The Case for an Electronic Laboratory Notebook: A White Paper

The Case for an

Electronic Laboratory Notebook:

A White Paper

 

Infotrieve Corporate Headquarters

11755 Wilshire Boulevard, 19th Floor

Los Angeles, California 90025

Phone:  310-445-3000

email:  eln@infotrieve.com

www.Infotrieve.com

 

 

CROSS-DISCIPLINARY VS. SPECIFIC: CHOOSING THE RIGHT

ELECTRONIC LABORATORY NOTEBOOK

 

DEFINITION OF AN ELECTRONIC LABORATORY NOTEBOOK

The Collaborative Electronic Notebook Systems Association (CENSA), an international trade association for Electronic Laboratory Notebook (ELN) technology and standards defines an ELN as:

 

“A system to create, store, retrieve, and share fully electronic records in ways that

meet all legal, regulatory, technical and scientific requirements.”1

 

The wide range of ELNs on the market reflects the broadness of this definition; some provide specific scientific software tools while others may have more robust document management capabilities. However, all ELNs share the same basic purpose – to create laboratory notebook entries that record their protocols, reagents, data, and interpretations just like a paper notebook, only the entries are in an electronic format.

 

How then are ELNs advantageous compared to a paper notebook? ELNs benefit a company at the corporate level by ensuring that scientific data is available for use so that individual scientific knowledge can become corporate knowledge. At a more concrete level, ELNs provide substantial time savings for the scientists who use them, allowing them to move on to more experimentation rather than spending copious amounts of time recording results by hand or deciphering handwritten notations.

 

INTRODUCTION

ELNs can be classified according to how specific their capabilities cater to a particular group of researchers. “cross-disciplinary” or generic ELNs now compete in the marketplace against more specialized or “specific” ELNs. Evaluations of these choices often ride on differing opinions from various departments within the same company. What issues should a company consider in selecting between a cross-disciplinary or a specific ELN solution? Which features will benefit the entire company and which features are necessary for each department, from R&D to legal, to most effectively leverage the institutional knowledge officially recorded in the ELN?

 

DEFINING THE CHOICES

Specific ELNs contain features intended for researchers who work with particular types of applications, scientific instrumentation and data. Specific ELNs focus on integrating electronic/software tools for that scientific discipline. For example, some of the initial ELNs on the market contained features that a pharmaceutical chemist would find useful, such as chemical structure searching, chemical drawing tools and reaction planning. Several of these early ELN products arose from chemical software tool companies who took a ‘top-down’ approach to target their own customers with the electronic notebook concept.

 

Cross-disciplinary (or non-specific) ELNs are designed from a completely different perspective – from the ‘bottom-up’. Cross-disciplinary ELNs are designed using best-of-breed industry standards for file types, recording features, formatting, storage, and architecture. By choosing common standards, cross-disciplinary ELNs have a much broader appeal and applicability across multiple industries and to many types of research scientists. These types of ELNs allow all kinds of scientists to record, sort and organize data without having a structural bias toward data of any particular research specialty. They contain features that are discipline-agnostic, with add-on modules that may cater to specific end user groups such as combinatorial chemists. These ELNs also typically feature strong intellectual property (IP) protection, workflow management and electronic signature capabilities.

 

Applicability and Adoption

“Usability is next to profitability…Usability is a ‘good investment’ that can produce ‘dramatic results’.”

– Business Week, Dec 2002

 

One hallmark of a well-run company is its efficiency, a maximized use of resources to generate products to drive profitability. All ELNs are designed to increase efficiency but in varying manners. Specific ELNs address productivity needs of a subset of scientists through their specialty tools and data recording features. This efficiency increase primarily aids a single research department since the tools are significantly less valuable and may be confusing to non-scientists or even different types of scientists. The formatting and structuring of these notebook entries make sense to a subset of scientists, but are less applicable to recording or storing other types of research data. For example, discovery chemists may rely upon ELN features such as an automated theoretical yield calculation, which is not useful to a molecular biologist. Given that chemists typically do not work in very large teams, ELNs created for them cannot offer enterprise-wide search, broad collaboration capabilities, or flexibility in the notebook entry review process which are critical requirements for any matrix organization or department that requires cross-disciplinary work. Specific ELNs are focused purely on individual productivity – to the great benefit of the Discovery Chemical department, for example – but to the exclusion of others. Each research group would therefore need to purchase their

own discipline-specific ELN system, significantly increasing the overall total cost of ownership to the organization. Thus, the specific ELN, while being very useful for an individual department or group, does not offer broad applicability for many core ELN features such as search and collaboration.

