Clarity LIMS - A Complete Solution for Regulated Laboratories

Clarity LIMS - A Complete Solution for Regulated Laboratories

Executive Summary A laboratory information management system (LIMS) can provide significant support to lab directors and managers in CLIA-certified environments by helping them to attain and retain their certification, demonstrate compliance during audits, mitigate risk, and reduce turn around time as part of their organizations overall quality management system. Clarity LIMS provides capabilities that help lab directors meet and demonstrate the following CLIA guidelines: Specimen Identification and Integrity Procedure Manual Control Procedures Laboratory Director Responsibilities Test Records Clarity LIMS supports key requirements for ensuring data integrity, allowing for enforcement of data entry and workflows, monitoring processes, and record keeping. Page 1 2012 GenoLogics Life Sciences Software, Inc.

Introduction to Clarity LIMS support for CLIA Environments Introducing genomics tests to regulated laboratory environments can be a challenging endeavor for laboratory directors, management and staff. These organizations need to meet CLIA standards for mitigation of potential risks, attain accreditation through governmental agencies, and undergo periodic audits, all while maintaining a high sample throughput. In this challenging environment a laboratory information management system (LIMS) built specifically for the support of genomics tests provides significant benefits. Obtaining certification and periodic audits demand that lab management maintain detailed records for demonstrating compliance. Lab directors and lab managers can rest easy knowing that with Clarity LIMS they have data entry enforcement in place to track all compliance related information, quick electronic access to compliance demonstration information, easy tools for monitoring systems and strong supporting documentation, all of which create a well-prepared environment for the certification and re-certification process. This document provides a detailed description of the CLIA standards supported by the system such as: Specimen Identification and Integrity Procedure Manual Control Procedures Laboratory Director Responsibilities Test Records Page 2 2012 GenoLogics Life Sciences Software, Inc.

Clarity LIMS Support for CLIA Requirements CLIA Subpart K, Quality Systems for Non-Waived Testing 493.1232 Standard: Specimen identification and integrity The laboratory must establish and follow written policies and procedures that ensure positive identification and optimum integrity of a patient s specimen from the time of collection or receipt of the specimen through completion of testing and reporting of results. Support for Specimen Identification and Integrity Used in conjunction with written policies and procedures, the sample tracking, data entry enforcement and workflow enforcement capabilities of Clarity LIMS can help ensure identification and integrity of a patient s specimen from receipt through testing and results reporting. When a sample arrives at the lab, sample name, information and container identifiers are uploaded into the LIMS, which automatically assigns a unique LIMS identifier (LIMSID) to the sample (Figure 1a). As the sample undergoes processing, the lab scientist is required to execute lab-configured workflows and follow lab-configured data entry requirements (Figure 1b). The LIMS maintains the association of the LIMSID with each successive container ID/well position, ensuring that the appropriate results and data are associated with the sample on the completion of testing. All activities are recorded in an access-controlled, secure and centralized environment. Tracking all samples end-to-end throughout an enforced laboratory workflow along with configuring enforcement of data entry for SOP required information not only provides support for CLIA regulations for Specimen Identification and Integrity, but also ensures that these procedures are followed each and every time a sample is processed. Laboratory management can feel confident in the integrity of the data produced for every sample that enters the lab. Figure 1a: LIMS Assigns Each Sample a Unique Identifier that Tracks all Downstream Processes Through the Lab. Figure 1a An example of sample information collected and assigned upon receipt is shown below. When a sample arrives at the lab the sample name (Heart study sample 267, for example), information and container identifiers are uploaded into the LIMS that then automatically assigns a unique identifier. The LIMS maintains this association with the LIMSID with each successive processing step in the laboratory. Page 3 2012 GenoLogics Life Sciences Software, Inc.

Data Entry Enforcement Figure 1b Laboratory management can configure fields required for data entry to match standard SOPs such as reagent lot numbers, as seen in this example below. The system will not allow samples to move onto a sequential step unless required data is entered thus ensuring all required data are collected according to laboratory procedures. Page 4 2012 GenoLogics Life Sciences Software, Inc.

CLIA Subpart K, Quality Systems for Non-Waived Testing 493.1251 Standard: Procedure manual (a) A written procedure manual for all tests, assays, and examinations performed by the laboratory must be available to, and followed by, laboratory personnel. (c) Manufacturer s test system instructions or operator manuals may be used, when applicable, to meet the requirements of paragraphs (b)(1) through (b)(12) of this section. Clarity LIMS Documentation Supports Procedure Manual Requirement Documentation provided with Clarity LIMS may be included in the laboratory s written test procedure manual. Along with kit protocols and other materials, the workflows configured within the LIMS and the recommended procedures and best practices for LIMS utilization provide a framework for the laboratory s procedure manual (Figure 2a). Figure 2a Further examples from the Clarity LIMS manual. Page 5 2012 GenoLogics Life Sciences Software, Inc.

