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Copyright 2011 ©Labtronics Inc Page | 2 Table of Contents Chapter 1: Introduction ......................................................................... 5 Chapter 2: ELN Primer ........................................................................... 8 7 Great Reasons for Buying an ELN ................................................................................ 9 The Benefits of Making the Transition from Paper to an ELN ....................................... 12 A New Breed of Electronic Laboratory Notebook ......................................................... 16 Reduce the Cost of Data Quality .................................................................................. 19 Grow Green - the right choice for your business and the environment ........................ 22 The Benefits of Web-Based Applications for the Laboratory ........................................ 24 The Paperless Laboratory: Realities and Expectations .................................................. 26 Configuring an ELN for Routine Analyses ..................................................................... 31 Laboratory Resource Management - If it isn't in real-time, when is it? ........................ 37 Why Doesn't a Traditional Electronic Laboratory Notebook Work in a QA/QC Lab? ..... 40 Chapter 3: Understanding the role of ELN in the Lab .......................... 44 The Automation Dilemma............................................................................................ 45 The Real Costs of Paper in the Laboratory ................................................................... 53 Laboratory Data - Safety, Security and Traceability ...................................................... 57 Go Paperless and Improve Procedural Execution ......................................................... 60 Keeping Tabs on the Lab - Real Time, On-line Management of Laboratory Workload .. 63 ELN Reduces Regulatory Compliance Costs .................................................................. 66 ELN Cures 4 Common Laboratory Headaches .............................................................. 69 Chapter 4: Examples of ELN installations ............................................ 72 Automated Control and Documentation of Daily Calibration Requirements ................ 73 Error Free Preparation of Reagents ............................................................................. 75 Case Study: Rapid Deployment of an Integrated ELN/SDMS/LIMS Solution ................. 82 Chapter 5: Instrument Integration ...................................................... 85 Page | 3 Application Note: Chromatography Workflow with Nexxis iLAB .................................. 86 Choosing the Right Balance Automation Solution ........................................................ 90 Chapter 6: Managing and Planning ELN Projects ................................ 95 Case Study: Rapid Deployment of an iLAB (Integrated Laboratory) .............................. 96 Planning a Successful ELN Project ................................................................................ 99 Project Management – On Time and On Target ......................................................... 107 Paperless Automation Part 1 - Conservative Solution, Radical Technology ................ 111 Paperless Automation Part 2 - Right Down the Middle of the Road ........................... 114 Paperless Automation Part 3 – The "I want it all" Solution ......................................... 118 ELN Pilot Projects Pave the Way for the Paperless Lab............................................... 122 Chapter 7: Legal and Regulatory Issues ............................................. 124 Don't Hold Your Breath Waiting for a Test Case on Electronic Laboratory Notebook Records .....................................................................................................................125 ELN Meets 21 CFR Part 11 Compliance Requirements ...............................................129 Chapter 8: ROI Calculator .................................................................. 132 Calculating ROI for an ELN Project ............................................................................. 133 Chapter 9: Connectivity to other Lab Systems .................................. 137 LIMS and ELN: 1 + 1 = 3.............................................................................................. 138 What is an iLAB? ........................................................................................................ 141 Application Note: Environmental Monitoring with LimsLink and Nexxis iLAB ............. 147 Nexxis ELN and Nexxis CIM Integrate for Real-Time Chemical/Solution Management151 Page | 4 Chapter 1: Introduction I have been involved with Labtronics Inc since its inception, 25 years ago. Initially the company focused on interfacing instruments to LIMS and then expanded to interfacing any lab system. Over the last 5 years we have also been involved in developing other types of laboratory informatics systems. For 25 years we have worked closely with developers of systems such as LIMS, SDMS and ELN, helping them interface their products to instruments and to each other. We have seen the market place from the point of view of the informatics systems developers and at the same time we have worked directly with their customers giving us an understanding of their point of view. This has given us a unique insight into this industry. It is a combination of this unique perspective and our realization that many people do not understand ELN that led us to launch ThePaperlessLab.COM web site several years ago. This web site is filled with technical information that helps users to better understand the tools that can help them reduce or eliminate paper use in the lab. Much of the focus is directed on ELN. This year we decided to take this project one step further, by publishing this book. The purpose of this book, "ELN, and The paperless Lab" is to bring together some of the best articles that have been written about ELN in the last couple of years. This book will be a great reference book for anyone who is in the process of implementing an ELN or considering the implementation of an ELN. It will also be a good information resource for anyone who is interested in the automation of labs. This book is a collection of essays, each of which has been written to stand on their own as separate articles. Rather than try and rewrite them to fit a standard book format, we have decided to leave each one as originally written. You will find some overlap in topics, but this format will allow you to read the essays in any order that suits your needs. The Evolution of Electronic Laboratory Notebooks A very pragmatic view of ELN is that it is an electronic replacement for the old fashioned lab paper notebook. Wikipedia does not indicate when ELN was first invented but I suspect it was the early 1990's. By 2000, some commercial products were being offered and some early adopters were implementing ELN. In the next 5 years ELN started to become more prevalent. Companies were 'test driving' products to give the technology a limited try. Most of this activity was taking place in R&D labs. Page | 5 The initial driving force for ELN was to provide a better way to capture Intellectual Property (IP) and the customers most interested in this were synthesis chemists working in pharmaceutical companies. Capturing discoveries for this group was a significant issue and the promise of a better, electronic way, to capture IP was very attractive. Synthesis chemists led the way. Initial commercial ELN products were very much geared to R&D work. What these customers required was a secure way to 'write' out their experiments. The work that is done in R&D requires a system that is very flexible – as flexible as a blank piece of paper. An ELN for R&D fulfills those requirements and also prevents alternation of the data, incorporates electronic signatures to ensure proper tracking of IP information and provides better tools for data mining. In 2005 Labtronics Inc was the first company to release an ELN specifically designed for the QA/QC market place. To differentiate it from 'R&D ELN' it was given the product class designation "qELN". Over the next 5 years the R&D ELN gained a solid foothold on the market place and many customers have adopted those products. Much slower growth was seen in the QA/QC labs. For them the concept of an ELN is still very new today. The requirement for a QA/QC ELN is quite different than for an R&D ELN. The QA/QC lab is all about process control. Each analyst should be doing each test exactly the same way. "Flexibility" in documenting work is just not acceptable. This is the main reason for the development of two distinct types of ELN. These differences are further explored in some of the essays in this book. Understanding the differences will help you to better understand your own requirements. In the last couple of years there has been an increase in interest for an ELN for biology and biotechnology. This group also has special requirements. This ELN needs to be more flexible like the R&D ELN, but it also has to deal with more complex data such as DNA profiles. There are now some 30 different commercial ELN products on the market. With the exception of two companies who are focused on the QA/QC side, they all focus on R&D ELN. What do Customers Think? The above section is written from the perspective of a market analyst, but what does the customer think? Atrium Research (Atrium Research & Consulting LLC) has done a number of surveys over the years and is a very good resource for more information. The 2010 Atrium report1 indicates that: - 47% of Biopharmaceutical organizations have at least 1 department using ELN - 18% of QA/QC labs make some use of ELN 1 Atrium Research & Consulting LLC, " 2010 Electronic Laboratory Notebook Survey" Page | 6 - 25% of the market knows little or nothing about ELN - 40% of the market understands the difference between ELN and LIMS (from 2008 study) These numbers confirm what we see in the market place. Much of the "talk" about using ELN is focused on the R&D labs and ELN trade shows focus on R&D products. QA/QC labs are just now starting to consider ELN as a product for solving some of their issues. The essays in this book discuss many of these issues. For the most part customers are not clear about the role ELN, LIMS and SDMS play. Why is this? For one reason, most customers have never worked in a lab that has been automated with all three systems. It is difficult to understand a system if you have never used it. Secondly, software developers are trying to be everything to everyone. A prospect commented to me that a leading R&D ELN developer had told them that their product would meet their LIMS needs. That statement is not true. LIMS companies on the other hand are making significant claims about "ELN functionality" in their product. There is certainly some overlap when you compare ELN and LIMS, but rarely will one replace the other. It is important to understand the basic design of ELN, LIMS and SDMS and their specific purpose. Articles in this book will provide that information and once you understand the differences you will be in a better position to evaluate commercial products. The 2010 Atrium survey also measured ELN perceptions. Participants in the survey who had some interest in ELN or who had used ELN were asked "What statements most closely matched your view of an ELN": - 42% said an ELN is a portal or entry point into all of the laboratories systems and databases I find this surprising. As far as I know companies selling ELN do not position their product as a portal into other labs systems. In fact most commercial ELN shy away from integrating their product into other systems. The idea of using an ELN as a way to review results in LIMS or to view documents in SDMS is not practical, except in those cases where the ELN generated the data in the first place. The essays in this book will help clarify the role of ELN for your lab. Robert Pavlis President, Labtronics Inc. Page | 7 Chapter 2: ELN Primer Page | 8 7 Great Reasons for Buying an ELN Here's a light-hearted list with 7 real life, day-to-day reasons for starting an ELN project. If your CFO has a sense of humor, this just might work. If not, we have included a "translated" version of the list that even the most tightfisted CFO, COO or CEO will want to buy into. Pick the list that works for you, sit down with "the boss" and get ready for big changes. Real-life Reasons for Buying an ELN 1. Calculators are passé In a world where we can listen to music and surf the web on cell phones, do we really need to pull out a calculator to do the same routine calculations over and over again? Of course not, an ELN can automate those calculations so that they are done the same way every time and nobody ever hits the wrong key by mistake. 2. Pens that work are in short supply It must be one of Murphy's Laws that the first five pens you pick up when you need to write something down quickly, either don't work at all or leak ink all over the page so that nobody can tell what you wrote. Use an ELN to record your data electronically and forget all about trying to hang onto your favorite pen, the only one that works. 3. We need to save the trees No kidding. By now everyone must realize that we need to start conserving our resources and one way to do that is to cut down on the amount of paper we use. Replacing paper forms with an ELN at your lab will make a contribution to that effort. Go Paperless – Save the World! 4. Where did all that leisure time go? In the 1950's Popular Science promised us that the biggest problem technology would create would be what to do with our leisure time. It's time for technology to deliver on that promise – use an ELN to get more done in less time - and start planning your next vacation. 5. Repetitive Strain Injuries from entering test data into LIMS Repetitive Strain Injury (RSI) is caused by performing repetitive tasks, such as typing, writing, or clicking a mouse. Any kind of manual data entry is not only repetitive it's also tedious, time-consuming, error prone and downright boring. Let an ELN do that work for you. 6. Brown cardboard boxes are for moving day – not storing lab data Page | 9 Does it make sense to take all of your lab data, stuff it in a box and then lock it away, making it a chore to actually go back and see it again? An ELN can give you electronic on-line access to all that data and information and save you a ton of money on storage costs. 7. You would like to get through the year without someone asking for a sample result that was written on the page in your notebook where you spilled the coffee. Another one of Murphy's Laws? The likelihood of a paper document or notebook getting lost or damaged increases proportionally with the importance of the document. As soon as you see that cup tip over and your last three sips of "tall non-fat latte" splash across the page in your notebook – you know that is going to be the sample, the test, the result that the auditor is going to want to look at during your next FDA audit. Get an ELN that saves all your work as a PDF that can be stored and accessed electronically – and you'll never cry over spilt coffee again. Translation – Business Benefits of an ELN Project 1. An ELN automates manual calculations, reducing the amount of time analysts spend processing samples and giving them more time to run more samples. It also eliminates manual calculation errors, reducing time spent on secondary review, investigation and rework. 2. Legibility is always an issue with results that are hand written on paper documents – is that number an "8" a "3" or a "5". Using an ELN to record data electronically eliminates time spent on secondary review and rework due to "legibility" issues. 3. Eliminating paper not only saves trees it eliminates costs associated with purchasing and storing paper supplies 4. An ELN applies the latest technology (web access, industry standard database platforms, etc) to provide faster access to data and information. Laboratory personnel don't waste time trying to find the information they need, they are able to find the information they want, when they need it. 5. Eliminating manual keying of data delivers all of the benefits outlined in item #2, plus the added advantage of increasing employee job satisfaction by eliminating a tedious and time consuming task. 6. Long term on-site and off-site storage of paper forms and documents is costly and generates added cost and frustration when documents need to be retrieved for problem resolution or audit purposes. An ELN that saves completed forms as a PDF can replace costly physical storage with cost-effective electronic storage that can be quickly accessed. Page | 10 7. Paper documents and forms are always at risk due to loss or damage. A simple spill or a careless misfiling of a document Free ROI Calculator for ELN can result in hours of time being wasted trying to find or Determine the real dollars and cents recreate test results. An ELN can remove that risk by storing value of an ELN project at your lab. field data from electronic worksheets in an industry standard database (SQL*Server or Oracle) and also storing an image of Click here to download. the completed forms and documents in a secure electronic environment. Page | 11 The Benefits of Making the Transition from Paper to an ELN The dependence of science on technology grows relentlessly. From the basic application of computational power to undertake scientific calculations at unprecedented speeds, up to the current situation of extensive and sophisticated laboratory automation, black box measurement devices and multiuser information management systems, technology is causing paper notebooks to become increasingly rare in the laboratory landscape. Over approximately the last decade, paper has transitioned from being the unchallenged archive medium for permanent records of scientific experimentation, to becoming a convenient, portable but temporary medium for print-outs and odd notes. In its place the Electronic Laboratory Notebook (ELN) is progressively taking over the role of the preferred system for formal record keeping. But the ELN offers more than just a transition from paper-based working to electronic. The obvious benefits are easier accessibility of information, search-ability, collaboration and sharing. Furthermore, taking paper out of the equation opens up the opportunity to progress towards a fully integrated electronic laboratory, although the systems that we currently use in our laboratories are often a legacy of application-centric approaches that are based on the demands of specific laboratory technologies and are limited by integration difficulties, incompatible file formats, and other technological inconsistencies. The benefits of the transition to an Electronic Laboratory Notebook seem to be obvious, but inevitably there are a number of factors to take into account such as costs, long term preservation of electronic records, the acceptability of electronic records to support legal and regulatory compliance, and the ability and willingness of scientists to work electronically. The costs associated with the transition, and the return on investment will always be amongst the initial, albeit short-term considerations in deploying an ELN. But the true value of the ELN may be long term and therefore be far more difficult to measure since the value will be determined by unquantifiable benefits. There is a growing body of evidence being presented at conferences on Electronic Laboratory Notebooks by companies that have implemented an ELN, showing that the short-term time savings associated with the electronic solution are significant. Astra Zeneca, Biovitrum and Eastman Kodak, amongst others, have all claimed time savings in the order of 10 -15%. But each of these organizations lists a number of other non-quantifiable, long-term benefits such as: Scientists can spend more time in the laboratory It is easier to find information in a searchable archive It is easier to share information Increased efficiency can be achieved through the elimination of paper – no more cutting, pasting, copying, filing, etc. Page | 12 There is a reduced need to repeat experiments (knowingly or unknowingly) Data quality (legibility) is improved A smooth transition when people leave the Company – their notebooks are readily accessible. On-line use in meetings – less need to prepare summaries, presentations, etc. when the notebooks can be viewed on-line. This demonstrates to a large extent where the true value lies; that a successful deployment of an ELN can deliver long term benefits aligned to corporate business strategies. As IP protection, knowledge management initiatives, sharing and collaboration rise higher on the corporate wish list, the limitations of paper-based systems become increasingly exposed. It is interesting to look at non-laboratory areas that have undergone an analogue to digital transition and to evaluate the benefits, or otherwise, of that transition. For example general communication, where email has replaced the traditional process of writing letters, putting them in an envelope, sticking on a stamp, and relying on a postal service to ensure delivery. Although there are some well known negative consequences of email, would we forsake the speed and convenience of electronic communication in order to revert to paper? Another example is digital photography; again, speed and convenience are major benefits, relative to taking a roll of traditional film to a processing house for prints to be made, and then to return for additional copies if we wanted to share them, before, of course, turning to the postal service again to facilitate delivery. In the case of digital photography, the ability to capture and upload a photograph to an on-line repository and then share with friends and family anywhere in the world can take place in a matter of seconds. But back to the laboratory; what are the practical benefits of an ELN? Overall, the transition from paper to ELNs offers benefits at two different levels, (a) in terms of business benefit, and (b) in terms of personal productivity. For the business an ELN can bring about productivity and efficiency gains. Furthermore, the development of an accessible, searchable knowledge repository of scientific experimentation helps resolve the Knowledge Management mantra 'we don't know what we know'. For multi-site, multinational operations, with the increasing need to share and collaborate with internal and with outsourced functions, a central repository becomes increasingly important. This brings with it some technological challenges about controlled access and IP protection, but as the technology advances, these challenges are progressively being overcome. Personal productivity gains accrue from the elimination of certain paper-based tasks such as cutting, pasting, copying, filing, etc. These tasks can be replaced with more efficient electronic functions. This helps to save time, but it is important to remember that the documentation process itself may be no quicker; typing skills vs. writing skills can vary considerably from person to person. However, a frequently reported benefit of an electronic laboratory notebook is the use of 'cloning', basically, copying and editing an existing experiment where only detail changes need to be made. This has Page | 13 proved to be a very popular feature that can, in certain circumstances, bring about considerable time savings. Another opportunity that ELNs offer in terms of productivity gains is the witnessing process, often considered a necessary chore, and one which doesn't rank too highly on anyone's priority list. The weekly, or monthly, witnessing 'party' with paper lab notebooks is a direct response to overcoming this lethargy. But this is another area in which technology delivers potential benefits through timely and automated routing of witnessing requests and deadlines. The witnessing process can be conducted on-line using electronic/digital signatures, and followed up with reminders if no action has been taken. The deployment of an ELN may be justified on measureable short-term gains in productivity, but the true benefit is likely to come from unquantifiable, anecdotal evidence from users as they recount instances where access to the knowledge repository uncovers previously unknown information and identifies others in the organization who have worked on the same or similar products, materials or services. Through the initial phases of an ELN deployment, it is quite common to hear these stories, but over time, as this new way of working becomes the norm, the stories disappear. There's an old adage amongst scientists that a day or two in the laboratory can save an hour or two in the library. With the current levels of scrutiny of laboratory productivity, if the 'hour or two' in the library can be reduced to a few seconds for an on-line search, then benefits will accrue, not only from finding information quickly, but also in eliminating rework. Just going back to personal productivity, one of the interesting observations about ELN deployments in general is the positive feedback from users about the operational aspects of the systems and the personal productivity benefits. This may be partly attributed to well-designed user interfaces and ease of use features, but can also be attributed to the care and attention taken by project teams to engage, encourage and support users through the requirements and deployment phases of the project. Derek Lowe, a medicinal chemist working on preclinical drug discovery in the US, wrote the following in an article published in 'Chemistry World' 1: "The electronic lab notebook (ELN) has made me into what I never would have gotten around to becoming on my own: an organised scientist. Structures are drawn on screen, stoichiometries adjusted, literature cited, reagents identified and sourced, the analytical data attached and cross-referenced - oh, it's something to see. And over the years, I would rather have eaten sand than do all that manually - and I'd strongly consider ingesting a sand sandwich rather than go back to using paper now. The transition would be so painful that my documentation would surely end up being even worse than before". The quotation from Derek Lowe may seem overwhelmingly positive, but it is not unusual to find this level of enthusiasm amongst users of ELNs. However, not all users will see it this way. We've talked about the benefits that an ELN can bring, but this is all subject to making the right decisions up front, and doing all of the ground work, with regard to change management from the perspective of technology, laboratory processes and preparing laboratory staff to adapt to the change. Page | 14 But furthermore, the laboratory is no longer an ivory tower; it is a critical element in the whole product lifecycle and forms an essential part of the overall workflow and information flow within the organization. The acquisition and deployment of an ELN must take this into account, and consider not only the functional requirements within the laboratory, but also consider how it will integrate with other corporate systems. The term 'Electronic Laboratory Notebook' is inherently ambiguous since it is far more than a direct replacement for a paper lab notebook. The mere fact that it is an electronic system will open up opportunities to seek a tight integration with other laboratory and corporate systems in order to extend the productivity benefits. This does raise some technology challenges, as the laboratory is not well served in terms of data interchange and integration standards. Nevertheless, these challenges can be overcome, but this is a factor that needs to be taken into account early in the requirements phase. In summary, the transition from a paper to an Electronic Laboratory Notebook is almost inevitable; the benefits of electronic working, and the capability to meet organizational productivity objectives though sharing, collaboration and other process improvements are unachievable with a paper based system. The evidence from organizations that have already deployed an electronic laboratory notebook demonstrates not only productivity gains, both at a corporate and personal level, but also points to unquantifiable benefits that can be accrued from having a shareable and searchable repository of scientific experimentation. 