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

2 Gr 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 Gr 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 Gr Detection of Virus Genome in Sample Fig 1a: 97/656 International Standard Ecstimated RNA Copies or PCR Detectable Units (log10/ml) neg IHCASIH AL B3 CAS IH TMA AS B3 CM M M M UCM CM M M M* N N CM N HIV NIBSC – Gröner 13. June 2007

5 Gr Detection of Virus Genome in Sample HIV Fig 1h: RU570 Subtype H (S02) Estimated RNA Copies or PCR Detectable Units (log10/ml) neg 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 – Gröner 13. June 2007

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

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

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

9 Gr 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