 

In contrast, cross-disciplinary ELNs can provide enterprise-wide efficiency through commonly used tools and calculators that can be adopted across many departments, from chemists and high throughput groups, to toxicologists and quality control departments. The flexibility of these ELNs allows each group to easily set up their own specific workflow templates for notebook

entries using the same familiar Microsoft® Word or Excel interface. This use of common, familiar tools affords several advantages over a specific ELN. First, the ability to quickly create many department-specific templates out of the same tool provides a measure of consistency within a department. Also, if many departments use a single ELN system for which they can each customize templates, all of them will benefit from consistency of notebook entries. Secondly, creation of templates increases the likelihood that the format will meet the needs for each department and thus, increases user adoption, both within a department and across an organization. In addition, most users will already be familiar with the standard interface due to their experience with Microsoft® products; this familiarity reduces resistance to change while increasing user adoption rates. This is particularly important given the mobility of today’s scientific workforce. Increased user adoption means that the total cost of ownership decreases as more of the organization utilizes the ELN.

 

Total cost of ownership also decreases for a cross-disciplinary ELN since the installation, training and ongoing IT maintenance for a single cross-disciplinary platform is much lower compared to the support required for several discipline-specific ELN packages. IT system complexity is particularly problematic at large institutions given the numerous legacy systems in place; adding multiple ELN solutions on top of this web and requiring these ELNs to exchange information with preexisting systems and each other is a project that few IT departments will undertake, particularly if specific-ELNs are tied to proprietary technology. However, the cost of installation and deployment for a single cross-disciplinary ELN, assuming it’s based on industry-standards, greatly reduces this IT risk to ensure a successful deployment.

 

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Figure 12:  Cross-disciplinary or Non-specific ELNs are applicable across entire research organizations to help break-down information silos.

 

COLLABORATION AND DATA SHARING

“This team approach will be the hallmark of the great companies of the twenty-first century. I am convinced of it.”

-Joel Arthur Barker, Business Author and Educator

 

ELNs offer access to experiment data from a single electronic data repository. For specific ELNs, this data sharing will occur for small groups of users. However, given the specificity of the ELN data structure and associated tools, it is unlikely that other departments will use it, and/or access this repository. Thus, the information in this ELN is not readily accessible to other scientific departments for collaboration, nor to management for broad strategic planning. Indeed, specific ELN offerings reinforce a significant problem found in mid-to-large sized organizations – the silo-effect of information aggregation which inhibits effective organizational communication. Instead of breaking down inter-departmental walls, specific ELNs inadvertently build them up, forcing each department to make discoveries on its own.

 

Cross-disciplinary ELNs, on the other hand, effectively break down information silos, and actually promote interdepartmental collaboration through electronic data sharing. Anyone with access privileges can review data for collaborative or business strategy purposes in a cross-disciplinary ELN. All appropriate executives will have access to the system and can immediately view ELN content, even if they do not have experiment authoring privileges or specialized scientific software applications on their desktop. The ability to search for data that is organized in project format makes the data much easier to find for those less familiar with that project’s history. Furthermore, since cross-disciplinary ELNs can be deployed across an enterprise that may have multiple sites, the data becomes globally accessible, not departmentally or geographically limited. Thus, the ability to drive real-time inter-departmental collaboration within a global company is now possible. Global access also ensures that historical experimental data is instantly accessible which can foster new relationships and sharing of scientific expertise that would likely not occur outside of the ELN environment. Figure 2 represents a schematic of how a cross-disciplinary ELNs help to drive important organizational initiatives.

 

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Figure 2: Promoting Collaboration, Communication and Consistency of Process with a Cross-Disciplinary ELN.

 

It can be argued that a scientist such as an organic chemist will never need to share his or her data with a geneticist or protein crystallographer. While this is undoubtedly true in some limited cases, the usefulness of stored data is in its ability to be extracted from an archive when needed, sometimes long after a scientist has departed from the company. Maximizing efficiency requires increasing communication and accessibility to knowledge, rather than siloing information. This principle was deftly It can be argued that a scientist such as an organic chemist will never need to share his or her data with a geneticist or protein crystallographer. While this is undoubtedly true in some limited cases, the usefulness of stored data is in its ability to be extracted from an archive when needed, sometimes long after a scientist has departed from the company. Maximizing efficiency requires increasing communication and accessibility to knowledge, rather than siloing information. This principle was deftly demonstrated in a case study where twenty small-to-medium organizations collaborated in a virtual web environment; as one entity, they performed more competitively and productively than if each had worked independently and not shared information3 .  Likewise, multiple departments of a single company working independently do not capitalize on the knowledge that each possesses if there is not an efficient medium to share data and information. Valuable time, money and precious reagents are often wasted in organizations through duplication of experiments due to poor information management. Since these are often failed experiments, the searchability of this data can eliminate the redundancy of effort.

 

Advances in Science, a Long-term Perspective

“Change is inevitable. Change is constant.”

