Electronic Laboratory Notebooks Progress and Challenges in Implementation

Abstract

Electronic laboratory notebooks (ELNs) are increasingly replacing paper notebooks in life science laboratories, including those in industry, academic settings, and hospitals. ELNs offer significant advantages over paper notebooks, but adopting them in a predominantly paper-based environment is usually disruptive. The benefits of ELN increase when they are integrated with other laboratory informatics tools such as laboratory information management systems, chromatography data systems, analytical instrumentation, and scientific data management systems, but there is no well-established path for effective integration of these tools. In this article, we review and evaluate some of the approaches that have been taken thus far and also some radical new methods of integration that are emerging.

Introduction

“Scientists have traditionally used paper notebooks to keep track of their experimental ideas, observations and research results. Maintenance of accurate records of the experiments performed is an important aspect of all laboratory work. Among scientific documentation, the laboratory notebook is the most prominent, being the official record of laboratory measurements and observations. For the researcher, a properly maintained notebook can be a source of useful information for many years. For a scientific organization, lab notebooks are a potential goldmine of knowledge and experience. Enabling electronic access to lab notebook data might greatly improve knowledge management capabilities, eliminate the waste of information that is inherent in the paper system and improve efficiency by helping to reduce work duplication.” ¹

An electronic laboratory notebook (ELN) for routine analyses takes over at the bench level, right at the point of analysis, providing real-time control and automation of testing procedures. ELNs ensure procedural execution, automate manual processes, collect instrument data, and perform calculations, limit checking, calibration checking, and inventory checking and updating. ELNs also provide electronic documentation and access to test results. These controls built in ELNs ensure compliance with standard operating procedures during the analysis and protect the integrity of collected data. ²

The ELN complies with 21 CFR Part 11 guidelines from the Food and Drug Administration (FDA) with respect to digital signatures, electronic records management, and software quality systems management. In using a standard PDF format for data storage, export, and printing, the ELN also complies with the FDA’s requirement that electronic copies be readily available for inspection. ³

The evolution of ELNs changed the industries’ traditional way of documenting the analysis and experiments in physical notebooks. Per Atrium Research, “Major Industry players saw the benefits of ELNs and started implementing them actively since 2002–2004 to replace the paper notebooks.” ²

Dominic John ⁴ from Accelrys believes that replacing paper-based processes with electronic workflow and process documentation is also a critical step in improving innovation productivity. Paper processes are inefficient and prone to errors; they are also not searchable and not traceable, and they hinder collaboration and information sharing. In contrast, a modern informatics system built on a common platform with integrated electronic laboratory notebooks supports a quality by design (QbD) strategy that lowers compliance costs and improves product quality―catalyzing the delivery of better therapeutic products, while being faster and at lower cost to patients. ⁴

Reports from Atrium Research in 2011 show an instant 20% accepted productivity gain over paper processes by enabling scientists to document experiments, find and reuse information, and collaborate more efficiently. ² ELNs are now playing a key role in early to late development and thus are an integral part of the informatics life cycle. The new evolution of the ELN to be able to create and capture workflows, as well as new data access and analysis, now supports pharmaceutical and biotechnology development to deploy and better support an informatics environment. ²

Many laboratories are eliminating paper notebooks in favor of paperless laboratory technology, but the implementation of these paperless technologies such as ELNs comes with practical problems during deployment and technical feasibilities. A driving force for deploying an ELN is to improve the scientist’s work in the laboratory. This is generally focused on improving efficiency in executing and documenting experiments. Integration of the ELN with other electronic-based systems in the laboratory greatly multiplies the effectiveness and return on investment (ROI) of the ELN deployment. Substantial time reductions can be achieved when creating and reviewing experiments while data integrity is improved. There are various specific ELNs on the market for quality control, process development, discovery and biology, and so on. Collecting the user requirements by understanding the relevant process will help make the configuration and deployment process efficient and effective.

There are different integration models—workflow-based architecture, enterprise modular integration, integration by service-oriented architecture (SOA), semantic repositories, and nano publications. The ideal integration depends on the type of laboratory (i.e., analytical laboratory, synthesis laboratory, clinical laboratory, discovery laboratory, research laboratory, etc.), type of data generated, and the tools used that need to be integrated. Of the different integration schemes presented, the workflow-based framework is the most likely to be successful in the short term since large-scale data analysis needs flexible workflow-based integration of different software tools and application from diverse domains, which can provide in silico experimental design. By using a workflow-based framework, we can also integrate web services, a semantic web, grid domain-specific tools, and ontologies for drug discovery. ³

• Implementation of an ELN will typically involve consideration of many matters specific to ELNs over laboratory notebooks. What could be the possible cost savings by implementing an ELN?

• What would be the quality increment?

• Which regulatory affairs the firm have to fill for?

• What kind of efficiency increment could the company reach?

• What is the effect of using an e-signature?

• How can ELNs fill the request of data security?

