To: Mr. Matthew Whitman
File: STN 125259/0 CERVARIX
RE: Clinical Assays
Date: November 2, 2007
The following questions pertain to your clinical assays:
1. On page 17/52, of the original BLA, you state that the phase III version of the assay is more sensitive to detect natural infection than the phase II version. Please state which statistical test has been used to compare sensitivity.
2. We noted a high level of operator variability, --b(4)---- for all serological assay validations submitted. For example, on page 27/53 of VALDOC: HPV31EIA, in tables 14 and 15, the operator component is the largest and exceeds -b(4)- Please explain why operator's contribution is that large.
3. In the R&R section on page 18/52 of VALDOC: HPV18EIA2PCV01, we noted that several samples demonstrated unusually high variability. For example, CV% for day+operator for sample 4 is above -b(4)- and CV% for day+operator+reagents is exceeding
-b(4)- for 6 samples out of 16 reaching almost 46% for sample 2. Please interpret those findings.
4. Please submit details on how new reference standards for the type-specific serological assays will be characterized and qualified for use.