By John Russell
Sept. 11, 2008 | The laboratory information management system (LIMS) market has long had a reputation for being a messy place where giant and tiny vendors compete with internally developed software. Among the criticisms commonly lobbed at commercial vendors are: that their products inevitably require major customization; that customization is difficult and costly; and that once installed their products are inflexible and difficult to change. Yet these lingering ideas may no longer reflect reality.
It’s still not a huge market. Health Industry Insights estimates LIMS sales in the U.S. at $184.5M for 2007 and at $348.3M worldwide. “LIMS is a mature market and continues to move towards standardized commercial solutions and away from internally developed implementations,” says HII research director Alan Louie.
What Heather Jordan found in her search for a LIMS for biotech ExonHit was a more nuanced marketplace that fulfilled and defied its stereotype. In the end, the director of operations for ExonHit Therapeutics (who also is responsible for its Paris-based lab) was able to find a solid commercial offering – Exemplar from Sapio Sciences - whose key strengths were flexibility, ease of use, and fast deployment. Jordan’s experience is instructive and perhaps more representative of today LIMS offerings.
“We evaluated 8 to 10 different vendors. The majority of them were very well-known types of providers which you hear about all the time, such as the ABI systems and LabVantage, etc. But there were also some small software companies,” says Jordan. The chief challenge was to find a LIMS suitable for ExonHit’s growing microarray processing work and which would be compliant with 21 CFR Part 11 and other regulatory requirements. Until last January, the company had a paper-based manual system.
ExonHit is a small Paris-based biotech founded in 1997. Its proprietary technology - DATAS (Differential Analysis of Transcripts of Alternative Splicing) – monitors alternative RNA splicing events. ExonHit applied its expertise in alternative splicing to a microarray platform and developed a novel design of probes to monitor the differences of highly similar transcripts. The company received patents on this probe configuration and currently runs a service operation that provides researchers with analyzed expression data on individual transcripts. Besides conducting internal and collaborative research programs around cancer and neurodegenerative disorders, the company also worked with Agilent Technologies to develop a commercially available version of its microarray format (SpliceArray) in late 2004.
“Agilent provided the chips to people who actually have core labs that run Agilent microarrays. At the same time, we launched a full service in-house, providing processed data and analysis to researchers,” says Jordan, based in the company’s Gaithersburg, MD, facility. “We also expanded our service offering to include the Affymetrix platform in the U.S. in 2006 and added a service lab in our Paris facility in late 2007. We can run standard gene expression microarray experiments, as well as alternative splice event profiling on our SpliceArray platform for customers on both the Agilent and Affymetrix platforms.”
Regulatory compliance led the list of Jordan’s LIMS criteria, as the company is very focused on achieving Good Laboratory Practice (GLP) status. She also wanted a single LIMS accessible to folks on either side of the Atlantic.
“We didn't want to worry about installing two different software packages. We just wanted one server that we could both access and not have issues with that. We wanted sample tracking, bar coding, reagent inventory, all of the items that go along with the electronic lab notebook, all the protocol tracking, from sample inventory, and quality assessment to QC [quality control] data,” Jordan.
The Sapio LIMS eventually chosen is hosted on a Dell PowerEdge 1950 running Windows Server 2003 R2. Because the LIMS application is written in Java, it is platform independent. The server is using an Apache web server to provide web start functionality to the LIMS user interface application. The LIMS application connects to a database server that is hosted on a Dell PowerEdge 1950 again running Windows Server 2003 R2. The DBMS installation is MySQL.
LIMS supplier responses to ExonHit’s inquiries were varied. A few big names showed little interest or were frankly and perhaps rightly discouraging. “One guy actually said to us, ‘You probably can't afford this system,’ and he didn't know what our budget was. He didn't even ask what our budget was,” Jordan says.
ExonHit is small. The U.S. staff is of roughly 20 and there are 50 in Paris. “We have four scientists here that regularly access and enter data into the LIMS, and there's an additional five or six people, such as our financial people and other managers, who access the LIMS to look at information and get reports; the numbers are the same in our Paris facility,” says Jordan.
