Cepheid Update POC QA. Gwynn Stevens, PhD Director Virology Programme HBDC

Transcription

1 Cepheid Update POC QA Gwynn Stevens, PhD Director Virology Programme HBDC

2 What will be covered? Quick intro to Cepheid Identification of the need Recognition of the challenges Technology as part of the solution 2 Cepheid Confidential.

3 A High Growth Company +14 Years as a Public Company 8,903 GX Worldwide 17 FDA Cleared Xpert Tests ~1,400 Employees +11M Anthrax tests with no false positives; only technology selected by government 182 Countries with a distribution presence WHO Endorses Revolutionary Xpert MTB/RIF Test 23 CE-IVD Xpert Tests Information as of July Cepheid Confidential.

4 System Placement History 4 Cepheid Confidential.

5 CE-IVD United States Current Test Pipeline Available Now HAI 17 Tests US, 23 Tests ex-us MRSA Surveillance SA Nasal Complete C. diff (US only) C. diff/epi Norovirus vana for VRE (US only) vana/b for VRE (CE-IVD only) MRSA/SA SSTI MRSA/SA BC Carba-R (CE-IVD only) Carba-R Group A Strep Trichomonas HIV Viral Load Breast CA Stratifier BCR-ABL Ultra Pertussis HPV GBS Ultra HCV Viral Load HBV Viral Load CMV Viral Load Bladder CA Monitor Bladder CA Symptomatic GI Panel Meningitis/Encephalitis Vaginitis/Vaginosis CLL Monitor Pancreatic CA Early Detect Breast CA Monitor Breast CA Resistance Monitor Breast CA Signature CID MTB/RIF EV Flu Flu A/B/RSV Ebola (EUA/WHO) Women s/ Sexual Health Virology CT (CE-IVD only) CT/NG Trichomonas (CE-IVD only) GBS & GBS Lim Broth (US only) HPV (CE-IVD only) HIV Qualitative (CE-IVD only) HIV Viral Load (CE-IVD only) HCV Viral Load (CE-IVD only) MTB/RIF Ultra Group A Strep HBV Viral Load BCR-ABL Ultra Bladder CA Breast CA Stratifier 28 Pertussis MTB XDR GI Panel Sepsis Panel Vaginitis/Vaginosis GBS Ultra CMV Viral Load Breast CA Signature CLL Monitor Breast CA Monitor Meningitis/Encephalitis Pancreatic CA Early Detect Pancreatic CA Monitor Breast CA Resistance Monitor Oncology/ Genetics BCR-ABL Monitor (CE-IVD only) FII & FV 5 Cepheid Confidential.

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7 NEED: Collapsing the HIV Treatment Cascade UNAIDS An ambitious treatment target to help end the AIDS epidemic. October Cepheid Confidential.

8 NEED: Large Gap of EID Testing within 2 Months of Birth 8 Cepheid Confidential.

9 Conventional Molecular Diagnostic Needs Cepheid

10 Molecular Diagnostics Complexity Cepheid For Each System: Significant Capital Investment Space, Possible Environmental Considerations Dedicated, Highly Skilled Labor & Ongoing Training Daily/Weekly Maintenance Requirements Maintenance Contract with Supplier Disposable Management

11 Key Components: A simple to use, quality controlled assay Reliable Connectivity In Country Support Let us take care of IQC 11 Cepheid Cepheid Confidential. Confidential.

12 Xpert System Part of the Solution 12 Cepheid Cepheid Confidential. Confidential.

13 Platform Scalability Same Module, Any Configuration, Any Assay Molecular server cabinet architecture enables system to grow with testing needs GX-16 GX-1 GX-2 GX-4 GeneXpert Module GeneXpert Infinity Cepheid Confidential.

14 GeneXpert Module Stand-alone, random access, assay capability Heating/cooling Optical detection Fluid movement Ultrasonic Horn Identical for all Xpert and Infinity Cartridges and Systems 14 Cepheid Confidential.

15 Cartridge Technology Complex Test Process Performed Automatically Within Cartridge Sample Prep, Amplification & Detection Significant Reduction in Hands-on Time Universal Sample Preparation Whole Blood, Plasma, FFPE Tissue, Fecal Material, Sputum, Urine, CSF, others Unique Cartridge Approach Same Interface For All GeneXpert Systems Rotary valve controls movement of fluid between chambers and into PCR tube Fluid moves between chambers or into PCT tube through a filter (sample prep.) or direct path 15 Cepheid Confidential.

16 Assay Control Strategy Each GeneXpert cartridge is a self-contained unit test device (all the complex steps required for PCR take place in the cartridge to minimize risk of contamination) Cepheid designed specific molecular methods to include internal controls that enable the system to detect specific failure modes 16 Cepheid Confidential.

17 Assay Control Strategy Four different elements of the molecular design were created to address all the key failures Probe Check Control (all assays) Specimen Processing Controls SPC / Endogenous Control ( for Xpert BCR/ABL) Sample Adequacy Control SAC( for Xpert CT/NG and Xpert HPV) Sample Volume Adequacy SVA (for Xpert HIV-VL) 17 Cepheid Confidential.