-Benjamin Disraeli, former British Prime Minister

 

Data in specific ELNs will typically be in a format unique to the software tools that generate it. These specific formats can be problematic for data retrieval in future decades. Since software and scientific instruments will inevitably change after several years, the format of new instrumentation output could change, making it more difficult to import data into a specific ELN system in future years. Typically, the longevity of most software versions is only a few years and usually the succeeding generations only are able to read files from one or two previous software versions. Moreover, some ELN vendors archive this data in an XML format only; since XML formats varies between vendors, there is no standard to ensure that all data is accessible and viewable over the long-term. This is not a problem with a cross-disciplinary ELN as many of them adopt generic file formats such Adobe ® Portable Document Format (PDF), which are guaranteed for archival retrieval for many decades by the Adobe ® company.

 

Cross-discipline ELNs are, by definition, unbiased or discipline-agnostic software solutions. As such, most ELNs that fall within this category adopt best-of-breed industry standards to reduce the amount of custom work involved in implementation and maintenance. By choosing an open architecture ELN platform based on standards, a cross-disciplinary ELN can more quickly adapt to changing software and hardware environments. An open architecture that is infinitely extensible enables rapid customization, in a modular format, that can still achieve specific discipline or departmental needs.

 

ENABLING ENTERPRISEWIDE COLLABORATION WITH THE INFOTRIEVE/ELN

The Infotrieve/ELN is an example of a powerful cross-disciplinary software system that allows many types of researchers the flexibility they need for experimental design and analysis. The Infotrieve/ELN stores its content in a common repository accessible to the entire organization so it can be queried at any time by any user who has access. Its interface and features are reminiscent of the ubiquitous Microsoft® Office programs; this familiar look-and-feel aids in broad adoption across all departments, requires little training to learn, and offers a standardized format for global collaboration. More importantly, unlike other specific ELNs, the Infotrieve/ELN is enterprise-ready, and can be scaled from a few to thousands of users by leveraging industry standard technologies.

 

CONCLUSION

Some of the specific ELNs in the market may be useful for certain types of chemists due to their incorporation of task-specific drawing and analysis tools. However, this very trait makes them less useful across an organization and in fact, may make data less accessible to other researchers such as the biological screening groups or toxicology groups. In contrast, cross-disciplinary ELNs provide the necessary flexibility and extensibility for many departmental settings to directly increase information sharing for effective collaboration and communication. This can be achieved without losing the access to and benefit of task-specific tools. User adoption of ELNs also increases with an easy to learn, cross-disciplinary system that can be immediately deployed on an enterprise-wide scale. This flexibility also extends to archived data which must be retrievable in future decades. In general, cross-disciplinary ELNs provide more value through a lower total cost of ownership due to decreased installation, maintenance and training costs.

 

As ELNs continue to evolve, the two types of ELNs – cross-disciplinary and specific – may begin to converge as specific ELNs move towards the goal of organizational-wide adoption and increasing net productivity. In the current ELN marketplace, however, only cross-disciplinary ELNs are able to deliver these valuable capabilities today, demonstrating that their inherent flexibility, extensibility and maintainability is superior for both short and long term consideration.

 

KNOWLEDGE MANAGEMENT & EFFICIENCY GAINS

 

INTRODUCTION

In recent years, the biotechnology and pharmaceutical industries have faced increasingly stiff competition due to global consolidation, shortening of patent life, and the increasing cost of drug discovery4 . Recent scientific and information technology advances have resulted in the mass production of data, and the subsequent increased use of electronic data storage. Longer drug development cycles have also increased the amount of scientific data and the length of time that data may be useful to scientists. Furthermore, the emergence of the human genome project, large-scale DNA sequencing, proteomics and high throughput screening technologies have all profoundly increased scientists’ capability to generate larger quantities of data and analysis, through computerized mass production means. While electronic data in general solves storage concerns, there has been no complementary advance in documenting the experimental procedures and analysis of that stored data; currently most experimental processes continue to be recorded in a written, paper laboratory notebook format. Indeed, the potential risk for misplacing important data files in a mountain of paper or even electronic files increases with the growing volumes of data. To help scientists keep pace, organizations must now address the questions of how to most efficiently input, store and retrieve experimentally relevant information.

 

Electronic laboratory notebooks provide an attractive solution to the information recording, storage and retrieval issues surrounding paper notebooks and management of large volumes of data. ELNs allow organizations to efficiently  leverage new experimental knowledge for informed decision making, at both the laboratory and management levels. This paper details the many ways in which ELNs facilitate the creation of electronic notebook entries, and how the productivity gains can create a competitive advantage in the race to discover innovative first-in-class drugs.

 

Knowledge Generation is Maximized by Knowledge Management

“Knowledge management is the only long-term, sustainable source of competitive advantage.”