1 Derek Lowe, In the Pipeline, Chemistry World, April 2010, Available on line at http://www.rsc.org/chemistryworld/Issues/2010/April/ColumnInpipeline.asp About the Author John Trigg is Founder and Director of phaseFour Informatics, a UK –based consultancy specializing in the Electronic Laboratory Notebooks and laboratory integration. He has over 25 years' experience working in the field of R&D data, information and knowledge management, including 10 years experience of the world's first enterprise level implementation of an Electronic Lab Notebook in the Eastman Kodak Company. John is author of a number of publications on Electronic Laboratory Notebooks and Knowledge Management in the Laboratory and has presented papers and run workshops at conferences in the UK, Ireland, mainland Europe, USA and Australia. John is also the founder of The Integrated Lab website. He was the recipient of the 2000 International LIMS Award and is currently the Chairman of the Automation and Analytical Management Group of the Royal Society of Chemistry. Page | 15 A New Breed of Electronic Laboratory Notebook What is an Electronic Laboratory Notebook? The Collaborative Electronic Notebook Systems Association (CENSA) describes an Electronic Laboratory Notebook (ELN) as follows: "An Electronic Notebook is a system to create, store, retrieve, and share fully electronic records in ways that meet all legal, regulatory, technical and scientific requirements." This is a very broad definition that can encompass a number of possible options. As a result specifications for an ELN can vary dramatically, making selecting an ELN quite difficult. In evaluating an ELN it is important to consider your specific requirements. Is a blank page what you really want? When most people think of an ELN, they visualize an electronic version of a traditional laboratory notebook where a screen displays the notebook, and allows the analyst to do anything that they could do in a paper notebook. The added benefit of an ELN is being able to electronically store and retrieve the pages in the notebook. In a purely R&D facility, this concept can work well. It is an advantage to have maximum flexibility – a blank page, if you like. As we move closer to a QC environment, the requirement for an ELN begins to change. The freedom that is found in the R&D environment is no longer the norm. The ELN for a QC lab needs structure. There is a need to control the information that is recorded in order to ensure that it meets requirements and standards. Unlike the R&D environment, it is not acceptable or desirable to record any observation or any data that the analyst feels is appropriate. Instead the requirement is for a much more controlled set of data. For example the data needs to be associated with proper sample ID's, and tests need to be carried out according to accepted procedures. The visualization of such an ELN is no longer a blank page, but well-defined forms, with rules applied to control the analysis and the analyst. It is important when considering your ELN requirements to understand the kind of data that is being collected and the purpose for collecting the data. Leverage your existing data management capabilities The definition for an ELN includes the need to "store, retrieve and share fully". Everyone certainly requires this functionality, but does it need to be part of the ELN? For many laboratories, the ability to Page | 16 store the data in the ELN would be a duplication of the capabilities they currently have using their existing storage facilities. If a laboratory already has a LIMS, ERP or SDMS (scientific data management system), does it not make sense to use these applications to store the data produced by the ELN? These systems have already been designed and implemented for the purpose of storing and reporting laboratory data. Introducing an ELN with a separate data storage capability could be an unnecessary duplication of functionality. An ELN that can integrate with existing systems, leveraging their capabilities, is going to provide the most effective and productive use of resources. Nexxis ELN – A New Breed of ELN As we have seen the definition of an ELN is very broad and no commercial ELN meets all of the requirements equally well. In selecting an ELN it is important to understand which functionality is most important to your organization. Nexxis ELN is a powerful new breed of ELN that meets laboratory requirements in a way that is unmatched by any other solution. Using SOP management as its core component, Nexxis ELN allows the laboratory to create a structured data collection and information management environment that is based on their established practices and procedures and is fully integrated with their existing information management systems. Structured Data Collection At the core of Nexxis ELN is the ability to automate and enforce the carrying out of analytical SOPs. A Nexxis method not only guides the analyst through each step of the SOP, it also becomes a single access point for all of the information resources required for monitoring and documenting the SOP. The Nexxis Method for a specific SOP can be designed to ensure that the proper instrumentation is used, that the instrumentation has been calibrated according to schedule, that only analysts that are fully qualified are performing the analysis, that analysts comments and observations are stored along with the data, and so on. The possibilities are endless because of the flexibility of Nexxis ReDI technology. Integration with laboratory instrumentation Nexxis ELN collects data directly from laboratory instruments, in real time, using a variety of technologies including PCs, tablets, notebooks, PDAs, wireless systems, etc. As Nexxis ELN guides the analyst through each step of the SOP, it also manages all communications with the instrument including sending commands to the instrument as well as collecting data. The sophistication and flexibility of Nexxis' integration with laboratory instruments fully supports the structured data collection environment created within the Nexxis method. Page | 17 Integration with Information Management Systems Unlike other Electronic Laboratory Notebooks, Nexxis ELN is designed for maximum flexibility when interfacing with existing data storage applications such as LIMS, ERP and SDMS. This integration can be a two way street. Instead of viewing these systems as simply a place to store data, Nexxis ELN can use them as a source of information that is critical to the SOP. Nexxis ELN can query a LIMS for a worklist of samples that need to be run or automatically look up calibration records for the instrument that is being used or even check results against a limits table for the analysis that is being run. A unique strength of Nexxis ELN is its ability to interact with a wide variety of existing systems and to fully incorporate those systems into the automation of the SOP – at the time of analysis. A Best of Breed Solution Nexxis ELN combines the most advanced technology for data collection and SOP automation with the ability to integrate with existing LIMS, ERP and SDMS applications. The result is an Electronic Laboratory Notebook solution that integrates instrument data collection and analysts input with laboratory procedures and systems within a controlled and automated environment. Page | 18 Reduce the Cost of Data Quality In today's competitive and challenging economic climate laboratories face a real challenge as they balance the need to maintain the high quality of the data that they produce while having to cope with the necessity of keeping operating costs at a minimum. One way to address that challenge is by introducing automation and control over the everyday laboratory tests that are carried out manually and recorded on paper forms or in notebooks. These paper based analyses depend on costly and time consuming manual review procedures and investigations to ensure data quality. With these manual procedures, errors are often caught after the analysis is complete so there is also an added cost for rework that can be prevented if procedural errors and omissions are prevented at the time of analysis. In this article we will show how an Electronic Laboratory Notebook (ELN) for Routine Analyses meets the challenge of maintaining or even improving on the high level of quality that already exists while reducing the cost of data quality on three fronts: 1. Reducing the amount of time spent on data review 2. Reducing the amount of rework that the laboratory needs to do 3. Reducing the amount of time spent on investigation and resolution when problems do occur Spend less time on review Paper-based, manual processes are inherently open to errors in data recording, calculations and transcription. There is a rule of thumb in the industry that every level of manual data transcription incurs a 3% - 5% error rate. So the two simple steps of recording a sample result manually and then keying it into a software application like Excel or LIMS, will add a 6% - 10% margin of error to the data. Of course a 6% - 10% error rate is unacceptable, so laboratories need to carry out thorough multi-level reviews to confirm the quality and accuracy of the manually recorded data. Each review takes time and often requires a senior person, so there is a significant cost to the laboratory. Manual processes are also open to risk of error in procedural execution - forgetting to complete a step in a process, using an instrument that hasn't been calibrated, selecting a reagent that has expired, etc. Review processes also need to be in place to catch any actions, or lack of action, that may have occurred during the analysis that would affect the quality of the end results. Having to manage paper documents through a review process can be also be costly and be an exercise in frustration. File folders can get "lost" in somebody's "In" tray. If a customer calls in to find out if their test results are ready, there can be a frantic search to see whose desk those results are on and if Page | 19 they have been approved or not. The amount of time spent on reviewing results can be extremely inefficient simply because everything is recorded on paper. An ELN for Routine Analyses reduces the amount of review that laboratories need to conduct for their routine analyses and simplifies the process of carrying out the review. Automated data collection, calculations and recording eliminates manual errors and the need to review for manual errors "Right first time" procedural control ensures that SOP requirements are met every time eliminating the need to review for procedural errors On-line management of electronic documents eliminates "paper shuffle", simplifying the review and approval process Spend less time on rework Whenever the quality of a test result is in question, valuable personnel time has to be diverted away from regular lab activity and over to determining the cause of the possible errors, correcting the situation and rerunning the test. In addition to the time costs, the cost of any supplies that are used in the process of the test (solutions, reagents, etc) is increased when samples need to be re-analyzed. As we have already seen, the automation and procedural controls that an ELN for Routine Analyses provides are going to reduce the amount of rework that needs to be done by reducing the number of errors that occur in the laboratory. In addition, speeding up the review and approval process by managing it on-line means that any problems that do occur are discovered sooner and rework is assigned faster. In addition to those two benefits, there is one more way that an ELN can speed up the rework process in order to reduce costs for the laboratory. For most routine analyses, the sample result from the test is expected to fall within certain limits or test specifications. An ELN for Routine Analyses can apply those specifications to each sample result, as it is collected or calculated, to see if it is within specification. If a sample is out of specification it can be highlighted so that the analyst will know right away, at the bench level, that something needs to be done. They can then take immediate action to either rerun the sample or to ensure that all of the necessary materials are retained in order to facilitate a proper investigation of the result. Reducing the possibility of errors, automating the process of identifying errors and speeding up the process of initiating rework are all benefits that an ELN for Routine Analyses can introduce to reduce the amount of time spent on rework and the cost of rework for a laboratory. Page | 20 Spend less time on problem resolution With all of the automation and control that an ELN for Routine Analyses can provide, there will be fewer errors and problems for the laboratory to investigate and resolve, so less time will need to be focused on these activities. However, even in this controlled environment problems are going to occur. For example, an analysis may use a reagent that the laboratory purchases from an outside source. The supplier may discover that there is a problem with that reagent and send the laboratory notification that results for any tests that used that reagent may not be accurate. The laboratory then needs to determine the scope of the problem - how many samples may have been affected, how many results have already been reported, etc. In this scenario an on-line, electronic system delivers significant benefits and cost savings over a paper- based system. Instead of having to search through boxes of documents that might be stacked away in a store room or at an offsite storage facility, one person can do a quick on-line search to find out exactly which samples may have been affected by the suspect material. The sheer speed and ease of searching electronically combined with the accuracy of an electronic search provides a clear advantage over searching manually. The laboratory spends less time identifying the extent of the problem allowing them to act quickly and effectively to initiate an appropriate resolution for the problem. Conclusion Laboratories that use an ELN for Routine Analyses to transfer their paper based processes into highly automated and controlled electronic Free ROI Calculator for ELN processes are able to spend less time on review, rework and problem Determine the real dollars and cents resolution without sacrificing the high standards of data quality that are value of an ELN project at your lab. critical to their success. Click here to download. Lowering the cost of quality can make the laboratory more profitable and more competitive by lowering their internal costs for each analysis. Spending less time on monitoring quality can increase laboratory sample handling capacity opening up opportunities to bring new clients on board while maintaining high standards of quality and service. Page | 21 Grow Green - the right choice for your business and the environment Deciding to "grow green" - improving business capabilities while simultaneously making the right environmental choices - is a choice that forward looking organizations are making in order to ensure long term success and sustainability for both their business and for the world we live in. Laboratories that are currently using paper worksheets and SOPs to carry out their everyday routine analyses can make the choice to "grow green" by transforming their paper based processes into online, electronic procedures that deliver real benefit to their business… Making them more efficient and more productive Reducing operating costs Increasing revenue and profitability … and also deliver a strong "green" advantage on a daily basis. How much paper can a laboratory save? At Labtronics we are working with a life sciences company that has selected Nexxis ELN to create electronic versions of the paper forms and documents that they are currently using in their QA department. Their decision to use Nexxis ELN is based primarily on the improved efficiency that they will gain in workflow management, input validation and automated calculations and by having online access to their electronic forms rather than having to spend time searching for paper documents. However, they are also able to estimate the green advantage that an ELN will provide by reducing paper usage. Their QA department performs approximately 12,000 tests a year and each of those tests uses a pre- printed form. The forms vary in size from one page to five pages, but in some cases they also attach print outs of instrument data so the final data packet for a test could be up to 30 pages. On average a data packet is somewhere between 5 and 10 pages, so their estimate is that they will save between 60,000 and 120,000 pages per year in that one department alone, by using ELN to manage their test data and documentation electronically. Page | 22 What is the environmental impact of not using 100,000 pieces of paper per year? If you go on-line and type in the question "How many pieces of paper come out of one tree? ",one common answer is that 1 tree produces 8,333.3 sheets of paper. Using that number, we can calculate that ELN saves approximately 12 trees every year – one tree every month, or 1 tree for every 1,000 tests that they run. Saving twelve trees is a great step in the right direction for one department in one lab. If we multiply that by all of the laboratories that use paper documents for routine testing on a daily basis, then we can clearly see that there is a significant environmental advantage to having laboratories "go paperless" for their routine analytical procedures. Grow Green, the right choice Take the "green advantage" of reducing paper use. Add on the benefits of eliminating the costs of purchasing, managing and storing paper. Toss in the improvements in workflow management and test execution. It all adds up to "growing green" as the right choice for your business and for the environment. Page | 23 The Benefits of Web-Based Applications for the Laboratory The increased opportunity to use web-based applications brings significant benefits to a number of work environments including the laboratory. Primary among these benefits are issues related to the ease of installation and validation; the advantages that the architecture of these applications provide; and the ability to potentially have multiple users access the applications from a variety of locations. Specific advantages are detailed below. Ease of Deployment The use of web-based applications significantly reduces client-side issues such as software deployment, management and updates. Installation is as simple as pointing the browser to a url. The client of web- based applications is always consistent across all of your workstations. No need for scheduling access times to physical PCs and adjusting work schedules of users. Less Validation Validation activity related to installation and operation can be significantly reduced as a result of the removal of the requirement for individual physical installation processes on PCs. The absence of a traditional client application removes the requirement to spend time and resources testing the install of that client on individual PCs. Tiering of Components Consider a traditional PC-based application that includes everything required to run (the user interface, data storage, business logic, etc.). This configuration can be viewed as single tiered or 1-Tier. The primary drawback of this approach is the lack of separation of components resulting in a lack of scalability. A 2-tier architecture is essentially a terminal-to-server or browser-to-server environment. The client usually handles the display, while the server handles the information storage. The business logic may be handled in either or both of these levels. The basic model of a web server pushing pages to a browser can be considered an example of 2-tier. This improves upon scalability, but still lacks a high degree of separation of components thus restricting scalability. The typical approach today for business and web applications is a 3-tier architecture. In a typical example of the web browser acting as the client, an application server handles the business logic and the database is managed in a separate tier. Page | 24 Breaking down the function of any of these tiers further leads to an n-tier environment, which further increases the potential for easy scalability. It typically results in a more modular approach with the potential to scale to your particular needs. A web-based application designed to be n-tier can be run from the full range of a single PC deployment, all the way up to a large-scale enterprise installation. Reduced Client Hardware Requirements Web-based applications have lower hardware requirements than locally installed programs. Since the application is run on a server, the users are not likely to encounter frustration related to an underpowered PC running a traditional application. Multi-User Environments Web-based applications by design are able to be accessed and used by multiple users from multiple physical locations, all at the same time. Users simply need to be able to access the server resources over the network in order to launch and interact with the system. Centralization Administrative costs are reduced by centralizing data storage and administrative activity. This decreases risks of data loss by users as a result of local PC activity (i.e. hard drive crashes and viruses). This also significantly improves aspects related to disaster recovery and business continuity planning. Use of Standardized Technologies Since web-applications are designed around web standards, training for both end users and administrative members are simplified. In addition, the use of standardized technologies provides a degree of future-proofing the application over time as new operating systems and technologies arise. Conclusion Applications that are web-based have significant advantages over traditional standalone or client/server applications. These advantages result in the savings of time and resources in today's workplace. Installation, administrative and management tasks are reduced through the use of these technologies and architectures. Training and administrative tasks are also simplified. The centralization of data storage saves administrative activity, related to backing up data and potentially restoring systems. The use of web technology allows systems to be presented to users through a mechanism that they are comfortable with – a web browser. Page | 25 The Paperless Laboratory: Realities and Expectations Is it possible for a laboratory to become fully paperless with the technology available today? The answer is 'yes' – while the process may not be painless, it does offer tremendous improvements in both the efficiency and quality of the data collected. Laboratories are highly automated, but much of that automation is in the form of instrumentation and instrument data systems. When you look at the flow of information and the management of daily activities in laboratories, you quickly realize that much of this is still performed manually. The Laboratory Information Management System (LIMS) is the major system used to automate a lab, and its use is quite prevalent; it is used to track samples and their results, and can also be used to produce a work list (although this is often produced as a printed report). The LIMS can also be used to receive sample results electronically from instruments. A recent survey indicated, however, that although many companies may have a few instruments interfaced, very few labs have all of them interfaced and a significant number have no instruments integrated. Where integration does exist, it is usually fairly basic. Results are sent to the LIMS, but work lists are usually not sent to the instrument. The information collected is limited to what that specific instrument produces, and much of the associated metadata is missing. LIMS is not a particularly good tool for managing workflow in a laboratory. This may come as a surprise to the reader, but LIMS has a fundamental limitation in its ability to control workflow. Since it was originally designed to store sample information, it is not involved with the analyst at the bench level, in real time, minute by minute. It does not control the testing or the analyst doing the testing, and as a result the LIMS has limited control over workflow. Although instruments take centre-stage in a laboratory, the reality is that much of the work is still manual. Processes such as the preparation, weighing and movement of samples are usually all manual; taking measurements with simple instruments such as a pH meter, making reagents and making visual observations are also manual. Many times, these manual steps use paper to both control the process and to collect data onto paper forms. WHY IS PAPER STILL SO PREVALENT? People like paper – they like to hold it and read it. There is some inherent comfort in creating paper – perhaps it makes us feel productive. It is also accepted that a signature or written sign-off somehow validates the data. Page | 26 Since existing procedures were specifically designed for paper, they also enforce the use of paper. It is interesting to watch people move from paper procedures to electronic ones; they still want to maintain their current procedure, even though it is not suitable for an electronic environment. To be successful, the procedure needs to be redesigned for the electronic system. This is time-consuming and complicated, and is one of the key reasons why people don't automate. In general, laboratories use too many diverse software systems; in addition to the LIMS, there is the electronic laboratory notebook (ELN), the scientific data management system (SDMS), the chemical inventory, the training records module, the stats package and so on. Having all these systems is not a problem in itself; the real problem is that these systems do not function as one unit. There is no connectivity between them, and this means that manual paper procedures are used to move data from the one to the other. The integration of systems is key to eliminating both manual procedures and paper. CAN A LABORATORY BECOME FULLY PAPERLESS? Tools are available today to remove at least 95 per cent of the paper in a laboratory. In order to achieve this, it requires a change in procedures and a high level of integration between systems. The following simple principles must guide the change: No piece of information should be entered more than once No piece of data should be written; it must be entered directly into a software system Data already in a system needs to be readily available, where and when it is needed Take the simple example of an ELN and a LIMS. Typically these are two separate systems, and in order for data to go from one to the other it must be manually transcribed. This dramatically reduces the value of the two automated systems. Following the above principles we can see how LIMS, ELN and other informatics systems can interact without using paper or manual processes: Sample information in LIMS must be available when it is needed in the ELN Results are recorded once in the ELN, and then automatically transferred to LIMS ELN, should be able to connect to the training module, check the analyst's training records and prevent them from proceeding if they don't have the correct level of training Training information – such as date of training and version of course – should be automatically added to the collected data as metadata. Page | 27 ELN should also be able to interact with other systems such as chemical inventory and instrument calibrations in the same way Completed ELN worksheets should be saved electronically (PDF) and sent to SDMS for long- term storage of the raw data. Sample results in LIMS should include a direct link to the raw data in the SDMS so that it is easy to look up the information. Integration is the key to making this happen. Each system operates as an independent application – but when integration is complete, they function as though they were one system, eliminating manual steps and the need for paper. Is this integration available today? The answer is 'yes' – but only indirectly. The individual systems have not been designed to work well with each other. There are no integration standards and, despite the efforts of a number of groups over the last 15 years, no standards are expected in the near future. The solution is to use a third-party integration tool, like LimsLink, that is configurable, generic and able to integrate just about any system. Using LimsLink allows laboratories to continue to select 'best of breed' products for each application with the understanding that LimsLink will be able to provide the integration with other systems. Laboratories also have the flexibility of replacing or updating one application without affecting the integrity of the whole system. With LimsLink providing the integration between systems, there is no technological reason why the whole process of managing samples and generating results cannot be paperless. WHAT ABOUT WORKFLOW CONTROL? Workflow control can be divided into two different processes: control of the individual analyst and control of the laboratory as a whole. Workflow control of the individual analyst requires that a system control their every action on a minute-by minute basis. The system should be sophisticated enough to prevent the analyst from making a mistake. This can only be accomplished by a system working at the bench level, in real time, as the analyst is performing their job. The goal is to eliminate any variation from analyst to analyst, and this cannot be accomplished if there is paper involved in the process. Everything needs to be electronic and automated. Page | 28 Each step of the analysis process needs to be controlled, and this control needs to be automatic and – for the most part - transparent to the user. Examples of having full control over the individual analyst and the process include being able to: Validate the correctness of the data in real time Check training records before the procedure is started to ensure that the analyst has been trained. Check that the selected instrument is calibrated Confirm that the selected batch of reagent has not expired This functionality is available in Nexxis ELN, an ELN for the QA/QC lab that controls both the test that is being run and each individual step in the test. With Nexxis ELN, the technology exists today to make all of this possible. Once implemented, the whole process becomes paperless. But what about workflow control of the whole lab? Can it be a paperless process? Workflow control of the whole lab deals mostly with scheduling and allocation of resources – both equipment and human. Many systems claim to have 'workflow management' capabilities, and they do provide some aspect of the functionality – but despite these claims, true workflow management does not exist as a commercial offering. Until it does, labs will not be completely paperless. SO WHAT IS COMING DOWN THE PIPELINE? Perhaps the most interesting development in the last couple of years has been the introduction of a new type of laboratory system called an iLAB or Integrated Lab. This system is a total lab solution that enhances existing systems, like LIMS and chromatography data systems (CDS), by integrating them and adding missing functionality such as real-time workflow control. The system works at both the bench level and the lab level, giving it the potential to provide complete workflow control in the future. For the analyst, the iLAB functions in a similar way to Microsoft Outlook. It provides a work schedule, messaging system and planner, as well as a simple way to access the various applications operating in the lab. It becomes the analyst's dashboard and access point to their work, providing easy access to the LIMS, ELN, SDMS and CDS at the same time. For the manager, iLAB provides a control and real-time monitoring system for the whole lab. A resource shortage is easily identified; approaching deadlines are highlighted; resources are rescheduled as needed; and problems in the lab are automatically flagged so that immediate corrective action can be taken. With the introduction of the iLAB the possibility of a paperless lab has taken a huge step forward. The key is the ability to integrate independent applications into a single system that provides real-time Page | 29 automation and control at every level in the laboratory, eliminating manual processes and the paper work that goes with them. The process of going paperless still won't be painless – but it will deliver tremendous improvements in both the efficiency of the laboratory and the quality of the data collected. Page | 30 Configuring an ELN for Routine Analyses In laboratories that are performing routine analyses on a regular and on-going basis, there are real advantages to having an ELN that simply records results and observations. Even more benefit can be delivered to the laboratory by expanding the role of the ELN, making it a pro-active component controlling the analytical process and ensuring that every aspect of an SOP is being fulfilled. In this article we will take a step by step approach to configuring an electronic laboratory notebook, starting with the most basic implementation and then showing the additional layers of automation, logic and control that can be applied and the additional benefits that are introduced at each step of the way. Step 1 – Start by Eliminating the Paper The most basic goal of an ELN for Routine Analysis is to move from paper based systems to electronic systems. So we can start by simply doing that, taking existing paper worksheets, documents or SOPs that are used on a regular basis and creating simple electronic versions that can be managed by the ELN. It's a real eye-opener to see how much benefit can be delivered by taking that first step and removing the costs and inefficiencies associated with managing paper. Eliminate illegibility problems created by hard to read manual data recording An immediate advantage for even the simplest electronic worksheet is that you completely eliminate the problem of having to decipher results that are hard to read because of illegible handwriting. A simple electronic worksheet that lets analysts key in results, eliminates any doubts surrounding "legibility" Eliminate problems due to lost or damaged paper forms Paper forms and note books are extremely vulnerable to being misplaced or exposed to all kinds of damage in the laboratory environment. With a simple electronic form we can quickly eliminate those possibilities. Simplify management of the worksheet lifecycle Even if we assume that paper worksheets never get lost or damaged, we still need to deal with physically moving the paper through the cycle of scheduling, monitoring and reviewing completed worksheets. Knowing where a certain worksheet is in that process can be a real challenge when you are dealing with paper. Page | 31 Eliminate paper storage and retrieval costs Moving from paper to electronic documents not only saves on physical storage costs, it also reduces document retrieval time with direct on-line access to completed worksheets. Provide better access to data With a paper system, when you finish your testing you still have a lot of work to do to make that data available within the organization. Even a simple electronic worksheet can be setup to store results in a database, where it is immediately accessible and ready to use. So you can see that simply moving from paper to electronic documents delivers real and significant advantages by increasing confidence in the data that is reported, simplifying management processes, reducing storage and retrieval costs and providing better access to data. Step 2 - Add automated data collection, calculations and limit checks With a simple, basic electronic worksheet in place, we continue to configure our ELN by adding automation capabilities that deliver added value when executing routine analyses. Collect data directly from instruments The simple worksheets that we have discussed so far have depended on the analyst to key in test results, which is an improvement over writing them down on a piece of paper but it is still a process that is open to error. There is a rule of thumb in the industry that every level of transcription Nexxis ELN includes an incurs a 3 – 5% error rate. We can eliminate that possibility for error by Instrument Library that simplifies connecting with the lab instruments and collecting data directly from data collection from over 400 of the instruments right into the electronic worksheet. the most popular laboratory Instead of manually entering results, analysts can automatically collect instruments. and record data with a single click of a button. With that one additional layer of automation we ensure that the data generated by the instrument is the same data that is recorded in the worksheet, each and every time. Automate calculations to ensure consistency and accuracy Once the data has been automatically collected into the worksheet, it makes sense to automate the manual calculations that the analyst may need to do in order to produce a reportable result. These can include weight corrections, applying dilution factors, averaging of results and so on. Our users have told us that if there is one place in the lab where mistakes occur on a regular basis it is with manual calculations and that significant time needs to be spent checking and correcting calculation errors. When we automate these functions for them in the electronic worksheet, they not Page | 32 only save time for the analyst, they also get a 100% reduction in calculation errors and get back the time that is being spent reviewing the manual calculations. They now have a consistent, accurate and documented process for calculations - that is being applied each and every time. Automate limit checks A result that comes directly from an instrument or that is the result of an automated calculation is usually expected to fall within certain limits or test specifications. Another layer of automation that we can build into our ELN is to apply those specifications to each sample result, as it is collected or calculated, to see if it is within expected limits. If a sample is out of limits, it