• What is the cost of implementing an ELN?

• What kinds of resources are required for life cycle management?

• Is it possible to interface to enterprise systems (i.e., enterprise resource planning or manufacturing execution system)?

• Which analytical instruments can be connected to the system?

• Which interface software package is required?

• What will be the influence on my company’s infrastructure?

• How big is the ROI?

Limitations of the Paper Notebooks

According to Lass, ⁵ the needs created by collaborative work are hampered by the functionality of paper notebooks. Sharing information recorded in separate notebooks requires a scientist to copy the information and send it to the requesting scientist. This takes time and effort and distracts the scientist from his or her primary work. It also creates issues for the scientist receiving and using the information. It is hard to record and preserve the audit trail for the information contained within the copied pages.

Paper notebooks do not lend themselves to easy searching. Although external databases can correlate notebook numbers to users, the content of paper-based experiments is not indexed for searching. Thus, it is not possible to find experiments that used a specific target compound or all experiments using a specific pathway for synthesis. ⁵ Paper notebooks also present issues when recording information in the same experiment or the notebook requires physical proximity of the scientists. This limits where and with whom scientists can collaborate. It also forces scientists to record information one by one. Signing and witnessing can also cause issues, if it is not clear who was responsible for specific entries within an experiment. ⁴

Scientists have been literally cutting and pasting computer printouts. An unscientific poll showed that depending on the area of research, scientists pasted 25% to 80% of printouts. ¹ The notebooks easily swell to triple their original size. It is a nightmare for archivists, not to mention frustrating for the intellectual property staff. Manually copying documentation into a paper notebook is counterproductive and takes up the valuable time of the highly qualified workforce. Worse still, in the growing area of in silico studies or in studies where massive amounts of digital raw data are generated, the mere idea of putting everything down in a bound paper notebook seems absurd. In addition, bound lab notebooks, sequential in nature, are ill suited for documenting events occurring automatically and simultaneously, such as parallel synthesis. The result of all this is a steadily decreasing quality of documentation that needs to be addressed immediately. ¹

Advantages of ELNs

ELNs can be connected to and integrated with other laboratory informatics systems: laboratory information management systems (LIMS), analytical instrumentation, chromatography data systems (CDS), scientific data management systems (SDMS), modeling and simulation programs, chemical inventory systems and scientific databases, and business-level systems such as document management systems, Systems Applications Products and manufacturing execution systems. ³ The electronic lab environment provides a number of advantages for the scientist:

• Consistent data input

• Reduced documentation time by half

• Reduced time for review and cycle times

• Easy to search data

• Information capturing and reuse, avoiding repeats and reinvention

• Ability to share experiments

• Custom dynamic reporting

• Elimination of illegibility problems created by hard to read handwriting

• Elimination of problems due to lost or damaged paper forms or paper notebooks

• Reduction of paper storage and retrieval costs

Difficulties in Implementing ELNs

The following are a few difficulties in the implementation of ELNs:

• ELN implementation is expensive: ELN implementation will cost the companies based on the number of licenses used.

• Implementation time: Implementation time varies depending on the scope of the project.

• Integration with instruments: Integration depends on the number of instruments that need to be integrated and the compatibility of the instruments with the ELN.

• Method conversion/coding: This process is time-consuming as the method needs to be coded, and the user requirements will be provided by the subject matter experts to the coders, who do not understand the workflow of the methods.

• Lack of flexible custom reporting

• Managing user resistance

• Dealing with technology

• Training the user base

• System configuration per the laboratory workflow

• System customization: code changes

• Experienced users and administrators

• Project management

• User requirements

• Design requirements

• Functional requirements

• Configuration requirements

• Risk assessment

• Validation plan

• Computer system validations

The Pharma IQ study found that 41.9% of firms saw integration with other laboratory systems as the most challenging area of ELN adoption. Similarly, 25.8% named the continued integration of ELNs with existing lab infrastructure as a key obstacle in the long term. More than three-quarters of firms questioned in the survey described interoperability as a “concern” going forward. Although 47.1% admitted that there were other more pressing obstacles to overcome, 35.3% ranked interoperability between their ELN and other lab equipment as a primary concern. Companies must also know how to integrate the semantic capabilities of their ELNs. ⁶

ELN Implementation Success Factors

A successful ELN implementation lets scientists quickly create and edit experiments and, more important, share and reuse experiments they or other scientists have created. Integration of ELN with other applications essential to their work within the laboratory for compound registration, chromatographic data, LIMS, SDMS, and inventory systems will result in less time spent on manual data entry. ³ Managers gain visibility into research to track experiments in progress and gauge efficiency and make appropriate decisions.

The business case for an ELN, however, can be harder to make. Business sponsors view ELN deployment as an investment intended to improve research and development (R&D) efforts and typical laboratory process efficiency. Thus, success is measured by ROI, the measure of money saved over a specified period of time.

