One of the most hotly contested research areas currently is in the area of CRISPR, the gene editing technology platform that has spawned a billion-dollar industry and countless biotech startups.  This technology was developed by multiple organizations, including researchers from the Broad Institute, Harvard University, MIT and University of California – Berkeley. First developed in prokaryotic cells at UC Berkeley, later, the Broad Institute implemented the technology in eukaryotic cells. At issue is whether genome editing in eukaryotic (mammalian) cells is made obvious/trivial once it is accomplished in non-mammalian cells. Obviously, this dispute has required both sides to pour over experiment records to search for evidence to support arguments, as well as to establish timing and a full audit trail of events leading to the invention. If your organization is working on bleeding edge technology platforms such as CRISPR or novel biologic therapeutic classes, for example, considering your IP protection strategy is business critical and could have major impacts on your company’s future.

Today, most established companies and many academic labs involved in R&D have made the shift from paper to electronic laboratory notebooks (ELN) in order to create a searchable repository of experimental data that researchers can access to facilitate collaboration. An ELN can also be a key element in your IP protection strategy by supporting scientists in keeping complete, accurate and witnessed records of all research. If you are looking for a new ELN, or want to bolster your IP protection for an existing ELN implementation, there are many elements to consider in order to effectively secure IP.

Baseline Features in ELNs for Securing IP

R&D partnerships continue to increase, and many organizations are looking to the cloud to host ELN systems to open up data sharing and experiment data capture across the globe. With new and emerging cloud-based ELN vendors having developed commercial offerings in the last five years or so, it is important to take a close look at the ‘baseline’ features and security controls that should be there to protect your IP. Many of these features are in fact commoditized and readily available in most platforms for the last ten years, but it is always important to check the boxes – particularly when you are working with a smaller, less established ELN vendor who may be new to the market.

Features which you should look for when choosing an ELN to support IP protection include:

21 CFR Part 11 Regulations on Electronic Records and Signatures

The regulations established in 21 CFR Part 11 dictate many of the features that should be in any ELN. As such, any ELN should have the ability to time, date and user stamp any data entered into the system. Equally important, audit trails should be available to track all the changes to a record, as well as chain of custody for the data.  Electronic signatures should be assigned as a result of a controlled workflow that is consistent with the organization’s policies and procedures for witnessing experiments.

Data/Experiment Hiding

Any quality ELN will have the ability to close off access to all or parts of the experiment to selected user groups.  With so many collaborators and experiments being developed jointly across organizations, it is critical that the system provide a way to fence off certain programs, projects, or individual experiments to the appropriate people – creating a path to assign IP ownership rights accordingly.

Electronic (Structured) Environment for Projects, Programs and Targets

Paper notebooks are stand-alone – meaning you can’t easily back them up, you can’t search by keyword, and when they’re archived, they are essentially lost. Trying to find information in a paper notebook world is often so cumbersome and difficult that it’s faster to just redo the experiment. Having the information in an electronic format increases the likelihood that the knowledge will be shared rather than lost, and sometimes more importantly, can help show a concerted progression of work against a piece of intellectual property.

To make it easier to navigate, the system should support many ways of structuring the experimental data, consistent with the scientific programs, projects and targets. Being able to quickly pull up all of the sample data by scientist and experimental results for a given program or project by target class or other meaningful criteria is not only convenient but may also be critical for building your case in court or simply working with a collaborator to flesh out ownership rights.

Archiving Immutable Experiment Records

In order to secure IP, the ELN should support creation of immortalized, time-stamped, unalterable record for archiving (usually PDF of completed experiment) that documents everything that was done during the experiment. This document needs to be archived either within the ELN itself or in a database behind the company firewall.

Security Features

ELN’s must protect company IP from possible theft by both external parties and company employees. For protection against internal theft, your ELN should have a folder-based security paradigm in which security permissions (read, write, modification, delete) are set at the root folder of a notebook, project, study or experiment. These rights will then cascade down to the new folders and entities underneath the root. Once an experiment record has been approved and locked down with the electronic signature workflow, it can be released to a wider audience for data-sharing purposes. Users performing searches in the system should only be able to see records for which they have been given viewing rights.