-David Smith, Head of Knowledge Management at Unilever

 

Pharmaceutical and biotechnology research and development efforts can be classified as knowledge generation, acquired through experiments designed to test scientific hypotheses. Using paper notebooks for recording this knowledge, particularly when large volumes of data are part of the experiment, presents three major downfalls.

 

1. Paper notebooks do not make knowledge easily accessible.  Paper notebooks cannot easily be searched or shared. When the knowledge of why an experiment was performed and how it was interpreted resides within a paper volume, a company’s access to that knowledge is physically limited by the location of that volume or the availability of the person who generated it. Despite the accessibility of the raw data on corporate servers, the usefulness resides in the interpretation of the data, which in turn relies on understanding the experimental protocol, sample identification, reagents used, and more. In addition, the contents of paper notebooks cannot easily be cataloged and thus are not easily searchable, if at all, to those not familiar with the experiments. To fully leverage the value of successful and failed experiments, the company must make this knowledge accessible to others in the company. In a paper format, knowledge is captured at the individual, not institutional level.

 

2. Extracting knowledge from paper notebooks depends on difficult or unreliable channels. Since the knowledge within a laboratory notebook is only as good as its accessibility, the cataloging of the experiments must be extremely detailed and elaborate for a scientist to find it without prior knowledge of its existence. Such detail is rare and requires a time-intensive process of sifting through a notebook to find exactly what one wants to know. The easiest route to finding scientific knowledge buried in a paper lab notebook involves having the author of the notebook guide you to the desired information; however, the era of lifetime employment with one company is over, and when scientists transfer to another company, they take the knowledge of the notebook content with them. Since notebook security and the tenure of scientists are never guaranteed, historical knowledge captured in paper notebooks rarely becomes institutional knowledge. This is particularly troublesome given that the drug discovery process oftentimes lasts 12 to 15 years.

 

3. Keeping intellectual property in a paper notebook presents an unnecessary security risk. Using the paper notebook as the primary evidence for first discovery means resting evidence on a physical book that can easily be damaged by a simple coffee spill or removal of pages, lost or even stolen in a briefcase. An ELN eliminates this unnecessary risk because all experimental data is secured in a backed-up database.

 

The task of recording and cataloging experiments has only become more intensive with the recent mass production of data. Though paper laboratory notebooks have served well in the past, they are simply not efficient enough for the massive influx of data generated, at some facilities, around the clock. Thus, knowledge generation must be accompanied by knowledge management and protection to maximize the accessibility and usefulness of discoveries for informed decision making. ELNs provide an easy and efficient manner to capture the most important knowledge generated by scientists. ELNs accomplish accessibility by providing organization-wide, permission-based access to a company’s recorded data through secure password accounts. In addition, their  extensive search functions allow massive amounts of data to be scanned by the user through simple keyword, metadata, or chemical structure searches. In each of these areas, ELNs effectively manage a company’s data so it truly becomes secure organizational knowledge rather than being lost or forgotten.

 

INCREASING EFFICIENCY & PRODUCTIVITY THROUGH ELNS

Knowledge use and management represents a more qualitative measurement of improved productivity as a competitive advantage. ELNs also provide quantitative productivity benefits that can be more easily defined and measured. A leading market research organization (Atrium Research) reports that ELN users consistently report a greater than 20% increase in operational efficiency5 , as measured through time savings in entering and finding data, and in having a more organized, streamlined workflow for individuals within the organization. These resulted in an increased number of experiments performed per scientist per week. In addition, collaboration is more efficient through real-time access to scientific data to accelerate decision making across multiple departments and levels of the organization (see Table 1).

 

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Table 1. Individual and Organizational Benefits of an ELN.

 

SIMPLE ENTRY OF DATA/WORK LOGS

The laborious process of recording information into a paper notebook is greatly reduced by an ELN since it accelerates many of the repetitive recording tasks that scientists must perform. Data on how research scientists spend their time indicates that at least 20% of a scientist’s time is spent working with a paper laboratory notebook, writing reports and entering data into notebooks6. Notebook time can conceivably include data analysis, so up to 30% of a scientist’s time is allotted to working in a lab notebook (Figure 1)7 . If even 20% of the notebook time each workday can be saved through an ELN, nearly a day’s worth of time per week could be used more productively for each scientist, producing tremendous savings across an organization over the course of a year. A detailed financial breakdown will be presented later in this paper.

 

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Figure 1. Typical Time Allotment for a Research Chemist.8

 

Time saving from the ELN arise from a number of labor-saving features.

·         Simple entry of data into an ELN is simplified by drag-and-drop functionality.

·         Recording similar experiments that differ only slightly from previous ones is an effortless task with an entry cloning feature.

·         Subsets of entries can be duplicated into new ELN pages to both eliminate repetitiveness and prevent errors when copying from previous experiments.