can be highlighted so that the analyst will know right away, at the bench level, if a sample fails the limit check. They can then take immediate action to either rerun the sample or to ensure that all of the necessary materials are retained in order to facilitate a proper investigation of the result. Figure 1 Automate limit checks so analysts know right away if samples are out of specification That completes the next step in configuring our ELN for routine analysis, taking the simple electronic worksheet that we started with and adding automation that reduces analysts' workload and increases the consistency and quality of the process, by automating basic day to day data management functions. Step 3 - Provide step-by-step control over execution of the SOP The next step in configuring an ELN for Routine Analyses is to add a layer of logic to control completion of the electronic worksheet. In an environment where you are executing routine tests on a repeated basis, an ELN can be used to create a very controlled environment that ensures that every aspect of an SOP is being followed and that procedures are carried out the same way, every time. Page | 33 Use Logon ID to control access to worksheets We can start by controlling access to the electronic worksheets based on the user that has logged onto the system. Analysts can be limited to only working with worksheets that they are authorized to work with. If an analyst isn't authorized to run a certain test, then that analyst won't have access to the worksheet for that test. Assign specific instruments to specific tests We can also apply the same principle to equipment and instrumentation that is used in the analytical process. Electronic worksheets can be associated with specific pieces of equipment in the lab that meet the requirements of the SOP. If a weighing application requires a balance that weighs to 5 decimal places then the worksheet can be setup to only allow analysts to use balances that meet that requirement. Figure 2: Analysts can select from a drop down list of balances that meet the requirements of the SOP. Ensure that each step in the SOP is completed correctly before continuing The worksheet can also be setup to provide step by step access to the procedure, only allowing the analyst to move to the next step if they have fully and accurately completed all the requirements for the current step. For example, in Fig 2 you can see that an error message has been generated because the analyst tried to take a pH reading for the first buffer without entering a buffer Lot number. You can also see that the analyst can't proceed to take a reading from the next buffer until the first reading has been successfully completed. Figure 3 Warning messages ensure that analysts follow SOP requirements Page | 34 Include conditional branches (calibration, out-of specification) Logical controls can also be incorporated into the electronic worksheet so that if a particular condition occurs (an instrument needs to be calibrated or a result is out of specification) the worksheet can branch to a path that takes the analyst through the right steps to follow for that condition. For example if a balance needs to be calibrated, the ELN worksheet can automatically branch to a calibration procedure that needs to be successfully completed before continuing with the analysis. Real time control over the execution of the analysis ensures that the SOP is followed, each and every time. Step 4 - Create a fully integrated informatics infrastructure We have one more layer to add before we finish configuring our ELN for Routine analyses – connecting the ELN with other laboratory systems. One of the strong advantages that we have seen of moving from paper to PC is that electronic data is more accessible. So it makes perfect sense to share data and information between the ELN and your other applications. Instead of making analysts access a number of different applications to retrieve the information they need or to update applications, a fully integrated informatics infrastructure delivers information to the analyst and automatically updates other applications as work in the ELN is completed. Connect with LIMS… An obvious and common example is to automatically send sample results from the ELN to LIMS. But that is only half of the equation. LIMS stores sample information, results from other tests, limit tables, etc, that is important to the analytical process. Rather than have the analysts looking up this information it is more efficient to have the ELN automatically retrieve this information from LIMS and deliver it to the analyst as they are doing the analysis. The exchange of data between the ELN and other systems is best if it is a two way exchange and if it takes place in real time at the point of analysis. Connect with inventory management… Another good example of two way information exchange is to have the ELN worksheet interact with an inventory management system. The worksheet can be setup to collect information from a bar code on the container of a solution that is being used in a step of the worksheet. Page | 35 The ELN can use that information to query an inventory system to confirm, right then and there, that the solution is the right one for that step and that it has not passed its expiry date. When the step has successfully completed, the ELN can automatically update the inventory to reflect the amount of solution that was used in that step. Connect with any informatics application… That principle of real time integration can be applied to the automated transfer of information back and forth between the ELN and virtually any informatics application (calibration management, training records, etc). A fully integrated informatics infrastructure ensures that the information contained in all of your systems is automatically included and updated as analyses are carried out. Configuring an ELN for Routine Analyses – step by step We have seen how an ELN for Routine Analysis can deliver immediate benefit by simply eliminating paper and then be built up from that point to include automation of manual tasks, control over SOP requirements and integration with other informatics applications, delivering increasing benefits at each step of the way. A properly selected ELN will allow you to select where in that process you want to start with the implementation. It will let you convert paper worksheets into simple electronic documents as a starting phase and then add automated data collection and calculations as needed. When all of the automation has been added the result is a sophisticated electronic laboratory notebook that transforms paper based manual analyses into electronic processes that are fully integrated into the day to day operation of the laboratory. Page | 36 Laboratory Resource Management - If it isn't in real-time, when is it? Management of laboratory resources (i.e. personnel, inventory and instrumentation) has developed in two directions - paper based systems and electronic systems (spreadsheets, stand-alone applications, LIMS modules). Both systems are used to record and store information regarding resource suitability, availability and usage. Both of these approaches suffer from two inherent drawbacks: 1. They are open to inaccuracies due to errors and omissions because they depend on laboratory personnel to manually keep them up to date and accurate. 2. They are not able to control resource use because they are not directly connected with the activities in the laboratory that use resources. In this article we will see how both of these drawbacks can be eliminated through real-time, event driven integration of resource management with laboratory activities. What is real-time, event driven integration? In the context of laboratory informatics, real-time, event driven integration refers to the ability to transfer information between two separate processes or applications - at precisely the time that the information is needed or generated. A specific event is used to identify exactly when the transfer of information should take place. A simple example is that of using an interfacing solution like LimsLink to transfer data from a laboratory instrument to a LIMS. As soon as the instrument creates a result, LimsLink captures that result and transfers it to LIMS. The integration is driven by a specific event (generation of the result) and it is happening in real-time (as soon as the result is available). How does that get applied to resource management? As we mentioned earlier there are two drawbacks to resource management that want to resolve. We want to be able to control the use of resources and we want to be sure that the information we have about resources is always accurate and up to date. So there are two points, where we can apply real- time, event driven integration - when resources need to be used and when resources are created or updated. Page | 37 Example A chemist needs to weigh out 5 grams of chemical A. To do that the chemist needs to use two resources - a balance and chemical A. Without real-time event driven integration, the chemist needs to take a number of manual steps in order to make sure that these two resources are available and suitable - does the balance meet the precision requirements of the SOP, has the balance been calibrated, is the material that they have in their hand actually chemical A and is it within its expiry date? Most of the time, those checks will be done and done correctly. But because they are manual processes, there will be occasion when errors and omissions will occur. With real-time, event driven integration that single event - the need to weigh 5 grams of chemical A - will initiate real-time integration with two applications. There will be an automatic check with the calibration management application to confirm that the balance has been calibrated and that it meets the SOP requirements. There will also be an automated check with the inventory management application to confirm the suitability and availability of chemical A. The next event, actually weighing out the material, provides another opportunity for real-time integration. Instead of depending on the analyst to subtract the 5 grams of chemical A from inventory, we can use real-time integration to automatically adjust the inventory level. When a resource is needed - real-time, event driven integration can automatically check to see if it is available and if it meets the requirements for the procedure (is the analyst fully trained, is the instrument calibrated, is the chemical within its expiry date). When a resource is used or created - real-time, event driven integration can automatically update the application managing that resource (record completion of training, record calibration of instrument, adjust inventory levels) How do you create real time, event driven resource management? The very first step in creating real-time, event driven resource management is to get rid of paper. Paper based systems can't be automated and they can't talk to each other. Your resource management applications (training, inventory, calibration) need to move from paper (or spreadsheets) to database applications that can be queried and updated in real time. This can be done within LIMS or using stand-alone applications. The key is that these applications need to be able to communicate with other applications. Page | 38 You also need to transform the many resource intensive activities in the laboratory, like sample preparation, that are paper based. An Electronic Laboratory Notebook (ELN) can replace that paper with electronic forms that control the step by step execution of the procedure and communicate with other applications, as the procedure is being carried out. With the paper gone, the ELN becomes the focal point for real-time, event driven resource management. Every time an event in a process uses a resource, the ELN can confirm with the appropriate resource management application that the resource is available and meets the SOP requirements. Every time a resource is used or created, the ELN can automatically update the appropriate resource manager. What are the benefits of real-time, event driven resource management? At the beginning of this article we identified two significant drawbacks to most resource management systems - inaccuracies due to errors and omissions in manual processes and lack of control over the use of resources. The process we have described for implementing real-time, event driven resource management introduces real benefits for the laboratory by overcoming those drawbacks: Mistakes are caught before they happen o Availability and suitability of resources is confirmed before they are used Resource information is always accurate and up to date o Event driven automation removes the human factor from resource management Reduced overhead for analysts o Manual tasks are taken away giving them more time to focus on execution Documentation is quickly and easily available electronically for investigation, audit or inspection o Electronic forms are stored in SDMS A totally integrated lab solution can provide these benefits today. Page | 39 Why Doesn't a Traditional Electronic Laboratory Notebook Work in a QA/QC Lab? Historically, Electronic Laboratory Notebooks have been designed to accommodate research laboratories. Little, if any, consideration has been given to the needs of QA/QC labs. However, the requirements of QA/QC labs are significantly different from research labs. This article will discuss these differences and identify the requirements of an ELN for the QA/QC lab. R&D Requirements The traditional view of an ELN is that it is an R&D tool. It provides three main functions to the R&D lab: A means to document and protect intellectual property and meet legal requirements for patenting new discoveries Documentation throughout the discovery process to meet regulatory requirements A collaboration platform so that scientists can share their research with their colleagues In an R&D environment the ideal ELN is one that provides the most flexibility and freedom for the researcher – a blank page that allows the researcher to do anything that they would in a paper notebook. The researcher should be able to record data, make observations, describe procedures and include images, drawings and diagrams. All information related to their research should be stored electronically in a format that allows for easy retrieval and sharing with other researchers. The format also needs to be flexible enough to adapt to changing requirements as the research program moves through successive stages. QA/AC Requirements The requirements for an ELN are quite different in a QA/QC environment. Quality Departments typically conduct routine tests. They, therefore, need a structured environment to ensure that they conduct these tests the same way every time. To do this they use worksheets and/or Standard Operating Procedures to help guide the analysts through the testing process. Page | 40 Sample of a paper worksheet converted to an electronic spreadsheet An ELN for the QA/QC lab should create an electronic version of your existing worksheet. An ELN should not dictate how you do business; it should just help you to get it done more efficiently and effectively. The freedom and flexibility that is found in the R&D lab gives way to the need in the QA/QC lab to control the information that is recorded, in order to ensure that it provides a consistent and accurate base for monitoring production quality. This requires a more structured environment for data collection that ensures analysts adhere to established SOPs laid out in the worksheet. Once the worksheet is completed it typically needs to be approved and in many cases that approval process is multi-layered. An ELN can help to manage and expedite that approval process to ensure it is followed and completed without anyone having to track down a paper worksheet. The data that is collected in the QA lab must be available to existing systems such as Laboratory Information Management Systems (LIMS), Process Information Management Systems (PIMS), and Enterprise Resource Planning (ERP) systems such as SAP. All of this must be accomplished in an environment that fully meets the laboratory and regulatory security requirements. Based on the requirements we have identified for the R&D lab versus the QA/QC lab it is easy to see why a traditional ELN that has been developed for an R&D lab does not satisfy the needs of a QA/QC lab. The remainder of this article will focus on providing an overview of how an ELN can be designed to accommodate the needs of the Quality Department. A Structured Environment for Data Collection The starting point for creating a structured environment for data collection is to eliminate manual transcription of data. Automatically collecting data directly from the instruments ensures that the data generated by the samples is the data that is recorded in the ELN. There is no room in the QA/QC lab for inaccurate or inconsistent data that is the result of manual data collection and entry errors. Page | 41 An ELN that automatically collects data directly from your instruments provides many benefits: Eliminate manual data entry Reduce transcription errors Automate calculations Ensure data falls within specified limits Automate and Control the SOP In a QA/QC lab Standard Operating Procedures are developed to ensure the accuracy and consistency of sample data. It is essential that these procedures be followed exactly, for each and every analysis. If a sample result is out of range the lab knows that it is because of something in the sample and not in the way it was analyzed. Ensuring that an SOP is being followed means monitoring and controlling all the parameters involved in the analysis including: Ensuring the appropriate instrumentation is being used to conduct the test Ensuring instrumentation has been properly calibrated Verifying the analyst is qualified to conduct the test Controlling the execution of each specific step of the procedure Automating the worksheet ensures full control and documentation of every aspect of the analysis. Integrate With Existing Systems For many QA/QC laboratories, being able to store data in the ELN would be a duplication of the capabilities they currently have with their existing storage facilities. If a laboratory already has a LIMS, ERP or other data management system, it makes sense to use these applications to store the data collected by the ELN. An ELN that can integrate with these systems will provide the most effective and productive use of existing resources. Not only should an ELN be able to store data in these systems, the ELN should also use them as a source of information that is critical to the SOP. The ELN can query a LIMS for a worklist of samples that need to be run, or automatically look up calibration records for the instrument that is being used, or even check sample results against a table of limits for the analysis that is being run. The ability to interact with a wide variety of existing systems and to fully incorporate those systems into the automation of the SOP leverages your current investment in technologies. Page | 42 Meet Security Requirements Data security and regulatory compliance are important issues for any QA/QC laboratory. Put quite simply, data that is captured electronically must be protected from any possible means of corruption at any point in the creation, collection and reporting system. Password protection, electronic signatures, audit trails and archiving are all components that can be implemented to provide the level of security that meets regulatory compliance requirements. An ELN for the QA/QC Lab This article has discussed how the requirements for an ELN in a quality environment are quite different than those in R&D. QA/QC labs have routine tests that they conduct using standard worksheets. An ELN needs to automate those existing worksheets to make it easy for analysts to use. In the QA/QC lab, the need for freedom and flexibility found in the R&D lab is replaced by a need for structure and control. An ELN that uses instrument interfacing and SOP and approval process management as its core components can meet QA/QC laboratory requirements in a way that is unmatched by any other solution. This solution allows the laboratory to create a secure, structured data collection and information management environment that is based on their established practices and procedures and is fully integrated with their existing information management systems. Page | 43 Chapter 3: Understanding the role of ELN in the Lab Page | 44 The Automation Dilemma The automation dilemma exists between customers and vendors. The customer understands their business and the specific problem that they need to solve, but they don't fully understand the best way to use available technology to solve the problems. In fairness to the customer it is always hard to visualize a solution without seeing it. The vendor understands the technology and knows how to solve problems with their products. Unfortunately they really don't understand the specific problems of a customer. This is the automation dilemma; two parties who do not really understand each other's problems and solutions. The Laboratory Automation Plan (LAP) In an effort to solve the automation dilemma, Labtronics Inc developed the Laboratory Automation Plan (LAP). This plan follows a 4 step process: Step 1. Labtronics engineers perform a site visit so that they can see the lab workflow first hand. They interview management to better understand the key problem areas of the business. They also spend time with the analysts to get a detailed understanding of the workflow and the processes used. Step 2. Labtronics uses the information gained to develop a detailed analysis of the workflow, identifying bottlenecks and areas which could be improved by automation. Step 3. Labtronics develops a detailed automation plan to solve the key problems Step 4. Labtronics and the customer review the plan so that there is full understanding on both sides of the table. To better understand the benefits of a Laboratory Automation Plan it is instructional to examine one in more detail. The following description uses examples from an actual LAP with some of the names changed to protect the confidentiality of the client. The Problems This client is a service testing laboratory that approached Labtronics with a couple of general problems. Firstly, they had a centralized LIMS that tracked results, but most of the analytical data resided on paper in a number of satellite labs. Reviewing any data except final results was a very laborious process. Secondly, they felt that they should be able to improve operational efficiency by eliminating some of the paper currently being used in their processes. Page | 45 The client had an automation dilemma. They understood the problem, but they did not know which technology would be best to solve their problem nor did they have a way to go about trying to understand various options. The client agreed to have Labtronics develop an LAP. The Analysis - the Role of LIMS An analysis of the lab's overall workflow was performed to determine which parts of the lab are automated and which are not. That analysis led to an understanding of the role of LIMS, which is illustrated by the chart below (Figure 1). Figure 1: The Role of LIMS The chart clearly shows that although the LIMS is an important automation tool in the lab it does not assist in the automation of the majority of the work being done in the lab. Most of the tasks where LIMS is not involved are still manual and paper based tasks. These tasks can certainly be made more efficient using automation. This is fairly typical for most labs. The LIMS is an important part of the automation solution, but its role is limited and it plays only a minor role for the analyst at the bench level. This client had a number of testing facilities across the country that all reported results to a central LIMS. It was easy for management and for the QC/QA group to view results in the LIMS. However, the LIMS did not store raw data nor did it store any of the QC data. Without this information it was next to impossible to really understand the results. If a problem had to be researched or if the QC department wanted to analyze QC data across a number of sites, the information had to be collected manually. Each lab had to be notified and they had to manually search through their filing system to collect the needed data. Clearly this was not an efficient system. Page | 46 The Analysis - Understanding Workflow The next step is to better understand specific details of the workflow at the bench level. In order to do this the Labtronics engineers spent time with the analysts getting time data about each step in the process. This data was collected for a variety of tests including some that are highly automated such as chromatography and some that are mostly manual such as pH measurements. The following is an example of one of the time studies included in the LAP (Figure 2). The test is broken down into categories such as sample preparation, analysis, reporting and archiving. The results are recorded for the current process and these are compared to the same process after it has been automated by Nexxis iLAB. In this example, the analyst takes the instrument results and performs a fairly complex process for compound identification using an excel spreadsheet. Much of this work can be automated. Data is currently entered into LIMS manually and the sample reporting step can be eliminated completely by automation. This automated reporting process will also eliminate the archiving step. The following table (Figure 2) shows results for a test cycle of 100 samples. Test Name: Test A Current Process Nexxis iLAB Process Lab Role: Chemist Step Time Step Time (documented Percent of Test Percent of Test hours per test Cycle Time spent (As per Lab Cycle Time spent cycle) on Each Task Automation Plan) on Each Task Sample Preparation 1.00 13.30% 1.00 40.00% Sample Analysis 4.00 53.30% 1.50 60.00% Sample Reporting 2.00 26.70% 0.00 0.00% Data Archiving 0.50 6.70% 0.00 0.00% Hours Required to Analyst Complete 1 test 7.5 2.5 cycle: Number of work hours per day: 8 8 Maximum Number of 1.1 per analyst 3.2 per analyst test cycles per day: Time spent by Analyst to prepare Rate Limiting Step: Instrument Capacity sample, perform analysis, and With sample analysis time reduced Sample analysis time and AIMS greatly, and sample reporting time Comments / Explanation: reporting time consume 6 hours eliminated, analyst can focus on out of an 8 hour day. testing. Reduction in Analyst Time per Test Cycle: N/A 67% Potential Sample through-put Improvement: N/A 300% Figure 2: Productivity Summary for Test A The LAP also provides the results in a more graphical format to make it easier for the client to understand the data. The following charts show the same data as above. Page | 47 Figure 3: Productivity comparison Current Process vs. Nexxis iLAB Process Fig 3a: Time spent on operations using current process Fig 3b: Time saved using Nexxis iLab The Analysis - Potential for Automation The table below (Figure 4) shows a summary of the data for a number of tests. It is important to analyze a number of different tests since each one has a different potential for automation. Page | 48 Figure 4: Productivity Improvements with Nexxis iLAB In addition to looking at the time that can be saved with automation, this table also looks at the tests from different points of view. Staffing Efficiencies - evaluates the ability to reduce the manpower after automation. Increased Sample Throughput - looks at the ability to increase the number of samples being analyzed. This looks at things such as the available instruments, and their ability to handle larger sample loading. Instrument Consolidation - is a measure of the ability to reduce the number of existing instruments. In a case where there are several similar instruments an increase in efficiency may result in the ability to eliminate an older instrument. For example, the time saved by Nexxis iLAB in Tests A and B allows those instruments to be used for Test C as well allowing the client to retire an old instrument and save significant maintenance expense. Efficiency is just one way to analyze the value of automation. The LAP also looks at other evaluation techniques. In this example tests B and D are performed by more skilled labor and the hourly cost is higher. Even though the time saving for test D is not great, the cost savings are significant. Page | 49 Test H has one of the lowest efficiency improvements but the test involves many manual calculations which lead to a higher error rate than is found on some more automated tests. The real value of automating these tests is an improvement in quality not an improvement in efficiency. The Analysis - Comparison of Sites For this client the LAP was performed at one of their main sites. The client then decided to repeat the process at 4 more sites on their own. The goal here was to verify the data Labtronics had produced. This effort resulted in two important findings: a) The data in the original LAP compared well with the average of the clients findings, validating the original LAP b) The client found large differences from site to site (Figure 5). Site 1 Site 2 Site 3 Site 4 Site 5 Laboratory Locations: Current Current Current Current Current AVERAGES Process Process Process Process Process Time Spent Time Spent Time Spent Time Spent Time Spent Time Spent Analysis Breakdown: on Task on Task on Task on Task on Task on Task (minutes) (minutes) (minutes) (minutes) (minutes) (minutes) Collected Laboratory Task Times for Each Lab Samples 115 45 188 54 24 85 prep Samples 119 40 54 54 48 63 analysis Samples Current 30 11 18 11 24 19 reporting Process Archiving 30 30 30 15 6 22 Calculated Improvement Cycle Time from current with 294 126 290 134 102 189 process Current using iLab Process Calculated iLAB Task Equivalents for Each Lab Samples 115 45 188 54 24 85 0% prep Samples 38 13 17 17 15 20 68% analysis Nexxis Samples 0 0 0 0 0 0 100% iLAB reporting Process Archiving 0 0 0 0 0 0 100% Calculated Cycle Time with 153 58 205 71 39 105 45% Nexxis iLAB Calculated Reduction 48% 54% 29% 47% 62% 45% N/A per Cycle with Nexxis Figure 5: Comparison of sites The results from the sites indicated that there was more than a 100% difference in the time it took to perform the same test between sites. The reason for this is that each site uses a different procedure Page | 50 for the test. When this client automates, they plan to use an ELN to manage many of these tests. This will make it easy for them to select the most efficient test processes and standardize on them across all sites. This standardization alone will have dramatic impact on their overall efficiency. The Result The Laboratory Automation Plan provided a very detailed study of the client's processes in one lab. The information was so useful that they decided to expand the study to other satellite labs. In addition to providing the financial evidence that was needed to justify automation, the study also provided the client with a detailed proposal on which areas to automate, and which technology would be best to accomplish the automation. The client was looking for an overall productivity improvement of 20% and they concluded that the proposed automation would give them that. In addition to the improvement they would also achieve some softer goals such as; a) Elimination of transcription errors resulting in higher quality results b) Standardization which makes it easier to gain ISO 17025 compliance c) Centralized storage of documents and raw data ensuring that such data is not lost d) Ability for QC/QA to easily perform audits at the site level The client is in the process of implementing a Nexxis iLAB system which will include: 1) Integration between instruments and the LIMS 2) An ELN to automate work at the lab bench 3) An SDMS for the central storage of information. Once this implementation is complete the automation in the lab will look more like this (Figure 6): Page | 51 Figure 6: The Integrated Lab As a second phase in the project, the client will consider automating with the Nexxis iLAB chemical inventory system and instrument calibration system as well. This will have an impact on both efficiency and the quality of the results. Page | 52 The Real Costs of Paper in the Laboratory A study that looked at the life cycle of paper in a typical office environment determined that a sheet of paper that cost $.003 to purchase ends up costing the company $.0447 by the time it is finally disposed of. [http://www.docstoc.com/docs/5676508/The-Real-Cost-of-Paper] That is almost 15 times the original purchase price of the paper. Who would have imagined? In the office environment those costs come from photocopying, printing, faxing, mailing, couriers, storage and disposal of paper. In the laboratory environment any or all of those costs can be applied plus specific costs related to: Illegible and inaccurate data recording Investigation and rework when forms are lost or damaged Managing paper documents through the cycle of scheduling, completing, reviewing and reporting The extremely long term storage requirements for meeting regulatory and legal requirements Even with the tremendous impact of laboratory informatics applications (LIMS, Chromatography Data Systems, SDMS, etc) much of a