Submission Type: BLA
Submission ID: 125419/0
Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted
ID Biomedical Corporation of Quebec
Telecon Date/Time: 09-Nov-2012 03:29 PM Initiated by FDA? Yes
Telephone Number: email@example.com; firstname.lastname@example.org, Jillian.M.email@example.com
1. Information Request
Author: KIRK PRUTZMAN
IR regarding the minimum release acceptance criterion (MRAC) for the H5N1 Antigen
FDA Participants: KIRK PRUTZMAN, CARMEN COLLAZO, JEREMY WALLY
Non-FDA Participants: MICHAEL SCHWARTZ, ROBERT BROBST, JILLIAN HORVATH
Trans-BLA Group: No
Related STNs: None
Related PMCs: None
From:Prutzman, Kirk C
Sent:Friday, November 09, 2012 3:29 PM
To:Michael Schwartz; 'Robert Brobst'; 'Jillian.M.firstname.lastname@example.org'
Cc:Collazo, Carmen; Wally, Jeremy
Subject:STN 125419 - Information Request
Dear Drs. Schwartz, Brobst, and Horvath,
We have the following Information Request (IR) regarding the minimum release acceptance criterion (MRAC) for the H5N1 Antigen.This IR is a follow-up to the Amendment you submitted on September 28, 2012 (STN 125419/10).
You used a statistical method, as described in the WHO document cited in the BLA, Amendment 10 (STN 125419/10), to estimate the minimum release acceptance criterion (MRAC), taking the loss of potency over the proposed shelf-life into consideration. You also interpreted CBER’s current/historic influenza vaccine lot release requirements as implying that the lower 95% confidence limit of a mean of (b)(4) ug/mL, which is (b)(4) ug/mL, is an acceptable level of expiry acceptance criterion (EAC) for the calculation of MRAC. Nevertheless, you set your EAC at (b)(4) ug/mL in order to align with the European requirement. Thus, you set the variability requirement at (b)(4) such that the lower 95% confidence limit of a mean of (b)(4) ug/mL would be (b)(4) ug/mL.
While the statistical method used for calculating your MRAC for ---(b)(4)----- final container is acceptable, we do not agree with your using (b)(4) ug/mL as the EAC in the calculation of MRAC.The historic CBER influenza vaccine lot release requirements were set with the expectation that all acceptable lots should contain at least the label claimed amount of antigen content, i.e., 15 ug/mL. The reportable potency value for a given lot (i.e., the mean of n values), however, can be lower than 15 ug/mL due to assay variability. The rationale behind the historic requirement is that the potency for a given lot should not be significantly lower than 15 ug/mL. For the assay format of 3 gels, a reportable potency value (mean of 3 values) of (b)(4)ug/mL would be considered not notably lower than (b)(4) ug/mL. For the assay format of 6 gels, due to the improved precision about the mean, a limit of (b)(4) ug/mL is required to demonstrate that the potency is not notably lower than 15 ug/mL. Therefore, although CBER’s lower release limit of ---(b)(4)-- ug/ mL for the 3 gels or 6 gels format, set decades ago, can potentially be statistically interpreted in the way you interpret it, the CBER requirements do not intend to mean that CBER considers the lower 95% confidence limit of a mean of (b)(4) (i.e., (b)(4)) an acceptable limit for the reportable potency value of a stability lot at the end of shelf-life. We consider a reportable potency value of ---(b)(4)----- ug/mL the stability limit (EAC) that should be used in your MRAC calculation. When the number of gels used is >3 (i.e., 4, 5, or 6), the EAC to be used will be (b)(4) ug/mL
Please submit your revised MRACs for the final container and final bulk with detailed calculation information, including the formula and the values used in the formula.
If you have any questions about this communication, please contact Kirk Prutzman, Carmen M. Collazo, or Jeremy Wally.
Kirk Prutzman, PhD
Food and Drug Administration
Primary Reviewer/Regulatory Project Manager
1451 Rockville Pike (WOC2)