The Future of Reference Materials Science and Innovation

Size: px

Start display at page:

Download "The Future of Reference Materials Science and Innovation"

Rudolph Johns
6 years ago
Views:

1 Status and Trends in In-Vitro Diagnostics and Considerations for Reference Materials The Future of Reference Materials Science and Innovation Conference in the frame of the 50th anniversary of the JRC s Institute for Reference Materials and Measurements Geel, Belgium, November 2010 Frank Vitzthum, Siemens Healthcare Diagnostics Products GmbH Protection notice / 2010 Siemens Healthcare Diagnostics Products GmbH. All rights reserved.

2 Overview Status of laboratory diagnostics in healthcare Global trends and trends in in-vitro diagnostics Proteomics research Considerations for reference materials Page Protection notice / 2010 Siemens Healthcare Diagnostics Products GmbH

.. Patient care space IVD / laboratory space Page 3 23.

3 In-Vitro Diagnostics Status Quo In-vitro diagnostics is hardly visible any more... Patient care space IVD / laboratory space Page Protection notice / 2010 Siemens Healthcare Diagnostics Products GmbH

IVD: the hidden treasure in healthcare Minimal IVD expenditures save lives and money. Still, IVD expenditures are deemed too high, and their value is underestimated.

4 IVD: the hidden treasure in healthcare Minimal IVD expenditures save lives and money. Still, IVD expenditures are deemed too high, and their value is underestimated. Impact of IVDs contribute up to 94 % of the objective data in clinical records influence % of critical decision making reduce mortality and morbidity improve quality of life and patient care reduce health care costs Health Expenditures World-Wide 2,780 BIO US $ ~ 1-2 % IVD Page Protection notice / 2010 Siemens Healthcare Diagnostics Products GmbH

Megatrends shape our future Globalization From 1950 to 2004, the volume of global trade has increased 27.5-fold. The number of global players has grown from 17,000 in 1980 to over 70,000 today.

Urbanization 2007: for the first time in history, more people live in cities than in rural areas.

6 Megatrends shape our future Globalization From 1950 to 2004, the volume of global trade has increased 27.5-fold. The number of global players has grown from 17,000 in 1980 to over 70,000 today. Ocean freight has increased over the past four decades from less than 6,000 billion ton-miles to over 27,500 billion ton-miles a year. Urbanization 2007: for the first time in history, more people live in cities than in rural areas. Today 280 million people live in megacities (> 10 million residents) 2030: 60 % of the world s population will live in cities Urban conglomerations contribute a high share of a nation s economic output: Tokyo provides 40 % of Japan s GDP, Paris generates 30 % of France s GDP. Page Protection notice / 2010 Siemens Healthcare Diagnostics Products GmbH

Today we face the highest CO 2 concentration in the atmosphere for the past 350,000 years. Demographic Change Average life expectancy worldwide will increase to 72 years in 2025 from 46.

7 Megatrends shape our future Climate Change The average global surface temperature has increased by 0.76 C compared to the 18th century. 11 of the 12 years between 1994 and 2005 rank among the 12 warmest since weather observations began. Greenhouse gas emissions haven risen dramatically since industrialization. Today we face the highest CO 2 concentration in the atmosphere for the past 350,000 years. Demographic Change Average life expectancy worldwide will increase to 72 years in 2025 from 46.6 years in World population will grow from more than 6 billion now to 8 billion by % of the global population growth is taking place in developing countries. The 65+ generation will nearly double worldwide by 2030 (from 7 % to 12 %), Page Protection notice / 2010 Siemens Healthcare Diagnostics Products GmbH

8 Key impacts of Megatrends on In-Vitro Diagnostics Infectious Disease Diagnostics Disease of aging or lifestyle, e.g. Neurological diseases Cardiovascular diseases Diabetes Cancer Disease prevention Globalization of healthcare: standardization & harmonization Page Protection notice / 2010 Siemens Healthcare Diagnostics Products GmbH

