A Look at the State of Electronic Lab Notebook Technology
Stephen Bruce
What's needed for ELNs to replace and improve on paper
Information technology is a familiar and essential component of many aspects of research, dramatically enhancing efficiency and productivity in these areas. CDS are an obvious example in the context of this supplement and, together with cheminfomatics, bioinfomatics, scientific data management systems (SDMS) and so on, they have transformed the generation and management of raw scientific data. Equally, IT has had a similar effect at a strategic level.
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| Figure 1: Thinking and doing in the experimental process |
However, in most labs, the crucial experimental layer between raw scientific data and business context remains served by the paper lab notebook, which becomes a major bottleneck between the two.
The problem with paper
The paper lab notebook is the root of some fundamental inefficiencies within the R&D process — both for individuals and for companies at large. Paper is:
•time-consuming to write up work in
•tedious to index
•difficult to search
•expensive to archive (both in itself, and when microfilmed)
•vulnerable to damage and loss
•an obstacle to teamwork and collaboration, both within individual labs and across departments, sites and geographies.
Paper records are often of inconsistent legibility and formatting, and it can also be extremely hard to co-ordinate work across multiple lab notebooks (much less across departments and geographies). In many companies, there are serious flaws in the paper record-keeping process for patenting purposes.
The co-existence of sophisticated computing in some areas, and ongoing paper-based working in others, typically leads to one of two situations:
•Physical cutting and pasting of printouts into paper lab notebooks (and, in many cases, the discarding of all but the most obviously essential raw data from the main scientific record)
•Different records stored in different places in different ways with, at best, time-consuming cross-referencing and indexing.
Overall, paper places R&D (an area already under constant pressure to produce more work in less time with fewer resources) in a "lose-lose" situation: complete records are painstaking and time-consuming to create and manage; incomplete records risk the loss of valuable intellectual property.
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| Figure 2: A flexible ELN-based IT infrastructure for R&D |
Unsurprisingly, then, there is increasing interest in electronic lab notebooks (ELNs). CENSA (1) has been meeting for many years to discuss ELNs and associated issues. More recently, there has been broad coverage of ELNs on the conference circuit and in industry press.
There is also substantial ELN activity at a departmental level in many companies. However, whilst these departmental ELNs demonstrate demand for systems that can replace paper, they also create significant potential problems. As with most IT currently in the lab, they are typically optimized for a specific discipline or toolset, which can create inter-departmental systems integration issues and knowledge-sharing problems, not to mention the likelihood of differing record keeping practices across key processes such as patenting.
Tellingly, though, there are very few enterprise-scale deployments, especially within the pharmaceutical sector where the regulatory climate makes systemic change harder to achieve (Amphora's largest deployments to date — DuPont and Kodak — are in non-regulated industries). So why, given that the benefits of replacing paper are obvious and intuitive, are deployments so few in number?
Regulatory pressures in the pharmaceutical sector and general economic uncertainty are contributing factors, but the real answer is two-fold:
•The implications of replacing the paper lab notebook are huge.
•Until recently, ELNs have not been sufficiently mature proven technologies to remove the risk from deployment.
The implications of replacing paper
To understand paper's place in the lab — and thus what ELNs need to do — it is necessary to look at the scientific process and how it is currently supported and served. Broadly speaking, science consists of two intertwined and complementary facets: "thinking" and "doing" (see Figure 1).
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| Figure 3: The frequency with which scientists need to search for old work (CENSA) |
"Doing" generates mainly structured data (analysis, results, processes) and is already well-supported by IT, for two reasons:
•The need to generate and manage raw data was the more obvious and pressing need for IT to solve, hence CDS and informatics is an older and more mature "industry."
•Managing structured data is what IT systems most naturally lend themselves to.
The benefits of such systems are obvious, but the data recorded in them isn't principally what scientists record in their paper lab notebooks (even if they might paste it in as "supporting" evidence).