Records Custodian

Why are unalterable experiment records archived in a secure environment so critical?  The U.S. Federal Rules of Evidence (FRE) govern whether evidence like laboratory records are admissible in a patent interference or a civil case. There are two ways to admit laboratory notebook records. First, the author who created the records of the experiments can testify as to their validity. This would satisfy the requirement that the evidence was made by the declarant. But, what if the case is many years later, and the inventor is no longer available?

The second way is to classify them in what is commonly called the “business records” exception to hearsay (Rule 803). This exception allows business materials, e.g., lab notebooks, to be admitted as evidence if a proper foundation is established to prove their authenticity. This consists of five elements:

• Records must be kept in the ordinary course of the business.
• The particular record at issue must be one regularly kept.
• The record must be made by or from a knowledgeable source.
• The record must be made contemporaneously.
• The record must be accompanied by testimony from a custodian.

An often-overlooked consideration is the custodian. A custodian is an individual who, in the usual course of a company’s operation, is responsible for the management of business records. A custodian can be called into court to attest to the company’s policies and procedures for documenting and securing the records desired to be admitted. They will be asked to substantiate that procedures are generally followed and the records in question adhere to those standards. Without a designated custodian, there is a risk of non-admittance of company records in a court case.

Best Practices for Laboratory Notebook Policies and Procedures

An ELN can be a big improvement over paper for IP protection, in that it helps to enforce established policies and core capabilities such as time stamping and audit trails. The organized and searchable records that an ELN facilitates can also better prove diligence and reduction to practice. If a company does not have good notebook policies in place to facilitate custodian of record, however, an ELN is no better than paper for securing IP. Good practices always trump technology. Once the necessary foundational notebook policies are in place to protect IP, an ELN can be leveraged to further improve the current state.

Some best practice ELN policies include:

Recording Experiments

Notebook records can be vital in winning or losing a patent battle, and all records must be incontrovertible. Scientists need to create an accurate, complete and organized record of their work. Laboratory notebooks should include a clear and detailed description of:

• The experiment’s purpose
• How and when the experiment was performed
• What materials and reagents were used (e.g., sources, lot numbers, animal numbers for antisera, etc.).
• What results were obtained
• Citations for publications referenced in notebook entries
• All software used for data analysis.
• Where related computer files, samples, slides, or photos are stored
• Interactions with collaborators, including discussions, data, and exchanges of materials
• Any other information that you or another scientist in your field would need to precisely replicate your experiments

Signing and Witnessing Electronic Records

• All experiments should be signed and dated.
• Joint work should be signed by all the contributors. The text should set forth who is responsible for each part.
• Entries should be witnessed (including the date of the witnessing) in a timely manner.
• Entries for crucial or pivotal experiments should be witnessed immediately upon completion.
• All other entries should be dated within a reasonable period after completion. To be a proper witness, a person must be able to understand the entries they are witnessing
• Any entry which relates to a possibly patentable invention should be signed and dated by two witnesses — with their signatures under the caption, “disclosed to and understood by….”
• A possible co-inventor or other person who was directly involved in the described experiments IS NOT a valid witness.

Archiving Electronic Records

Like paper records, electronic records must be immortalized and witnessed:

• Electronic entries should be regularly (preferably daily, or at least weekly) immortalized in an unalterable form (e.g., read only disk or tape, electronic archive).
• Each unalterable form should be marked with an identification of the software (including version number) needed to read the data contained therein.
• The creator of the unalterable form should sign and date the disk or tape or record.
• The unalterable form should be signed and dated by two witnesses other than the primary creator.

Security

Additionally, proper governance of signed, dated, witnessed, archived unalterable experiment records is vital to prevent potential internal theft of sensitive IP. An appropriate balance needs to be set in terms of who can access stored experimental data – data sharing between scientists needs to be enabled to prevent unnecessary duplication of work, but access must not be so wide that unnecessary opportunities are provided to unscrupulous employees to download and depart with confidential data.

Conclusion

The emergence of ELN technology has helped countless organizations organize and retain research knowledge in ways that support IP protection. A quality ELN, however, is only one element of a successful strategy to protect your IP – poor documentation and inconsistent business processes can drive up risk regardless of the technology chosen.

Companies who are considering an ELN for IP protection must focus first on establishing a proper foundation for IP management with good notebook policies and business practices. Once this is in place, an ELN should be selected that best supports the companies IP protection needs as well as other requirements. Finally, the ELN should be configured/customized to support and enforce the business practices and notebook policies. A quality informatics consultant can support you with the business process analysis and technology selection, development and implementation necessary to optimize your IP protection strategy.