·         Templates for pages in a particular project can be produced to provide workflow consistency, ensuring that essential information is included for every entry and that all entries follow similar formats.

·         Consistency provides a familiarity that allows scientists to rapidly read or scan documents as they review them.

·         Typed entry content eliminates problems with deciphering illegible handwriting.

 

A well-designed ELN system will be easy for users to adopt. Systems such as the Infotrieve/ELN embed Microsoft ® Office products such as Word or Excel. As nearly all scientists frequently use these software products, the familiar interface allows scientists to adopt and quickly become proficient in the ELN.

 

Transfer of electronic data files from instrumentation is also vastly streamlined with an ELN since the information is either imported into a notebook entry or electronically attached, eliminating the need to physically cut and paste data printouts into paper notebooks. Finally, data are securely stored so as to prevent data loss should a paper notebook be misplaced or destroyed.

 

FASTER AND MORE EFFECTIVE WORKFLOW & PLANNING

ELNs enable advanced searching capabilities including full-text, Boolean, chemical structure, sub-structure or reaction queries. Moreover, the use of metadata such as author, date, or any other customized fields can be leveraged for a powerful database query. These search features promote simple and rapid information identification and greatly increase the accessibility of data compared to paper notebooks. Knowledge management and standardization significantly increases the usefulness of the data collected during experiments. Rapid access to data enables scientists to plan the most appropriate experiments based on past data, while avoiding costly repetition of previously performed failed experiments. Unfortunately repetition and/or verification of failed experiments is common in the laboratory; any way to reduce this effort saves valuable employee time, reduces precious reagent consumption, and leads to faster project progress.

 

Advanced searching capabilities of an ELN are complemented by logically organized folder structures which allow the data to be viewed in an ontologically relevant manner. Many entries in paper lab notebooks are often interspersed throughout a notebook with data mixed from concurrent projects. Instead, an ELN can organize data according to project rather than chronologically. Project-oriented organization of notebook information allows a scientist to see data in context of the entire project or organization, which helps them to synthesize the data more easily. Since the history of experiments is easily viewable and searchable, scientists from other departments can also find the right information and contact the appropriate author with questions.

 

INTRODUCING THE INFOTRIEVE/ELN

An example of an ELN that encompasses all of the above capabilities and more is the Infotrieve/ELN. The Infotrieve/ELN opens the communication lines between research and development departments by providing data access in easily accessible formats. Data accessibility and security ensure that the right people get access to the correct information in real-time, so that the best decisions can be made quickly. In addition, the Infotrieve/ELN produces tangible productivity gains through department specific workflow templates which save significant time, and by creating organizational-wide standards for the notebook. The Infotrieve/ELN’s project-based organization, tracking of metadata, and storage in an electronic format, makes searching for information effortless compared to paper notebooks.

 

Return on Investment (ROI) of the Infotrieve/ELN

A concrete measure of financial gains provided by the Infotrieve/ELN can be seen in this mock calculation which demonstrates time savings. The numbers used in the calculations were derived from interviews with scientists using the Infotrieve/ELN application. For this example, a conservative estimate of 25% of a scientist’s time was spent using a paper notebook over a 2000 hour work year at an annual salary of $100,000. From a study on actual users of the Infotrieve/ELN, tasks took 37% less time than those same tasks performed in a paper notebook.

 

Our calculations indicate that a company would save nearly $15,750, or 15.7% of a scientist’s annual salary by adopting an ELN system over paper notebooks. Factoring in the cost of licensing the Infotrieve/ELN, at $3,600 per scientist per year, a company would save well over $12,000 a year per user. At this rate of savings, each scientist would recognize the ELNs return on investment in 2.74 months (see Table 2). These financial and productivity benefits are in addition to real-time collaboration, stronger security measures, and improved intellectual property protection.

 

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Table 2. Infotrieve/ELN Time and Dollar Savings.

CONCLUSION

As the scientific marketplace continues to develop new high throughput methods for data generation, the need for increased efficiency in the documenting of experimental procedures will follow suit. To maintain a competitive edge in the dynamic life science marketplace, corporations must aid their scientists with tools that convert individual knowledge into institutional knowledge so it can be more efficiently leveraged throughout the entire organization. The Infotrieve/ELN enables scientists to record information in nearly a third of the time that they spend on paper notebooks, freeing researchers to perform more experiments. Ease of use and time savings can translate to hundreds of thousands of dollars per year in addition to the often intangible knowledge-sharing benefits. These cost savings provide a compelling reason to choose an ELN solution such as the Infotrieve/ELN to significantly accelerate product development lifecycles through increased efficiency in use of human and material resources.

