Laboratory notebooks contain a literal wealth of information to advance research enterprise-wide, to protect and support patents, and to streamline the regulatory submissions process—if only they could be easily accessed. For most companies, the kernels of insights contained in those notebooks are about as useful as college notes, collecting dust on bookshelves, filed onto microfische, or locked away in a warehouse, inaccessible to all but the most tenacious.
Electronic lab notebooks (ELNs) are changing that scenario, making information accessible enterprise-wide, extending from R&D to legal and regulatory departments. The typical result is efficiency gains of 15–25% for biology—about four times that of medicinal chemistry, according to Glyn Williams, vp of marketing and product management at IDBS (www.idbs.com).
Benefits include increased bench time for scientists attained by minimizing the time needed to write-up experiments, reduced report writing for team leaders, better decision-making support, reduced IT infrastructure cost and complexity, and improved data security and organization.
AstraZeneca (www.astrazeneca.com) is among the vanguard in championing ELNs. “Here, their main strategic use is to aggregate and mine data that have historically resided on paper or in various formats on individual hard drives,” according to Joseph Logan, global change program manager, IT services.
“That,” he says, “allows us to tease out the stories residing in the data.” Although that is true of any business data, in this case, the information has “particular promise in discovery and development where scientists can establish previously unavailable correlations and especially in mission-critical aspects of research such as safety and efficacy.”
The minimal productivity gains realized from generic ELNs in the past decade, coupled with the rigidity of lab information management systems (LIMS), have slowed adoption. According to Michael Elliott, CEO of Atrium Research(www.atriumresearch.com), less than 20% of the market is implementing ELNs now.
That segment, driven by 21CFR Part 11 and a spate of mergers and acquisitions, is seeing ELNs as a collaboration tool that bridges the silos erected by scientific discipline and technologies to “offer tangible benefits beyond IP concerns, such as a searchable reaction database and the ability to reuse experiments done even by others to avoid duplication,” Elliott says, and to use those insights to refine experiments.
“We’re seeing a broader adoption process that’s changing rapidly,” notes Dave Dorsett, vp and general manager of software at Symyx Technologies (www.symyx.com). Enterprise-wide and extra-corporate (for CROs and partners, for example) adoption are becoming popular among companies that have switched to ELNs, Dorsett says, improving the legibility of records, data handling, and retention of institutional knowledge as people leave.
New Biology Tools
“Products for biology are just now entering the market,” Elliott says. Biology is a diverse space built upon different nomenclatures. Thus, biologists need software tools designed not only for biology but with the flexibility to be used in a variety of subspecialties.
Biology, for most ELN companies, is a tough nut to crack. “It isn’t as exact a science as chemistry,” Paul Denny-Gouldson, product manager at IDBS, maintains. There’s more speculation and supposition, so “flexibility is the key to this type of research,” Williams emphasizes.
The IDBS E-WorkBook Suite addresses the need for flexibility with a two-step approach. First, it uses a general ELN framework to provide the basic functionality for elements like electronic signatures, audits, creating lab and legal documents, and supporting intellectual property.
The second, more specific phase employs the BioBook and ChemBook extensions that provide the ability to capture, manage, analyze, report, and mine structured (factual) and unstructured (contextual) data. It handles complex, multidimensional data in late-stage development as well as in vivo testing and preclinical work, according to Denny-Gouldson. This system can integrate easily with existing systems using a combination of Web and data federation services.
At the “IQPC ELNs” conference in London held recently, Rescentris (www.rescentris.com) and the U.S. Air Force received the Global Automation Award for best knowledge management software for biological R&D, awarded by the Collaborative Electronic Notebook Systems Association (www.censa.org). That application, called CERF for collaborative electronic research framework, aims to be “the desktop of scientists,” according to Adel Mikhail, Ph.D., CEO.
Based on ontologies, it allows searches through full text content, metadata, and controlled vocabularies and captures annotations and scientific interpretations, thus facilitating collaborations across the enterprise, notes Dr. Mikhail. In addition, it meets the technical provisions of 21CFR Part 11.
Symyx is working with partners to address the biology space by building a modular approach to ELNs. “Our goal,” Dorsett says, “is to offer specialized, vertical tiers of ELNs. When released, it will join the company’s other ELN components, including Discovery Notebook, which allows scientists to quickly design and record new reactions or begin with reactions found in the corporate ELN database; Process Notebook, which enables planning and recording of synthetic campaigns (from lab to pilot plant); and Analytical Notebook, which saves time by recording analytical data in custom templates that enforce business rules.”
Symyx’ Formulations Notebook enables scientists to design formulations, create custom batch tickets, and record batch data and analytical results, while BioProcess Notebook is designed to record bioprocess and analytical data in a corporate repository. The Symyx Vault platform provides core infrastructure for the specialized electronic lab notebooks. It also complies with the 21CFR Part 11 technical requirements.
