on the road to harmonisation?

Transcription

1 on the road to harmonisation? Prof. Dr.med.Michael Spannagl Munich- Heart of? 1

2 O zapft is - Oktoberfest 1 Key facts Date: September - October (1 days) Location: Munich - Theresenwiese 6,3 Mio. Visitors 7,4 Mio. Liter beer= 7,4 Mio. Maß sold Exactly 7,4 Mio Liter? 3 How to standardize the Maß? 1. Standardization of the Maß in the Kingdom of Bavaria. Standardization to the German Liter "Coalition against fraudulent pouring [of beer]" = 1,69 Liter 1, Liter Is it really one liter?

3 Potency Labeling How to declare F VIII content?? FVIII:c ( RV Jan 3: Refacto E iv in sev. hemophilia) 7 % clotting Chromogenic substrate 6 3

4 ReFacto AF vs. Xyntha previous ReFacto Xyntha/ReFacto AF Worldwide CS Assay WHO 6. IS Europe CS Assay WHO 7. IS USA/Canada OS Assay WHO 7. IS ReFacto 1 IU 83 μg ReFacto AF 1 IU 9 μg Xyntha 1 IU 131 μg 7 Instand e.v. 8 Employees in Düssseldorf 14 Experts 36 EQA-programs Participants in 93 countries 8 4

5 Number of participants from german participants foreign participants INSTAND e.v. - EQAS worldwide Gesellschaft zur Förderung der Qualitätssicherung In medical Laboratories in medizinischen e.v. Laboratorien

6 Number of EQA-schemes Number of shipped samples

7 RiliBÄK - Guidelines of the German Medical Association on Quality Assurance in Medical Laboratory Testing Section A Sections B1 B B3 B4 B 13 New Guideline for of the German Medical Association (RiliBÄK) -> mandatory for all medical laboratories in Germany Section A Fundamental requirements for quality assurance Effective since 1 April 8 Specific Section B 1 Quantitative analyses in laboratory medicine - internal QA - external QA Specific Section B Qualitative analyses in laboratory medicine - internal QA - external QA Specific Section B 3 Direct detection and characterization of pathogens - internal QA - external QA Effective since 1 April 8 Effective since 1 July 11 Effective: 1 June 1 Specific Section B 4 Analyses of ejaculate - internal QA - external QA Specific Section B Molecular- and cytogenetic analyses - internal QA - external QA Effective since 1 July 11 Effective since 1 October

8 Guideline of the German Medical Association on in Medical Laboratory Examinations (RiliBAEK) (extract from annex B1) INSTAND Reference Laboratory 16 8

9 Reference laboratory Accreditation according to ISO 17 and ISO Cholesterol 9 Chloride, Potassium, Sodium, ALT, AST, GGT, CK, LDH Creatinine, Urea, Cortisol, Total Protein, HbA1c, Theophyline 1 Calcium, Lithium, Magnesium, Uric Acid, Total Gycerides, Testosterone, Thyroxine 1 Glucose, 17-ß-Estradiol, Progesterone, Digoxin, Digitoxin 17 Reference measurement procedures established in the reference laboratory of INSTAND e.v. Before : Cholesterol, Cortisol, Creatinine, 17ß-Estradiol, Glucose, Progesterone, Testosterone, Thyroxine, Total Glycerides, Uric Acid : Theophylline 3: ALT, AST, CK, GGT, LDH, Calcium, Chloride, Potassium, Lithium, Magnesium, Sodium, Digoxin, Digitoxin 4: HbA1c, Total Haemoglobin, Total Protein 6: Urea 18 9

10 coefficient of variation [%] coefficient of variation [%] AFP EQAS results manufacturer RO time target values set by consensus value principle 19 CRP EQAS results - 1 manufacturer BE 1 1 time target values set by consensus value principle 1

11 coefficient of variation [%] coefficient of variation [%] Glucose EQAS results all manufacturers time target values set by reference measurement procedure 1 GGT EQAS results all manufacturers time target values set by reference measurement procedure 11