 

PROTECTING INTELLECTUAL PROPERTY

 

INTRODUCTION

A recent market study indicates that the cost of developing a new drug was nearly $1.7 billion, 55% higher in 2003 than in the period from 1995-20009 . As drug development costs soar, the value of a drug’s intellectual property skyrockets since the patent rights guarantee exclusive sales right for 17 years after the approval date. These exclusive rights often factor into corporate valuation by investors so the ability to document and defend intellectual property is essential to the financial well-being of a biotechnology or pharmaceutical company.

 

How does a company protect the intellectual property of its scientific discoveries? Claims of first invention often rely on the paper laboratory notebook where the original research on the drug was recorded. Until recently, the paper notebook has been the only option for recording data and it has often served as evidence in court. Recent developments in electronic laboratory notebooks not only make them more efficient for data recording and organization, but they have the added benefits of being far more secure than paper notebooks while carrying equivalent legal clout as compared to their physical counterparts. An electronic laboratory notebook aids compliance with United States Food and Drug Administration regulations, authenticates entries for security purposes, and strengthens the intellectual property and knowledge management position of a company that wants to proactively prepare to defend future drug development efforts. Intellectual property protection is becoming an important strategic driver in today’s research environments. ELNs can play a central role in driving this type of internal strategic initiative to better protect stakeholder investments. This is particularly important for smaller organizations whose valuation may be entirely based upon its intellectual property portfolio.

 

As Weighty as Paper Notebooks

“Pursuant to 37 CFR 1.671, electronic records are admissible as evidence in interferences before

the Board of Patent Appeals and Interferences…”

-Bruce H. Stoner, Chief Administrative Patent Judge

 

A primary question regarding notebook entries in ELNs is whether they serve as adequate legal records. Due to their recent emergence on the market, ELNs have not yet been contested in court. While there is no case law specifically involving ELNs, electronic records in general have precedence as evidence for documenting patents and other types of admissible evidence. In fact, pursuant to 37 CFR 1.671, the rules governing evidence for patents, electronic documents are considered admissible records before the Board of Patent Appeals and Interferences in interferences, as well as in contested cases, where they have been accepted under the Federal Rules of Evidence10 . The Federal Rules of Evidence affirms the suitability of electronic records as acceptable evidence if the record can be authenticated and the author can be reliably verified. ELNs authenticate notebook entries by incorporating electronic signatures, time/date stamping, and complete audit trails into the system. These features ensure that the ELN records meet the criteria as evidence for the Federal Rules of Evidence and the United States Patent and Trademark Office. International requirements for electronic documents are similar. In the United Kingdom, the Electronic Communications Act 2000 specifies that electronic documents bearing electronic signatures are admissible evidence in a court of law11. The European Union also states that electronic documents with authenticated electronic signatures are admissible as evidence12. Thus, those ELNs that contain authenticated electronic signatures associated with each notebook are best positioned to protect and establish a company’s intellectual property in Europe and the United States.

 

There is also general legal precedence for the admissibility of electronic records. In one legal case involving research patentability, electronic records in the form of e-mail served as evidence of research activities; the integrity of the electronic e-mail records was not challenged13. ELNs provide a higher degree of authentication and audit trails than e-mail, which suggests that, if contested, they would also serve as acceptable evidence in court.

 

ELN records have a distinct advantage over paper notebooks in the area of author authentication since digital signatures actually provide multiple sources of supporting evidence as compared to a wet signature. Digital signatures secure the time, author and message through built-in time and date stamping. Furthermore, other forms of user authentication such as a secondary password, or encrypted passkeys or passwords that confirm the authorship of the ELN notebook entry may also be employed.

 

The United States Food and Drug Administration also lends support to the use of electronic documents by the fact that it accepts electronic drug approval submissions in the form of Adobe ® Portable Document Format (PDF). PDF format is the specified electronic format for filing new drug applications (NDA’s) and for data submission to the U.S. federal courts system14. The Paperwork Reduction Act and the United States Food and Drug Administration require new drug applications to be submitted electronically by 2005, driving the corporate-wide adoption of electronic file formats such as PDF. Internationally, the governments of the United Kingdom and Germany also use the PDF format as the standard for electronic document exchange. Thus, ELNs which use the PDF as their file format are not only acceptable to the Unites States Food and Drug Administration and international organizations, but they have the advantage of following a widely-adopted international standard format.

 

FDA REGULATORY COMPLIANCE & AUDIT TRAILS

“Audit trails can be particularly appropriate when users are expected to create,

modify, or delete regulated records during normal operation.”