Paper is used primarily for recording the "thinking" side of science (ideas, connections, conclusions), which acts as an essential "wrapper" for "doing," giving it context and meaning. Paper brings together and co-ordinates data from many sources and is therefore a powerful — albeit primitive — systems integration tool. This is crucial to understanding paper's importance and its central role: it is a "hub" and focal point for some of a company's most important records and processes:
•Generating and maintaining the scientific record
•Identifying and exploiting intellectual property
•Compliance with internal and external standards.
As data management systems have come to dominate the "structured" elements of science, so the nature and importance of paper's role has been clarified. To replace and improve on paper, an ELN must:
•Be intuitive and easy to use
•Be flexible enough to incorporate different disciplines and working practices
•Co-ordinate and integrate with existing toolsets
•Produce patentable records
•Facilitate compliance
•Archive responsibly, so that records can be recalled and understood many years hence.
In other words, to transform efficiency and productivity, an ELN needs to both embody paper's positive qualities and eliminate its negative ones. At the same time, for it to be viable, all risk of working electronically needs to be removed.
ELNs replacing paper
Ease-of-use
One of the main reasons paper has endured is the ease with which it can be used and adapted — the concepts of experiments, pages and notebooks are proven, intuitive and powerful. Accordingly, most ELNs retain these, which also helps with the cultural transition from paper-based to electronic working.The single largest benefit of an ELN, though, is to reduce or eliminate the administrative tasks usually associated with paper. Electronic records are instantly legible, and — through the use of stored experiment templates, both for teams and company-wide — they can be created in consistent formats, both of which greatly reduce the burden on quality control departments. Electronic records are also easily shared and information can be easily copied — for example into a report.
Moreover, all the information in an ELN (including, sometimes crucially, "failed" experiments) can be automatically indexed and searched — two tasks which currently require a lot of many scientists' time (see Figure 3). In Amphora's ELNs, scientists can choose exactly what gets copied from their individual notebooks to be stored and searched centrally. Scientists are used to a great deal of autonomy in their paper lab notebooks, and sharing needs to be organically encouraged. Within two years of deploying their ELN on a largely voluntary basis, Kodak's surveys found that 100 percent of users benefited from improved sharing (2).Overall, then, an ELN resolves a culture of record-keeping with a culture of productivity: something that simply isn't possible using paper.
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| Figure 4: Repeatable signing and witnessinf for patenting purposes in an ELN |
Flexibility
Disciplines and research requirements vary, not only between companies, but also across and within departments, groups and teams. Working practices and tools evolve over time, and vary between scientists and tasks. There is no obvious "one-size-fits-all" system that caters for all the rich variety found in most companies.
However, consistency is desirable — even essential — across key processes such as patenting and compliance, and there are obvious knowledge management, research management and collaboration benefits from a shared system. Information relevant to patents is also quicker and easier to find.
Paper provides a sufficient level of abstraction for all scientists to use; Amphora achieves a similar balance between standardization and flexibility in an ELN by implementing a server to handle company-wide procedures where consistency is necessary (such as audit-trailing, security and signing for patenting), and specific clients optimized for particular groups and processes. (See Figure 2)
This "modular" approach is an excellent way of separating out different working practices — non-regulated discovery from regulated developmental work, for example (which can greatly assist compliance with 21 CFR Part 11 where necessary).
Integration
As mentioned, paper is a "hub" for many different research activities and information, but an imperfect one owing to the discontinuity between electronic and paper. For an ELN to be truly compelling, it should be a similar "hub," working naturally with the scientists' tools, to create a dynamic "one-shop" working environment.
No one vendor can hope to adequately cater for all the IT needs in the lab; not only is the range of needs simply too wide, but existing systems represent significant investments, which makes their replacement unviable. Accordingly, an ELN should integrate with these tools and, in doing so, make the "joins" as seamless as possible, minimizing administration and maximizing information flow.