laboratories day-to-day routine operations are still carried out using paper-based systems for everything from recording test results to managing chemical inventories to documenting and scheduling instrument calibrations. This reliance on paper is not just expensive, it also decreases the efficiency of the laboratory workplace and leaves the laboratory vulnerable to having valuable data misplaced, lost or destroyed. So where do we begin to measure the real cost of paper in the laboratory? A good place to start is by looking at how data is recorded in a paper-based system. Inaccurate and Illegible Data Recording When busy technicians are manually recording information - everything from writing test results on worksheets to entering inventory levels in notebooks - they are going to make errors. Numbers will get transposed, entries will get left out and updates will get overlooked. That's a fact of life. They also may not always take the time to make sure that every entry is absolutely clear and legible. Is that a "5" or is it an "8" or is it a "3"? Page | 53 So the laboratory ends up spending time and money on reviewing these results and entries. And there is always the risk that when these results are being reviewed by another analyst or a supervisor, they might not catch the error or they may incorrectly decipher an illegible number. By comparison, electronic systems immediately eliminate any costs associated with illegible data as results and entries are no longer handwritten. Inaccurate recording of test results can be completely eliminated by collecting data directly from lab instruments. Invalid or overlooked entries for systems like inventory management can be eliminated by connecting those systems directly with the processes. For example when a step in an electronic worksheet calls for 5ml of a solution, the inventory management application can be automatically updated by having the electronic worksheet deduct the 5ml of solution from the inventory database, as soon as the step is completed. Electronic forms eliminate the costs associated with manual data recording and manual updating of paper-based systems. Lost or damaged paper forms Even if all of the information is recorded 100% accurately and legibly, paper forms and note books are still extremely vulnerable to being misplaced or exposed to damage in the laboratory environment. Chemicals or even a cup of coffee can be accidently spilled on a lab notebook. A test worksheet can get lost in the "In Basket shuffle". US companies spend about $20 in labor to file a document, $120 in labor to find a misfiled document and $220 to reproduce a lost document. —Cooper & Lybrands 15% of all papers are lost, 30% of our time is used trying to find these lost documents -Delphi Group In the laboratory, documents that are misplaced, lost or damaged create real costs for the organization due to the investigation and rework required to replace the results that have been lost with the paper. There is also the very real risk of misreporting data or delaying the reporting of critical data to a client or a key decision maker. In a paperless laboratory, electronic forms can be easily and cost effectively backed up and stored eliminating the costs and concerns of lost or damaged forms. Managing the paper lifecycle A real shortcoming of paper is that it can only be in one place at a time. So even if we assume that paper worksheets never get lost or damaged, we still need to deal with physically moving the paper through the lab as it goes through the cycle of scheduling, completing, reviewing and reporting. Page | 54 Knowing where a certain worksheet is in that process can be difficult, making it a real challenge for managers and supervisors to effectively monitor and manage laboratory workflow. Time is lost, resources may not be effectively allocated and reporting can be delayed at almost every step of the way. On-line management of laboratory forms and information makes supervisors and managers much more efficient at scheduling, monitoring, and balancing the laboratory workload. A critical part of the laboratory lifecycle is making test results available to end users and clients as quickly as possible. With a paper system, when you finish your testing you still have a lot of work to do to make the results available within the organization. Time and money are spent manually transferring those results from paper into informatics systems for reporting and storage. Test results that are recorded electronically can be transferred into informatics systems electronically eliminating manual data transfer costs and making the results immediately accessible and ready to use. Paper storage and retrieval costs In addition to the initial cost of purchasing paper, laboratories face additional costs of having to maintain records and have them accessible over the long term in order to protect intellectual property, meet regulatory requirements and provide historical documentation of test results. On-site and off-site storage and retrieval of paper documents is a cost that only increases as time goes by as volumes of paper and costs for storage continually increase. A surprising number of laboratories end up spending time and resources on scanning paper documents so that they can be stored in a Document Management System. Moving to a paperless laboratory will eliminate that cost as information that is already electronic can be transferred directly into the Document Management System. Whether or not you have a Document Management System, being able to store documents electronically rather than physically is going to generate ongoing savings by eliminating the costs of long term storage and providing faster access to archived documents when they are needed. And of course with an electronic document, your chances of losing or misplacing the document are almost non-existent. Free ROI Calculator for ELN Determine the real dollars and cents value of an ELN project at your lab. Page | 55 Click here to download. Conclusion The initial cost of buying paper, paper forms and notebooks is just the tip of the iceberg when it comes to determining the real costs of paper in the laboratory. At every step of the way the inflexibility of paper, the opportunities for error, the risks of loss or damage all add up to costs that far exceed the original purchase price. Transferring from paper systems to electronic management of data and systems in the laboratory is a clear investment in reducing costs and improving laboratory efficiency. Page | 56 Laboratory Data - Safety, Security and Traceability Laboratories working in all industries and sectors face legal, regulatory and corporate requirements to provide secure and ongoing access to the data and documentation that supports their reported test results. At any time they may be called upon to provide evidence of how a result was determined and to prove that the result they reported is indeed the correct result. This can be as a result of a customer audit, a corporate audit, a regulatory investigation or even a legal proceeding. In a paper based environment, safely and securely storing paper documents and being able to access them in a timely manner is both time consuming and expensive. Safety and Security "Companies on average spend $25,000 to fill a typical four-drawer file cabinet, and $2,000 to maintain it annually ". The Delphi Group As surprising as that figure might be, a room full of filing cabinets or storage boxes is only the start of paper related storage costs for today's laboratory. In most cases, even more costly off-site storage needs to be maintained for long term storage of documents in order to meet regulatory requirements, protect intellectual property and provide historical or legal documentation of analytical results. In addition to the physical costs of storage there are also procedural costs related to managing the physical transfer of documents through multiple levels of storage and tracking their location in order to be able to retrieve them as they are needed. Laboratories also need to consider the safety and security of their business as it relates to their data. What are the potential consequences of losing all or part of their paper based data and documentation? 70% of today's businesses would fail within three weeks if they suffered a catastrophic loss of paper- based records due to fire or flood - Coopers & Lybrand Losing a single analytical result because a piece of paper has been lost is costly for a laboratory in terms of the time and resources required to redo an analysis. Losing a significant portion of their paper documentation could prove to be disastrous. Some laboratories have recognized that electronic storage of documents is safer, more secure and more cost effective than on paper, so they are now scanning all of their paper documents and storing Page | 57 those scanned documents electronically. Unfortunately, the cost of scanning those documents significantly reduces the cost benefits of electronic storage. The most effective way to reduce storage costs and ensure the safety and security of documents is to manage them electronically throughout the entire document lifecycle. Traceability A key requirement for analytical laboratories is traceability of results, the ability to show on a step by step basis how an analytical result was generated. The supporting documentation that meets this requirement for even a single sample can include instrument results, calibration information, solution preparation procedures, certificates of analysis for raw materials and more. It isn't uncommon for the QA documentation for a single test to run into dozens of pages. In a paper based system, accessing those documents as part of a problem investigation or an audit means having to manually search through boxes of forms that have been put away in filing cabinets, stacked in a store room or even sent to an offsite storage site. A study conducted by Price Waterhouse required a staff of paralegals to search over 10,000 documents looking for a specific topic, author and date range. Manually searching through paper files turned up 15 documents in 67 hours. The same search done electronically found 20 documents in 4.5 seconds. That study points out two critical concerns that every laboratory should have with traceability and their paper based systems: 1. The amount of time it takes to manually search for documents and the cost of that time to the organization. The sheer speed of searching electronically is a clear advantage over searching manually. 2. The likelihood that key documentation that supports the traceability of a result may not be found in a manual search. In the study 25% (5 out of 20) of the documents that met the search criteria were not found in the manual search. When documents are stored electronically instead of on paper, laboratories can very quickly and accurately identify and retrieve all of the documentation that they need in order to resolve problems or to satisfy auditors and investigators. Managing Documents Electronically As mentioned earlier, the most effective way to manage documents is to manage them electronically throughout their entire life cycle. Even a hybrid solution that combines paper and electronic forms management is still subject to many of the costs, inefficiencies and risks of a purely paper based system. Page | 58 When properly integrated, an ELN with an SDMS will work together to provide laboratories with paperless management of their laboratory documentation from data generation right through to long term storage and retrieval. PDF documents that are created in ELN can be sent to SDMS where they can be archived, searched and retrieved electronically. This gives laboratories a cost effective solution for managing the entire lifecycle of a document electronically and also provides them with fast, secure and accurate access to the documentation. For example, if a particular lot number of a solution or a reagent or a chemical is found to be suspect, the laboratory can very quickly establish the scope and impact of the problem by searching the SDMS to find all of the ELN worksheets that reference the suspect material. Manually searching through paper documents to find that information would be extremely time consuming and would not provide the same level of accuracy. Conclusion Electronic management of scientific data and documentation ensures the security, safety and traceability of analytical results at a level that simply isn't possible with paper based systems. Page | 59 Go Paperless and Improve Procedural Execution Along with the cost benefits of eliminating paper, implementing an Electronic Laboratory Notebook (ELN) for Routine Analyses provides laboratories with an opportunity to also improve their procedural execution by providing a level of control and automation over every aspect of their routine analyses that is simply not possible in a paper-based environment. Analysts work more efficiently as they have direct access to the information that they need to run their tests Automated data collection, calculations and limit checking eliminates opportunities for error and reduces time spent on peer review Advanced control over procedural execution eliminates rework and investigation due to procedural errors On-line review of electronic forms eliminates costs and delays of circulating paper through the review process On-line access to completed forms simplifies problem investigation and resolution Let's look at each of those points in more detail to see the real improvements in procedural execution that an Electronic Laboratory Notebook for Routine Analyses can deliver - every single day. Get the information you need, when you need it With a paper based system there can be a lot of up front work required to gather the information that is needed to run even a simple test. Analysts may have to access LIMS to generate a work list. They might have to look up the SOP in the Document Management System to confirm the details of the analytical procedure. Then they may need to find out if their instrument has been calibrated or if the reagents they are using haven't expired, or if there is enough reagent in inventory… and it just goes on and on. This all takes time and reduces the efficiency of the laboratory. An ELN that is integrated with your other laboratory informatics systems can automatically deliver all of this information right to the analyst right at the time of analysis. The ELN can pull a work list from LIMS, check chemical inventory levels and expiry dates, confirm that instruments have been calibrated and even give the analyst direct access to the SOP. Page | 60 Rather than having analysts search through a variety of different resources in order to compile that information themselves, a well implemented ELN is going to remove that responsibility from the analysts' shoulders and free them up for more productive activities. Analysts can focus on the execution of the test with the confidence that the information they are working with is accurate and up to date. Eliminate opportunities for errors During the analysis, an ELN can automate manual functions such as data collection, calculations and limit checking. When these functions are automated you not only reduce the analyst's workload you also eliminate any opportunity for errors. You can have real confidence that data is always accurately recorded, that calculations are always correct and that out-of –specification results are always caught. This "right first time" environment generates additional benefits by reducing the amount of time that analysts and supervisory staff need to spend on data review. Real time control over procedural execution An ELN for Routine Analyses can create a very controlled environment that interacts with the analyst and other informatics systems at the time of analysis to ensure that every aspect of an SOP is being followed and that procedures are carried out the same way, every time. Access to the electronic worksheets can be controlled so that analysts are only working with worksheets that they are authorized to work with. If an analyst isn't authorized to run a certain test, then they won't have access to the worksheet for that test. The same principle can also be applied to equipment and instrumentation that is used in the analytical process. Electronic worksheets can be associated with specific pieces of equipment in the lab that meet the requirements of the SOP. For example, if a weighing application requires a balance that weighs to 5 decimal places then the worksheet can be setup to only allow analysts to use balances that meet those criteria. The worksheet can also be setup to provide step by step access to the procedure, only allowing the analyst to move to the next step once they have fully and accurately completed all the requirements for the current step. Logical controls can also be incorporated into the electronic worksheet so that if a particular condition occurs (an instrument needs to be calibrated or a result is out of specification) the worksheet can branch to a path that takes the analyst through the right steps to follow for that condition. Page | 61 Real time control over the execution of the analysis ensures that every aspect of the SOP is followed, each and every time. Review and approve on-line. We have already seen that the "right first time" environment in an electronic worksheet can reduce the amount of time that is spent on data review. In addition to that, a paperless notebook makes it much easier and more efficient to circulate results through the review and approval process. Moving a paper document from desk to desk in order to get approvals is not a model of efficiency. It is a slow process at best and in worst case scenarios documents can easily get "lost" or "misplaced". If someone needs to see results right away it can be a real challenge to find out whose desk those results are on and if they have been approved or not. With an electronic system we improve the review and approval process by eliminating the time and energy that is spent on paper management. When a document is ready to review, it can be accessed on-line at the click of a mouse. As soon as one person is done it is immediately ready and available for the next person to review. If someone needs to know the status of a certain test result right away, the laboratory has direct on- line access to all of the worksheets and can see exactly where they are in the review and approval process. In a paperless system, when the last review is done you don't have to wait while the data is entered into a LIMS or other informatics systems before it becomes available for use. The instant it receives final approval, data can be automatically transferred to these systems and available for clients and decision makers. Speed up problem investigation and resolution Even in a paperless lab issues can come up that are beyond your control. Fortunately being paperless can help you to quickly identify the extent of the problem and prepare the most effective plan for resolving the issue. For example, a laboratory may receive notice that there is a problem with a particular lot of a solution that they received from one of their suppliers. In a paper environment, identifying the scope of that problem will require manually searching through paper documents and notebooks to try and find all of the tests that may have been impacted by that suspect solution. That task can require hours of valuable time and can be made even more difficult if the documents have already been archived or sent to an off-site storage facility. With an ELN for Routine Analyses that process can be completed in minutes. With a simple search of the ELN database you can know right away exactly which tests were affected by the suspect solution. Page | 62 Keeping Tabs on the Lab - Real Time, On- line Management of Laboratory Workload What do you do when rush samples show up and the lead analyst doesn't? Grab your running shoes… If you are the lab manager, you might want to grab your running shoes because you are going to have to be ready to quickly assess what resources you have available, what the workload is in the lab and what the immediate priorities are - in order to figure out how to get those rush samples run and still keep the rest of the lab flowing efficiently. In a paper-based environment, it can take some real running around to pull all of that information together and do it quickly. You may have to start by going through a logbook to get an idea of how much work has been assigned and which analysts it has been assigned to. Then you will probably need to track down each analyst to determine the status and the priority of the work that they already have on the go and how long it will take to complete. Of course the analysts will probably need to track down all of their worksheets or notebooks before they can provide you with the information that you need. When all of that information is finally collected and compiled, then you can start to work out who might be available to run those rush samples and when they will have time to do it. Or find a better way… In a world where time is of the essence and priorities are continually shifting, lab managers and supervisors need a more effective way to access the information they need to manage and balance laboratory workload – in real time. Nexxis ELN provides better access to that information by moving paper-based analyses into the electronic environment and giving the lab a truly effective tool for real time scheduling, monitoring and balancing of the laboratory workload. Page | 63 All of the information that is needed to manage the efficient and productive flow of samples through the laboratory, is made available on-line and organized to provide a meaningful at-a-glance picture of real time workflow in the lab. All the information you need, right on your desktop… When those rush samples show up, instead of having to track down analysts, worksheets and log books, you can use the Nexxis ELN web client to see, right from your desktop, the current, real time status of all the worksheets that have been assigned in the lab. Nexxis ELN shows at-a-glance which worksheets haven't been started, which are in process, and how many worksheets are scheduled to be completed that day for each analyst. With that information at your fingertips, you can use Nexxis ELN to initiate new worksheets for the rush samples, assign them to the analyst that is in the best position to run those samples and specify them as a "Rush" priority, so the analyst knows right away that this is work that needs to be done. You don't even have to track down the analyst to tell them that they have been assigned those samples. As soon as the worksheets are scheduled, the analyst will see them in their Nexxis ELN list of Active Worksheets, which shows all of the worksheets that are scheduled for them and their priority. They just have to select the "Rush" worksheet and start working. At any time during the day, you can use the Nexxis ELN client to check on the status of the rush samples, view a worksheet in progress and get a full, real-time picture of the overall laboratory workload. As soon as a worksheet is completed, Nexxis ELN can automatically start the review and approval process by emailing the reviewer to notify them that a PDF version of the completed worksheet is now available for on-line review. From their desktop, reviewers can see all of the results, audit trail information, date and time stamps, electronic signatures, etc associated with that worksheet. They have immediate access to all the information that they need to complete their review and approve the results for release. When the final review is complete, Nexxis ELN can automatically report the results to the LIMS or other reporting systems, so those rush results are immediately available for the client. Page | 64 Hang up your running shoes… In the Nexxis ELN paperless laboratory, laboratory managers and supervisors don't need their running shoes to quickly track down logbooks, paper worksheets, notebooks and analysts. They can schedule work, adjust priorities, balance laboratory workload and monitor the progress of electronic worksheets, right from their desktop. Having on-line access to all of this information delivers significant improvements in their ability to manage their laboratory workload, maintain operational efficiency and provide the highest level of service to the laboratory's customers. Page | 65 ELN Reduces Regulatory Compliance Costs It has been estimated that laboratories in a regulated environment dedicate up to 70% of their resources to compliance-related functions.1 Clearly, these laboratories can achieve significant reductions in their compliance costs by reducing the amount of daily time and resources that are spent on maintaining regulatory compliance Replacing routine paper based processes in the laboratory with an Electronic Laboratory Notebook (ELN) that manages, controls and automates the execution of routine analysis is an effective way of delivering those savings, while ensuring that laboratories continue to meet or even improve on the high level of compliance that they have already established. In this article we will consider four areas where an ELN can help regulated laboratories reduce their compliance costs: Electronic documents eliminate compliance costs associated with the use of paper-based forms Automating data collection and calculations eliminates errors, reducing the time and cost of secondary review Control of the analytical process automatically ensures step-by-step compliance with the analytical SOP Real-time integration with other informatics systems reduces the time analysts spend confirming that additional SOP requirements (calibration, inventory, etc) are being met. Electronic documents eliminate compliance costs associated with the use of paper-based forms Laboratories realize immediate reductions in compliance costs by simply moving from paper to electronic documents. For example: The ongoing cost of purchasing paper notebooks that meet regulatory compliance requirements is eliminated. 1 Pharmaceutical Formulation& Quality magazine, Dec/Jan 2005 Page | 66 Regulatory compliance requires storage of documents for an average of 10 – 15 years, sometimes longer. The long-term costs of on-site and off-site physical storage of notebooks and paper forms are replaced with cost-effective storage on electronic media. Retrieval of paper documents, particularly from off-site storage, can be costly and time consuming. Direct on-line access to electronic documents reduces the time and costs required for document retrieval during an audit situation or for internal problem resolution. Electronic documents, with supporting audit trail and electronic signatures, present auditors with a clear and accurate picture of the results, simplifying audit procedures. For example, an electronic worksheet that let's analysts key in results eliminates any doubts or questions surrounding illegible handwriting that may come up during a compliance audit. Automated data collection and calculations reduce the cost of secondary review Every time an analyst takes the time to manually record data or manually calculate a result, there is an opportunity for error. In fact, there is a rule of thumb in the industry that every level of manual transcription incurs a 3 – 5% error rate. Every time there is an opportunity for error, there is a need for secondary review of the analyst's work An ELN can eliminate the possibility for manual error by collecting data directly from the lab instruments right into the electronic worksheet. With that one additional layer of automation we reduce the need for secondary review by ensuring that the data generated by the instrument is the same data that is recorded in the worksheet, each and every time. Once the data is in the electronic worksheet, the ELN can further reduce the opportunity for error by automating any calculations that the analyst had been doing manually on paper. Control of the analytical process ensures compliance to the SOP In an environment where routine tests are executed on a repeated basis, an ELN can be used to create a very controlled environment that ensures that every aspect of an SOP is being followed and that procedures are carried out the same way, every time. Analysts can be limited to only working with worksheets that they are trained and authorized to work with Page | 67 Electronic worksheets can be integrated with specific pieces of equipment in the lab that meet the requirements of the SOP so the lab always knows that instruments that meet SOP requirements are always used for the analysis. Electronic worksheets can be setup to provide step-by-step access through the procedure, only allowing the analyst to move to the next step if they have fully and accurately completed all the requirements for the current step Real-time integration with other informatics systems reduces the time analysts spend confirming additional SOP requirements One of the strong advantages of moving to a paperless system is that electronic data is clearly more accessible than paper based data. We can leverage this advantage by integrating the ELN with other informatics systems to create a two- way exchange of data and information that takes place in real time, at the point of analysis. Analysts can spend less time looking for and updating compliance related information in other systems and more time running analyses. For example, the ELN can automatically collect and record information from the bar code of a container for a solution that the analyst is using. That information can be used to automatically query an inventory system to confirm, right then and there, that the solution is the right one for that step and that it has not passed its expiry date. When the step has successfully completed, the ELN can automatically update the inventory to reflect the amount of solution that was used in that step. That automated exchange of information between the ELN and the inventory system has assured and documented that the material used in the worksheet has met all of the SOP requirements and that the inventory records for that material are always accurate and up to date. Page | 68 ELN Cures 4 Common Laboratory Headaches Even the most efficient laboratories have to deal with everyday "headaches" caused by manual processes that are used to record, gather, access and update data from a wide variety of sources (LIMS, instruments, calibration applications, inventory applications, etc). The following are examples of 4 common laboratory headaches that can be eliminated by using an ELN to automate manual processes and make data and information always available, when and where it is needed most… Laboratory Headache #1 – Results that are invalid because an analyst didn't follow an SOP No matter how good and careful your analysts are, and no matter how clear and complete your manual processes are, there are going to be times when analysts miss a step in an analysis or overlook an aspect of your SOP. ELN takes control over the SOP at the bench level, guiding the analyst through each step of the process, not letting them move to the next step until they have finished the one they are on and ensuring that every aspect of the SOP is being satisfied… in Real Time Being sure that your procedures are being followed every time doesn't just eliminate a headache. It also reduces the amount of time that needs to be spent on reviewing test results and gives you absolute confidence in the quality of the results that the lab is generating. Laboratory Headache #2 - A test that can't be run because you ran out of a chemical or reagent This is the headache that seems to always crop up when the lab is busiest and you have a rush sample for your biggest client. Instead of delivering the test results, you end up scrambling to place a rush order for the chemical or reagent and paying top dollar for Express shipping. Page | 69 Whether you manage your inventory with a software application, with spreadsheets or simply record your inventory with pen and paper, you can still get this headache simply because somebody used a chemical and forgot to update the inventory. If you already have an application for chemical inventory management, ELN can connect it with your daily analyses, so that every time a chemical or reagent is used the inventory level is automatically adjusted. Your inventory always automatically reflects exactly what you have in stock – right now. If you don't have a chemical inventory management system, don't worry. You can add one to ELN easily. Laboratory Headache #3 - A batch of samples that have to be rerun because the instrument wasn't properly calibrated If you are managing your instrument calibrations with pen and paper, then you are probably familiar with this headache. Even if you have a traditional Calibration Management software application, you still experience the problem of keeping the calibration records up to date and making sure that analysts check the records before using an instrument. An ELN worksheet can automatically check your Calibration Management Application – at the time of analysis - to make sure that the instrument being used has been successfully calibrated according to schedule. If it hasn't, ELN can either stop the analysis or branch to a calibration routine. Once the instrument has been successfully