-U.S. Food and Drug Administration15

 

As in most cases of documentation, “paper trails” or audit trails that follow the flow of product development serve as the most authoritative source for tracking information changes. Many types of trails are specified in the United States Food and Drug Administration regulations for developing clinical products, so these audit trails can also aid in related intellectual property claims. Specifically, two key regulations directly address the documentation in patent claims. 21 CFR Part 11 regulations define the parameters by which pharmaceutical or biotechnology companies can create, store and verify electronic documents and signatures as equivalent to paperwork and handwritten signatures16. 21 CFR Part 820 sets guidelines for quality system processes that must be enacted to ensure product quality17. The most useful ELN systems contain all of the features required by 21 CFR Part 11 (see Table 1). Compliance requires complete audit trails, retention and maintenance of records and verifiable electronic signatures18. ELNs provide complete versioning of every electronic notebook entry, allowing auditors to view the record in any stage of completion, pre- or post-signature. All actions such as viewing, editing, printing or creating a new draft are logged for tracking purposes. No longer will the history or veracity of a paper notebook be in doubt. With an ELN solution, there is no ambiguity as to whether a scientist changed experimental data at a later date.

 

Electronic signatures for authoring and approvals are achieved through the use of Public Key cryptography which leverages key pairs to verify a signer’s identity. Each key pair consists of a unique ‘private’ key for data encryption, and a unique ‘public’ key which is needed for user authentication. The content of each notebook entry version is encrypted by the private half of the signer’s unique key. The public half of the key is subsequently used to verify and authenticate the signer’s signature. The witnessing process employs the same technology standards. While not adopted by all ELNs in the marketplace, this type of technology can ensure that customers adhere to the compliance requirements outlined in 21 CFR Part 11.

 

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Table 1. ELN Features Addressing FDA Regulations.

 

ELNS AND INTELLECTUAL PROPERTY: DATA ACCESSIBILITY AND MULTI-LAYERED DATA SECURITY

ELNs contain multiple layers of security to protect against unauthorized data access. The best systems have multiple security layers; overlapping protection ensures only authorized personnel have access to experimental results and analysis. Some ELN offerings permit multiple authors for a single notebook entry. Other, more secure ELNs (such as the Infotrieve/ELN) permit single authorship per notebook entry so that accountability and data integrity are maintained. For ELNs that permit only one author per notebook entry, there are several options that an organization may choose between depending on security and compliance goals: digital signature security can be implemented by:

 

·         A single login password

·         A combination of primary and secondary passwords, or

·         A hardware token in combination with a certificate server

 

A hardware token may be a portable USB device that plugs into a computer for access, or one that is physically associated with a single computer, depending on organizational preferences. Single passwords give people access to the system and data according to their permissions on their account. In some ELN systems, a second password may be engaged for an additional security layer surrounding the signing and witnessing process; this second password would prevent any unauthorized signing and witnessing in the case where the primary password security has been compromised. The hardware token feature further increases the data security by guarding against hackers who may gain unlawful access to a corporation’s security files. A combination of hardware and software security measures provides the greatest level of security while also validating the identity of those submitting electronic signatures.

 

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Table 2. Security Features in ELNs.

 

Full audit trails with time/date stamping provides a robust, detailed record for tracking the history of changes. Any action taken on a record is stored in its history, meaning that all edits, deletions and even viewing or printing of documents can be tracked. Versioning and storage of all previous drafts also prevents notebook entries from being deleted from the record, an important feature for data security. These comprehensive history features can be helpful in intellectual property litigation where date of discovery and knowledge of data must be contested or proven.

 

An ELN which uses the Adobe ® PDF format provides added security because it contains tamper-proof features to prevent unauthorized document changes, whether accidental or malicious, and built-in electronic signatures. ELNs that offer a PDF file format for entry storage and export can instantly be duplicated and stored in secondary locations to ensure data recovery in the rare case of server failure. In addition, the recoverability of PDFs is likely to last decades as many large organizations and governments, (such as the U.S. government, the U.S. Federal Courts, the U.S. Federal Aviation Administration, the U.S. FDA, First Union Corp. (sixth largest bank in the U.S.), Cisco Systems and others19, 20) have selected the PDF as their long-term information storage medium.

 

Surpassing the Standards:  Infotrieve/ELN

“The Infotrieve/ELN™ system incorporates security and encryption IP that, when used properly, meets PTO (Patent and Trademark Office) requirements for protecting intellectual property in an electronic format… The level of attention [Infotrieve] has devoted to this critical issue will be immediately recognized by corporate legal department[s].”

– Richard Warburg, Esq. Partner, Intellectual Property Department of Foley & Lardner

 

All of the document security qualities described herein are an integral part of the Infotrieve/ELN software platform. Its robust security measures support single, double signature and hardware token usage, as well as full audit trails through versioning control. The digital signatures provide state-of-the-art encryption for validation of author and witness identities to meet all 21 CFR Part 11 United States Food and Drug Administration standards for electronic signatures and documents.

 

In addition, Infotrieve’s ELN was created under 21 CFR 820 standards so documentation is readily available for any quality audits a company might face. In meeting these standards, the Infotrieve/ELN also exceeds all current criteria for electronic records as legal evidence in the United States and international arena.