Three of the LIMS ExonHit evaluated were more suited for R&D. “They weren't geared toward sample tracking, data management capabilities – the processes I knew I really needed. I needed something with extensive capabilities,” she says. “For example, we have a large array inventory that includes custom arrays on the Affy[metrix] format and Agilent format, different slide array formats, as well as standard commercial arrays from these vendors – and I need to have a lot of detail on my array inventory tracking.”
Other LIMS products didn’t have needed flexibility or would have required substantial programming to make ongoing changes.
“The majority of our clients at this point are academic labs. Many want to do custom-type projects with their favorite gene lists, so Agilent is a nice flexible format for that. We have a portal on our website where researchers can go and select their favorite gene and get a splicing microarray designed for them. These customers have smaller projects, 2, 4, 8, 20 arrays. [But] we also have some pharma with large projects, hundreds of arrays.”
The result is the need to track projects that can have either hundreds of samples or projects that have two to four samples, “so we needed something that was very flexible. We needed something that was capable of not only tracking the samples that came in, but also from the time that we receive either cells or tissue or blood or the total RNA, whatever they decide to send us, we needed to be able to ensure that we could track those from receipt all the way through an array hybridization experiment.”
Jordan adds, “If we had an outlier in an experiment, it's much easier to go into the LIMS and look at lot numbers of reagents that were used or lot numbers of arrays and the date processed, the scanner information from that particular date, and actually troubleshoot and identify the problem, such as an RNA sample that failed the QC and so we eliminated that RNA sample from the study.”
Compatibility with ExonHit’s workflow and speedy deployment were also important, says Jordan. “Exemplar had a lot of array protocols and procedures already programmed in for both Affy and Agilent. It allowed for import of the data files. It just had a lot of the proper protocols already and we were really happy we could hit the ground running,” says Jordan.
Jordan was not looking for a LIMS-cum-analysis-tool-suite. ExonHit hit currently uses the Partek Genomics Suite, which is outside the LIMS. She has added some device management functions: “We can [now] take some of our data output files directly from the lab and have them parsed into the sample sheet. So data information like absorbance values and QC metrics, customized plug-ins – you push a button and it pulls all the data in and fills in all the fields and you have your yes-it-passed-QC answer and you're ready to go.”
She also purchased tablet notebooks and says they’ve been very useful. “Obviously we have a lot of computers in the lab that are hooked up to our scanners and things like that, but much of the wet chemistry can't be tracked on a computer unless they have the tablet there and can enter data as they're working; it's a time-saving thing and it's real-time accessible, so as they're working on something in the lab, I can access it at my desk in my office or the Paris office can look at the LIMS and actually see real-time what's going on and what is happening there.”
Performing due diligence on LIMS products took place last summer. Jordan presented the proposal in the fall to management, which took a couple of months to review it, and signed off towards the end of the year. In the end Jordan found two offerings that were suitable, but preferred Exemplar for its functionality and proximity (Sapio Sciences is roughly an hour away). Deployment took a few weeks, says Jordan, and was surprisingly painless for such a big piece of software. The main challenge turned out to be something she hadn’t anticipated: rethinking workflows to take advantage of the LIMS.
“I haven't done a lot of ROI [return-on-investment] measurement yet because we're working on some higher-profile projects and diagnostic collaborations that have been taking my time. We also do a lot of profiling for internal research projects, and those projects aren't considered in that number. I would say we're saving maybe 40 percent of time involved in non-experimental processes.
“A lot of my time used to be spent writing reports and taking the output files and sorting them for people, burning them on DVDs, all that kind of stuff. Now I can set up a custom report and just click a button and it consolidates all the data and generates a report for me,” she says.
Score one for the commercial vendors.
This article first appeared in Bio-IT World’s Predictive Biomedicine newsletter. Click here for a free subscription.