calibrated, ELN can update the Calibration Management Application and let the analyst continue. ELN should never allow a test to be run on an un-calibrated instrument. If you don't have an Instrument Calibration Management application, don't worry. You get one with the ELN. Laboratory Headache #4 - A "5" that looks like an "8", or is it a "3"? If your laboratory depends on manual recording of critical data, then you know all about this headache. You have struggled to decipher numbers that are hard to read because of illegible handwriting or coffee spilled on a lab notebook. You have searched for lost worksheets, tried to make sense of transposed figures and spent time fixing incorrect manual calculations. These are headaches that happen every day, simply because busy analysts are manually recording data on worksheets or in notebooks. ELN eliminates these headaches by automatically capturing and recording data from all of your lab instruments and automating the calculations that your analysts are currently doing manually. Page | 70 Conclusion Not all ELN will solve all of these headaches but leading ELN designed for QA/QC labs will meet these requirements. This new breed of informatics technology collects and combines information from your laboratory informatics systems, your laboratory instruments and your analysts and uniquely integrates it into every aspect of the laboratory's daily routine. ELN gives laboratories a solution that eliminates manual processes, breaks down communications barriers and manages the sharing of data and information between people, instruments and data management systems. It may not cure the common cold, but it will take care of some of your headaches. Page | 71 Chapter 4: Examples of ELN installations Page | 72 Automated Control and Documentation of Daily Calibration Requirements The Problem A common requirement in regulated laboratories is to perform and document a daily calibration of electronic balances, prior to using the balances for testing. Using a paper-based system to document the calibration process has some distinct disadvantages: High costs associated with the storage and retrieval of calibration records Inefficiencies associated with the use of analysts' time searching paper records to confirm that calibration has been completed prior to running any tests Risks associated with analysts inadvertently running tests on a balance that has not been calibrated, or in a worst-case scenario on a balance that has failed a calibration Risks associated with being unable to provide documented proof of a successful calibration during an audit Nexxis ELN (Electronic Laboratory Notebook) integrated with Nexxis CAL (Instrument Calibration Manager) provides an electronic solution that eliminates paper management costs, ensures that only calibrated instruments are used for testing and provides documentation of the entire calibration process for audit purposes. The Solution In our solution, Nexxis CAL is used to record calibration results. Nexxis ELN is used to control the calibration process and to ensure that balances that have not been successfully calibrated as scheduled are not used for testing. Calibration worksheets are setup in Nexxis ELN to control the daily calibration process. In many cases this may be a simple High/Low check. Nexxis ELN can automatically record the nominal mass and serial number of the weights that are used, tare the balance, collect the actual calibration weights directly from the balance and determine a Pass/Fail based on the acceptability criteria for that calibration. The calibration results are then automatically transferred to Nexxis CAL and stored in the Nexxis CAL database, providing a historical record of calibration results for that balance. At the same time Nexxis ELN automatically creates a PDF record of the calibration worksheet, showing the calibration results and including any audit trail entries associated with the process and any reviewer approvals and comments. This electronic record, which replaces a paper notebook entry, can Page | 73 be used as documentation of a specific calibration on a specific instrument on a specific date, in the event of an audit. Routine weighing applications that are also setup as worksheets in Nexxis ELN can then check the Nexxis CAL database to ensure that the balance has passed its daily calibration before allowing the analyst to proceed with the test. If calibration was not done that day or if the balance failed the calibration, then the analyst can be prevented from using the balance until appropriate action has been taken. The Result Integrating Nexxis ELN with Nexxis CAL creates a unique level of control and automation for instrument calibrations, right down to the point of analysis. Eliminates high costs associated with storage and retrieval of paper-based records Reduces compliance risk by automatically ensuring that only successfully calibrated instruments are used for testing Increases laboratory efficiency by eliminating the need for analysts to search through calibration records prior to testing Provides electronic documentation of calibrations for audit purposes Page | 74 Error Free Preparation of Reagents Overview This article describes how Nexxis iLAB provides an integrated on-line electronic system for automating and documenting the preparation of a reagent. A Nexxis ELN worksheet is used to guide the analyst through the process of creating a reagent. As we look at each of the steps in this process we see that a single action by the analyst sets off a series of actions and interactions between Nexxis ELN, Nexxis CIM (chemical inventory) and Nexxis CAL (instrument calibration) as they work together to ensure that: Eliminate Time Spent on The formulation process is being followed correctly Manual Documentation A key benefit of this system is the That the balance used has been properly calibrated elimination of the time that analysts The right materials and quantities of materials are spend on manually documenting the always being used preparation process. That the inventory is always accurately updated in A customer has reported to us that real time as materials are used and the new even a simple 5 minute preparation procedure requires 15 - 20 minutes reagent is created of paper documentation. At the end of the process a PDF of the completed worksheet is automatically saved. Eliminating that manual documentation reduces the time The completed worksheet can be reviewed and spent on preparation by up to 80%. approved on-line Approved worksheets can be viewed at any time using Nexxis ELN Worksheets are also stored in Nexxis SDMS where extensive search and retrieval capabilities provide instant access if they are needed for problem resolution or as part of an audit. As part of the Nexxis iLAB application suite, Nexxis ELN, Nexxis CIM and Nexxis CAL are developed with this close integration in mind, easily sharing and updating information with each other in order to eliminate manual tasks for the analyst and to eliminate the possibility of error in the process. Page | 75 The Reagent Preparation Worksheet Labtronics' exclusive ReDI technology provides a drag and drop interface for quickly converting your current paper-based worksheets into highly automated electronic worksheets, without any custom coding. The example worksheet used in this article represents a typical workflow for preparing a reagent by adding a solid chemical to a known volume of liquid chemical to create a desired concentration and volume of reagent. Similar worksheets could be used to creating other types of preparations such as standards, and serial dilutions. Page | 76 Figure 1: Nexxis ELN worksheet representing a typical workflow for preparing a reagent. Table Showing Workflow The following table shows the interaction between the analyst and the Nexxis applications at each step of the reagent preparation process. It is important to note that most of the actions are taking place automatically and totally hidden from the analyst unless there is a problem. The analyst is only involved with the worksheet itself and does not work directly with Nexxis CIM, or Nexxis CAL. Analyst Nexxis ELN Nexxis CIM Step 1 Selects the required concentration for Records the value the reagent from a drop down list Step 2 Selects the size of the volumetric flask Records the value that they will use from a drop down list Automatically calculates the required weight of solid chemical. Step 3 Scans the bar code label on the Sends the container Confirms that it is the container of the analyte and clicks on number and the right chemical, that it Check Container required weight to has not passed its Nexxis CIM expiry date and that there is enough chemical in the container Designates the container as either "pass" or "fail" and sends that status to Nexxis ELN If "fail" then the analyst is prompted to scan another container and the confirmation checks are repeated If "pass" then the expiration date and the required weight for the chemical are added to the worksheet in non- Page | 77 editable fields Step 4 Selects a balance from a drop down Connects with Nexxis list and clicks on Select CAL to determine the calibration status of the balance If "fail" the analyst is prompted to select another balance If "pass" the calibration date is recorded in the worksheet Step 5 Puts the required amount of analyte, Collects the weight as indicated in the "Please weigh out" directly from the field, on the balance and clicks Get balance and records it Weight in the "Actual weight" field Checks that the actual weight is within limits of the target weight using error limits that have been assigned to this field during setup of the worksheet If "out of limits", displays an error message, highlights the field in red and requires that the analyst reweigh the sample If "in limits" sends the Automatically subtracts actual weight value to the actual weight of the Nexxis CIM solid chemical from inventory Step 6 Scans the bar code label on the Sends the container Determines the status container of diluents and clicks on number and the size of of the container and Check Container the volumetric flask to contents as in Step 3 Nexxis CIM The expiration date of the chemical is recorded on the worksheet in a non- editable field Page | 78 Step 7 Enters the lot # for the new reagent Records the lot # and into the worksheet and clicks Prep sends it to Nexxis CIM Complete confirming that the reagent has been made Subtracts the amount of diluent used from inventory Creates a new container for the reagent Adds container information including reagent name, quantity, actual concentration, lot # and a calculated expiry date Prints a bar coded label for the new container Adds the expiry date and the container number of the new reagent to the Nexxis ELN worksheet Calculates and displays the actual concentration Step 8 Clicks on the Electronic Signature icon Enters the analyst's on the worksheet name on the signature line with a date and time stamp Saves the completed worksheet as a PDF Electronic Retrieval of Worksheets ELN data is stored in two ways. Firstly, each value on a worksheet is stored in a structured database. Secondly, PDF copies of every worksheet are stored in Nexxis SDMS, a Scientific Data Management System. The laboratory now has a significant advantage if the worksheet is needed as part of a problem investigation or an audit process. For example, if the laboratory receives a recall notice from their supplier regarding a particular container of the chemical that is used in preparing reagents it can quickly find all of the reagents that are affected using the structured database. Page | 79 A search can be made in the SDMS to find every reagent preparation worksheet that used the chemical in question. You would also be able to mine the data using the extensive reporting tool in Nexxis ELN. If the laboratory includes a Reagent container number on all ELN worksheets that use the reagent for testing, they can also get a list of all samples that were tested with a faulty reagent. In minutes they can have all of the information they need to accurately identify the scope of the problem and plan a corrective action. This is a huge improvement over a paper-based system where finding a document may involve having to dig through stacks of old laboratory notebooks or having to find worksheets that have been stored at an off-site storage location. Figure 2: Nexxis SDMS can quickly and accurately find all of the Nexxis ELN worksheets that are needed as part of a problem investigation or an audit process. Page | 80 Conclusion Using Nexxis iLAB to create an on-line electronic system for automating and documenting the preparation of a reagent delivers significant benefits to the lab: Automated checks ensure that the right chemicals are always used and that they have not passed their expiry date Weighing of the solid chemical is always accurate o The calibration status of the balance is automatically checked before use o Weights are collected directly from the balance eliminating the possibility of manual recording errors o Reagents can't be created with the wrong amount of chemical Inventory levels are kept accurate, in real-time, as chemicals and regents are used or created. All metadata (chemicals used, expiry dates, balance used, reagent container number, etc) is automatically recorded in the worksheet ensuring that records are complete and accurate. Metadata recorded in the worksheets can be used as search criteria to quickly and accurately identify Reagents and samples that may be affected by a suspect chemical. The high level of real-time interaction between Nexxis ELN, Nexxis CIM and Nexxis CAL as demonstrated by this formulations process can be applied to virtually any routine procedure in the laboratory. Page | 81 Case Study: Rapid Deployment of an Integrated ELN/SDMS/LIMS Solution Case No: CS-124-ELN-WD Systems Integrated: ELN, SDMS, LIMS, Instruments Industry: Analytical testing in the power industry Implementation Time: 1 month Overview An ongoing problem in the laboratory informatics industry is the time that it takes to deploy a working solution. Informatics projects that last for months and even years are the norm, rather than the exception. Being able to shorten deployment time reduces the overall cost of the project and allows organizations to gain the benefits of the solution sooner. This case study outlines how, in just one month, Labtronics' Electronic Laboratory Notebook (ELN) and Scientific Data Management System (SDMS) were deployed and fully integrated with our customer's existing in-house LIMS. The Customer: This project was deployed for an organization that owns multiple analytical laboratories providing analytical testing and engineering services to the power industry. Due to rapid growth, they were looking for a solution that would improve their data management efficiency as they open additional laboratories. Project Milestones: June – Develop a Laboratory Automation Plan before purchase of Nexxis ELN Oct 25 – Site visit to customer to gather requirements Nov 1 – Start work implementing system Dec 6 – Install completed system on site – 85% complete Summary: 1 month to configure the system Page | 82 Scope of Project: The project consisted of a Nexxis ELN implementation, including integration with Nexxis SDMS, LimsLink, and Nexxis Report Manager 22 Nexxis ELN worksheets 13 LimsLink integration methods 5 Nexxis ELN concurrent user licenses Project Highlights: Instruments and Nexxis ELN were connected to their in-house LIMS o LimsLink was used to integrate automated instruments and connect them to the LIMS. o 2/3 of the instruments are either manual or have no electronic data output. This set of instruments was automated using Nexxis ELN worksheets for data collection. Once the worksheet was complete, results were sent to LIMS. LIMS worklists now automatically create Nexxis ELN worksheets and populate them with LIMS information so that the worksheets are ready for use by the analysts. The customer had existing paper-based forms. These were converted to Nexxis ELN worksheets using ReDI™ technology. The customer had an existing Excel spreadsheet that performed extensive PCB calculations. Nexxis ELN's Microsoft Office integration capabilities allowed Nexxis ELN to use this Excel spreadsheet, reducing development time. Their LIMS was not able to have direct connectivity with other programs. Labtronics developed a Link Server that allows any lab system to communicate with the LIMS, overcoming its limitations. Nexxis SDMS was implemented to store raw data which the LIMS was not able to store. Nexxis SDMS is also used to store the ELN worksheets. Success Factors: 1) Development of the Laboratory Automation Plan provided the customer with a clear understanding of their options for automating the lab. The plan provided a blue print for moving forward and showed them a solution. Page | 83 2) Throughout the development phase of the project, the customer had on-line access to their system. This meant that they could review and comment on developments on a daily basis. The customer and Labtronics knew day-to-day that the work was being done correctly. 3) Connectivity to the LIMS was not supported by the LIMS and development of this functionality would have taken a long time. Using the extensive experience of Labtronics, we were able to develop an alternate system to overcome this limitation. Conclusion: This project is not large, but it was technically challenging and it required the integration of a number of instruments. 85% of the project was delivered on time, after only 1 month. The remaining 15% of the project is on hold until the customer makes some final decisions. It can be delivered within a couple of weeks. Labtronics strives to deploy complete systems rapidly. The success of this project is due to several factors: A process that is very streamlined and efficient Highly technical people that are very familiar with our products and have experience automating labs ReDI™ technology. Nexxis iLAB makes use of a unique technology that allows Labtronics and our customers to quickly configure automation requirements Labtronics is committed to deploy lab automation projects more quickly than is common in this industry. We have the products and the know how to make it happen. Page | 84 Chapter 5: Instrument Integration Page | 85 Application Note: Chromatography Workflow with Nexxis iLAB Introduction This Application Note shows how Nexxis iLAB can be used to manage the complete chromatography workflow from sample prep to final approved results. This application makes extensive use of ELN to capture chromatography metadata. It will show how an integrated laboratory system improves the efficiency of the analyst and centralizes the data for the complete chromatography process. Chromatography Workflow in a Non-integrated Lab In a non-integrated lab, chromatography work flow - from sample login through to reporting of results - consists of a series of separate events that are either manual, paper based processes or take place in applications that are not connected to each other. For example: Sample information needs to be manually transcribed onto sample preparation worksheets Analysts need to manually check that instruments are calibrated and correct materials are used Analysts need to manually perform calculations, etc Results from the CDS need to be manually entered into LIMS All of the information that is needed to thoroughly review the chromatography results is saved across multiple systems (some of which may be paper based) This creates additional work for the analysts and reviewers, provides little control over processes and creates opportunities for error. Page | 86 Chromatography Workflow with Nexxis iLAB A Nexxis ELN sample prep worksheet (Figure 1) is the focal point for the chromatography workflow with Nexxis iLAB. The worksheet is integrated with the other Nexxis iLAB applications to: Automatically access information from other applications as it is needed Use information from other applications to control the sample prep process in Nexxis ELN Automatically report chromatography results to Nexxis ST Automatically store all raw data and documents in Nexxis SDMS for easy retrieval With Nexxis iLAB, chromatography workflow becomes a series of automated, controlled and connected activities that reduce the workload for the analyst and provide a single source for reviewing all of the chromatography data. The Nexxis ELN Worksheet - Integration, Automation & Control If we take a closer look at the sample preparation worksheet we can see four examples of the integration, automation and control that Nexxis iLAB provides. Figure 1: The Nexxis ELN worksheet integrates with CDS and other Nexxis iLAB modules to create a single source for all chromatography data. Page | 87 1. Initiation of the Worksheet (Nexxis ST & ELN) a. When samples are logged into Nexxis iLAB and a chromatography test is assigned, a Nexxis ELN sample prep worksheet is automatically created and added to the system b. Sample information from Nexxis iLAB is automatically added to the ELN worksheet c. An email is automatically sent to the analyst letting them know that work is pending. 2. Verification of the Standard (Nexxis ELN, CIM & SDMS) a. When the analyst scans the bar code on the standard container, the container ID is automatically added directly to the Nexxis ELN worksheet. b. Pressing the "CIM Check" button on the worksheet automatically checks with the chemical inventory system (Nexxis CIM) to makes sure that they using the right material and that it has not expired. c. If everything passes, metadata for the standard is added to the worksheet. If not, the analyst is prompted to select another container. d. Because the Nexxis ELN worksheet that was used to prepare this standard is being stored electronically in Nexxis SDMS, a link to that worksheet can also be added. A reviewer can simply click on this link to go directly to the ELN worksheet that was used to prepare the standards. 3. Addition of CDS Results (CDS, Nexxis ELN & SDMS) a. Chromatography data is automatically added to the Nexxis ELN worksheet. Values such as "instrument name" and "column used" come from the CDS report. Information about the calibration comes from Nexxis CAL, the instrument calibration module. b. The calibration values confirm to the user/reviewer that the instrument was in a calibrated state at the time of analysis. c. There is also a link to the raw data file from the CDS which has been automatically stored in Nexxis SDMS. A reviewer can click on that link to open the report and see the raw data. 4. Calculations & Reporting (Nexxis ELN & ST) a. The Nexxis ELN worksheet automatically applies a dilution factor and calculates the actual concentration for each component b. The worksheet also calculates the total Acid value c. Final concentrations are automatically reported into Nexxis ST. Conclusion Using Nexxis iLAB to manage chromatography workflow delivers significant benefits to the laboratory: Integration results in automation, which in turn means less work for the analyst. Page | 88 o ELN worksheets are created automatically o Sample information is transferred to ELN worksheets o Training records are checked o Instrument data is saved to the SDMS o Instrument calibrations are checked o Results are calculated o Results are sent to LIMS o Chemicals are validated Integration reduces the number of mistakes o Each time a step is automated the analyst does not have to remember to perform it, and they can't make a mistake. The Nexxis ELN worksheet is a single source for all chromatography data o Approvals can now be completed without checking a variety of sources for information. o Investigations take minutes, instead of hours, since all of the relative information is in one place. o Auditors can have all of their questions answered by looking at one ELN worksheet Nexxis iLAB can provide this level of integrated chromatography workflow with any LIMS, CDS or SDMS. If your laboratory does not already have the LIMS or SDMS, we can also supply these components. Page | 89 Choosing the Right Balance Automation Solution Overview At one level, a balance is a pretty easy instrument to interface and there are certainly a lot of simple applications that will collect a weight from a balance and transfer it somewhere. However, with the amount of laboratory work that is dependent on balance data, an interface that does more than simply transfer data has the potential to deliver significant improvements in laboratory efficiency and quality of results. To fully realize that potential, you will want to select a balance automation solution that moves beyond data collection and introduces a high level of automation and control over all aspects of your weighing procedures. In this article we will look at five areas to consider when choosing a balance automation solution that will have the most impact on your laboratory operations. Communication - How does the solution interact with the balance, other applications and with the analyst? Context – Can the solution add additional information to the raw balance data to make it useful for other applications? Calculations –What options are there for automating calculations and confirming results? Control – How far can the solution go in controlling the weighing procedure to make sure that the weighing SOP is being followed? Confidence – Is there a security component in place that will give you full confidence that the data generated by the balance is always the data that is being reported? Communication There are a number of different levels of communication to consider when selecting a balance automation solution. At the most basic level it should be able to collect data from the balance and pass it to another application. An interface that simply retrieves data from the balance is referred to as uni-directional. Page | 90 If the solution is able to send information to the balance as well as collect data, it is described as bi- directional. A bi-directional interface is typically used to send control commands to the balance, adding an additional level of automation. For example, instead of having the analyst press the print key on the balance, a bi-directional interface can send the balance a command to wait until the balances stabilizes and then send a weight. Other control commands that a bi-directional interface might use would be to open or close balance doors or to automatically tare the balance before weighing a sample. A bi-directional solution may also communicate with external applications such as databases and LIMS. It could collect sample data from a LIMS, check a calibration database to see if the balance has been calibrated and even automatically update a chemical inventory database when stock items are weighed out. A bi-directional solution with this level of communication can significantly reduce an analyst's workload and help to automate other laboratory procedures. A good balance automation solution should also interact with the analyst, allowing them to add comments or observations to the data or even guiding the analyst through the weighing process. Context Balance data is very simple, basic and completely lacking in context. 10mg - what does that mean? What sample is the weight for? Who weighed the sample? When? Why? How? By itself, a weight from a balance is not a very meaningful piece of information. A balance solution that can communicate with other applications can provide context by automatically gathering the information that is needed to build an "information wrapper" around the basic balance data: Sample information from the LIMS Comments and observations from analysts A date and time stamp A user ID A test ID All of this additional information can be automatically collected by the balance automation solution and added to the raw balance data, giving it the context that it needs to be useful to other applications. Page | 91 Calculations In almost every case there is some type of calculation that needs to be carried out with the balance data. There are a number of weight-based tests that require taking multiple weights from a sample over a period of time (e.g. loss on drying) or tests that perform calculations using a number of weights collected from different samples (e.g. content uniformity). For some tests, results can be calculated as the data comes out of the balance and immediately displayed for the analyst. For other tests, data will need to be stored in either a spreadsheet or a database and then combined with other data to calculate a final result. Ideally the balance automation solution will be able to store and recall data without having to use another application. Another feature to look for in a balance automation solution is the ability to check final calculated results against the specifications for that test to determine if the result is within expected limits. Being able to highlight or flag out of specification results gives analysts the immediate feedback they need to take appropriate action. Control All laboratories have procedures that need to be followed every time a sample is weighed. For laboratories working within a regulated environment, it is imperative that these procedures are followed to the letter every single time. A balance automation solution can control a weighing process by: Only letting an analyst use a balance that meets the SOP requirements for the analysis Checking a calibration database to make sure that the balance has been properly calibrated before weighing any samples Confirming that the analyst is qualified to run the test Guiding the analyst through each step of the weighing process Using passwords, electronic signatures and audit trails to document the weighing process A sophisticated balance automation solution can ensure that every aspect of an SOP is always adhered to. Confidence That brings us to our final area for evaluation. Is there a security component in place that will give you full confidence that the data generated by the balance is always the data that is being reported? Page | 92 Does the solution use a User ID and password to control access? Should some users be able to edit data? If so, is there an audit trail that records the original value along with the changed value and the reason for the change? Can an electronic signature confirm the identity of the user at key points during the process? Whether or not your laboratory operates in a regulated environment, you will want to be confident that your balance automation solution provides the same high level of data security and accountability that you expect from your other laboratory applications. Choosing the Right Solution For some laboratories a balance interface will always be simply a way to transfer a number from one place to another. Others will recognize the important role that balances play in the laboratory and see that a true balance automation solution will deliver real value to the lab every day. Those people will take the time to fully consider their options and seek out a solution that delivers on Communication, Context, Calculations, Control and Confidence. Choosing the right balance automation solution can be a significant step towards creating a highly automated and highly integrated laboratory environment. Solutions from Labtronics Labtronics offers two balance automation solutions for you to consider when choosing the right balance automation solution: LimsLink is a fully configurable solution for creating bi-directional instrument interfaces that interact with instruments, other applications and analysts providing automated data collection, calculations and reporting. Nexxis ELN is a worksheet based Electronic Laboratory Notebook that automates data collection and calculations while providing a unique level of control over weighing processes and interaction with other applications to ensure that every aspect of an SOP is followed, every time. LimsLink Nexxis ELN User Interface Spreadsheet style interface User interface created from existing worksheets or SOP documents Create custom display screens Accept manual input (comments, observations) from the analyst Control and guide the analyst through the weighing analysis Instrument Integration Page | 93 Uni-directional interfaces Bi-directional interfaces Interfaces are configured using pick lists, selection buttons and graphic tools Includes instrument library with setup information for over 400 instruments Simple parser processes basic data Drag and drop data parser processes complex data files Data Management Data is stored in an integrated spreadsheet Data is stored in a searchable database Perform real time calculations Real time limit checking and highlighting of out-of –specification results Create PDF of results for on-line review and approval Use balance data to automatically update inventory applications Reporting Create customized reports Fileless or file-based reporting to LIMS and other database applications Report to target applications via API Integration with other applications Query LIMS for sample information Send results to LIMS ODBC compatible for database queries and reporting Use information from other applications to control processes Security User Logon controls access to the application Audit Trail documents activity within the application Electronic Signature challenges can be added at key points Data files, methods and processes can be archived to a secure server Optional Validation Toolkit provides assistance with IQ and OQ of installations and processes System Architecture Scalable n-tier architecture Smart client collects data performs calculations, processing and reporting Web client eliminates the need for installing software on the client side All data is collected directly to a central server Page | 94 Chapter 6: Managing and Planning ELN Projects Page | 95 Case Study: Rapid Deployment of an iLAB (Integrated Laboratory) Case No: CS-123-iLAB-SP Systems Integrated: ELN, Sample Tracker, Chemical Inventory and Instruments Industry: Nutraceuticals Implementation Time: 5 weeks Overview An ongoing problem in the laboratory informatics industry is the time that it takes to deploy a working solution. Informatics projects that last for months and even years are the norm, rather than the exception. Being able to shorten deployment time reduces the overall cost of the project and allows organizations to gain the benefits of the solution sooner. This case study outlines how, in just 5 weeks, Labtronics' Nexxis iLAB was implemented and configured to provide an automated and integrated laboratory management system. The Customer: This project was deployed for an organization that produces high-quality nutritional supplements in accordance with the Food and Drug Administration's good manufacturing practice requirements. They were in the process of deciding whether to continue development of their in-house LIMS or look for a commercial solution. Nexxis iLAB was selected as a solution that would automate their data collection and data management processes and fully integrate with existing systems and instrumentation. Project Milestones: Dec 1 – 3 day fact gathering meeting at Labtronics Dec 21 – Project start date, start configuration work Dec 23 – First review date – review completed sample log-in forms Feb 3 – 1 week onsite visit to install completed system, integrate and test instruments, train users. Summary: 5 weeks to configure the complete system Page | 96 Scope of Project: Nexxis iLAB implementation, including Nexxis ST (Sample Tracker), Nexxis ELN, Nexxis CIM (Chemical Inventory Manager), LimsLink, Nexxis Report Manager, Nexxis Database Viewer and Nexxis Contact Manager 120 tests 1800 sample templates 4 unique log-in forms 12 ELN worksheets 10 instruments integrated 150 products were defined 5 Reports 13 concurrent user licenses Project Highlights Nexxis ELN worksheets integrated manual instruments such as balances Samples entered into Nexxis ST automatically initiated all required Nexxis ELN worksheets Nexxis ELN was integrated with Nexxis CIM to retrieve purity values for reagents. These values were subsequently used in automated calculations. LimsLink was used to connect automated instruments directly to Nexxis ST to report results. Selected data was also populated into Nexxis ELN worksheets. Nexxis Contact Manager was used to store product information including test limits for each product. This data was then dynamically retrieved by Nexxis ELN worksheets to verify that test results were within scope. Nexxis Report Manager was used to retrieve a worklist of samples from Nexxis ST. The report included a bar code containing sample and test information. The analyst used this report to automatically transfer the sample information into the analytical instrument software by scanning the bar codes. This eliminating a lot of manual data entry. The Nexxis Database Viewer was set up to report on 'retained samples'. This is now a 2 second process compared to an hour process previously. Page | 97 Success Factors: 1) The customer was well prepared for the initial fact gathering meeting. By holding the meeting at Labtronics, there were fewer interruptions and the whole team could focus on the job at hand. 2) Throughout the development phase of the project, the customer had on-line access to their system. This meant that they could review and comment on developments on a daily basis. The customer and Labtronics knew day to day that the work was being done correctly. 