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

An IVD Sector

• r Vi

View o

• f 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

High Sample Throughput Clinical Analyzers Low Sample Throughput Point-of-Care-Devices

IVD Companies Develop Clinical Instrumentation for Patient Care

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*

• Roche
• Abbott
• Siemens
• Lifescan
• Biomerieux
• Becton Dickinson
• OCD
• Sysmex
• Thermo Fisher
• Bio-Rad
• Alere
• Bayer
• Hologic
• IL
• Diasorin
• Cepheid
• Qiagen
• Grifols
• Immucor
• Diagnostica Stago

Total IVD Worldwide Revenue

* Source - boston biomedical consultants, inc.

Reference Procedure Primary Reference Material

(pure substance) (e.g. IDMS)

SI unit

Traceability (based on ISO 17511)

Routine Procedure Patient sample result

TRACEABILITY

Patient sample results are equivalent to the reference procedure results

Secondary Reference Material

(matrix)

Mfr Selected Procedure Mfr Product Calibrator Mfr Working Calibrator Mfr Standing Procedure

(calibrator)

The IVD companies and clinical laboratories need

Reference Measurement Procedures Certified Reference Materials Reference Measurement Laboratories

• 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

JCTLM – What has it provided?

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.

 CRM comparability independent of analyte level

The measured/certified ratios for this set of CRMs are:

• ~ normally distributed
• with a standard deviation of ~0.7%

150 200 250 300 150 200 250 300

JCCRM H JCCRM M SRM 909b l-1 SRM 909b l-2 SRM 968c l-1 SRM 968c l-2 SRM 1589a SRM 1951a l-1 SRM 1951a l-2 SRM 1952a l-1 SRM 1952a l-2 SRM 1952a l-3

Measured Value, mg/dL

Comparability of Cholesterol in Serum CRMs on JCTLM LIST

U(Med) = 0.0055 Med:s = 0.0069 Med = 0.9933

1.01 1.00 0.99 0.98

SRM 1952a l-3 SRM 1952a l-2 SRM 1952a l-1 SRM 1951a l-2 SRM 1951a l-1 SRM 1589a SRM 968c l-2 SRM 968c l-1 SRM 909b l-2 SRM 909b l-1 JCCRM M JCCRM H

Measured / Certified Value

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: The vertical axis reports the ratio between the measured and certified values of each CRM, Xi/Ci. 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, Ci; the vertical reports the average measured values, Xi. 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. Fig 1: Ratio Display Fig 2: Scattergram Display

Lev3 956a SRM Lev2 956a SRM Lev1 956a SRM Lev2 909b SRM Lev1 909b SRM H 111-5 JCCRM M 111-5 JCCRM L 111-5 JCCRM

0.98 0.99 1.00 1.01 1.02

Measured / Certificate

Certified 95% CI Average Ratio Ratio ~95% CI

956a 3 956a 2 956a 1 909b 2 909b 1 111-5 H 111-5 M 111-5 L 1 2 3 4 5 6 1 2 3 4 5 6

Certified [Potassium], C i , nmol/L Measured [Potassium], Xi , nmol/L X i = (0.003 ±0.013) + (0.9993 ±0.0028)×C i

Source (country of origin ) of CRMs in JCTLM Database

JCTLM Database Update – January 2015

JCTLM Database Users

IVD D Manuf anufac acturer er, 20% 20% Ref efer eren ence e Meas easur uremen ent Labor Laborator

• ry, 20%

20% Clini nical Labor Laboratory, , 33% 33% Ref efer eren ence M e Mat ater erial Produc

• ducer, 5 %

5 % NMI/D /DI, 7 I, 7% Accred editat ation n Body

• dy, 2%

2% Othe her I Indus ndustrial Com

• mpan

pany, 3% 3% Oth Other 10% 10%

Key Comparison Database (KCDB)

13

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

The “Quality Behind the Product”

JCTLM Database: www.bipm.org/jctlm/

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”