The benefits of such an approach can be dramatic. Kodak achieved a 10 percent reduction in cycle time when their LIMS system was integrated with their ELN: scientists could submit LIMS requests from within the ELN, analysts could view the research context for the request without needing to query the scientists, and results could be placed straight back into the context from which the test request was made. Connecting systems in this way also makes the ELN the natural place to begin searching for information, be this for research or patenting purposes.
XML is the "lubricant" that vendors — both of ELNs and of other scientific software — are agreeing on as a common integration standard. This collaborative approach minimizes the custom integration costs which might otherwise dominate an ELN project, and serves as evidence of the maturity of the emergent ELN "industry."
Patenting
Patents are the lifeblood and goal of the research process, and many companies are therefore cautious of relying on electronic records in court, given the lack of case law.
The irony in this is that, under close inspection, paper processes for patenting are failing many companies — especially those subject to US patent law. Records are often only signed and counter-signed long after the work is done — sometimes in bulk — causing relevant dates for patent purposes to be significantly delayed, and the "read and understood" aspect to be seriously questioned where many pages have been signed at once.
By contrast, work-in-progress can be signed repeatedly in an ELN. Each time, a copy of the work at that point is made in a separate, secure database, where it can be signed and counter-signed with timestamps, so building up a complete history of its development over time. Throughout, work can continue on the original document. (See Figure 4.)
Moreover, when all the data relevant to a patentable idea is accessible and searchable in an ELN — including its context and supporting data — it can be quickly and precisely identified.
The U.S. Patent Office has stated that electronic records are admissible in patent interferences (4), and some ELN users have publicly stated their reliance upon their ELN for patent purposes. Moreover, for companies with a conservative "risk profile," many ELNs also offer a "hybrid" option, where electronic records can be printed out, signed and retained as hard copy. PatentPad from Scrip-Safe is special paper for just this purpose.(5)
Compliance
For those that it applies to — and, conversely, some that it doesn't — compliance is another huge stumbling block for many companies looking to deploying ELNs.
A major difficulty can be deciding what does and doesn't fall under regulation. As a rule, owing to the stricture that regulations impose, it is crucial not to implement them unless absolutely necessary. Whilst every company needs to form its own compliance policy, 21 CFR Part 11 (for example) is only definitely applicable in the developmental end of the pharmaceutical drug pipeline, and never applicable in a non-regulated industry. A flexible ELN architecture will allow companies to implement a compliant environment where necessary, without imposing it where it isn't — another compelling reason for a modular approach.
Obviously, where compliance is necessary, systems need to be rigorous: a failure here could cost a company millions of dollars. Whilst an ELN can not in itself be compliant — as a major part of compliance is a company's procedures — it can certainly facilitate compliance, by both supporting the implementation of procedures and providing thorough audit trailing. In general, a better-organized system can also make inspections quicker and easier.
Archiving
Given the importance that research records have over time — i.e. the length of the product "pipeline" and the ongoing need to defend patents — it is essential that they can be accessed in a meaningful way years later, without reliance on any particular technology or vendor. Paper can be damaged or lost, but it remains an "open" standard, and will not become obsolete in the way that many electronic data formats do.
A vendor "locking in" a customer by using proprietary file formats is simply not acceptable given the importance of the records stored in an ELN and, again, XML is emerging as the archiving standard to prevent this6, being an open and well-supported format with extremely high longevity. It is also vendor-neutral, which places the customer firmly in control, allowing easy migration between systems and vendors.
The state of ELN technology
ELNs are now available that can deliver transformative benefits, whilst also being "safe" from patenting, compliance and archiving perspectives, and there is a growing number of enterprise-wide deployments, both large and small, that bears this out. In some cases, ELNs have been in use for over five years, proving the longevity of the technology and allowing firm conclusions to be drawn about the transformations effected and the absence of risk involved in converting to an electronic working environment.
It can be argued that there are no reasons from a technical perspective why ELNs cannot now be deployed in every company. Where ELNs' technical capabilities are called into question, the cause is either a lack of awareness of the issues — both the extent to which paper is failing, and the fact that ELNs can now safely replace it — or reluctance to address the cultural challenges a system with an ELN's scope inevitably raise.