Clarity LIMS Supports Procedure Manual Enforcement Requirement (Figure 2b & 2c) Clarity LIMS allows only protocols and workflows in the Active state to be viewable and executable by laboratory staff (Figure 2b). Additionally, once a protocol or workflow is made Active by laboratory management it cannot be further modified. Protocols and Workflows can be modified and configured by lab management in the Pending state, these protocols and workflows are viewable by laboratory management only and are not executable by other lab staff (Figure 2c). Creating enforced protocols and workflows ensure that laboratory procedure manuals are followed by laboratory staff and all data are tracked appropriately. Allowing for new protocols to be created by lab management in the Pending state provides flexibility to introduce new protocols and workflow into the laboratory without creating risk that these new procedures will be applied prior to validation. Procedure Manual Enforcement Figure 2b An example of an enforced workflow is show below. Options for performing next steps are limited to laboratory approved SOP steps only. In this example below the lab scientist may only: repeat the sample step, escalate the sample for lab management review, remove the sample from future work or perform QC and repair ends as next steps on the samples. These enforced workflows are fully configurable by laboratory management to meet the organizations standard procedures. Active and Pending Workflows Figure 2c An example of a screen, viewable by Laboratory Management only, which lists Active and Pending Workflows. The selected Active Workflow is not modifiable and can only be archived. Pending Workflows are modifiable until they are placed onto Active status. Page 6 2012 GenoLogics Life Sciences Software, Inc.

CLIA Subpart K, Quality Systems for Non-Waived Testing 493.1256 Standard: Control procedures a) For each test system, the laboratory is responsible for having control procedures that monitor the accuracy and precision of the complete analytic process. (c) The control procedures must (2) Monitor over time the accuracy and precision of test performance that may be influenced by changes in test system performance and environmental conditions, and variance in operator performance. Clarity LIMS Addresses Control Procedures with Reporting Capabilities Clarity LIMS provides reporting functionality to enable lab directors to monitor process quality, accuracy and precision of laboratory instrumentation. Figure 3a shows an example of a report available upon install in Clarity LIMS. The Sample History report shows detailed information for a single sample, including the original information submitted when it entered the lab, and all the key processes that were run on the sample while it was in the lab, along with other relevant data associated with each step. Figure 3a Example of a Sample History Report available in Clarity LIMS. The report shows detailed information for a single sample, including the original information submitted when it entered the lab and all the key processes that were run on the sample while it was in the lab, along with other relevant data associated with each step. Page 7 2012 GenoLogics Life Sciences Software, Inc.

The Process Summary report, shown in Figure 3b, provides detailed information on processes performed and key data collected for a group of samples. Figure 3b Clarity LIMS provides two types of reporting functionality to enable lab directors to monitor process quality: custom built reports and out of the box reports such as the Process Summary Report below The Process Summary shows an example of a quality control (QC) process summary screenshot that displays pass/fail assignment and QC test data. For every single QC step performed by the technician, Clarity LIMS records the technician s name and the date it was run, as well as test data and test result. This way Clarity LIMS provides a detailed record of which samples failed QC and the reasoning for the failure, facilitating the record keeping on the condition and disposition of failed samples. Page 8 2012 GenoLogics Life Sciences Software, Inc.

The Run Summary Report (Figure 3c and 3d) is produced at the completion of a sequencing run that enables monitoring of performance of the sequencing runs over time. This Run Summary Report provides contextual information and primary analysis metrics per lane, as well as, a summary of the metrics for the total run. Also included in this report are the historical run metrics for the previous runs performed on the same sequencer. The report automatically highlights values that are more than one standard deviation outside the average value of the five previous runs, so lab directors can easily monitor performance over time. Sequencing Run Summary Reports (Part 1) Figure 3c Run information includes instrument ID, type of run, number of cycles, flow cell ID, start date, finish date, SBS reagent lot. Sample information shows sample name, LIMS ID and flow cell lane for each sample included in the run. Illumina Sequencing Report Instrument Name Flow Cell ID Start Date Finish Date Output Folder SN196R FC7024KABXX 2011-04-25 2011-04-29 \\hw-isilon\mfg\hiseq\sn0697 Additional Run Information Illumina Experient Name FIT Run Instrument Details Name SN196R Illumina Run ID 110118_SN697_0025_AFC7024KABXX Model HiSeq 2000 Genus LIMS Run ID SBS-JRO-110429-24-14849 Software HCS/RTA Output Folder \\hw-isilon\mfg\hiseq\sn0697 Run Type Single Read Run Number of Cycles 102 Flow Cell ID FC7024KABXX Flow Cell Version HiSeq Flow Cell v1.5 Flow Cell Position A TruSeq SBS Kit lot # 20101231 Sample Information Lane Sample Sample LIMS ID 1 DNA frag library #17 clusters ADM19A41SB2 2 DNA frag library #23 clusters ADM19A42SB2 3 DNA frag library # clusters ADM19A43SB2 4 RNA-Seq library 23 clusters ADM19A44SB2 5 E_coli reseq clusters ADM19A45SB2 6 Liver transcriptome Sample X34 clusters ADM19A46SB2 7 Liver transcriptome Sample X35 clusters ADM19A47SB2 8 Liver transcriptome Sample X36 clusters ADM19A48SB2 Page 9 2012 GenoLogics Life Sciences Software, Inc.

