1. Cepheid Symposium IAS 2017 Gwynn Stevens, PhD Director of Virology
24 July 2017

2. UNAIDS 90-90-90: Viral Load Essential Tool
Delivering a better way to improve patient outcomes by enabling access diagnostic testing everywhere.
Cepheid’s Mission is clear — at the end of the day, our purpose is to improve healthcare for all of us through fast, accurate diagnostic results that drive treatment decisions.

3. WHO Prequalification of In Vitro Diagnostics
The aim of the WHO PQ DX is to promote and facilitate access to safe, appropriate and affordable diagnostics of good quality in an equitable manner
WHO PQ undertakes a comprehensive assessment of the quality, safety and performance of IVDs
Focus is placed on products for high burden diseases and their suitability for use in resource-limited settings.
Cepheid’s values are an important part of who we are — it’s the backbone of our brand and the way in which we strive to do business.

4. Laboratory evaluation Prequalification decision
WHO PQ Process
Dossier review
Site inspection
Dossier incomplete
 Laboratory evaluation
Prequalification decision
Dossier complete
Dossier screening
Priority product
Yes No
Pre-submission form

5. Performance Characteristics
Analytical Performance
Precision
Linearity
Limit of Detection
Cross Contamination
Clinical Performance
Trueness of measurement – bias or mean difference
Misclassification
sensitivity and specificity
Confidence intervals
Discrepant results - >0.5log difference

6. Partners Analytical Study Clinical Study Oversight
International Laboratory Branch,
Division of Global HIV and TB
CDC Atlanta
Clinical Study
NHLS HIV PCR LAB,
Charlotte Maxeke Johannesburg Academic Hospital
South Africa
Oversight
Prequalification of In Vitro Diagnostics Programme
World Health Organization
Geneva, Switzerland

7. Results: Analytical Study Reference Material

8. Results: Analytical Precision
All %CV <3%
Precision of measurement is acceptable

9. Results: Analytical Linearity
Linearity verified in subtypes A, AG, B,C,D
All slopes <5% from the ideal value of 1
R2 values all >99% - good correlation with the reference method
Serial dilutions of stock panels, 7 members per dilution series
5 of each concentration
Linear regression

10. Results: Limit of Detection (LOD)
The claimed LOD was verified and estimated to be 22 copies/ml
Lowest viral concentration detected with a positivity rate equal or higher than 95%
WHO 3rd HIV-1 International Standard was used

11. Results: Cross Contamination
No cross-contamination was detected
20 Subtype C alternating with 20 HIV neg

12. Results: Clinical Study Trueness of Measurement
N=439 EDTA Plasma samples
Correlation is within range (R2=0.941, P<0.001)
Bias or mean difference log10 copies/mL (95% CI: ; 1.073)
Trueness of measurement using Bland Altman
Upper and lower limits of agreement, 2SDs, CI

13. Results: Clinical Study Misclassification
Overall invalid/error rate 2.94%
Sensitivity (95% CI): 225 /239= % ( )
Specificity (95% CI):197/200 = % ( )
False treatment failures: 3/ 200 = 1.50%
False treatment successful: 14/239 = 5.86%

14. Conclusion
Xpert HIV-1 VL Assay successfully meets all WHO prequalification requirements

15. Questions?