3) The deployment required a number of complex integrations that for most systems would be difficult to accomplish. With Nexxis iLAB, creating integrations between Nexxis ELN, Nexxis ST, and Nexxis CIM, takes only seconds. Integration of instruments is almost as fast. Conclusion: This project is on a scale similar to a mid-sized LIMS project, but has a greater requirement for integration than most LIMS projects. The complete project was delivered on time, after only 5 weeks of work. Only minor adjustments needed to be made after installation as the customer became more familiar with the system. Labtronics strives to deploy complete systems rapidly. The success of this project is due to several factors: A process that is very streamlined and efficient Highly technical people that are very familiar with both our products and have experience automating labs ReDI™ technology - Nexxis iLAB makes use of a unique technology that allows labtronics and our customers to quickly configure automation requirements Labtronics is committed to deploy lab automation projects more quickly than is common in this industry. We have the products and the know how to make it happen. Page | 98 Planning a Successful ELN Project Overview This paper provides strategies, tips and recommendations to help plan and manage deployment of an ELN, while maximizing the benefits your organization will receive with the new system in place. During the course of the paper we will be looking at: Step 1 – Assembling the team Make sure that the key stakeholders in the project are involved and understanding what part they will play in the process. Step 2 – Project goals Establish the key accomplishment or accomplishments that the organization wants to achieve through this project. Step 3 – Project scope Identify which processes are prime candidates for conversion from paper to electronic format. 4 "Keys to Success" Four key components that make an ELN project successful. Step 1 – Assemble the team An ELN project will have an impact throughout the organization. In order to ensure that the impact is positive for everyone, it is essential to include representatives from each group within the organization, right from the very earliest stages of the project. We have identified 5 key groups that need to be involved in the planning and execution of a successful ELN project. Each group will bring their perspective to the table and contribute to the eventual success of the project. Figure 1: Each group contributes to the overall success of the ELN project Page | 99 Laboratory Management Laboratory management will be responsible for identifying the corporate Goals and Objectives of the project. They can identify the business problem or problems that the project will be expected to solve and what the current cost is to the organization. They can also set corporate expectations as to how success will be measured – what will be the ideal situation at the end of the day and how the laboratory will quantify improvement. For example, if a particular process in the laboratory is taking 20 hours a week because of manual activity then management may determine that the measure of success would be to reduce that process to 5 hours per week. Being able to quantify the improvements that the project will deliver will allow laboratory management to determine a financial budget as well as the time and resources that can be allocated to the project. Development of the project specifications and implementation plan will take place with the input from all stakeholders but final approval will usually lie with laboratory management who will want to see that the plan meets the project goals and objectives and provides a good balance between the needs and wants of the laboratory. Laboratory Personnel Laboratory personnel are vital to the success of the team and the project, providing a "reality check" on what will be truly practical and beneficial to the day to day operation of the lab. They play a key role by identifying where bottlenecks exist right now in the laboratory and evaluating what features, functions and capabilities will deliver the best value in terms of eliminating those bottlenecks and improving laboratory efficiency. During the implementation planning process, laboratory personnel can provide the best insight into how to minimize disruption of the daily laboratory workload as well as identifying the best people from the laboratory to participate in implementation and training on the new system. Keeping laboratory personnel involved in the planning process, from day one, will help to create a high level of user acceptance for the ELN project. IT Department During the initial planning stage the IT group will be looked at to ensure that the IT requirements of the proposed solution are compatible with the existing IT infrastructure of the organization and that they also support future IT planning. They will be able to identify if the solution supports existing and planned standards for Operating Systems, database platforms and network infrastructure. Page | 100 IT will also be required to evaluate the hardware requirements of the solution and report on opportunities to incorporate existing hardware into the solution as well as on the need to provide additional hardware. It will be their responsibility to establish technical bench marks for the Nexxis Validation Toolkit system and to ensure that the necessary infrastructure for deployment The Nexxis Validation Toolkit includes is in place and operational at the start of the project. detailed IQ and OQ documents that significantly reduce the amount of A key function for IT during the implementation stage is to co-ordinate time that validation groups spend internal technical resources with the technical resources from the compiling the information that they vendor side to avoid time loss and delays by ensuring that the right require to initiate and execute a people are available at the right time. thorough IQ/OQ validation of Nexxis Validation Group ELN. For laboratories that work within a regulated environment the The IQ documents provide a detailed validation group will need to be involved in the planning process to listing of hardware requirements, identify compliance and security requirements and prepare a validation step-by-step descriptions of software plan. installation procedures and a listing As part of that process they will want to assess the validation tools and of all required files showing the expected filename, size, and version services that are available from the ELN vendor. number. Within many organizations, the workload for the validation group is extremely heavy and validation can become a real obstacle to getting OQ documents include detailed testing procedures that guide the the solution into production. Any assistance the validation group can receive from the vendor will help to keep the project on track. user through verification of User Identification, Application Security, The vendor may be able to provide IQ and OQ documents that can Method Execution, etc. guide and direct the validation group as they execute a thorough IQ/OQ validation. Having these documents available can provide a real head start on the Validation services supplied by the vendor can range from consultation validation process. and assessment of validation requirements to actual execution of steps in the validation process. The ELN Vendor The fifth part of the project team comes from outside the organization. In most cases the laboratory will already have established a good working relationship with the ELN vendor during the course of selecting the solution. Now is the time to really leverage the skills and expertise of the vendor to assist in the planning and execution of the project. At the planning level, the vendor will obviously be contributing with detailed information about the core capabilities of the application as well as providing insight that they have gained from previous implementations of the solution. Page | 101 For laboratories that are embarking on their first ELN project, having access to this combination of expert input and outsider perspective can really assist the planning team in developing goals, setting expectations and defining measures of success. During the implementation stage of the project, the vendor will be called on to provide resources that provide specific levels of expertise and that supplement the laboratory project team. These resources can be applied at every stage of the process from development of specifications right through implementation to training and support. A key success factor in the planning process is to identify and co-ordinate resource requirements and availability between the laboratory and the vendor. Step 2 – Set Project Goals With the team assembled it is now time to clearly define the goals and objectives of the project. What do we want to accomplish? This step will start with a corporate level view of the scope and intent of the project. What is the problem that we want to solve and how will this specific project help us to solve it? If the laboratory is trying to reduce the cost of operations, then the project may be intended to assess the ROI that ELN will deliver by improving operational efficiency. There may be a specific issue that the laboratory needs to address and the project is focused on resolving that issue. Or the laboratory may have already determined the benefits of going paperless and is fully committed to rolling out the ELN throughout the organization. A clearly stated high level understanding of what the project will accomplish for the organization is fundamental to communicating the value of the project throughout the organization. Having a clearly stated vision of where the project is going and what it will deliver, will simplify decision making through every stage of the project. When every decision is measured against the goal of the project, then the right choices will always stand out. How will we measure success? With a clear understanding of what the project should accomplish the next step is to clearly define how to measure if the project is successful in achieving its goal. Regardless of what the goal is, measuring success starts with an understanding of the current situation and then applying a measurable improvement that the project will deliver. For example if the goal of the ELN project is to reduce operation costs, then the lab will need to document the current status in all the areas that the ELN can impact. How much time is being spent on Page | 102 manual data recording and calculations, how much time is spent on review, how much time is spent transferring results and information to other systems, etc? With that information in hand, the laboratory can then set realistic and measurable criteria for success – for example, to eliminate the 3 Free ROI Calculator for ELN hours per day that are spent on manual data recording and calculations and to reduce the time spent on review by 50%. Determine the real dollars and cents value of an ELN project at your lab. Having clear quantifiable measures of success will not only serve to justify the current project but will also lay the groundwork for future Click here to download. projects that deliver continuous improvement in the laboratory. What will we do next? Now that we know where we are going and we know how we are going to measure our success at getting there – we need to plan for how the success of the ELN project will continue to move the laboratory forward. This can be considered at the project level. For example, if the project demonstrates a significant ROI for a particular analysis then the lab will want to expand the ELN solution to include all analyses in that group. Or if the lab shows success from a project that quickly transfers paper processes to electronic documents, then they may decide to initiate a project to add additional levels of automation to those documents. The success of the ELN project can also impact the future direction of the organization at a corporate level. A project that reduces operating costs will increase profitability which may in turn provide funding for additional equipment and expansion. A project that increases laboratory sample handling capacity can open opportunities to bring new clients on board while maintaining high service levels. Incorporating "next step" planning into an ELN project will prepare the laboratory to leverage the success of the project and the business benefits it delivers. Step 3 – Set the project scope With a clearly defined goal we are ready to define the scope of the project, setting priorities for the processes or worksheets that are going to be included in the conversion process and choosing the right level of automation for each form. Again this will need to be closely aligned with the goals of the project – worksheets and automation levels should be identified that will deliver the most benefit, as defined by the project goals, in the shortest time. Demonstrating initial success with high priority worksheets will provide ongoing confidence and justification for continuing and expanding the project. Page | 103 Determine which processes should be a priority for conversion The decision as to which processes are automated first should be based on the success criteria that your team has defined. For example, if the goal of the project is to determine the Return on Investment that an ELN for Routine Analyses will deliver, then you will want to focus on a limited number of processes that represent a range of analyses, from simple to complex. Understanding how the ELN will function and the ROI that it delivers over this range will help the laboratory to extrapolate and evaluate the benefits of implementing the ELN for all of their processes. If the goal of the project is more focused on a specific problem or problem area in the lab, then all of the processes that impact that area will need to be considered. For example, if the lab is hoping to improve on traceability of solutions that are prepared in house and then used for testing - then they can focus on worksheets that follow the life cycle of a particular solution from preparation through to the analyses where it is used. A full understanding of the complete work flow for one solution will create a model that can then be rolled out for all of the in- house prepared solutions. Another project goal might be to simply "go paperless" to deliver the benefits of eliminating the costs of paper management. In that scenario the lab can focus on quickly converting all of their documents to electronic format with minimal automation within the worksheets. Choose the right level of automation for each form Once the forms have been identified for the project, the team can then assess the level of automation that is right for each form. Automation choices can range from no automation (simply making paper electronic) right through to highly automated worksheets that control work flow and integrate with other informatics applications. The degree to which you automate a particular form should take into consideration the time and resources available for the project and the goals for the project as well as the benefits that automation will deliver in each case. For some procedures, for example chromatography sample preparation, a high degree of automation and data validation is desirable to ensure accurate completion of the form and adherence to the SOP. For others, a less controlled approach allows the analyst more flexibility to make decisions on the fly. It is important to remember that you don't need to be tied into a specific level of automation for all analyses or worksheets – you can mix and match making sure that each one gets just the right fit. Page | 104 Step 4 – Build the implementation plan With the team in place, the goals and objectives clearly stated and the project scope and priorities well defined, the implementation plan may not quite build itself but there should be enough information and direction to put together a plan that will result in a successful project. Resources and responsibilities can be identified and allocated by all the groups on the team Timelines for IT deliverables will need to be coordinated with the schedule of the implementation team Milestones and success points need to be clearly laid out and defined A training plan will need to be developed that accounts for technical training at the IT level as well as end user training. Even with all of the planning and preparation that has taken place there will be changes along the way, so an essential component of the implementation plan will be a clear process for change management. As changes are proposed, the benefits of the change will need to be measured against the goals of the project and the impact of the change on project costs, resources and delivery. Maintaining control over change management is essential to keeping the project focused, on time and on budget. 4 Keys to Success Proper planning of an ELN project gives the organization an opportunity to realize the full benefits of going paperless, providing a healthy return on their investment for years to come. The guidelines that we have provided in this White Paper for creating an ELN implementation plan, can be best summarized by emphasizing these four key components in a successful ELN project. The Team Assemble a first rate team that represents all stakeholders and includes all of the areas of the organization that will interact with the ELN. The Project Goals Have that team clearly and concisely develop project goals that address the issue(s) that the organization wants to resolve. These goals should include clear criteria for measuring success and incorporate "next step" planning to keep the organization on the path of continuous improvement. Decision Making Throughout the life time of the project, there will continually be decisions to make regarding requirements, resources, schedules and more. If the project goals are used as the criteria that drive every decision, the project has a much higher chance of success. Page | 105 Managing Change It is inevitable that there will be changes in plans throughout the life cycle of the project. Aligning changes with the project goals and documenting both the changes and the expected impact of the change will help to keep the project on track and will provide valuable input to a post project evaluation. Page | 106 Project Management – On Time and On Target The Professional Services Group at Labtronics recognizes the importance of the implementation process in delivering optimal value to our customers, so they have developed a team-based, step-by- step process that is focused on ensuring that each project stays on time and on target. Our Project Teams The personnel in the Professional Services group are organized into Project Teams consisting of a Project Manager, one or more Application Specialists and one or more Application Developers. Depending on the length and complexity of the project, the actual makeup of the team will be scaled to match the project requirements. On very short projects, one person may manage all of the roles on the team, taking full responsibility for all of the team functions. On larger projects the team may include several people in the Application Specialist and Application Developer roles. The Project Manager is the person who is ultimately accountable for the performance of the team and the successful delivery of the project. They are the focal point of the project at Labtronics, working directly with the project sponsor on the client side to ensure that the goals and deliverables of the project are understood, that the right resources are available at the right time, monitoring the project progress and taking action if it appears that a project is not staying on track. The Application Specialist is the team member that provides the most direct interaction with the end users. Their unique mix of IT, application and laboratory skills helps them to analyze and understand laboratory requirements, communicate those requirements to the project team and to provide hands on implementation and training services as required by the project. At Labtronics our Application Specialists have an average of almost 5 years of hands on laboratory experience combined with over 5 years of experience working at Labtronics with our products. Application Developers bring programming skills and an in depth technical knowledge of Labtronics applications to projects that require advanced configuration of our applications to meet unique or complex customer requirements. No matter how large or small the team is, they always follow a regular schedule of internal status meetings and reviews to ensure that every member of the team is held accountable for their tasks and that the project remains on time and on target. Page | 107 Our Process Labtronics' projects follow a multi-step process that, like the Project Team, can be scaled to match the length and the complexity of the project. The following steps would be applied to any project of reasonable complexity - smaller projects may use a subset of these steps Initiation Letter & Meeting The project process kicks off with an Initiation Letter that is sent to the customer, Labtronics' Project Manager, Technical Lead and the Account Manager informing all parties of the start of the project and proposing an initial phone meeting between the customer and members of the Project Team. That initial phone meeting serves to introduce everyone, confirm the deliverables of the project, describe the project management process and make sure that everyone is in agreement on the general expectations regarding the timelines and the next steps in the project. Project Plan A detailed Project Plan is then prepared with input from the customer, the Project Manager and the Analyst(s) working on the project. This plan includes milestones that represent major accomplishments in the project that have a clearly defined and measurable end-point. Completion of specifications, implementation of specific components, end user training, etc are all examples of possible project milestones. Each milestone is divided into smaller tasks that provide shorter, measurable accomplishments that can be used to monitor the ongoing progress of the project. Specification Document Any project that requires method development or extensive configuration of the application will include a specification document that is created by the Analyst who works closely with the customer to ensure that the specifications meet their requirements and fit within the initial scope of the project. Co-development of the specification document is of critical importance in ensuring that the project remains true to the original goals of the customer while staying within the time and resource expectations that were initially set. Issue/Change Management On larger more complex projects, issues and changes will inevitably arise that have the potential to affect the outcome of the project. With the understanding that clear communication and effective management of issues and changes is critical to project success, the Professional Services Group utilizes a management process that focuses on working with the customer to identify, document, assess and resolve any issues that arise or requests for change that come up during the course of the project. Our Issue Management process consists of: Page | 108 a) Identification and review of the issue b) Logging of the issue c) Resolution of the issue d) Closing the issue The Change Management process can be summarized as follows: a) The need for change is identified b) The change is logged on a Change Request form c) The cost and schedule impact of the change is noted d) The Change Request form is approved by the customer Status Reports Regular status reports keep the lines of communication open throughout the project by keeping all parties up to date on tasks and milestones that have been achieved, due dates that might not have been met and identifying the next steps of the project. Particularly in a large scale project, regular status reports are an important opportunity to let everyone know where the project currently stands in relation to the schedule and cost. Labtronics' procedures require that a status report should be issued at least every two weeks for any active project of reasonable size and complexity. Completing the Project Labtronics' Professional Services Group will verbally confirm with the customer that all of the milestones and tasks for the project have been completed before initiating the process of closing a project. The stage of formally closing the project provides an opportunity to: a) Ensure that the all tasks and milestones are completed b) Ensure that all documentation and correspondence related to the project is assembled and archived c) Get feedback from the customer regarding our project methodology and performance d) Generate internal feedback regarding our project methodology and performance Page | 109 The feedback generated at the conclusion of each project helps the Professional Services Group to continually evaluate the effectiveness of their process and to improve the framework that they have created for project success. Achieving Real Success The success of a project is ultimately measured by more than just how long it took and how much it cost. These are certainly critical business considerations that must be measured and monitored but the ultimate measure of a project is whether or not it fulfills the original vision that got it started in the first place. At the end of a truly successful project the laboratory should be able to see immediate, measurable and lasting improvements in how their business operates on a daily basis. Labtronics' professional Services Group is confident that they have the people and the processes to deliver real success. Page | 110 Paperless Automation Part 1 - Conservative Solution, Radical Technology Nobody will question that going paperless will improve the efficiency of your laboratory operations. But there are questions about how much automation should be introduced as you go paperless. How much automation is the right amount? Can you automate too much? What issues do you need to understand in order to develop the correct amount of automation? This article is the first in a 3 part series that will investigate paperless automation by showing three possible automation options for a typical analytical laboratory to choose from. Our "typical" analytical lab For this series of articles we will consider a lab that has 12 analysts running a wide range of tests on both raw materials and finished product. Some of the more sophisticated instruments produce good reports but the less sophisticated instruments like balances and pH meters require the analyst to record all data by hand. The lab has a lot of manual operations as well, including sample prep, microbiological colony counting, reagent preparation etc that are manually recorded and tracked on paper. In total, there are about 200 worksheets that are used to walk analysts through analyses and to record data and final results. The lab also has a LIMS that is used to register samples, assign tests, and record final results. Most data is entered into LIMS manually. Instruments at this lab are calibrated on a routine basis, but the scheduling and tracking of calibration results is all done in log books. The lab has a very basic chemical inventory program that needs to be updated manually, so it is rarely completely up to date and accurate and is therefore rarely used as a reference during sample analysis. This "typical" laboratory could add tremendous efficiencies and value to their operation by eliminating their manual paper based analyses and procedures. In our series of three articles we will take a look at how three different lab managers approached the problem of eliminating the paper in this typical lab. Page | 111 The "conservative" solution Our first lab manager looked at the problem and realized that getting rid of all of their paper and using electronic forms was going to be a challenge. Taking this one step further and automating each worksheet was even more of a challenge. With a limited budget, and limited human resources, he had to decide how much automation they could implement at one time. He quickly realized that the "best bang for the buck" for the laboratory came from simply going paperless and creating an on-line, electronic environment to schedule work, review work in progress, let analysts to do their work on line, and automatically store completed worksheets electronically. This delivered the most immediate value to the lab by eliminating paper storage and retrieval costs, eliminating problems due to lost or damaged forms and simplifying management of the worksheet lifecycle by bringing it on-line. Now, he had to consider how much automation he should add to each worksheet. Reviewing the options, it became clear that worksheets can be made electronic and kept very simple or they can become highly automated. For example, a highly automated worksheet could connect directly to their chemical inventory system to retrieve expiration dates for chemicals used in the worksheet and automatically update inventory amounts as they are used. Or the worksheet could connect to LIMS and