XX So GAT Meeting Warsaw 12 13 June

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

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 Gr 070613 2 – Gröner 13. June 2007

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 Gr 070613 3 – Gröner 13. June 2007

Detection of Virus Genome in Sample Fig 1 a: 97/656 International Standard 14 NIBSC - 2002 13 12 HIV 11 10 9 8 7 27 UCM 6 60 M 64 N 17 TMA 22 M 04 N 67 IH 17 M 63 M* 30 CAS 09 CM 61 M 59 IH 14 B 3 58 B 3 56 M 48 N 54 IH 45 AL 65 AS 05 CM 57 CM 5 4 3 2 1 0 12 IH neg 0. 0 0. 5 1. 0 1. 5 2. 0 2. 5 19 CAS 3. 0 3. 5 4. 0 4. 5 Ecstimated RNA Copies or PCR Detectable Units (log 10/ml) 4 Gr 070613 4 – Gröner 13. June 2007 5. 0 5. 5

Detection of Virus Genome in Sample Fig 1 h: RU 570 Subtype H (S 02) 14 13 NIBSC - 2002 HIV 12 11 10 9 8 7 6 5 61 M 4 3 2 1 0 30 27 CAS UCM 64 N 58 B 3 04 N 12 IH 0. 0 0. 5 67 IH 1. 0 1. 5 2. 0 54 IH 2. 5 60 M 09 CM 63 M* 17 TMA 48 N neg 56 M 14 B 3 22 M 05 CM 17 M 65 AS 45 AL 59 IH 19 CAS 57 CM 3. 0 3. 5 4. 0 4. 5 5. 0 Estimated RNA Copies or PCR Detectable Units (log 10/ml) Monitor assays 5 Gr 070613 5 – Gröner 13. June 2007 Nuclisens b. DNA 3 Abbott LCx In-House Ampliscreen TMA 5. 5

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

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

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

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 Gr 070613 9 – Gröner 13. June 2007