12 sample deviation from target value [%] sample HbA1c EQAS results [mmol/mol] n = 11 n = 61 sample 1 sample 1 EQAS January 9 EQAS May 1 acceptability range: ± 18 % from RMP value 3 EQAS for HbA1c with lyophilized and fresh whole blood samples Immunoassay 1 1 lyophilized samples fresh samples Jan 14 Juli 14 Okt 14 May 1 EQAS run 4 1

13 deviation from target value [%] HPLC 1 1 lyophilized samples fresh samples Jan 14 Juli 14 Okt 14 May 1 EQAS run RiliBÄK Specific Section B 3: Direct Detection and Characterization of Pathogens - Quantitative Detection of Nucleic Acid of HIV-1 Table B 3-a Evaluation thresholds for external quality assurance of nucleic acid detection of pathogens transmitted by blood/plasma/serum 1 No. Analyte 3 Acceptable deviation of log1 value of participant from log1 target value of EQA scheme 4 Range of valitity in respect to column 3 from to unit Traget value of EQA scheme 6 Frequency of EQA scheme 1 CMV DNA -,8 to+,8 IU/mL Target value x/year HBV DNA -,6 to+,6 IU/mL Target value x/year 3 HCV RNA -,6 to +,6 IU/mL Target value x/year 4 HIV-1 RNA -,6 to +,6 copies/ml Target value x/year 6 13

14 INSTAND-EQA schemes for quantitative HIV-1 genome detection for mimicing therapy monitoring quantitative genome determination - basis for therapy monitoring decrease of >=log 1 copies/ml within 1 month - indicator for antiviral efficacy - if not: antiviral resistance? target - get viral load below level of detection example for EQA scheme dilution series of one and the same HIV stock: - 1 : x : x : 1, x : 3,1 x INSTAND-EQAS for HIV-1: Sample Dilution Series EQAS Sep 1, PCR/NAT HIV-1 (36) sample 368 (median 1,438 = 3.16 log 1 copies/ml) log 1 log 1 copies/ml 3 +. log 1 median -. log 1 within succes rate +/- 1. log 1 = 1.% (8/8) +/-. log 1 = 96.3% (79/8) +/-. log 1 = 7.% (9/8) - 1. log 1 N 8 N 4 N N 1 N 43 N 3 N N 1 N 3 all methods RO Amplicor AB RealTime QG artus RG RO TaqMan SI Versant in house AX NASBA SI bdna Methods 8 14

15 INSTAND-EQAS for HIV-1: Test Performance 6 EQAS Nov 8, HIV PCR/NAT (36) sample 1114 (median 4,3 = 3.64 log 1 copies/ml) log 1 copies/ml log 1 +. log 1 +. log 1 -. log log 1-1. log 1 all methods N 9 N 1 N 1 N 8 N 43 N 1 N 1 N 4 11 PCR RO 11 PCR ZX 98 TM AB 13 TM RO 13 TM ZX 4 LC ZX 1 bdna SI Methods 9 INSTAND-EQAS for HIV-1: Sample Dilution Series 6 EQAS Nov 8, HIV PCR/NAT (36) all methods (3 samples: dilution factors: 1 9, 1 8, 1 7 ; 1 sample: neg.) median.68 median 3.64 neg. sample median 4.8 cv 8.9% cv 4.71% cv 3.7% log 1 copies/ml 4 3 N 9 N Samples N 9 N 9 3 1

16 INSTAND-EQAS for HIV-1: Sample Dilution Series all methods (4 samples: dilution factors: 1:x1 7, 1:x1 7, 1:1.x1 7, 1:3.1x1 7 ) 6 EQAS Sep 1, PCR/NAT HIV-1 (36) median.4 cv 9.9% median 3.16 cv 7.1% median 3.7 cv 6.% median 4.31 cv.% 349 copies/ml 1438 copies/ml 1 copies/ml,6 copies/ml log 1 copies/ml N 8 N 8 N 8 N Samples 31 The last problems The survey manager and EvidenceBasedM.. No punishment Communication with manufacturers Harmonization of acceptance criteria 3 16

17 TO Make RILIBAEK a success Improve control material (like vs like, commutability ) Skip artificial surveys (not to test the control mat ) Introduce new concepts (virtual, educational..) 33 Miles vs. Kilometer Will this ever be standardized? 34 17

18 Thank you for attention 3 18