automatically report results. Although this type of automation would add real benefit to the lab, it was decided that they just did not have the resources to do everything at once. The lab manager decided to focus on going paperless as quickly as possible, getting the immediate benefits of going paperless and saving the full automation of the worksheets for Phase 2 of their paperless project. Figure 1: Adding more automation increases value but also increases the amount of effort and the cost required to convert the form Page | 112 The radical technology The laboratory elected to use the ReDI™ technology available with Nexxis ELN to quickly convert all 200 paper worksheets into electronic forms in less than a week. At runtime, the analyst selects the form they want to use and simply drags and drops entry fields right onto the electronic worksheet entering sample results, observations, comments, and more as they go. When the analysis is finished, the completed worksheet is automatically saved as a PDF and can then be scheduled for on-line, multi-level review. A record of the review process, including reviewer's comments, is automatically appended to the PDF. The result Installation, training and conversion of the 200 paper worksheets into electronic forms took only 5 days. The analysts view the switch to an on-line paperless system as a giant leap forward. They no longer spend time looking for lost worksheets, tests are no longer overlooked and their worksheets are now stored electronically in one easy to retrieve location. In a very short period of time the lab has gone paperless. A significant degree of automation was achieved in their processes by bringing them on line but there are still additional phases to go through to add automation to their individual worksheets. Since the project was finished so quickly, the lab reaped the benefits of their investment almost immediately, and the risk of a failed project was almost non-existent. Page | 113 Paperless Automation Part 2 - Right Down the Middle of the Road In Part 1 of Paperless Automation we started our 3 part series with a look at a lab manager who wanted to get rid of the paper in his laboratory and also understood the real Our "Typical" Analytical Lab benefits that the lab could gain by adding a high level of For this series of articles we are considering a automation to the electronic worksheets they would be representative lab with the following creating. characteristics: However with limited resources he chose to take a 12 analysts running a wide range of conservative approach, focusing on going paperless as tests on both raw materials and finished product. quickly as possible and saving the full automation of their worksheets for later. Using Nexxis ELN's new ReDI A combination of sophisticated technology he was able to convert all of his 200 paper instruments that produce good worksheets into electronic forms in only 5 days. reports and less sophisticated instruments like balances and pH In this article we continue with a look at a lab manager meters that require the analyst to record all data by hand. with an additional problem to solve – she wants to go paperless by eliminating their paper worksheets, but she A lot of manual operations also needs a solution that will help to reduce the number including sample prep, microbiological colony counting, of errors and oversights that are occurring in their manual reagent preparation etc that are processes. manually recorded and tracked on paper. Simply making the worksheets electronic doesn't provide the degree of automation and control that she wants. About 200 worksheets that are However she has a tight budget to work with and needs to used to walk analysts through analyses and to record data and show results as quickly as possible. final results. She is looking for a solution that takes her right down the A LIMS that is used to register middle of the road, introducing the benefits of going samples, assign tests, and record paperless and providing just enough process control to final results. Most data is entered protect against errors while not incurring high costs and into LIMS manually. long implementation times. Scheduling and tracking of instrument calibration results is done manually in log books. Balance the need for automation against A very basic chemical inventory time and budget restraints program that needs to be updated For example, she knows that worksheets aren't always manually, so it is rarely completely filled in completely and even important information can be up to date and accurate and is therefore rarely used as a reference during sample analysis. Page | 114 left out. Her lab supervisors are spending too much time reviewing the worksheets for completeness and having to go back and find or reconstruct missing information. So her automation solution definitely needs to include the ability to prevent analysts from submitting incomplete worksheets by clearly identifying and enforcing mandatory fields. The laboratory also needs a solution that can highlight when an analyst enters a result that is out of specification (OOS). With their current paper system, OOS results can be entered and are not likely to be caught until the review process. At that point, a lot of time is taken up as lab personnel investigate the root cause of the OOS result and determine how many additional samples might be affected. Being able to highlight OOS results as soon as they are recorded will provide a significant benefit to the laboratory by reducing the amount of time spent on review, investigation and rework. Figure 1: Highlighting OOS results as soon as they are recorded helps the laboratory to reduce the amount of time spent on review, investigation and rework. Unfortunately most paperless automation solutions that provide control over the process have capabilities that are beyond our lab manager's capabilities and are also well beyond the limits of her budget and the time frame that she has been given for implementing a solution and showing results. They are simply too expensive to purchase and too costly to implement to be realistically considered as a viable solution for her lab. The "Middle of the Road Solution" Fortunately she has found Nexxis ELN with ReDI™, a new eForms deployment technology that offers the "middle of the road" solution that she is looking for - delivering the benefits of going paperless and meeting her automation needs while keeping within her time and budget constraints. She has chosen to implement her forms using the ReDI technology: ReDI™ forms meet her need for automation and control with the ability to make it mandatory for analysts to enter information into designated fields and the ability to apply warning and error limits to numeric fields. Analysts will not be able to overlook missing information or OOS results. Page | 115 ReDI™ forms also meet her time and budget constraints. Electronic forms are typically created in less than an hour by simply dragging and dropping controls onto a PDF image of an existing paper document to make a "mask" or template that controls completion of the electronic form. The forms creation process is simple enough that lab personnel can be trained to convert their paper documents. Figure 2: A middle of the road solution requires more effort but it produces a more automated system The Result Our lab manager decided to start with a project that focuses on implementation of Nexxis ELN with installation, training, and automation of 50 of their most critical worksheets. The scope of the project was within her budget restraints and would deliver tangible results to the lab within a very short time frame. In fact the project was completed in just two weeks. The first week focused on Nexxis ELN implementation combined with training of 3 members of the laboratory staff in creating electronic forms using the ReDI technology. During the second week of the project the 3 staff members easily completed the creation of the 50 worksheets. The benefits to the lab were almost immediate. In addition to eliminating the costs of managing paper worksheets, our laboratory manager now has greater confidence in how the worksheets are being completed, as this process is now more controlled. She has seen a significant reduction in the amount of time spent on reviewing work and in the amount of time needed to correct errors. With the training that they have received, the 3 staff members continue to add a few more worksheets to the system each week. Page | 116 This laboratory manager took a less conservative route than the lab manager we met in Part 1 of our series. She chose a higher level of automation which did increase her risk slightly and also required a larger initial investment. However the pay off for her is a system that truly walks the middle of the road by meeting her automation and control needs while keeping within the restrictions of her limited time and funding resources. Page | 117 Paperless Automation Part 3 – The "I want it all" Solution In the first two parts of our 3 part series on Paperless Automation we met one lab manager who focused on going paperless as quickly as possible without automating his Our "Typical" Analytical Lab electronic worksheets, and we also met another lab manager For this series of articles we are considering a who needed to include enough process control in her representative lab with the following electronic worksheets to protect against errors but had to characteristics: keep within limited time and budget constraints. 12 analysts running a wide range of Our third manager wants it all. In his words, "A partial solution tests on both raw materials and finished product. is no solution". His vision is a fully paperless laboratory that automates and controls every step of their analytical A combination of sophisticated procedures ensuring that no mistakes can be made and that instruments that produce good their informatics systems are always accurate and up to date. reports and less sophisticated instruments like balances and pH The electronic worksheets should collect data directly meters that require the analyst to record all data by hand. from instruments. No more manual data entry. A lot of manual operations When someone selects a reagent, he wants the including sample prep, electronic worksheet to automatically check the expiry microbiological colony counting, date in the chemical inventory application. reagent preparation etc that are manually recorded and tracked on Test results should be automatically reported to LIMS. paper. About 200 worksheets that are Electronic worksheets should check for out-of- used to walk analysts through specification samples using limits that are retrieved analyses and to record data and from the ERP system. final results. For him, full automation means automating and controlling A LIMS that is used to register every step of the procedure so that no mistakes can be made. samples, assign tests, and record final results. Most data is entered into LIMS manually. The "I want it all" solution Scheduling and tracking of This type of solution requires considerable up front instrument calibration results is preparation and planning. For example, instead of just creating done manually in log books. simple entries on a worksheet, this level of solution requires A very basic chemical inventory that each data entry field needs to be examined and defined. program that needs to be updated Where does the data come from? What are the business rules manually, so it is rarely completely up to date and accurate and is therefore rarely used as a reference Page during sample analysis. | 118 for entering a value? What are the business rules for accepting, or rejecting a value? The planning process needs to involve lab management, lab personnel, IT personnel, possibly representatives from a validation group as well as the solution provider. This team will work together to establish the project goals, define the requirements for the system and create an implementation plan. Once the planning is complete, the solution then needs to be implemented. With a more complex project like this, there is a higher risk that it might not get completed. Virtually all IT projects benefit from breaking the project down into manageable phases, and implementing each phase, one after the other. This approach allows the implementation team to demonstrate success with the completion of each phase and it provides the user with a chance to get familiar with the technology step by step, making adoption of the new technology more successful. The Result This laboratory decided on a phased approach to implementing this solution, using the Nexxis ELN ReDI TM technology. With some solutions the process of turning a paper document into a highly controlled and automated electronic form can require a great deal of custom programming and testing time. ReDI makes the implementation of these worksheets as easy as possible, but clearly this still requires much more time and effort than the other two solutions we have discussed. The first phase of the project was to get some initial electronic forms up and running within a few weeks. With that phase completed, the team then focused on developing and adding a few additional forms each week. Completing the implementation of this solution took 4 months and required significant input from the IT group, but at the end of the process the ELN was fully implemented and the project was considered a huge success. While the "I want it all" approach takes considerably more effort, it delivers significantly higher value through the added automation and control that each electronic form provides (Fig 1). The lab manager achieves his goal of creating a working environment where no mistakes can be made and their informatics systems are always accurate and up to date. Page | 119 Figure 1: A full automation solution requires the most preparation and planning but delivers the highest value through advanced automation and control What is the right amount of automation? As we have seen from the 3 different laboratory environments that we have looked at, there really isn't one right answer to the "how much automation" question. The answer depends on a number of different factors, but mostly it depends on the amount of resources (time, budget & personnel) that will be available for the project. As you add more automation to an electronic form, you increase the value of that form to the organization but you also increase the amount of effort and the cost required to convert the form. However, as we have seen from the first two examples we looked at, there are very real benefits that can be delivered at the lower and middle ends of this scale where fewer resources are required to deliver the solution. With the introduction of ReDI (Rapid eForm Development and Implementation) laboratories now have an implementation solution that covers the full scope of the scale. Conclusion In this series of articles we have shown examples of three possible solutions, but in reality the right solution may be a hybrid solution. Most laboratories will have some simple worksheets that need very little automation. Tremendous gains can be achieved just by changing these paper worksheets into simple electronic forms that can be scheduled, completed, reviewed and approved electronically. They will likely have other worksheets Page | 120 that will benefit from increasing levels of automation and they may also have complex worksheets that require a high level of control and automation. With the right application, the laboratory doesn't need to be tied into a single approach to automation. Automation inside each electronic worksheet can be done in stages, either by automating just a few at a time, or by incremental degrees of automation - the level of automation for each worksheet can be tailored to meet its specific requirements. When selecting an ELN technology it is important to select one that provides both for today's needs and tomorrow's expansion. You may not need all of the automation today, but you want to know that it is available should you decide to add it. Comparison of Low and High Levels of Automation Degree of Automation Pros Cons Low – simple worksheets with - very fast to implement - limited automation minimal automation that can be managed electronically - virtually no IT - limited control over the involvement user - immediate payback on - limited system investment integration High – complex worksheets with - maximum reduction in - more effort to design a high degree of execution procedural errors and to implement control, automation and integration with other systems - maximum increase in - higher risk with a longer efficiency and more complex project - better integration with other systems Page | 121 ELN Pilot Projects Pave the Way for the Paperless Lab When a laboratory makes the decision to move to a paperless environment, they open up a wealth of opportunities for change and improvement in how they carry out day-to-day analyses and how they manage the resulting data. Eliminate costs associated with the management, storage and retrieval of paper documents Simplify the review, audit and management of laboratory worksheets Ensure full conformance to SOP requirements Eliminate manual transcription and calculation errors… These are all possibilities that are created with the transition from paper to the electronic environment. In fact, the potential for positive impact is so far reaching that many laboratories choose to start with a pilot project that gives them the opportunity to evaluate and quantify the full scope of change that can be introduced by going paperless. Get going in just a week… A Nexxis ELN pilot project quickly delivers a system that lets the laboratory perform their evaluation using their everyday forms and real data to demonstrate the potential of the paperless lab. During a one week on-site visit, a member of Labtronics Professional Services Group will work closely with laboratory personnel to accomplish the following: Transfer 2 or 3 paper worksheets or SOPs into Nexxis ELN to show how Nexxis ELN works with real forms and real data Provide training in the daily scheduling, completion and approval of worksheets using the Nexxis ELN web client Page | 122 Provide configuration training to show how new worksheets are added to Nexxis ELN, so that the laboratory can continue to expand their system after the pilot project is completed At the end of the week, with the Nexxis Pilot Project in place, the laboratory is ready to thoroughly evaluate and understand the advantages that a paperless environment delivers: On-line scheduling of tests and review of results Step by step control over the analytical procedure Automated data collection from instruments Integration with other applications such as chemical inventory and instrument calibration… On the road to success… With the Nexxis ELN pilot project, the laboratory gains both the internal training that they need to continue to expand the system and a platform that simplifies that expansion. Using the Nexxis web client, the laboratory can bring additional people into the system without having to install any additional software. New users can simply use the Nexxis web client to access Nexxis ELN from any network PC using Internet Explorer. Authorized users who received the configuration training can continue to expand and fine-tune the system by adding new worksheets or making changes to existing worksheets. The laboratory is now prepared to smoothly transition from the pilot project to a full scale Nexxis ELN implementation that will achieve maximum user acceptance and deliver maximum benefits. Page | 123 Chapter 7: Legal and Regulatory Issues Page | 124 DON'T HOLD YOUR BREATH WAITING FOR A TEST CASE ON ELECTRONIC LABORATORY NOTEBOOK RECORDS 1 By Colin G. Sandercock2 1 These materials reflect only the personal views of the author and not the views of Perkins Coie LLP or any other lawyer of the firm, or any of its past, present and future clients. 2 Colin G. Sandercock is a partner in the Washington, DC office of Perkins Coie, LLP, and has counseled clients for twenty seven years in life science matters including district court litigation, interferences, licensing and procurement and management of patent portfolios. He is listed in the Best Lawyers in America in the fields of Biotechnology and Intellectual Property (2007- 2011), as a Washington DC Super Lawyer in the field of Intellectual Property Law (2008-2011), and listed in Chambers USA: America's Leading Lawyers for Business (2009-2011). Mr. Sandercock previously chaired the Electronic Records ad hoc Subcommittee of the AIPLA Interference Committee, served as legal counsel to CENSA (Collaborative Electronic Notebook Systems Association) and frequently lectures on the topics of electronic record keeping for use in research, litigation and patent interferences. Page | 125 Electronic laboratory notebooks ("ELNs") have been around for well more than fifteen years, although in truth, commercially viable systems from vendors who are still in business have been available for well less than ten years. During this time, discussions concerning the legal admissibility of ELN records have invariably drifted to the question of whether there has ever been a test case involving the admissibility of an ELN record? To be sure, numerous corporate patent counsels have at one time or another expressed their firm opposition to adopting an ELN system until there is a test case. Given the increasingly steady deployment of ELN systems by most of the large pharmaceutical companies over the last five years, however, such resistance has largely waned. That is fortunate because, for the reasons discussed below, it is extremely unlikely that there will ever be a true "test case" on the admissibility of ELN records. First, generally speaking, records created and/or stored electronically have been admitted into evidence in U.S. court proceedings for over thirty years, and thus litigants and judges are thus well accustomed to using such records in court proceedings.1 In fact, electronically-created business records such as e-mails, internal company memoranda, electronic transaction records, and sales records now constitute a significant percentage of the documents produced in many litigations. In this regard, ELN records are simply another kind of business record that has been created and/or maintained in electronic form, and thus the treatment they will receive from courts will be similar to the treatment given other electronic business records. Second, to qualify as a true "test case" that would meaningfully address the admissibility of ELN records, a litigant would first have to ask a judge to exclude an opponent's ELN record from use in a court proceeding because of the way in which it was created and/or stored. Under our judicial system, the decision whether to admit evidence into a court proceeding is a matter that is left to the discretion of judges. (Similarly, Administrative Patent Judges determine the admissibility of evidence in a Patent Office proceeding such as an interference.) But because electronic records are commonly accepted in court proceedings, absent unusual circumstances indicating a lack of trustworthiness about a particular record, it is unlikely that a litigant would seek to exclude an electronic record on the basis of how it was created and/or stored. In other words, there would be nothing for a litigant to accomplish (except to annoy the judge) by challenging an ELN record if the information it conveys is consistent with the other evidence in the case. A case on point is the 2002 decision by the Court of Appeals for the Federal Circuit in In re Jolley,2 which involved an invention by employees of the Dow Chemical Company. In Jolley, the Court considered whether a May 1988 e-mail from one employee to another evidenced that they had conceived of an invention. The facts of this case were such that the information about the invention conveyed in the e-mail was fully consistent with the actions of the co-inventors before and after the e- mail was written. For example, other evidence in the case documented the inventors' efforts to actually make the invention following their May 1988 e-mail. Thus, there was no reason for Dow's 1 For a more complete discussion on the admissibility of electronic records in the U.S. courts and the U.S. Patent Office, see Sandercock & Agarwal, Under Strict Rules, Electronic Records Can Enter, The National Law Journal (June 22, 1998). 2 See, In re Jolley, 308 F.3d 1317 (Fed. Cir. 2002). Page | 126 opponent in the litigation to challenge either the date or content of the May 1988 e-mail. In fact, the Federal Circuit's decision mentioned the e-mail over 20 times, but the Court never once considered whether it the e-mail be excluded or denied credibility because of its electronic origin. Third, modern ELN systems from reputable vendors can be implemented with appropriate safeguards, policies and procedures so as to create and archive records that are difficult (or practically impossible) to falsify. Thus, where appropriate safeguards, policies and procedures exist, the likelihood that a record from such an ELN system actually could be falsified will be so low as to deter an opponent from even challenging the credibility of the record. Finally, there are several practical considerations that weigh against the possibility that we will ever see a test case decision, or at least that we will see a decision anytime soon. First, most patent litigations or Patent Office proceedings settle before reaching the stage where there would be a decision on the admissibility of an ELN record. Hence, even if there were a case in which the credibility of an ELN record might be meaningfully challenged, the likelihood that the issue would even be decided by a judge is small. Second, even if such a case did not settle before the issue were decided by a judge, the judge's decision would only be helpful if it found its way into a published, written opinion. Published written opinions on evidentiary matters are not uncommon, but most decisions concerning the admissibility of evidence are not included in published opinions (and instead are mentioned only in court transcripts). If such a ruling did not make it into a published opinion, then unless the aggrieved litigant raised the judge's evidentiary ruling on appeal, it likely would not become known. And, even if it were raised on appeal, appellate courts often rule without specifically addressing all of the issues raised by litigants on appeal. Finally, as was illustrated by the Jolley decision discussed above, the time between the creation of an invention record and the time that the record is addressed in a published court decision can be quite long. In Jolley, where the invention involved a chlorine-free refrigerant, the interval was fourteen years. If a record of such an invention had been made five years ago on one of the earliest- implemented, commercial ELN systems, and assuming against all odds that a decision on the admissibility of that record eventually were to be published, it could be almost another decade before the decision would be available. For pharmaceutical products, it could be even longer. Such products require long pre-clinical, clinical and regulatory approval periods. Once approved, there also is a period of regulatory exclusivity during which the patent(s) on the product may not be challenged. Add to that the length of time it takes to litigate a patent until a decision is published by either a district court or an appellate court, and the total lag time easily could be twenty years or longer. In such a case, again assuming that five years ago an ELN record was created for a drug that eventually will obtain marketing approval and then be the subject of litigation, and again assuming that a decision on the admissibility of that record is eventually Page | 127 published, it likely would be at least another fifteen years or more until it would be available. By that time, the cows will be long gone from the barn. Conclusion Assuming that reasonable ELN system safeguards, policies and procedures are implemented, then ELN records will be as admissible as any other electronically created record. The decision to implement an ELN system, therefore, should be based solely on whether it can enhance productivity and knowledge management in the intended environment – not on whether there has been a test case. Page | 128 ELN Meets 21 CFR Part 11 Compliance Requirements What should you look for in an ELN to ensure that it will meet 21 CFR Part 11 compliance requirements? The following table provides an overview of regulatory requirements and the functionality that an ELN should provide in order to meet those requirements. Regulatory Regulatory Requirement ELN Requirement Reference # 11.10a Discern invalid or altered records ELN should have an Audit Trail that utilizes a CHECKSUM to ensure validity of all Audit Trail records. If a record in the Audit Trail has been altered, the record will be flagged. Provide a mechanism that will identify record Activation and accessing the Audit Trail should be modifications. The mechanism must be beyond restricted by a security system. the control of system users and enabled at all times. 11.10b Produce accurate and complete copies of the The Audit Trail should be able to print reports of all electronic record in human readable form. transactions. 11.10d Allow restricted access in accordance with pre- The security system should restrict access on a defined rules. functional basis. Each significant operation that can be done in ELN should have a separate security level. 11.10e Capture information relevant to all record Data to be recorded is minimally: time and date, creation, modification and deletion actions. unambiguous description of event and identity of operator. This record must occur independently of operator control and, once captured, must be unalterable. ELN must have an Audit Trail for recording this data. Retain original information if the record is The original value and the new value should be logged modified. in the audit trail along with a comment from the user stating the reason for the change. Retrieve the Audit Trail for review and copying. Authorized personnel should be able to query the audit trail to view entries. Entries should be able to be printed to a printer or a file. Page | 129 Regulatory Regulatory Requirement ELN Requirement Reference # 11.10f Enforce the sequence of operations when ELN should allow for the creation of a sequence of sequencing is required. operations, and then force the users to proceed in the defined order. 11.10g Restrict use of system functions according to pre- The security system should restrict access on a defined procedures. functional basis. Each significant operation that can be done in ELN should have a separate security level. 11.10h Verify the integrity of all devices that are sources ELN should confirm that the right source has been of input data or instructions. selected and that it is calibrated for use. 11.50 Ensure signed electronic records contain Ensure that the metadata for electronic signatures is information associated with the signing, which collected and saved as part of the electronic record. clearly indicates all of the following: 1) the There should be no way to manually alter this printed name of the signer, 2) the date and time information. of the signing, 3) the meaning (such as review, approval, authorship) associated with the signature. Control this information as other electronic records. Show this information whenever the record is shown, displayed or printed. 11.70 Link the electronic signatures to their respective The metadata for the electronic signatures should be records in a manner that would prohibit their saved to the audit trail and it should be saved right on modification, duplication or movement. the worksheet. The data on the worksheets needs to be protected from editing and the production of a PDF should clearly show to the reader that this is non- edited electronic signature metadata. A good way to do this is with a watermark stamp. Enforce uniqueness of electronic signatures, The security system should prevent duplicate users prevent re-allocation of electronic signatures, and and duplicate usernames. Records in audit trail should prevent the deletion of information relating to not be editable. If a change is made on a worksheet, the electronic signature once it has been both the before and after signature information needs executed. to be saved in the history of the worksheet. 11.200(a)(1) Require at least 2 distinct components of non- This requirement is met by using both a user ID and a biometric electronic signatures. password. 11.200(a)(1)(i) Enforce that both electronic signature Ideally the ELN allows multiple signings as work is components are entered at least at the first being completed. It should be able to enforce an signing, and following any break of system electronic signature each time work is saved. The activity. ability to log users off an inactive system, based on time, is also a requirement. Page | 130 Regulatory Regulatory Requirement ELN Requirement Reference # 11.200(a)(1)(ii) Enforce that both electronic signature The requirements for electronic signatures should be components are entered at each signing when configurable. signings are not performed in a continuous session. 