9 Major trends in In-Vitro Diagnostics Further economization also in healthcare cost pressure to persist Demand for increased efficiency & efficacy Consolidation (laboratories, IVD manufacturers, instruments, automation, miniaturization, etc.) Process & workflow optimization Information management (IT solutions) Near patient testing and POC when needed Nucleic acid diagnostics Improved treatment through IVDs (personalized/stratifying medicine) New technologies New biomarkers Standardization & Harmonization Page Protection notice / 2010 Siemens Healthcare Diagnostics Products GmbH

10 Reference materials: the hidden treasure in IVD No matter what trends will materialize or not IVD results should be the same in Geel and in Marburg and all over the world yesterday, today and tomorrow Reference materials are essential for reliable reference intervals and decision points to diagnose, monitor and treat patients appropriately. Page Protection notice / 2010 Siemens Healthcare Diagnostics Products GmbH

11 IVD Biomarkers Gases Electrolytes / Trace Elements Metabolites Amino acids (derivatives) Lipids Nucleic Acids Carbohydrates Peptides/Proteins Complexity of analyte Page Protection notice / 2010 Siemens Healthcare Diagnostics Products GmbH

12 Proteins will continue to dominate the emerging IVD biomarker arena Protein testing is usually close to the phenotype Page Protection notice / 2010 Siemens Healthcare Diagnostics Products GmbH

13 Proteomics New Horizons in Protein Diagnostics? Page Protection notice / 2010 Siemens Healthcare Diagnostics Products GmbH

14 Despite great expectations and investments for proteomics endeavour, the success in delivering new in-vitro diagnostics has been limited so far! Page Protection notice / 2010 Siemens Healthcare Diagnostics Products GmbH

15 Major challenges Reproducibility & comparability Preanalytics including the clinical question & study design Transferability to installed base and/or clinical workflow Verificationchallengesbyproteomicstechnologies Accuracy versus throughput & multiplexing Challenge to discover & measure low abundance protein biomarkers in complex samples such as blood specimens Verification challenges by immunoassays Resources & time for assay development (of multiple tests) (definition of the measurand, antibody development, etc.) Page Protection notice / 2010 Siemens Healthcare Diagnostics Products GmbH

16 Can we leverage the strengths of different fields to get clinical relevant and standardized immunoassays faster to the market for the benefit of healthcare and the patients? Page Protection notice / 2010 Siemens Healthcare Diagnostics Products GmbH

17 How can we leverage different strengths Communication & collaboration Leverage methodologies and know-how used in different fields Align & harmonize search for new biomarkers More rigorous examination of existing biomarkers Defining the clinically relevant measurand(s) Leverage existing and develop new reference materials Page Protection notice / 2010 Siemens Healthcare Diagnostics Products GmbH

18 Reference materials and mass spectrometry for protein & peptide testing in R&D & IVD Mass Spectrometry Research & Development (Proteomics) Research 4 Proteomics Research Standard Initiate Immunoassay development for a defined measurand Standardized Immunoassay Reference Materials 6 Support AQUA Mass Spectrometry 1 Reference Measurement System In-vitro Diagnostics Page Protection notice / 2010 Siemens Healthcare Diagnostics Products GmbH

19 1 ID-LC-MS² under consideration as reference measurement procedure C-Reactive Protein Myoglobin Cystatin C Insulin Etc. Page Protection notice / 2010 Siemens Healthcare Diagnostics Products GmbH

$2 Assessment of manufacturer s control for Proteomics research purposes Liquid chromatography fraction # m/z Aprotinin Overlay of Mean Differential Peptide Display of Human Plasma (red) and a$

20 2 Assessment of manufacturer s control for Proteomics research purposes Liquid chromatography fraction # m/z Aprotinin Overlay of Mean Differential Peptide Display of Human Plasma (red) and a Manufacturer s Control (N/T Protein Control SL Level L (blue)) Vitzthum F, Siest G, Bunk DM, Preckel T, Wenz C, Hoerth P, Schulz-Knappe P, Tammen H, Adamkiewicz J, Merlini G, Anderson NL (2007) Proteomics Clin. Appl. 1, Page Protection notice / 2010 Siemens Healthcare Diagnostics Products GmbH

