1. Feasibility of Synthetic Materials as Primary Standards
John Saldanha
Medical and Scientific Affairs, Roche Molecular Systems, Pleasanton, CA, USA
SoGAT XVIII, FDA, NIH Campus, Bethesda, MD, USA
24-25 May, 2005

2. YES!
BUT NOT YET

3. Biological vs Synthetic Standards
Parameter Biological Synthetic
Actual agent determined/quantitated
by assays √ X
Matrix similar to matrix of specimen √ X
Contains all sequences recognised by
probes in all different assays √ X
Different assays yield similar results √ ?
Long term stability √ √

4. Biological vs Synthetic Standards
Parameter Biological Synthetic
Homogenous material with little
inherent variability X √
Well-characterised material X √
Abundant source material X √
Consistency between replacement
lots X √
Ease of calibration of subsequent
replacement standards X √

5. Historical Results for the First WHO HCV International Standard
ndu/ml ge/ml
1st IS Study (1997) (25) (8)
WR Calibration (1999) (18) (3)
Genotypes Study (2000) (22) (1)
ndu : NAT detectable units from qualitative assays
ge : Genome equivalents from qualitative assays

6. Major Concerns Establishment of replacement International Standards
WHO collaborative study to establish standard includes all laboratories → bias, inconsistent quantitation
Stringent requirements by regulatory authorities regarding assay performance necessitates accurate calibration of replacement standard with regard to previous standards

7. Establishment of the Second WHO HCV International Standard, 96/798

8. Discussion Points
Commutability with previous IS essential to prevent ‘drift’ in IU
Variation in assay results ~ log
Limited study using proficient laboratories to establish replacement standards
Feasibility of using synthetic materials as calibrators
Establishment of SI standard which will include reference material, reference method and reference laboratory