Clarity LIMS also enables lab teams to build specialized reports, extending the reporting capabilities of the LIMS beyond the preconfigured reports available upon install. Sequencing Run Summary Reports (Part 2) Figure 3d Run Summary shows current run performance metrics including raw data yield, average Q score, % bases Q30 and above, cluster density, raw clusters, clusters passing filter, % clusters passing filter, cycle 1 intensity, % intensity cycle 20, phasing %, pre-phasing %, aligned %, error rate %. ) Historical Run Metrics provide historical averages for these metrics for the past five runs on this instrument. NOTE: Current run values that vary beyond +/- 1 standard deviation from historical average will be highlighted in the current run metric table. Run Summary (102 cycles) Lane Raw Yield (GB) Ave Q Score Bases > Q30 Cluster Density Clusters Raw (%) (K/mm^2) Clusters PF PF (%) Intensity Cycle % Intensity Phasing (%) Prephasing (%) Aligned (%) Error Rate (%) 1 Cycle 20 1 8.35 37.3 94.3 474 87,453,943 81,830,332 93.6 5,216 79.5 0.294 0.218 98.2 0.20 2 7.85 37.5 94.7 442 81,459,338 76,961,898 94.5 5,161 79.4 0.293 0.222 98.6 0.26 3 7.72 37.6 95.1 434 79,988,198 75,609,405 94.5 5,136 79.4 0.292 0.225 98.6 0.19 4 7.81 37.6 95.1 441 81,305,627 76,637,643 94.3 5,244 79.8 0.292 0.224 98.6 0.19 5 7.82 37.6 95.0 440 81,122,342 76,724,275 94.6 5,117 79.4 0.293 0.227 98.6 0.29 6 7.72 37.6 95.2 433 79,890,635 75,654,429 94.7 5,136 79.5 0.293 0.223 98.6 0.17 7 7.38 37.6 95.5 414 76,224,935 72,337,824 94.9 5,066 79.4 0.293 0.224 98.4 0.18 8 7.46 37.6 95.3 418 77,011,699 73,111,963 94.9 4,922 79.3 0.293 0.225 98.6 0.17 Summary 62.11 37.5 95.0 437 644,456,717 608,867,769 94.5 5,125 79.4 0.293 0.223 98.5 0.21 SN697 Historical Run Metrics Calculated using data from last 5 runs on the instrument (containing 40 lanes). Raw Yield (GB) Ave Q Score Bases > Q30 Cluster Density Clusters Raw Clusters PF PF (%) Intensity Cycle % Intensity (%) (K/mm^2) 1 Cycle 20 Phasing (%) Prephasing (%) Aligned (%) Error Rate (%) Lane Ave. 10.46 33.0 80.3 525 85,997,711 76,184,346 83.9 4046.1 82.7 0.267 0.302 0.0 Std. Dev. 8.48 5.4 17.8 179 52,146,619 46,113,040 16.9 1685.2 5.1 0.099 0.054 Max 18.79 36.5 92.7 808 149,022,448 129,170,523 94.1 5383.2 89.3 0.442 0.363 0.0 Min 0.54 23.5 49.2 315 4,108,497 3,725,583 54.2 1397.3 78.3 0.198 0.223 0.0 Flow Cell Total 418.46 3,439,908,44 3,047,373,85 0.0 Page 10 2012 GenoLogics Life Sciences Software, Inc.