21 3 Orientation measurements ,1 0,01 1E-3 1E-4 1E-5 1E-6 1E-7 1E-8 Serum Heparin plasma EDTA plasma Citrate plasma Reference intervals Human Proteome Organization Plasma Protein Project Pilot Phase 1E-9 Albumin IgG IgG 1 Transferrin Fibrinogen IgG 2 a2-macroglobulin Apolipoprotein A-I a1-antitrypsin C3c IgA Apolipoprotein B Orosomucoid Hemopexin IgM Haptoglobin Apolipoprotein A-II Fibronectin IgG 3 Ceruloplasmin Prealbumin Antithrombin III C4 IgG 4 Plasminogen RbP Apolipoprotein E CRP stfr ß2-Microglobulin Myoglobin Myoglobin IgE Ferritin Ferritin TPSA FPSA MMB HCG TSH CTNI -- Concentration (g/l) Reference specimens evaluation with traceable tests Page Protection notice / 2010 Siemens Healthcare Diagnostics Products GmbH

22 4 Assessment of performance of Proteomics methods Total protein spectral intensity [arbitrary units] E-3 Ig α1 chain α2-macroglobulin Ig ג chain Orosomucoid Transthyretin C4 β2-microglobulin Retinol-binding protein IgG1 Albumin Transferrin Ig к chain C3 Haptoglobin α1-antitrypsin Ceruloplasmin R=0.97 1E7 1E8 1E9 1E10 1E11 Assigned values of N/T Protein Control SL/M [g/l] OFFGEL electrophoresis (Agilent Application Note EN) into 24 pi-fractions (ph 4 7). Individual fractions were desalted, trypsinated and analysed by C18- RP-MS/MS. Page Protection notice / 2010 Siemens Healthcare Diagnostics Products GmbH

23 5 Clinical research on Factor VII-activating Protease (FSAP) Cardiac Atherosclerosis PDGF-BB Interactions with cells Cell death Inflammation NF-kappaB FSAP (HABP2) TGFs / PAR 1/3, RhoA,Rho kinase Matrix Remodeling Coagulation F VII & F VIII Prourokinase Fibrinolysis Thrombosis Page Protection notice / 2010 Siemens Healthcare Diagnostics Products GmbH

24 6 Detection of Marburg I Polymorphism (MRI) of FSAP LC-MS/MS (Standard Addition Calibration) WT FSAP MRI FSAP Calibration line parameters: R2 of , (WT and MRI) All points within ± 20% (±25 at LLOQ) precision All points within ± 20% (±25 at LLOQ) accuracy Richard Kay et al. Page Protection notice / 2010 Siemens Healthcare Diagnostics Products GmbH

25 6 Proteotypic peptide peaks of MR I FSAP 1 µg/ml STD MRI peptide No MRI peptide in plasma MRI peptide in plama Richard Kay et al. Page Protection notice / 2010 Siemens Healthcare Diagnostics Products GmbH

26 6 Plotted peak areas of both MRI peptide transitions Richard Kay et al. Page Protection notice / 2010 Siemens Healthcare Diagnostics Products GmbH

27 Conclusions Reference materials are the hidden treasure in IVD Standardization is important to generate high quality results Global comparability of test results is key for effective and safe clinical decision making International standardization and availability of respective reference materials directly impacts healthcare independent of trends Current trends will support reference material development and application There may be potential opportunities for standardization & harmonization for biomarker research & development Is it time to lift the reference material treasure for R&D? Page Protection notice / 2010 Siemens Healthcare Diagnostics Products GmbH

28 Thank you for your attention! Page Protection notice / 2010 Siemens Healthcare Diagnostics Products GmbH

Nephelometry and turbidimetry are liquid based immunoassays based on the measurement of scattered or absorbed light.

1 Nephelometry and turbidimetry are liquid based immunoassays based on the measurement of scattered or absorbed light. Light scattering is the physical phenomenon resulting from the interaction of light