11.300b Enforce the periodic changing of passwords and Self explanatory. the retention of the record of historic use of an ID/password combination, after the combination has been rendered inactive. 11.300d Provide urgent and immediate notification of Email notifications should be sent to defined attempted unauthorized use of passwords, and individuals or groups when such an event occurs. In take preventative measures to prevent another addition to this, the system should lock the (e.g., locking terminals, retaining access cards, application until unlocked by an Administrator. etc.). Page | 131 Chapter 8: ROI Calculator Page | 132 Calculating ROI for an ELN Project The ROI Calculator for ELN provides a spreadsheet that can be Free ROI Calculator for ELN used to calculate the cost benefits of implementing an ELN. It will allow you to enter costs for the project, identify the time Determine the real dollars and cents savings that you will generate by implementing an ELN for value of an ELN project at your lab. routine analyses and then calculate your annual savings and your ROI starting from year one through to the end of year five. Click here to download. How much does an ELN Project cost? Software Identifying software costs for an ELN project is pretty straightforward. There will be a fixed, upfront cost for the software that is based on the number of licenses you need. Licenses for an ELN are typically based on either named users (purchase a license for every person who will use the application) or concurrent users (purchase licenses for the maximum number of people that would use the system at any one time). Concurrent user licensing is often the best option in laboratories that run multiple shifts or where analysts don't need to use the ELN full time. It also provides inexpensive licensing for managers who only use ELN a few times a day to check on work. There will also be an ongoing annual support cost that typically provides for software upgrades, patches and fixes in addition to technical support and may also include membership in a User Forum. Annual support costs are usually calculated as a percentage of the original license cost. With those numbers you can quickly determine the software cost over the expected life span of the software and apply that to your ROI calculation. Validation Costs Laboratories that work within a regulated environment will need to account for validation of the installed ELN as part of Validation Tip the total project cost. Applications that utilize a zero Validation can be done by an internal validation group, by a footprint web client help to reduce third party validation company or by the ELN vendor. Most ELN validation costs with no software vendors provide validation tools that can help to reduce the installation on the client side. cost of validation. For example, they might provide a Validation Page | 133 Toolkit that includes detailed IQ and OQ documents that significantly reduce the amount of time that validation groups spend compiling the information that they require to initiate and execute a thorough IQ/OQ validation. Hardware Primary hardware costs include any additional workstations, servers, network upgrades that are required to support the interfacing solution. Identifying these costs requires a clear understanding of how the solution will be deployed and the specific hardware, network and operating system requirements of the interfacing solution. Secondary hardware costs can include peripheral items such as bar code scanners that may be used as part of the interfacing solution. To minimize your hardware investment, look for applications that run efficiently on the same platforms and operating systems, as your in-house "standard". This will leverage the existing hardware, infrastructure and technical knowledge that you already have within your organization. Implementation Implementation costs reflect the resources that are utilized to get the interfaces into production, once you have the software and the hardware in place. These typically include configuration of the solution to Implementation Tip meet your specific requirements as well as training both for end users and for IT personnel that will be supporting Solutions that allow the end user to the solution. take ownership of configuration and that offer a variety of training Another consideration for implementation costs on an ELN options will help to reduce project is the level of automation that the ELN provides. As implementation costs and therefore the complexity of the electronic worksheet grows so does increase your ROI. the investment required to create that worksheet. A simple worksheet with no automation can be created very quickly. At the opposite end of the scale a highly complex worksheet with calculations, instrument integration, logical controls and integration with other informatics systems will require a much more detailed development and testing cycle. Of course the trade-off is a higher level of automation which will deliver more return by having a more significant impact on laboratory efficiency and capabilities. Page | 134 Figure 1: More automation requires more effort (investment) but creates more potential return Show me the savings! An ELN for routine analyses will deliver different levels of savings to the lab depending on the amount of automation that is applied to the electronic worksheets or processes in the ELN. Eliminate paper costs A simple ELN implementation with minimal automation built into the electronic worksheets or procedures will deliver immediate savings by eliminating costs associated with buying, storing, managing, archiving and retrieving paper. Deciphering illegible handwriting, looking for missing notebooks, paying for long term storage and having to search through boxes and boxes of paper to find a worksheet for an auditor, all fade into the past when you move from paper to an ELN that provides on-line management and access to your electronic documents. Automate data collection and calculations More significant returns are delivered when ELN worksheets are connected with instruments - automatically collecting data, recording it in the electronic worksheets and automating calculations. Not only do analysts save time, but this level of automation also reduces the amount of time that needs to be spent on the secondary review of manual data recording and calculations because there is a consistent, accurate and documented process for calculations - that is applied each and every time. Control of analyst A 'smart" worksheet that controls how the analyst works their way through a procedure will provide even greater savings by enforcing consistent and accurate adherence to SOP requirements. This Page | 135 reduces or eliminates costs associated with investigations, rework and rejection of results where SOP requirements were not followed. Integrate with other Informatics applications Connecting the ELN with existing informatics systems like LIMS, Document Management Systems, Chemical Inventory, Instrument Calibration, etc can generate tremendous savings by eliminating all of the manual work that is involved in accessing information from these different systems as well as ensuring that the systems are automatically kept accurate and up to date. Sample information can be automatically collected from LIMS, chemicals can be checked to confirm that the right material is being used and that it hasn't expired, chemical inventory can be automatically updated as materials are used, etc. Page | 136 Chapter 9: Connectivity to other Lab Systems Page | 137 LIMS and ELN: 1 + 1 = 3 Wikipedia describes synergy as "a situation where the final outcome of a system is greater than the sum of its parts" (http://en.wikipedia.org/wiki/Synergy). That perfectly describes the result of connecting a LIMS with an ELN for Routine Analysis - two different systems that become stronger and more valuable when they work together. By itself, a LIMS (Laboratory Information Management System) is an effective solution for recording and managing sample information and test data. But LIMS is not connected with actual test execution, particularly routine tests that are executed using paper based documents and procedures. An ELN (Electronic Laboratory Notebook) for Routine Analysis replaces paper based tests with online electronic procedures and provides a high level of control and automation over test execution. Join those two together and you create a system that is greater than the sum of its parts. Leverage the information already in LIMS by delivering it directly to the lab bench at the time of analysis Enhance the quality of generated data by using ELN to automate and control procedural execution Speed up reporting of test results to clients and decision makers. In this article we will identify the different roles that these two systems play in the laboratory workflow and then take a look at the possibilities for interaction and the benefits these interactions deliver. Role of LIMS LIMS is focused on information management, storage and reporting– logging in sample information, test information, test results, instrument calibration, chemical inventory, billing information, etc. LIMS gets involved at the beginning of the analytical process when samples are logged in and tests are scheduled. LIMS comes back into play when the tests are completed - collecting, storing and reporting results. Limitations of LIMS LIMS does not get involved in the actual analysis of the samples, so it is not able to manage or control day to day analyses in real time. Page | 138 LIMS can check results against specifications and identify OOS (Out-Of-Specification) results but only after the tests have been completed and results have been entered in LIMS LIMS can monitor instrument calibration and even flag instruments that need to be calibrated but LIMS can't prevent the technician from using the instrument at the time of analysis LIMS can be used to manage inventory (standards, solutions, reagents, etc) but it cannot link inventory information to the test as it is being carried out. Accessing and updating inventory management in LIMS is dependent on manual activity that is often unreliable and inaccurate. LIMS typically can't display raw data from routine analyses as usually only results are stored in LIMS. A key limitation of LIMS is its inability to interact directly and in real-time with routine analyses as they are being carried out at the bench level. Role of the Electronic Laboratory Notebook for Routine Analysis An ELN for Routine Analysis takes over at the bench level, right at the point of analysis, providing real time control and automation of testing procedures. Ensures proper procedural execution Automates manual processes o Instrument data collection o Calculations o Limit Checking o Calibration checking o Inventory checking and updating Provides electronic documentation and access to test results This additional layer of control ensures compliance with SOPs during the analysis and protects the integrity of collected data. Limitations of an Electronic Laboratory Notebook While an ELN has a full understanding of the test and the test procedure, it has no inherent knowledge about the samples or the test specifications. That information has to come from somewhere else. In most laboratories sample information (Sample ID, test specifications, Due date, Assigned By, Client Name, etc.) will be stored in LIMS. Page | 139 Often other information that is important to the analytical process such as chemical inventory or calibration information is also stored in LIMS. LIMS and ELN Working Together We have seen that LIMS provides overall sample management. On the other hand an ELN focuses all of its attention on the point of analysis – what is happening in real time as the sample is being analyzed. The real-time, automated transfer of information back and forth between LIMS and ELN ensures that information in both applications is accurate, complete and kept up to date in real time. Sample and test information from LIMS can be automatically added to electronic worksheets in the ELN The ELN can automatically transfer sample results back to LIMS as soon as the analysis is complete Chemical inventory in LIMS can be automatically adjusted as chemicals and solutions are used or prepared using worksheets in ELN ELN can use LIMS to automatically check expiry dates on chemicals and solutions as they are being used Test limits stored in LIMS can be used by ELN to provide real time limit checking for OOS results Etc…. This real-time communication between the ELN and LIMS means that analysts don't have to spend their time manually looking for and recording information. This helps to reduce their workload, eliminate errors generated by manual processes and speeds up execution of the tests. LL+ ELN = More Value for the Laboratory Clearly, blending these two separate systems together into an integrated system is a natural fit. The value of each system is enhanced by the interaction between the two. Page | 140 What is an iLAB? iLAB, an acronym for "integrated laboratory", is a term that describes a new type of laboratory informatics system - a total laboratory automation system. Understanding the value of an iLAB starts with an understanding of 4 key problems with today's informatics systems. 1. No 'Real-Time' Control of Users: On a daily basis analysts are required to follow SOPs, but there is no way to enforce the SOP. For example, an analyst is expected to check that a reagent is suitable for the test that they are doing, but there is nothing in the system that ensures that the check is made. It is left up to the analyst to check SOP requirements and make decisions about each step in the process. Analysts are being asked to make far too many decisions about the processes they are completing. 2. Limited Management of Workflow: To illustrate this point, ask yourself the following question, "How does my informatics system adjust itself when an instrument breaks down at 2:00 pm?" What should your system be able to do in this case? It should check to see if a different instrument can be used for the same tests. If the other instrument is already booked, then it needs to re-assign samples so that the high priority samples are analyzed first. It might need to reschedule the work for someone, so that the repair of the instrument is a priority. The system may need to notify others outside of the lab that the test results will be delayed. All of these decisions should be automatic, and they need to take into account all of the available information about the lab and its resources. Today's informatics systems are not close to providing real management of workflow. Page | 141 3. Most processes are human driven or paper driven, not Event-Driven: As long as a process is paper-based, it is human driven, not Event-Driven. People are expected to make too many decisions - approving results, prioritizing work and making sure they are following procedures. A totally automated system will have almost all decisions made by the system. The system will check and ensure that the correct processes are being followed the same way, all of the time. These decisions will be based on events that take place. An event can be any action. It could be something that an analyst does, like select an instrument from a list or it could be an action that the system takes, like checking training records. 4. Limited integration of information: Anyone who is working with more than one software system in their lab will recognize this problem - the lack of integration between software systems and between instruments and software systems. With proper integration, you gain two very valuable benefits: a) Information is only stored in one place b) Information is instantly available when and where it is needed. When you look at these four key issues, you soon realize that they add up to "No Automated Workflow Control". If users are not removed from the decision making process and systems are not integrated, you cannot have automated workflow control. What does an iLAB look like? An iLAB system that solves all of the above problems can be visualized as follows: Page | 142 Figure 1: In the iLAB, applications are connected through the Real-Time Integration layer. Workflow Control automates workflow decisions by applying business rules to information from all applications. At the bottom of the diagram you have the main laboratory application systems LIMS, ELN, Instrument software, etc. Each of these operates on their own and carries out very specific functions for the laboratory. Each application is connected to all of the other applications through the Real-Time Integration layer, not directly to each other. This is critical in the design of the system to keep the number of integration points to a minimum. Any information in any of the applications is available to all of the other applications, when and where it is required. If ELN needs information about the calibration of an instrument, it gets it from the calibration application through the Real-Time Integration layer. Above the Real-Time Integration layer is the Workflow Control layer. This layer takes information from all applications and applies business rules to maximize the correct Workflows. If an instrument breaks down, it is this layer that reschedules work for everyone, so that the whole lab is best able to meet its targets. Real-Time Integration and Workflow Control are very critical concepts in the iLAB design. So, let's look at each of those in more detail. Page | 143 Real-Time Integration Real-Time Integration means that all data is available immediately, when and where it is required. Having data available immediately means that the system can perform a lot of automated checks, and it can prevent errors from occurring. It is also able to make decisions for users. Data and Events are validated immediately and automatically. Each new piece of data is evaluated, approved and stored in its correct location. Events are reviewed and approved by the system before subsequent events can be initiated. Data is stored in a single 'correct' location. Nothing causes more problems to an automated system than trying to maintain information in more than one location. Workflow Control Each event (anything that happens) automatically initiates other events. Some of these events will require a human to complete and others will be completed automatically. Some events will affect the current schedule and, therefore, future events will be re-scheduled and re-prioritized. For example, in an iLAB, an event like selecting a balance will automatically initiate the following series of events: Check for calibration Check suitability of the balance for the planned work Check training records Log use of the balance into an instrument log book Retrieve calibration information Retrieve an instructional SOP In this example, the single event of selecting a balance triggered an interaction with as many as 5 other applications. What is Nexxis iLAB and how does it compare to the iLAB described above? The following diagram illustrates Labtronics' Nexxis iLAB product. Nexxis iLAB can provide support for each of the applications excluding ERP and instruments. Page | 144 Figure 2: Nexxis iLAB meets all of the requirements of an iLAB, but it does not include applications for instrument software or ERP. Nexxis iLAB adds some additional functionality to the iLAB system. Plug & Play applications The design of the connection between the application and the Real-Time integration layer is critical to the iLAB's ability to support the selection of best of breed applications. Labtronics has designed a set of API standards for communication between the applications and the Integration layer. This means that the applications are interchangeable. For example, you can remove Nexxis SDMS and replace it with either NuGenesis (from Waters) or CyberLAB ECM (from Agilent) applications without losing functionality. Since the API design for the SDMS is the same for each of these applications, the replacement of one for another only requires a simple one screen configuration. Once configured, the Real-Time Integration layer is unaware of which SDMS is connected. Page | 145 Figure 3: Using Labtronics' API for communication, applications can be interchanged with just a simple screen configuration. Nexxis iLAB's API is so generic that even popular documentation systems could be used in place of the SDMS. This Plug & Play feature is very important when adding iLAB to a laboratory that already has existing informatics systems. There is no need to replace existing systems. Out-of-the-Box Configuration Much of Nexxis iLAB has been designed to provide you with simple configuration instead of scripting and programming custom solutions. For example, the ReDI Technology in Nexxis ELN lets you create automated worksheets with simple click and drag functionality. Connecting an ELN worksheet to instrument calibration information, training records and updating instrument log books is accomplished in a minute or two by simple configuration. Connecting to existing LIMS systems is done through standardized LIMS modules, which require only simple, one screen configurations. Page | 146 Application Note: Environmental Monitoring with LimsLink and Nexxis iLAB Environmental Monitoring can mean a number of different things, everything from monitoring a room's temperature to swabbing equipment in order to detect microbial contamination. For the purposes of this Application Note, we will define environmental monitoring as the automated measurement of environmental parameters. These parameters are measured by instruments and include physical measurements such as temperature and humidity as well as the measurement of chemicals such as solvent vapors in the air. This application note will also examine ways in which this data can be used to control the lab. Environmental monitoring is really a multi-stage process. It starts with the collection and storage of data. Once you have data it can be reviewed manually and used to control lab processes. The data can also be used to initiate warning systems and notify people by email and phone that a problem exists. This application note will look at various ways to use the collected data. Collecting Environmental Data Data is generated by instruments that are able to monitor a parameter like temperature and then send that data to a computing device. This type of instrumentation can be used in a number of situations: Monitor the temperature and humidity of the lab Monitor the temperature of storage chambers, or stability rooms Monitor pH and oxygen levels during a fermentation process Monitor online instruments in production Monitor solvent levels in a room In each case, the instrument gathers data and sends it to the computing device at specific intervals. LimsLink is a great product for collecting this kind of information. It is able to collect data from almost any type of device. It can then perform calculations such as averaging the data. For example, the data might be collected at 1 point per second and you may only want to store the average over a 10 second interval. Once the data is in the format you want, LimsLink will automatically save the measurements along with a date/time stamp. This data is now available to any system that needs it. LimsLink is generally set up on a central sever, and all of the environmental monitoring devices can report to the same LimsLink install. All of this happens in the background. Page | 147 Figure 1: LimsLink can capture data from environmental monitoring devices, perform any required calculations and save the data to a database Viewing Environmental Data Nexxis iLAB contains a module called Nexxis Report Manager (Nexxis RM). Nexxis RM provides a number of tools for reporting the data collected by LimsLink. This reporting process is a manual process where the operator goes to Nexxis RM, selects a report type, and supplies information for producing the report including such things as the location, parameter being monitored, and the time period for the report. Nexxis RM will then produce the report. The details in the report depend very much on the design of the report template, which can be designed to meet any needs. The report can be sent to Excel, a PDF, a printer and the report can even be Figure 2: Nexxis Report Manager provides a variety of tools for reporting displayed on the Nexxis iLAB environmental data. dashboard. Nexxis Mobile can also be used to view the data. Nexxis Mobile is a module of Nexxis iLAB that allows you to use a mobile device like an iPhone or Blackberry to retrieve data that has been stored by LimsLink. The mobile device can be used to display current or historical environmental data. For example you can log in, and retrieve the pH and oxygen values for your fermentation process to make sure that it is progressing as expected. Page | 148 Figure 3: Nexxis Mobile allows you to view current or historical environmental data on an iPhone or Blackberry Controlling Lab Processes A number of procedures in the lab are dependent on knowing the environmental conditions. Weight measurements may be affected by humidity Calibration of pipettes is affected by temperature, barometric pressure and humidity Stability studies depend on knowing the environmental conditions in the storage chambers Safety in the lab may requirement the monitoring of chemical vapors When a lab process is affected by an environmental process it is important to check the environmental parameters in real time as the lab work is being carried out. Nexxis iLAB allows you to do this. Consider the example where you are weighing samples that are very sensitive to humidity, e.g. weighing tissue paper. The standardized and approved procedure for this analysis requires that the weighing is carried out within a specific humidity range. It is important that the analyst is prevented from weighing samples if the room is not within the specified range. In Nexxis ELN, worksheets can be set up so that just before weighing begins, the system retrieves the current humidity values and determines if the process can be continued. Nexxis ELN can write the current value right onto the worksheet, along with weight values. This produces a report that has all of the important metadata in one place, and anyone reviewing the report in the future knows (a) that the work was done at the correct humidity level, and (b) they know the exact humidity at the time the test was completed. Figure 4: A Nexxis ELN worksheet can check environmental parameters in real time and use that data to control the process Environmental Warnings Environmental monitoring may be in place to prevent a problem from happening. For example you may want to ensure that storage conditions are maintained, or you might be monitoring for toxic Page | 149 gases. In such cases, you want a system that collects and stores the data, but you also want it to check the value of the data and take some kind of action when a limit is reached. LimsLink is already collecting and processing the data. It is an ideal system to use to also check the value of the parameters and to set the alarm if the data is not within acceptable limits. The processing of this data is a usually a bit more complex than just looking at a value. A single data point that is outside of limits may not be significant enough to trigger the alarms. You may want to look at a rolling average over a number of data points. This eliminates noise issues with the measuring equipment. You may also want warning levels. One way to do this is to calculate the current trend and check to see if the trend is heading towards a problem. If it is, a warning may be generated which would be a different action than an alarm. There are various algorithms that can be used for calculating the trend, depending on the consistency of the data and your specific goals. All of these calculations can be easily configured inside LimsLink. What happens when an alarm or warning level is reached? There are a number of options: Start an actual alarm such as a horn or flashing lights Send an email Send a report including current data Turn something on or off - for example a switching valve, heater etc LimsLink is capable of carrying out each of these actions in real time as the data is being collected. Conclusion LimsLink is an ideal tool for environmental monitoring. It will collect data from almost any device, process and analyze that data, store the data, and even take action if values exceed limits. Once the environmental data is stored, Nexxis iLAB can report on the data or use it to control the analyst in real time right at the bench level. The combination of LimsLink and Nexxis iLAB provide a complete environmental monitoring system. Page | 150 Nexxis ELN and Nexxis CIM Integrate for Real-Time Chemical/Solution Management In this application note, we will show how real-time management and control over solution preparation is attained when Nexxis ELN is integrated with Nexxis CIM, a Chemical Inventory Management application. The Problem Most laboratories prepare solutions that are entered into their inventory and then used in subsequent analyses. With a paper-based system, significant amounts of time and resources are dedicated to ensuring that SOPs are followed as solutions are prepared and that the solutions are correctly recorded into inventory. As solutions are being used, the laboratory needs to confirm and document that the correct solutions are used for the analyses and that the solutions have not passed their expiry dates. Of course, the inventory record needs to be updated to reflect the amount of solution remaining after each analysis, as it is imperative to know when solutions reach a minimum level so the lab can initiate preparation of new solutions for inventory. Occasionally, the lab will realize that there is a problem with a specific lot of a solution and will need to go back through their records to identify all of the analyses where that lot was used. With a paper- based system, this is tedious and time consuming and there is always the possibility of missing instances where the suspect solution was used. The Solution Nexxis ELN, combined with Nexxis CIM, provides an automated electronic system for controlling, managing and documenting solution preparation and the use of solutions in the lab. Nexxis ELN worksheets are used to control and monitor the preparation of each solution, ensuring that each step of the SOP is followed and providing documentation of who prepared the solution and when it was prepared. When the analyst completes the preparation process, the new volume of solution is automatically added into the Nexxis CIM inventory database. Page | 151 When an analyst uses a prepared solution as part of an analysis that has been set up as a Nexxis ELN worksheet, they can be prompted to manually enter the lot # of the solution they are using or to simply scan the barcode on the solution container. Nexxis ELN can then use that information to automatically query the Nexxis CIM database to confirm that the lot # entered corresponds to the appropriate solution for the test and that the solution has not passed its expiry data. If there is a problem, Nexxis ELN can inform the analyst immediately and they can take appropriate action. When the step that uses the solution is completed, Nexxis ELN can automatically update Nexxis CIM to reflect the amount of solution that was used. As soon as the inventory level reaches a minimum point set in Nexxis CIM, an email can be issued indicating the need to prepare a new lot of that solution. All of the information entered into the Nexxis ELN worksheet is saved into the Nexxis ELN database and an image of the completed worksheet is saved electronically as a PDF. If the lab realizes that there is a problem with a specific lot # of a solution, they can quickly search the Nexxis ELN database to find all of the worksheets and samples that used that lot #. The PDF versions of the worksheets can be called up to verify the work that was done with the suspect solution. The Result Together Nexxis ELN and Nexxis CIM provide an integrated solution that does away with the inconsistencies and oversights that are inherent in manually managing solution preparation and eliminates the time and resources required to maintain a paper-based system. Nexxis ELN ensures that SOPs are always followed throughout the solution preparation process, ensuring the consistency of prepared solutions. The Nexxis ELN database and worksheet PDF provide documentation of solution preparation and use for internal review and audit purposes, eliminating the need to retrieve paper records from storage. The Nexxis CIM inventory is automatically updated as solutions are prepared and used, ensuring that inventory records are timely and accurate. Nexxis CIM provides confirmation that the analyst is using the right solution at the time of analysis, avoiding errors due to incorrect use of solutions. Nexxis CIM provides confirmation that the solution has not passed its expiry date at the time of analysis, eliminating inaccurate results due to use of expired solutions. Email notification is automatically issued when solutions reach a minimum level, avoiding situations where tests are held up due to unexpected shortages of solutions. Page | 152

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