An IVD Sector or Vi View o of the C e CIPM-MR MRA Prepared By - PowerPoint PPT Presentation

An IVD Sector or Vi View o of the C e CIPM-MR MRA Prepared By Gary L. Myers, PhD. VP, Science and Practice Affairs, AACC Chair, JCTLM Executive Committee

Good laboratory medicine requires:  Total error of a clinical measurement is small enough that a result reflects a patient ’ s biological condition  Comparable results that are independent of  where and when a test was performed  the measurement procedure used

Why do we need accurate and traceable results If different measurements give different results for the same patient sample:  Clinical practice guidelines become less useful  Patients may receive incorrect treatment  Laboratory results in EHRs are less useful

IVD Companies Develop Clinical Instrumentation for Patient Care High Sample Throughput Clinical Analyzers Low Sample Throughput Point-of-Care-Devices

Total IVD Worldwide Revenue Worldwide revenue for 2014 - $55.8 Billion USD* Worldwide revenue forecast for 2019 - $68.9 Billion USD* IVD companies that account for >70% of industry revenue* • Alere • Roche • Bayer • Abbott • Hologic • Siemens • IL • Lifescan • Diasorin • Biomerieux • Cepheid • Becton Dickinson • Qiagen • OCD • Grifols • Sysmex • Immucor • Thermo Fisher • Diagnostica Stago • Bio-Rad * Source - boston biomedical consultants, inc.

Traceability (based on ISO 17511) Primary Reference Patient sample results are equivalent to SI unit Material the reference procedure results Reference (pure substance) Procedure Secondary (e.g. IDMS) Reference Material (calibrator) (matrix) TRACEABILITY Mfr Selected Procedure The IVD companies and clinical laboratories need Mfr Working Calibrator Mfr Standing Reference Measurement Procedures Procedure Mfr Product Certified Reference Materials Calibrator Routine Procedure Reference Measurement Laboratories Patient sample result

JCTLM – What has it provided? • JCTLM through BIPM maintains a database of Reference Measurement Systems http://www.bipm.org/jctlm/ • Coordinates the nomination and review process for database entries JCTLM database was developed to help the IVD industry meet metrological traceability requirements of the EU IVD Directive Database Contains: • 330 Certified Reference Materials • 170 Reference Measurement Procedures • 130 Reference Measurement Services

The JCTLM has a vetted, documented review process for assessing which reference materials, reference methods and measurement services meet the criteria for inclusion in the JCTLM Database.  However, every now and then, a reality-check is needed to check that the “paper review process” is working properly. • This has been achieved on a limited basis by having a single laboratory use a JCTLM-listed Reference Measurement Procedure under repeatability conditions to assess for comparability the JCTLM-listed Reference Materials for a specific measurand.

Comparability of Cholesterol in Serum CRMs on JCTLM LIST SRM 1952a l-3 1.01 Measured / Certified Value 300 Measured Value, mg/dL SRM 1951a l-2 1.00 JCCRM M 250 SRM 909b l-2 SRM 1952a l-2 0.99 JCCRM H 200 SRM 909b l-1 0.98 SRM 1951a l-1 SRM 968c l-2 SRM 1589a 150 SRM 1952a l-1 SRM 968c l-1 Med = 0.9933 JCCRM H JCCRM M SRM 1589a SRM 909b l-1 SRM 909b l-2 SRM 968c l-1 SRM 968c l-2 SRM 1951a l-1 SRM 1951a l-2 SRM 1952a l-1 SRM 1952a l-2 SRM 1952a l-3 Med:s = 0.0069 150 200 250 300 U(Med) = 0.0055  CRM comparability The measured/certified ratios for this set of CRMs are: independent of • ~ normally distributed analyte level • with a standard deviation of ~0.7%

Listed CRMs for Potassium in Human Serum were assessed for comparability by a single laboratory (NIST) using a reference measurement procedure under repeatability conditions: • to assess veracity of the Normative Standards-Based Review Process • To establish bias that could be introduced by randomly selecting any material from the List Fig 1: Ratio Display Fig 2: Scattergram Display 1.02 909b 2 6 956a 1 Measured [Potassium], X i , nmol/L 111-5 H 1.01 Measured / Certificate 5 111-5 M 1.00 4 956a 2 909b 1 111-5 L 3 0.99 956a 3 2 0.98 JCCRM JCCRM JCCRM SRM SRM SRM SRM SRM X i = (0.003 ±0.013) + (0.9993 ±0.0028)× C i 111-5 111-5 111-5 909b 909b 956a 956a 956a 1 L M H Lev1 Lev2 Lev1 Lev2 Lev3 1 2 3 4 5 6 Certified [Potassium], C i , nmol/L Certified 95% CI Average Ratio Ratio ~95% CI Fig 1: The vertical axis reports the ratio between the measured and certified values of each CRM, X i / C i . The dark vertical lines represent the approximate 95% CI about the ratios. The light horizontal lines represent the certified 95% CIs. The dotted line represents the expected ratio for the suite of all materials given the observed identity between the measured and certified values. (CI = Confidence Interval) Fig 2: The data demonstrate that these CRMs are comparable over a wide concentration range. The horizontal axis reports the certified values, C i ; the vertical reports the average measured values, X i . Each level of each CRM is displayed as approximate 95% CIs along both axes. The intersection of these intervals is bounded by an open circle to aid visual inspection.

Source (country of origin ) of CRMs in JCTLM Database

JCTLM Database Update – January 2015 JCTLM Database Users Othe her I Indus ndustrial Com ompan pany, 3% 3% Oth Other Accred editat ation n 10% 10% Body ody, 2% 2% IVD D Manuf anufac acturer er, 20% 20% NMI/D /DI, 7 I, 7% Ref efer eren ence e Clini nical Labor Laboratory, , Meas easur uremen ent 33% 33% Labor Laborator ory, 20% 20% Ref efer eren ence M e Mat ater erial Produc oducer, 5 % 5 %

The “Quality Behind the Product” JCTLM Database: www.bipm.org/jctlm/ Key Comparison Database (KCDB) The BIPM Key Comparison Database (KCDB) is a public website containing all results of the principal mechanisms of the CIPM MRA – measurement comparisons and CMC declarations 13

Summary • The JCTLM Database provides the products for traceability needed by these IVD Companies and laboratories • The Key Comparison Database provides “the quality behind the product”