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Unfortunately, many organizations have research data stored in ways that make effective knowledge gathering and collaboration between scientists difficult. Data storage in formats such as paper notebooks, computers and company IT systems, for example, often fails to capture the full breadth of researcher knowledge and the context in which that knowledge was created.

Today, most established companies involved in R&D have made the shift from paper to electronic laboratory notebooks (ELN) to address these issues. ELNs allow researchers to capture the experiment process, relevant data, and conclusions that were drawn, while simultaneously facilitating a searchable repository of experimental data that researchers can access for effective collaboration.

Effective implementation and integration of an ELN can have a transformational effect on the way research is conducted in an organization. However, due to a competitive marketplace and pressure from management for rapid ROI, many companies take a “paper on glass” approach to ELN implementation whereby existing paper notebooks are simply recreated in the ELN. This approach has the advantage of maintaining familiarity for end users and facilitating rapid implementations, but it falls short in providing key functionality and harnessing the full value that can be gained with these systems.

In this blog, we will discuss some of the key benefits that can be harnessed from effective utilization of ELN technology, along with best practices for implementing an ELN that will allow your organization to maximize business value.

ELN Benefits

Modern ELNs vary widely in their functionality. Some of the more basic options have a simple interface that functions like a word-processor, while more advanced models have functionality enabling data management, scientist collaboration, inventory management, and integration with laboratory (e.g., LIMS, SDMS, CDMS, etc.) and business-level (e.g., ERP) systems. When implemented and integrated properly, benefits afforded by the more advanced ELNs include:

More Efficient Research. Modern ELNs give you the ability to capture, share, search and query research and development (R&D) data in real-time, offering your organization the opportunity to transform the research process with improved efficiency in a secure, easy-to-use environment. Scientists can quickly create and edit experiments, and most importantly, share and reuse experiments that they or their colleagues have created to build on what has already been accomplished.

By integrating with other systems (e.g., registration, metrology, SDMS, LIMS, inventory systems, etc.) that provide information essential to a scientist’s work, an ELN can serve as a single repository and interface to data, meaning that scientists spend less time is learning and using other systems. In a fully integrated electronic lab, the ELN consolidates data from several different systems and thereby eliminates many paper-based documentation and review tasks.

Improved Researcher Collaboration. The ability to access and share all relevant experimental data (instrument data, LIMS content, statistical analysis, graphical data and text-based objects, human observations, etc.) allows for dramatically enhanced collaboration between scientists. By bringing together every aspect of an experiment in a single portal that is accessible to researchers across disparate research areas and sites in an organization, a properly implemented and integrated ELN can help to facilitate a level of collaboration between scientists that is simply not possible with paper notebooks.

Enhanced Regulatory Compliance. ELNs allow detailed audit trails for all experimental data to facilitate regulatory compliance. The auditing capabilities of ELNs make tracking experimental task history, along with QA and QC, much more efficient and effective. Legible, time-stamped and fully audit-trailed records accessible in ELNs allow effective tracking of all research tasks performed in an experiment, along with the ability to determine when, where, by whom, and under what conditions an experiment was conducted.

Improved Data Integrity. Integration with other systems allows direct access to data through the ELN central portal. As data automatically populates through the network, the possibility of transcription errors is eliminated and data integrity is ensured.

Efficient Report Creation. ELNs offer the ability to drag and drop content (e.g., graphics, data analysis, etc.) that is to be included in a report, making report creation fast and simple.

Better IP Protection. An ELN can be a key element in your IP protection strategy by supporting scientists in keeping complete, accurate and witnessed records of all research. Modern ELNs have as number of ‘baseline’ features and security controls (electronic signatures, audit trails, time/date stamps, security permissions, archiving capabilities, etc.) that help to protect your IP.

Best Practices for ELN Implementations

While the above-mentioned benefits are clearly compelling, they can only be realized for your organization when the ELN is effectively implemented and integrated. It is extremely important to follow a proven methodology for your ELN implementation in order to ensure that the project maximizes business value for your organization. Towards this end, we present the following best practice recommendations to help facilitate successful ELN implementations:

Do Strategic Planning. The first step in executing an ELN implementation project is to gain a thorough understanding of the day-to-day work processes and needs of the different scientists and groups (i.e., biology, discovery, analytical, management, etc.) involved in creating, reviewing, mining or managing research and research data. Understanding the current work processes and needs of all user groups creates a solid foundation on which to build, configure and deploy an ELN to multiple groups within the enterprise.

