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The Sense of Sensitivity I Dr. Matthias Gessner Plasma Control Europe/Plasma Analytics Baxter AG, Vienna.

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Presentation on theme: "The Sense of Sensitivity I Dr. Matthias Gessner Plasma Control Europe/Plasma Analytics Baxter AG, Vienna."— Presentation transcript:

1 The Sense of Sensitivity I Dr. Matthias Gessner Plasma Control Europe/Plasma Analytics Baxter AG, Vienna

2 Matthias Gessner/Gerold Zerlauth Regulatory Sensitivity WHO NAT Standards for HAV HBV HCV HIV Parvo B19 Guidelines validation of NAT ICH Guidelines on the validation of analytical assays. (CPMP/ICH/381/95 (Q2A) und CPMP/ICH/281/95 (Q2B)) Anforderungen an Validierung bzw. Routinebetrieb der HCV-NAT im Blutspendewesen (Paul Ehrlich Institut, 1998) Guidelines for validation of nucleic acid amplification technology (NAT) for the detection of hepatitis C virus (HCV) RNA in plasma pools (Council of Europe, PA/PH/OMCL(98)22, DEF, 1999). "European Pharmacopoeia, 4th edition"; published by the „Directorate for the Quality of Medicines of the Council of Europe (EDQM)“; January 1, 2002

3 Matthias Gessner/Gerold Zerlauth Regulatory Sensitivity Conversion „copies“ zu „IU“ –HCV: 1 IU = 2 cp (Collaborative Studies for WHO Standard) 1 IU = 4 cp (VQC) –HIV 1 IU = 0.4 cp (Collaborative Studies for WHO Standard) 1 IU = 1 cp (VQC) Factor of 4-5 between HCV and HIV International Units expressed in copies

4 Matthias Gessner/Gerold Zerlauth Regulatory Sensitivity Requirements for HCV, HIV NAT –Original:5000 copies/ml –Converted:5000 IU/ml

5 Matthias Gessner/Gerold Zerlauth Conversion „copies“ zu „IU“ The original requirement Thus it was implemented That‘s how it should have been implemented

6 Matthias Gessner/Gerold Zerlauth Conclusion If there was a basis for the original requirement in copies/ml – did it change? If not - apparently the outer packing seemed more important than the acutal content Scientists must be aware of this fact when creating standards – public perception may not coincide with scientific knowledge

7 The Sense of Sensitivity II Dr. Gerold Zerlauth Plasma Control Europe Baxter AG, Vienna

8 Matthias Gessner/Gerold Zerlauth Poolsize Virus: RNA / DNA Antibodies Antibody negative window NAT negative window INFECTIONDetection pool of 96SeroconversionDetection Single donation

9 Matthias Gessner/Gerold Zerlauth HCVHIV Infection to Seroconversion [d] 7022 Reduction by PCR [d] Busch et al., Transfusion 2000; 40; Diagnostic Window

10 Matthias Gessner/Gerold Zerlauth HCV Doubling time 17h 96-fold amplification –4.7 d HIV Doubling time 22h 96-fold amplification –6 d Busch et al., Transfusion 2000; 40; Poolsize

11 Matthias Gessner/Gerold Zerlauth Single donation testing HCV Virus: RNA / DNA Antibodies Antibody negative window NAT negative window d4.7 d 0.6/Mio.*0.05/Mio. *Roth et al., Transfus.Clin.Biol. 2001; 8; 282-4

12 Matthias Gessner/Gerold Zerlauth Theoretical gain by reducing poolsize HCVHIV NAT pos./ Million in pools of Theor. NAT pos. /Million single donations

13 Matthias Gessner/Gerold Zerlauth Pool-size reduction in reality HCV ARC S.L.Stramer et al,,US experience with Nucleic Acid Testing (NAT) for HIV-1 and HCV, 03/2001 Samples per pool NAT pos. in Positive per Mil. 3,03,3 Samples tested

14 Matthias Gessner/Gerold Zerlauth Pool-size reduction in reality HCV ARC S.L.Stramer et al,,US experience with Nucleic Acid Testing (NAT) for HIV-1 and HCV, 03/2001 JRC Dr. Murokawa, JRC NAT Research Group, Minisymposium of JRC, 2002 Samples per pool NAT pos. in Positive per Mil. 3,03,33,0 Samples tested

15 Matthias Gessner/Gerold Zerlauth Pool-size reduction in reality HIVHIV ARC S.L.Stramer et al,,US experience with Nucleic Acid Testing (NAT) for HIV-1 and HCV, 03/2001 Samples per pool NAT pos. in > Positive per Mil. ---0,22 Samples tested

16 Matthias Gessner/Gerold Zerlauth Pool-size reduction in reality HIVHIV ARC S.L.Stramer et al,,US experience with Nucleic Acid Testing (NAT) for HIV-1 and HCV, 03/2001 JRC Dr. Murokawa, JRC NAT Research Group, Minisymposium of JRC, 2002 Samples per pool NAT pos. in > > Positive per Mil. ---0,22---0,33 Samples tested

17 Matthias Gessner/Gerold Zerlauth Conclusion Increased sensitivity or smaller pool sizes do not necessarely yield higher detection rate of NAT- only positives Recent experience with pool testing have to be taken into consideration prior to establish requirements for sensitivity Optimal sensitivity/pool sizes can then be evaluated for optimal detection of targeted viruses


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