CLIA Subpart K, Quality Systems for Non-Waived Testing 493.1283 Standard: Test records (a) The laboratory must maintain an information or record system that includes the following: (1) The positive identification of the specimen. (2) The date and time of specimen receipt into the laboratory. (3) The condition and disposition of specimens that do not meet the laboratory s criteria for specimen acceptability. (4) The records and dates all specimen testing, including the identity of the personnel who performed the test(s). (b) Records of patient testing including, if applicable, instrument printouts, must be retained. Clarity LIMS Provides a System of Record Keeping (Figure 4a) By logging samples into the LIMS upon receipt, the date of receipt is captured and recorded in the sample genealogy. This logging process also supports identification of a patient s specimen from receipt through testing and reporting results. As the sample undergoes quality control (QC) testing, the results of these tests are attached to the appropriate step in the sample genealogy. Pass/Fail scoring is recorded within the genealogy both for individual QC tests and can also be configured for summary and aggregation of several different QC tests. The LIMS provides a record of which samples have failed QC, facilitating record keeping on the condition and disposition of failed samples in the lab. Clarity LIMS provides a sample genealogy view, which when used in conjunction with written policies and procedures, constitutes a system of record keeping for the following information pertaining to a given sample: All steps performed on the sample. The date each step was performed. Who performed each step. Identity of the lab instrument used in a step. The results from each step. The sample genealogy records the lab scientist who performed each step, as well as the date on which the step was performed. Lastly, the sample genealogy contains links to the data related to that sample, supporting data integrity from sample submission to data delivery. The information provided within this view can also be exported directly into a table format, allowing for sorting and sharing of this information. Page 11 2012 GenoLogics Life Sciences Software, Inc.

Figure 4a The sample genealogy records all steps performed on a sample, who performed the steps, and when. Clarity LIMS preserves the connection between the LIMS ID and the container/well ID for each successive container as the sample is processed. It also captures the date and technician ID for each step performed on the sample. Page 12 2012 GenoLogics Life Sciences Software, Inc.

CLIA Subpart K, Quality Systems for Non-Waived Testing 493.1445 Standard: Laboratory director responsibilities (e) The laboratory director must (1) Ensure that testing systems developed and used for each of the tests performed in the laboratory provide quality laboratory services for all aspects of test performance, which includes the preanalytic, analytic, and postanalytic phases of testing. (8) Ensure that reports of test results include pertinent information required for interpretation. Laboratory activities recorded in the Clarity LIMS are recorded in the sample genealogy for each sample. The data captured by the LIMS on sample and system performance are incorporated into reports including the Illumina Run Summary Report (shown previously in Figures 3c & d), Process Summary Report (see Figure 3b), and Sample History Report (Figure 3a). These reports help meet requirements for process monitoring and quality assurance. The sample genealogy enables lab directors to review laboratory procedures for accuracy and compliance to laboratory practices. Because the workflows provided in the Clarity LIMS reflect NGS protocols and procedures of sample preparation kits and sequencing protocols, the sample genealogy enables the lab director to review processes and procedures performed on that sample at a level of detail not provided by other off-the-shelf commercial LIMS solutions. The Run Summary Report provides lab directors with information upon completion of each sequencer run, such as: What samples were processed in the run. How the run was performed. Who performed the run. Which reagent lots were used. The report also provides run metrics on: Data quality Signal intensity Total yield of data Additional measures that reflect quality. This report also shows historical data on these same metrics for previous runs on the same sequencer, and highlights data from the current run that varies by more than one standard deviation from the expected value for that metric. Page 13 2012 GenoLogics Life Sciences Software, Inc.

Summary Laboratory directors and staff operating in regulated lab environments require systems that support adherence to protocols and practices that help to ensure compliance with regulatory guidelines and directives. Clarity LIMS provides powerful assistance to lab directors and managers in demonstrating compliance during periodic CLIA audits, and help organizations maintain their CLIA certification. Lab management can be at ease knowing that sample data integrity is not only maintained throughput complex lab processes, but also that this integrity is well documented for providing evidence of compliance. Specifically, Clarity LIMS provides capabilities that help lab directors meet the following CLIA guidelines: Specimen Identification and Integrity Procedure Manual Control Procedures Laboratory Director Responsibilities Test Records Clarity LIMS supports key requirements for ensuring data integrity, allowing for enforcement of data entry and workflows, monitoring processes, and record keeping. Clarity LIMS is a complete information support system for regulated laboratories performing genomics tests. Page 14 2012 GenoLogics Life Sciences Software, Inc.

genologics.com GenoLogics Life Sciences Software Suite 2302-4464 Markham Street, Victoria, B.C., Canada, V8Z 7X8 Toll free: 1-866-457-5467 Main: 1-250-483-7011 Fax: 1-250-483-7777 info@genologics.com