Submission Type: BLA Submission ID: 125363/0 Office: OVRR
Meningococcal Groups C and Y and Haemophilus b Tetanus Toxoid Conjugate Vaccine
Telecon Date/Time: 23-Nov-2011 03:20 PM Initiated by FDA? Yes
Telephone Number: firstname.lastname@example.org
Author: KIRK PRUTZMAN
Freyja Lynn's advice on GSK's preliminary serology response
FDA Participants: KIRK PRUTZMAN, DAVID STATEN, JOSEPH TEMENAK
Non-FDA Participants: JODY GOULD
Trans-BLA Group: No
Related STNs: None
Related PMCs: None
From: Prutzman, Kirk C
Sent: Wednesday, November 23, 2011 3:21 PM
To: 'Jody Gould'
Cc: Staten, David; Temenak, Joseph
Subject: Preliminary response
We received comments from Freyja Lynn regarding items you committed to provide to us in your complete response but were not listed in your November 22, 2011 email. Please see the following:
This is not everything we asked for. Note in their partial reply dated October 21st they also commit to providing the following:
Item 2b i: Provide trending analysis for ---b(4)------------------ values; show that –b(4)---------algorithm is independent of sample titer.
To address the question related to the impact of the ---b(4)-------- factor on variance of the samples per range of titers, we propose to establish a precision profile based on the historic data in our database. In the database between 2007 and end Feb 2009 we have repeat results in –b(4)------------------------------ formats. We propose to plot the %CV of samples as a function of titers for both ------b(4)-------------------- values.
Item 2b iii: Regarding QC charts (July 2009 – June 2010 & Feb 2009 – June 2010) presented in the validation document, although all points are within control limits, the range becomes much wider. Please explain why you conclude that the assay is stable.
These charts do not relate to the testing period for 009 and 010 (or 005). The two charts represent two different controls. In the first chart the definitive range of the controls (calculated on 81 values) was shown while on the second chart the range display of the chart was calculated on a more limited number of values (41) explaining the wider range. The range is being re-calculated on a greater number of values. Although the range is wider for the new control, it should be noted that the value display on the QC chart is centered around the target value. An explanation of the criteria for acceptance values will be included in the Complete Response.
Item 2b iv: Provide data that support the stability of the assay covering testing period for -005 through -010 (QC charts for controls with trending, reagent qualification data, sentinel data, detailed continuous timeline with change in controls and –b(4)- lots).
QC charts, trending, reagent qualification data, sentinel data and continuous timeline will be provided. Plots will show all bridging data (--b(4)-------------) over time, and indicate when –b(4)---- and other reagent changes occurred. The time periods for testing of the different Hib-MenCY-TT studies included in the BLA submission will be covered. Plots of the –b(4)------------ factors over time will be provided in the response to 2.b.i. These data will also support our response to Item 1.
Item 3: Please comment on:
- Missing data for sentinel 013 samples may bias the MenY assay results.
- GMRs suggest –b(4)---- in titers is also present for sentinel samples.
- Many samples with titers –b(4)- and near cut-off.
Trending plots and Deming regression on all the retesting results as presented in previous sections show that samples from study 013 behave similarly to the other studies without significant drift observed. However additional analysis performed specifically on the samples used as sentinels will be provided to demonstrate that although a lower trend was noted in the first week of testing, the results for the Hib-MenCY-TT-013 sentinel samples remained within the acceptance range, and that the testing was overall consistent week-by-week.
What they propose below does not address any of the issues cited above.
Kirk Prutzman, PhD
Food and Drug Administration
Primary Reviewer/Regulatory Project Manager
1451 Rockville Pike (WOC2)
Rockville , MD 20857
Phone: (301) 796-2640