Cultural challenges
An ELN forces re-evaluation — and in some cases, change — of some of the most fundamental processes within a company, and a successful ELN project requires both time (typically 12-18 months from inception to deployment) and sensitivity. An ELN needs to simultaneously satisfy many core interests, which means that the decision-making process is complex.
Looking at current research practice and its shortfalls is a sensitive process politically. Lab notebooks are very intimate to scientists, which makes replacing them a delicate matter. Moreover, scientists are a challenging group, culturally, used to autonomy and sometimes allied to their art ahead of their company. Overall, the power of the familiar is enormous, too, and can lead to inaction, despite the clear problems with paper and the obvious potential of ELNs.
With careful planning and handling, though, these cultural challenges can be overcome.
Overcoming cultural challenges
The two keys to a successful ELN project are:
•To combine thoroughness and practicality
•To demonstrate respect for all groups that would be affected by a deployment by involving them throughout.
The project team should include representatives from each of these groups (including legal, records management and IT) and reasons to support an ELN should be found for each: it is a brutal truism that people won't endorse something purely on the basis that it benefits somebody else.
An internal case built around savings in time, money and risk exposure is most compelling. As an example, CENSA estimates that up to 25 percent of scientists' time can be saved (7) — with a large R&D operation, this could mean annual savings of many millions of dollars. However, whilst references from other companies are reassuring, each company is unique and evidence needs to come from within to be truly compelling.
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| Figure 5: Kodak scientists' rating of their ELN compared with paper-based working |
In deciding the system's scope and anticipated benefits, it is important not to write too detailed a specification. Requirements change as understanding and experience grow, and there is no substitute here for evaluating a real system as early as possible. A flexible product and vendor should be able to adapt to accommodate evolving requirements.
Pilot schemes are an excellent means of learning about what is needed and generating internal evidence and metrics, without excessive organizational upheaval and budget commitment. For example, it was only when our customers' lawyers were able to see the actual records produced by our systems in a pilot scheme that they were able to give their full approval.
We recommend that adoption of an ELN be voluntary — certainly in the pilot phase, but often in roll-out, too. This really forces an ELN to prove value to those that will use it, and demonstrates faith in people to decide what works best for them. Recently released statistics show that 68 percent of Kodak's ELN users now rate the system as "better" or "much better" than working on paper, with a further 19 percent rating it as the same (8)(see Figure 5).
Conclusions
Nobody within R&D seriously believes that paper is the future of documenting research, even if it has many positive qualities that have pointed the way towards what an ELN should do.
ELNs are technically viable now. They can transform research productivity and efficiency by synergizing "thinking" and "doing," and allowing companies to better capitalize on existing IT investments, whilst solving the essential "hygiene" issues, such as patenting, compliance and archiving.
Successful deployments demonstrate that the inevitable cultural challenges are not insurmountable. In the ongoing quest for researchers to do more, faster, with less, now is the time for companies to develop an ELN strategy to avoid being left behind by their competitors.
References
1. The Collaborative Electronic Notebook Systems Association — an industry body comprised of large predominantly pharmaceutical corporations, and software developers. See www.censa.org
2. John Trigg & Sheila Davis, Transforming the Laboratory by Implementing an Electronic Laboratory Notebook, "Managing the Modern Laboratory", Volume 5, Number 4, p72.
3. Financial Times, February 5th, 1999, "INSIDE TRACK: Research made an open book".
4. USPTO Notice (1208 OG 35)
5. See www.patentpad.com.
6. e.g. www.gaml.org and www.censml.org
7. See Comparing Paper and Electronic Laboratory Notebooks - Part 2 by Rich Lysakowski, Ph.D. (www.censa.org/html/Publications/Comparing_Paper_and_Electronic_Lab_NotebooksP2_SC&A_May-1997.html)
8. op cit, Trigg & Davis, p70.
Stephen Bruce is Public Relations and Marketing Manager at Amphora Research Systems. He may be contacted at editor@scimag.com.
