with ELN, SDMS, and LES capabilities within a single package provides the best coverage for all IT functions and workflows. Such integration also helps processes achieve complete traceability.

    Only recently has interoperability of this sort become readily available. Software platforms were developed, sold, and deployed separately. Companies were forced into retrofit and programming situations to force interoperability, sometimes on products from multiple suppliers.

    Today the burden of seamless integration mostly falls on vendors. Laboratory and manufacturing data systems now available in web format completely eliminate the need for customers to understand and maintain these complex systems. And since upgrades and add-ons are also deliverable through the cloud, this additional IT burden disappears.

    Laboratory software packages may deploy in a single implementation or through a phased approach. “It is generally recommended that laboratory procedure harmonization occur before implementing any system, to help minimize any variance across global laboratory entities,” Stonecipher advises.

    After harmonization, implementation then occurs in a staged approach by selecting represented laboratories across the enterprise, or specific products.

  • Complexity Begs Automation

    In biomanufacturing, LIMSs are primarily employed to manage the heavy analytical workflows that support production. “The number of tests associated with each batch is much greater in bioproduction compared with small molecule manufacturing,” says Gene Tetreault, senior director of enterprise laboratory management at Biovia. “More coordination is required between testing and processing.”

    Gate stages arise that require results before moving forward. “It’s much more iterative,” notes Tetreault.

    Testing and sampling points for small molecules are few and well-defined (for example, with bulk materials, one or two intermediates, and finished products), and processes tend to be more formulaic. In the age of process analytical technology (PAT) and QbD, biomanufacturers are constantly collecting data. Hence the need for automation within a compliant, tamper-proof data collection and processing repository.

    Traditionally, ELNs were more for experiments and less for production, whereas LIMSs were relegated to sample- and test-heavy applications. Those lines are blurring. “During clinical manufacturing you’re likely to have an ELN with the capability of documenting recipe development, clinical batches, and managing those activities,” Tetreault explains.

    To complicate matters even more, the LES, a kind of ELN, is an option. It can guide laboratory workers through the execution of tests and captures all relevant features electronically.

    LIMSs have the shortcoming of involving manual operations. Operators still need to collect the sample; gather reagents; get instruments up and running; test the sample; and collect results and enter them into an electronic repository, which reports results back to the batch. Quality control laboratories that operate through standard operating procedures execute many steps in each test, all of which must be in compliance.

    “And that’s not something that LIMS are good at,” Tetreault observes.

    Users must follow analytical procedures ensuring that the proper reagents and solutions are used and that instruments are calibrated. Collecting data manually creates what Tetreault calls a “paper problem” and transcription issues in getting data from paper into a LIMS to associate with the sample.

    Now imagine a system that “knows” what the sample is and which protocols need to be followed. Moreover, the system is familiar with the instruments and their maintenance histories. And now imagine the system executes the test automatically and sends the results to the LIMS and further along to the batch record.

    “A lot of LIMS vendors recognize the value of this,” Tetreault says, “and are building LESs to complement their LIMSs’ sample management.” The LIMS-LES combination, can manage both samples and results. “That’s what an LES is good at.”