Strategically, the two major stakeholders are the scientists and corporate management. Scientists are using ELNs to optimize reactions and leads, develop better starting points, and otherwise leverage information, independent of organizational or technical silos. From the corporate perspective, having ELNs retains the knowledge base and provides better security and audit trails so you have a full chain of custody.
Dr. Mikhail estimates that “30 to 35 percent of scientists’ time is spent looking up information.” As an example, he cites a top-five pharmaceutical company that spent nine months combing through paper notebooks for the extra data the FDA needed for a submission on what he says was a billion-dollar drug. An electronic search could have been completed in a few minutes, leading to a significant competitive advantage.
ELNs also foster collaboration. Traditionally, people rarely search through others’ paper notebooks. “The pages are largely incomprehensible,” Elliott says. “But, with ELNs, you can at least read the notes,” and use some of the information in other studies. Knowing this, he says, “scientists tend to be more descriptive and use more annotations.”
At Array BioPharma (www.arraybiopharma.com), Dan Weaver, senior manager of scientific computing, doesn’t worry about return on investment measurements because “we know our implementation of ELNs is successful because of the way it has been adopted and the way it affects the execution of science.”
Array began an implementation of CambridgeSoft (www.cambridgesoft.com) products with its chemists and subsequently rolled out ELNs for biology. Where they’ve been implemented, everyone has switched to ELNs, he says.
“Five years ago,” Weaver says, “analytical data was stored separately. Now it’s stored with the scientific results,” making it easier to interpret experiments and to know what has been signed off.
ELN implementation is proceeding with the process chemistry group, which uses the notebooks to track and document changes for GMP batch processes and formulation.
During the coming year, Array plans to integrate bioassay result systems into its ELN system. But, right now, ELNs’ most strategic use is in providing consistent, universal access to experimental data.
The biggest challenge for corporations implementing ELNs is probably integration. “Integration cost is massively under-estimated, and the ongoing cost of custom integration is also rarely considered in the total cost of ownership analysis or a project,” Williams explains.
Beyond costs, however, potential users need to quit thinking of ELNs as just a research tool and think about integrating them throughout the enterprise so other departments can leverage the scientific data to better meet corporate goals. “Companies tend to buy ELNs based on the needs of a particular department, and then realize they can be used in other areas, which they didn’t think about ahead of time,” Elliott says.
On a more individual level, implementation involves change management. At Bristol-Myers Squibb (www.bms.com), a member of one of the early coalitions developing precursors to ELNs, Stephan Taylor, Ph.D., director of process R&D, recalls that some scientists were particularly proprietorial about their notebooks. “Eventually, they got over it,” he says.
There are practical considerations, too. Scientists have been trained in particular domains and need to adjust their ontologies so their information is useable across the enterprise. It is an issue of organizational standardization that requires scientific groups to compromise on file systems, definitions, and other details.
“At Array, scientists were reluctant to change,” Weaver says. “It took about three years.” The tipping point came when they saw meaningful workflow improvements, many of which were linked to the integration of analytical equipment to the ELNs and the ability to streamline the generation of legal records. The result, Weaver adds, is fewer errors in documentation, better morale, and fewer barriers to filing patents.
ELN or Hybrid?
Initially, only 12–15% of companies elect to go fully electronic, Elliott says, leaving at least 85% with hybrid systems. “After implementing ELNs, 30 percent switched over to fully electronic versions,” Elliott claims.
Many companies default to hybrid systems, ELNs that are also printed on paper, “because of the lack of legal precedence involving ELNs.” Yet, Elliott says, many top-10 pharmaceutical companies have gone entirely to ELNs and consider IP protection just as good as or better than paper or hybrid systems.
“This new piece of technology is merely a tool,” Logan emphasizes, to help companies achieve their goals. “ELNs can remove obstacles,” but the process changes and the rewards system to encourage new behaviors are more important.
“ELNs often are afforded grandiose expectations far beyond their capabilities,” Logan continues, and systems can’t necessarily live up to those expectations. That gap can be managed, however, by increased clarity not only about the technology but also about process and governance interdependencies.
Bristol-Myers Squibb set expectations with a basic rollout and then gradually added functions. “The more information that’s available through the ELNs, the more likely scientists are to use them,” Dr. Taylor reports. “We populated the ELNs with historical data,” taken from the chemistry and engineering that is used in the manufacturing facilities, including the reagents and structures, with references to the original process descriptions stored in the company’s document repository.
As these electronic systems gain functionality, they have reached the point where, Weaver believes, “ELNs are no longer options. Pharmaceutical companies not implementing ELNs will be behind the curve.”