1. XX. SoGAT Meeting Warsaw 12./13. June 2007 IU vs. NAT-Detectable Units Albrecht Gröner CSL Behring Virology Marburg, Germany

2. 2 Gr 070613 International Units vs. NAT-Detectable Units International Units inter-laboratory comparison of results (e.g., virus load in samples) release of pools for fractionation (e.g., OMCLs) NAT-detectable units (genome equivalent (GE)) detection of virus genomes in samples intra-laboratory comparison of results (if assay performance is very stable) 2 – Gröner 13. June 2007

3. 3 Gr 070613 Conversion Factor IU  GE Necessity to define conversion factor quantification of virus particles in sample defined by NAT in order to assess risk for virus transmission CPMP/BWP/5180/03 (Guideline on assessing the risk for virus transmission – new chapter 6 of the note for guidance on plasma-derived medicinal products (CPMP/BWP/269/95)) requests a quantitative estimation of the probability of a virus contaminant being present in a defined dose of final product taking into account - as a conservative approach - viral genomes as an indicator of potentially infectious virus particles in the starting material 3 – Gröner 13. June 2007

4. 4 Gr 070613 Detection of Virus Genome in Sample Fig 1a: 97/656 International Standard 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Ecstimated RNA Copies or PCR Detectable Units (log10/ml) neg0.00.51.01.52.02.53.03.54.04.55.05.5 121954 59 45 14 30 67 17 65 58 09 17 22 60 27 05 56 61 63 04 64 57 48 IHCASIH AL B3 CAS IH TMA AS B3 CM M M M UCM CM M M M* N N CM N HIV NIBSC - 2002 4 – Gröner 13. June 2007

5. 5 Gr 070613 Detection of Virus Genome in Sample HIV Fig 1h: RU570 Subtype H (S02) 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Estimated RNA Copies or PCR Detectable Units (log10/ml) neg0.00.51.01.52.02.53.03.54.04.55.05.5 04 48 64 12675465 17 45 14 58 30 59 22 60 27 19 05 09 56 61 57 17 63 N N N IH AS TMA AL B3 CAS IH M M UCM CAS CM M M M M* Monitor assaysNuclisensbDNA 3Abbott LCxIn-HouseAmpliscreenTMA NIBSC - 2002 5 – Gröner 13. June 2007

6. 6 Gr 070613 Detection of Virus Genome in Sample NIBSC - 2002 HIV 6 – Gröner 13. June 2007

7. 7 Gr 070613 Detection of Virus Genome in Sample Saldanha et al. Vox Sang 2005;89:52-58 HAV International Standard 7 – Gröner 13. June 2007

8. 8 Gr 070613 Detection of Virus Genome in Sample Saldanha et al. Vox Sang 1999;76:149-158 HCV International Standard 8 – Gröner 13. June 2007

9. 9 Gr 070613 Conversion Factor IU  GE Is a general conversion factor necessary (and justifiable)? Conversion factor can only be determined for each laboratory employing a validated assay A generic conversion factor for IUs to GE is not appropriate due to differences in analytical sensitivity of assays in different laboratories Quantitative infectivity of viruses (inf. units) vs. NAT detectable units unknown Relevance of Conversion Factor? 9 – Gröner 13. June 2007