 

CONCLUSION

ELNs such as the Infotrieve/ELN achieve a high standard for notebook entry security, authenticity and legal admissibility. As outlined in this paper, official ELN records surpass the security and validation levels of paper notebooks in many ways. Broad acceptance by governmental and regulatory bodies has validated electronic records in general, and ELNs specifically when compared to equivalent standards for electronic signatures and documents. In short, the Infotrieve/ELN provides a compelling platform for regulatory, legal, and security challenges in the 21st century.

 

ABOUT INFOTRIEVE

Infotrieve, Inc., is a global provider of content management technology and information services for the life sciences and other R&D-intensive industries that pioneer important scientific, technical, and medical (STM) breakthroughs. The company develops flexible enterprise solutions and integrated workflow applications that simplify research and development processes for improved efficiencies and outcomes. Infotrieve business solutions span electronic Research & Development (eR&D), Library & Information Services, and Product Marketing. Infotrieve was founded in 1988 and has offices in the United States, Europe and Asia Pacific.

 

Infotrieve Corporate Headquarters

11755 Wilshire Blvd., 19th fl.

Los Angeles, CA 90025

Phone: 310.445.3000

Toll free: 800.422.4633

Fax: 310.445.3003

www.infotrieve.com

 

Infotrieve Europe

Nikolausstrasse 121

D-50937

Cologne, Germany

Phone: 49-221-66067-0

Fax: 49-221-66067-67

marketing@infotrieve.de

www.infotrieve.de

 

Infotrieve Asia Pacific

Suite 3, 1st Floor

344 Ferntree Gully Road

Notting Hill, Victoria, 3168

Australia

Phone: 61(0)3 –9544-4911

Fax: 61(0)3-9544-3277

info@infotrieve.com.au

 

 


1 Collaborative Electronic Notebook Systems Association.

2 Image reprinted from “Electronic Laboratory Notebooks: A Foundation for Scientific Knowledge Management”. Atrium Research, Market Research Report, 2004.

3 Case study on the Agile Web Initiative for developing and validating collaborative commerce concepts among a group of small and mid-sized manufacturers. See

http://www.beepknowledgesystem.org/ShowCase.asp?CaseTitleID=134&CaseID=610

4 Ajit Biad, (Frost &Sullivan) in “Interactions: the Pharma Market: A Glimpse at What the Future Holds”, Drug Discovery & Dev. Mar 2004.

5 “Electronic Laboratory Notebooks: A Foundation for Scientific Knowledge Management”. Atrium Research, Market Research Report, p. 8-95, 2004.

6 “Electronic Laboratory Notebooks: A Foundation for Scientific Knowledge Management”. Atrium Research, Market Research Report, p. 8-95, 2004.

7 Ibid.

8 Reprinted from “Electronic Laboratory Notebooks: A Foundation for Scientific Knowledge Management”. Atrium Research, Market Research Report, p. 8-82, 2004.

9 Bain & Co. study, quoted in Chemical & Engineering News, 81(50), p 8. Dec. 15, 2003.

10 1208 Official Gazette Notice (OG) 35. Bruce H. Stoner, Jr. USPTO, March 10, 1998.

11 Electronic Communications 2000, U.K. , Online version available at http://www.hmso.gov.uk/acts/acts2000/20000007.htm

12 Directive 1999/93/EC on Electronic Signatures. Online version available at http://www.e-podpis.sk/laws/eu_ep_dir93_1999.pdf

13 In re Jolley, 64 USPQ 1901, U.S. Fed. Cir. 2002

14 Guidance for Industry: Providing Regulatory Submissions in Electronic Format – NDAs. U.S. Department of Health and Human Services, Food and Drug Administration, Center

for Drug Evaluation and Research (CDER), January 1999. See http:// www.fda.gov/cder/guidance/2353fnl.pdf

15 Guidance for Industry: Part 11, Electronic Records; Electronic Signatures – Scope and Application. U.S. Department of Health and Human Services Food and Drug

Administration. August 2003. http://www.fda.gov/cder/guidance/5667fnl.htm#P118_3013.

16 Ibid.

17 Ibid.

18 “A Risk-Based Approach to Compliant Electronic Records and Signatures”, ISPE (the International Society for Pharmaceutical Engineering), Feb 2005.

19 Adobe PDF: The Universal Document Exchange Standard for the New Millennium. Adobe Systems Corporation. 1999. Doc. No. BC 1338. Accessed from

http://www.adobe.com/products/acrobat/pdfs/pdf-y2k.pdf.

20 Adobe PDF: More secure, reliable electronic document distribution and exchange. http://www.adobe.com/products/acrobat/adobepdf.html. Viewed May 16, 2005.