18 Probe Check Control What is it? Just prior to starting thermal cycling, multiple fluorescence readings at different temperatures are made. The results are automatically compared to pre-established factory settings in the software. What does it do? Probe check verifies Bead re-hydration PCR tube filling Probe integrity Dye or quencher instability 18 Cepheid Confidential.

19 Sample Processing Control (SPC) What is it? Armoured RNA Detection probe: A fluorescently-labeled hybridization probe with different color reporter dye than that of the target probe(s) or the internal control (IC); present in primer-probe bead Primers: Can be the same as those for the target or IC or can be unique; present in primer-probe bead What does it do? Co-processed with target organism through entire sample prep process Co-amplified with targets - The SPC assesses the effectiveness of the sample processing steps, including and up to reaction tube filling - Detects degradation of enzyme(s) or other components of system - Detects sample inhibition 19 Cepheid Confidential.

20 Sample Volume Adequacy (SVA) What is it? The Sample Volume Adequacy is a in built pressure check to ensure the input volume of sample is adequate for testing. What does it do? The Sample Volume Adequacy ensures that the sample was correctly added to the cartridge. It verifies that the correct in-volume of sample has been added in the correct sample chamber. A negative SVA indicates an error 2096/2097 due to: insufficient volume No volume * used on Xpert HIV VL 20 Cepheid Confidential.

21 Sample Adequacy Control (SAC) What is it? The Sample Adequacy control is a in built check to ensure that the input sample is adequate for testing. An endogenous human gene is co-amplified to ensure adequate sample has been collected. What does it do? The SAC verifies that there is sufficient material to ensure confidence in a negative result. A negative SAC indicates an INVALID result 21 Cepheid Confidential.

22 Controls in regular PCR DNA Positive Control (PC) - Verifies reagent integrity DNA Negative Control (NC) - Detects 22 Cepheid Confidential. environmental or reagent contamination and verifies reagent integrity Internal control (IC) - Detects PCR inhibition and verifies reagent integrity

23 GeneXpert Real-Time PCR Assay DNA Positive Control (PC) - Probe Check Control DNA Negative Control (NC) - No need! No wet interface between instrument and cartridge and 1 cartridge for 1 sample Internal control (IC) Tube control Better : SPC, not only amplification but extraction too Does not compete with target RNA/DNA. 23 Cepheid Confidential.

24 External Quality Controls Any currently available proficiency panels can be used on this platform e.g. WHO, VQA standards, NEQAS, NHLS SAVQA panel Frequency of EQA testing is determined by the implementing programme 24 Cepheid Confidential.

25 Xpert Assay and System Control Summary Procedural Step & Condition Controlled Pre-, and during run Sample Addition Sample Processing Reagent Addition IQS Probe Check System Checks Final Results Sonication X Failure results in: ERROR Heating, cooling, pressure (clogging), electronics, optics X Failure results in: ERROR Sample aspiration X Failure results in: ERROR Cell lysis X Failure results in: ERROR Nucleic acid recovery X Failure results in: ERROR Bead Presence/Rehydration X X Failure results in: ERROR or INVALID PCR tube fill X X Failure results in: ERROR Fluorogenic detection X X Failure results in: ERROR Thermal cycling X X Failure results in: ERROR PCR Primer or target annealing X Failure results in: INVALID Inhibition X Failure results in: INVALID Quantitation Results Reported X Quantitative Value (IU/ml or copies /ml) Detected Above range Detected Below Range Not Detected 25 Cepheid Confidential.

26 Warranty Extension Purchase of a three year warranty extension contract upfront with the system will result in a total coverage of 5 years for a new GeneXpert (two years of initial warranty attached to the system = 3 additional years) Note that a calibration kit (Xpert Check) per 4 set of modules still need to be purchased to be run at the end of the first year of warranty of the GeneXpert. This is required to validate the second year of warranty attached to each system. 26 Cepheid Confidential.

27 Xpert Check Remote Calibration The Xpert Check kit is used to check the optical system, verify the thermal system and perform a series of system-level tests to ensure full system functionality within Cepheid s instrument servicing specifications. Cepheid recommends that the system be checked for proper operation on an annual basis. Based upon the usage and care of each system, checks may be recommended more frequently. The system is designed to detect module issues with the internal assay controls. At the completion of the Xpert Check data collection process, modules determined to require service will be flagged with an orange icon. 27 Cepheid Confidential.

28 28 Cepheid Cepheid Confidential. Confidential. Connectivity RemoteXpert

29 RemoteXpert A robust data management solution that Provides true, real-time visibility across multiple sites Automates remote data collection Generates end-user insight to improve productivity and performance Accelerates clinical decision-making and patient management Fosters best practice sharing and collaboration RemoteXpert platform is a real-time data management solution that will integrate information streams to enhance productivity and performance. 29 Cepheid Confidential.