Conducting a thorough workflow analysis is essential to develop optimized future-state system requirements that will guide the implementation and thus ensure your project will produce significant business value for your organization. The analysis should examine how data is produced and documented and what users do with the experimental data. When disparate work processes, vocabularies, terminology are discovered, the implementation team should work to harmonize across the organization. This will improve data mining and sharing efforts.

Design Your Laboratory Architecture with the ELN as the Central Integration Point. An ELN has the potential to dramatically improve information-sharing and collaborative efforts among scientists involved in R&D. In order to optimize this potential, the electronic laboratory architecture should be designed with the ELN as the central integration point to facilitate standardization and data sharing efforts. This means that the ELN serves as the central portal to access data for all users, as it connects to systems such as LIMS, CDS, SDMS, chemical inventory systems, modeling and simulation programs, ERP, etc.

Utilize a Phased Approach to the Implementation. There are a number of different approaches to ELN implementation, but a phased approach generally makes the most sense. The initial phase will consist of implementing the minimum viable solution to go into production with. Subsequent phases will then focus on implementing the specific needs of the various groups – scientists who create experiments, groups that make use of the experiments and data created by scientists, and business sponsors who finance the projects.

As the phases progress, business value will be added by activities such as designing/adding templates, the establishment of taxonomy and standardized data vocabularies, as well as configuring and managing metadata, scientific and document workflows, and process automations. The implementation plan will be guided by prioritized requirements that are assigned to the appropriate project phase based on overall ROI for the organization. The initial phases of the project will leverage out-of-the-box capabilities, while later stages may involve customization of the ELN if absolutely necessary for efficient and effective use.

Create an Integration Plan. The workflow analysis conducted during the strategic planning stage should also examine how experiments and data are shared amongst groups and what integrations with other systems may be necessary to facilitate efficient handoffs and document creation. These systems should be ranked as to the ROI they provide for the organization once integrated with the ELN. System integrations that provide the most ROI should be scheduled for early phases of the project.

Address Change Management. The success of an ELN implementation is measured not just from designing and implementing the phases but also from the acceptance of users of the standardization and structure that the implementation will facilitate. This is especially true when you are implementing a system across multiple functional areas in an organization where information sharing is necessary.

Users need to be consulted and involved in the development of system requirements and also during the iterative implementation process to give feedback on system prototypes. This helps to ensure that users will be invested in, and ultimately accept and use, a new and unfamiliar system.

In addition, change management activities should involve a comprehensive training program for users of the new system that helps to ease the learning curve. The training program should also include information about the overall business value that the new system will provide for the company. This information will help to sell users on why the new system is important and necessary to support the company’s success.

Conclusion

A properly implemented and integrated ELN gives research scientists access to an organization’s full array of experimental information and data, as well as the availability of resources needed to execute experiments. In this way, the ELN brings a new dimension of efficiency to the research effort, enabling scientists to get the information they need to further their research quickly and easily.

The process of ELN implementation should not stop after the initial deployment. Over time, scientific workflows will change and new functionality will likely be introduced in the ELN. Periodic reviews should be conducted so that implemented functionality in the ELN remains optimized to maximize business value for the enterprise.

An important measure of the success of an ELN implementation is the level of system adoption by research scientists. If researchers are still using Excel spreadsheets, paper lab notebooks or other paper or electronic based systems, then your ELN implementation is either not finished or has not been optimized.

If you would like to discuss your ELN project, or if you would like to have an initial, no obligations consultation with an Astrix informatics expert to explore how to optimize your overall laboratory informatics strategy, please feel free to contact us.

Rob Knippenberg is a Managing Director for Astrix Technology Group in the Informatics Professional Services Practice.  He is focused on customer informatics solutions delivery through strategic partnerships with many of the top scientific software and services providers. Mr. Knippenberg brings to the role over 25 years of experience in scientific software project and program management, directing widely distributed global teams.  During his career, Mr. Knippenberg has worked with hundreds of commercial, academic, and government institutions delivering scientific informatics solutions to many thousands of scientists

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