Expenses in ELN implementation include not just the cost of purchasing hardware and software but also configuring systems, instrument integration, training users, method coding, and maintaining systems over time (life cycle management). Savings are easy to identify but may be harder to quantify. ⁵

Factors influencing ROI include the following:

• Project efficiency: Are we conducting more experiments?

• Scientific efficiency: Are scientists spending more time in doing research and less on cutting and pasting data into notebooks?

• Cycle time within projects: How quickly are the samples analyzed, reviewed, and approved?

• Rework: How often are we repeating or duplicating experiments?

• Information-gathering processes: Is it easier to review research or collect information for intellectual property and regulatory filings?

• Systems used: Has the implementation enabled us to consolidate or decommission systems?

• Time: By using ELN, are we able to perform any of the above activities quickly?

The success can be defined by how well an implementation minimizes expenses while maximizing savings and improving productivity. Organizations can make a business case for an ELN by looking for streamlined configurations, support for critical document and scientific workflows, Cloud computing, cost-effective outsourcing options, integration with or elimination of existing systems, and strategies for achieving lower total costs of ownership. ⁵

The Future of ELNs

According to Charles, ⁶ by 2017, the global market for ELNs is poised to reach $284 million, with the life sciences industry responsible for a large proportion of this growth, but ELNs are also increasingly being used outside medical research, in fields including analytical chemistry. LabArchives’ latest ELN, released earlier this year, contains full functionality with tablets, including iPads and Android devices, essentially allowing users to access their lab data any time in almost any location, as a result of what the company said was growing demand from customers. ⁷ “Due to the prevalence of merger and acquisition activity today, the need to rationalise your portfolio of applications in a holistic manner will almost inevitably be an essential part of your decision-making process,” Peter Boogaard, founder of Industrial Lab Automation, and Patrick Pijanowski wrote for Scientific Computing World. ⁸

ELNs will eventually be used by all R&D scientists to record all of their research and will become their central application. ⁹ Scientists will expect to be able to extract information from ELNs efficiently and easily. This puts great pressure on the architecture of ELNs; in industrial terms, it must be open, extensible, scalable, and robust. ⁹ In addition, ELNs must be easy to use, simplify the user’s work process, and be fast. In the field of pharmaceutical R&D alone, ELNs must also be able to deal with many different types of data, for example, chemical structures, chemical reactions, experiment protocols, digital images, spectra and chromatograms, and sequences. ⁹ There are also opportunities for using ELNs within other industries, for example, in engineering where computer-aided design images will be needed. ⁹ ELNs in the future will be integrated with other laboratory informatics tools such as LIMS, CDS, and SDMS. ³

Over the past few years, the industry has increasingly adopted the ELN, a software application that eliminates paper from laboratories during analytical procedures. In a recent Pharma IQ survey, conducted with key members of the community on behalf of the forthcoming ELNS & Advanced Laboratory Solutions Conference, 91.2% of respondents claimed to be at least in the planning phase of ELN adoption and usage. Most participants in the study were pharma or biopharma companies, although almost a quarter were contract research organizations or vendors. Unsurprisingly, the survey revealed that research and development work was the key focus of companies’ ELN usage. In fact, 61.8% of companies are using their ELNs to enhance R&D processes, although many have applied them to help maintain a good manufacturing practice environment, as well as in formulation, chemistry, biologics, and bioanalytics. ⁶

Talbot et al. ¹⁰ believe that exposing the data and activity of ELNs through standard metadata representations and protocols will be an important step in bringing them into the broader world of the semantic web and knowledge grids. With growing automation of metadata capture through instrument control software, LIMS, problem solving environments, workflow tools, and other mechanisms, as well as the growth of project-spanning institutions and disciplines, ELNs will no longer be the sole source of, or interface for, scientific records to the extent that paper notebooks have been. However, Talbot et al. believe ELNs capable of contributing to a shared record with explicit semantics will be a key enabler of next-generation research.

The seamless integration of ELN with other systems in the enterprise can eliminate much of the tedious efforts of manual data aggregation and manipulation. The access to data across sources allows new data relationships to be uncovered. With the notebook oftentimes at the center of a scientist’s workflow, the desire to integrate with all the systems in the laboratory is very effective. ³ Careful thought and design, however, need to be considered to avoid issues of unmanageable integrations. ²

Integrating the ELN with enterprise resources can have a profound impact on enterprise research. Successful integration of the ELN with other electronic-based systems in the laboratory greatly multiplies the effectiveness and ROI of ELN deployment. ³ Substantial time reductions can be achieved when creating and reviewing experiments while data integrity is improved. By providing access to a vast array of information and data, the ELN keeps scientists apprised of the latest information affecting their research as well as the availability of resources needed to execute experiments or research. In this way, the ELN brings a new dimension of efficiency to the research effort, enabling scientists to get the answers they need in the least amount of time. The ELN eliminates physical barriers to sharing data and collaborating in the creation and documentation of experimental work. ⁵