30 RemoteXpert Features and Benefits Outcomes Feature Benefit Service & Support Solutions Situational Analysis Real-Time Communications Remote Diagnostics Data Security Asset Management Data Surveillance Fosters best practice sharing and collaboration System-wide alerts, user notifications, and file transfers Redeploy resources to enhance adherence to clinical practice Maximizes uptime through proactive instrument monitoring Real-Time service and support Reduce unplanned service visits Automatic RemoteXpert software downloads Control and monitor system-wide administration Authentication of user rights, roles, access and reporting Data integrity Enhances productivity and program efficiency Coordinate and supervise system-wide operations, logistics, and resources. Manage program costs through proactive inventory management Evaluate and enhance end-user performance training gaps Accelerates clinical decision-making and patient management Act on system-wide insight and performance trends o Epidemiological trends, Incidence vs. Resistance, % Positivity Rate o Quality control programs and reporting 30 Cepheid Confidential.

31 RemoteXpert User Profiles Ministry of Health National Programme Manager Authorised Data Users Cepheid Support RemoteXpert System Administrator Secure Cloud-based Data Repository Test Results - System messages Dashboards - Maps Laboratory Supervisor GeneXpert User GeneXpert 31 Cepheid Confidential.

32 RemoteXpert Pilot Program Insights M Continents Pilot Programs Systems Connected Cepheid Tests Results Collected 32 Cepheid Confidential.

33 Support Provides real time support throughout Africa Global 24 hour hotline support Team of applications specialists and engineers based both in South Africa and throughout Africa to provide onsite support We are establishing a network of regional distributors supported by full service centres in France and South Africa to provide rapid service interventions across Africa We are committed to continuously improving our technology and service Increased system robustness Improved MTBF Decreased downtime Proactive service through RemoteXpert monitoring Cepheid

34 34 The True Point of Care MDx System

35 Introducing the GeneXpert Omni Small and Portable Proven Cartridge Technology Durable Low Power Consumption Automatic Connectivity Solid State Integrated Battery 35

36 GeneXpert Omni Available in 2016 Price $2,895 36

37 Cepheid Cloud Control for Robust Data Management Real-time communications Automated remote data collection Accelerates clinical decisionmaking and patient management System-wide data surveillance 37

38 GeneXpert Omni: Emerging Markets Menu Xpert MTB/RIF Ultra Xpert HIV Qualitative Xpert HIV Viral Load Xpert HCV Viral Load Xpert Ebola Xpert HPV Xpert CT/NG Full Xpert Menu 38

39 What is needed: True Point of Care System Game-Changing MDx System for POC Robust In built IQC Powered Next Generation Connectivity & User Interface Cost Effective Solution Enabling Global Access 39

40 40 Cepheid Cepheid Confidential. Confidential. Internal Quality Control HIV-1 Viral Load Assay

41 Xpert VL Assay Controls ASSAY LEVEL CONTROLS Two internal controls Low and high internal quantitation standards (IQSL, IQSH) Added during sample processing Adjusts for PCR inhibition and recovery efficiency Algorithm utilizes both low and high IQSs Run internally with every cartridge Inhibition control Valid result requires Ct of both IQS to be in range Controls for reagent performance due to improper storage Confirms reaction components are set up correctly SYSTEM LEVEL CONTROLS Probe Check System Checks 41 Cepheid Confidential.

42 Xpert Controls Probe Check METHOD Sample preparation completed and PCR reaction components assembled and moved to tube Fluorescence readings prior to the start of thermal-cycling Valid range established for each lot VERIFICATION ERROR TERMINATES ASSAY BEFORE RT-PCR Bead dispensing Bead re-hydration PCR tube-filling Probe integrity Cleaved, degraded or missing probes Dye and quencher stability 42 Cepheid Confidential. Confidential Not For Distribution

43 Xpert Quant Assay IQS Composition Assay IQS Low Level High Level Point of Addition HIV Armored RNA 10 3 copies/bead 10 6 copies/bead Lysis HCV Armored RNA 10 3 copies/bead 10 6 copies/bead Lysis HBV Plasmid DNA 10 3 copies/bead 2x10 5 copies/bead Sample Confidential Not For Distribution 43 Cepheid Confidential. Contrived sequences Non-analyte to avoid competition Levels defined experimentally Quantitation accuracy across range Precision Lack of interference

44 Xpert HIV VL Key Specifications Attribute Assay Controls Sample Target Subtypes Cartridge LoD Linear Range Reference Assay Specification Two Internal Quantitation Standards (IQS) high and low; both are Armored RNA HIV: 1 ml Plasma; EDTA and ACD Tubes HIV: 3 -end of 5 LTR HIV: Group M Subtypes A-H, AB, AE, AG J, K, Group N, Group O All reagents on board HIV: Goal, 40 c/ml; Observed: ~ 20 c/ml HIV-1 copies/ml Abbott 44 Cepheid Confidential. Confidential Not For Distribution

45 HIV-1 Viral Load: Workflow Collect 5 ml whole blood in an ACD or EDTA plasma tube Centrifugation at x g for 20 minutes Transfer 1 ml of plasma to sample chamber via transfer pipette Scan cartridge barcode Load cartridge Time to Result in GeneXpert = 90 min 45 Cepheid Confidential.

46 Cepheid Complexity creates confusion, simplicity focus. Edward de Bono

47 Thank You. Visit us at 47