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Vaccines

Record of Telephone Conversation, November 5, 2012 -Q-Pan


Submission Type: BLA    Submission ID: 125419/0    Office: OVRR

Product:
Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted

Applicant:
ID Biomedical Corporation of Quebec

Telecon Date/Time: 05-Nov-2012 03:03 PM        Initiated by FDA? Yes

Telephone Number: michael.p.schwartz@gsk.com; robert.d.brobst@gsk.com

Communication Categorie(s):
1. Information Request

Author: KIRK PRUTZMAN
Telecon Summary:
IR regarding ---(b)(4)------ levels in the Adjuvant

FDA Participants: KIRK PRUTZMAN, CARMEN COLLAZO, JEREMY WALLY

Non-FDA Participants: MICHAEL SCHWARTZ, ROBERT BROBST

Trans-BLA Group: No

Related STNs: None
Related PMCs: None
Telecon Body:

 

From:                     Prutzman, Kirk C
Sent:                      Monday, November 05, 2012 3:03 PM
To:                         'Michael Schwartz'; Robert Brobst
Cc:                         Collazo, Carmen; Wally, Jeremy
Subject:                 STN 125419 - Qpan - Information Request

Attachments:          STN 125419 IR-regarding ----(b)(4)------ content.pdf
Dear Drs. Schwartz and Brobst,

We have the following requests for additional information regarding STN 125419 (Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted):

 

Please submit your responses in an amendment to the BLA submission.

If you have any questions about this communication, please contact Kirk Prutzman, Carmen M. Collazo, or Jeremy Wally.

Regards,

 

Kirk Prutzman, PhD
Food and Drug Administration
Primary Reviewer/Regulatory Project Manager
CBER/OVRR/DVRPA/CMC3
1451 Rockville Pike (WOC2)
Room 2241
HFM-481
Rockville, MD  20857
Phone:  (301) 796-2640

 

CENTER FOR BIOLOGICS EVALUATION AND RESEARCH
OFFICE OF VACCINES RESEARCH AND REVIEW
DIVISION OF VACCINES AND RELATED PRODUCTS APPLICATIONS

DATE:                       November 5, 2012     PAGES:  2 

TO:

ID Biomedical Corporation of Quebec (dba GlaxoSmithKline Biologicals)
Attention:  Michael Schwartz, Ph. D.
GlaxoSmithKline Biologicals
2301 Renaissance Boulevard, P.O. Box 61540
King or Prussia, PA 19406-2772
FAX: (610) 787-7063 TEL: (610) 787-4884
           
FROM:                      

Kirk Prutzman, Ph.D.
Primary Reviewer
FAX: (301) 827-3532             TEL: (301) 796-2640

SUBJECT:   

STN:  BL 125419/0 – Request FOR Information

 

Dear Dr. Schwartz:

Reference is made to your application dated February 22, 2012, for Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted.  We have the following request for information:

Regarding your tests to measure the levels of impurities in the squalene obtained from -(b)(4)- (section 3.2.R Excipient):

You indicate in the Squalene CoA that the release criterion for ----(b)(4)------- and the release criterion for ------(b)(4)------.

We would like to direct your attention to the WHO Executive Summary following the May 25-29, 1998, Consultation on “Assessment of the health risk of dioxins:  re-evaluation of the Tolerable Daily Intake (TDI)” that stated:

In view of the uncertainties in establishing a single, most appropriate LOAEL for derivation of TDI, the consultation concluded that the range of estimated human daily intake of 14-37 pg/kg/day provided a reasonable basis for the evaluation of health risk of dioxin-like compounds. By applying an uncertainty of 10 to the range of LOAELs of 14-37 pg TCDD/kg/bw/day a TDI, expressed as a range of 1-4 TEQ pg/kg bw (rounded figures) was established for dioxins and dioxin-like compounds.
We also want to direct your attention to the“Review: 2005 World Health Organization Reevaluation of human and mammalian toxic equivalency factors for Dioxins and Dioxin-like compounds” (Martin Van den berg et al. Toxicological Sciences 93(2) 223-241, 2006) that stated:
The values for congener-specific TEF are summarized in Table 1 of this review.  The authors point out that the fate and transport properties of Dioxin and Dioxin-like compounds differ widely between congeners and a single TEQ may not be appropriate.
In your BLA submission you indicate that for the purpose of further characterization of squalene, GSK has out-contracted -------------------(b)(4)---------------------------------------------------------, which is a laboratory accredited by the ---------------------(b)(4)------------------------------------------.  The analytical procedures employed by (b)(4) satisfy the normative standards (as presented in Table 5), and are done under GLP practices.  Importantly, (b)(4) operates in compliance with --(b)(4)-- standards and has a quality system complying with ---(b)(4)----- requirements.
On page 18 of Section 3.2 R Excipients, you indicate that, “the data generated so far on total --------------------------------------------(b)(4)-------------------------------------------------------------------------------------------- are in line with the results reported from ----(b)(4)---------------------------‘  You also point out that the results are consistent with limits set by the --------------------------------(b)(4)-------------------------------------------------- (commission regulation No 1881/2006 on contaminants in food stuff), and you indicate your plans to ultimately discontinue such screening on all incoming batches of squalene.  Finally, you indicate that “Supporting data for such decision will be made available.”
We have the following requests for additional information:

  1. Please provide data (actual results /calculated values for total (b)(4) content and (b)(4) content in terms of ppm-based units) for the (b)(4) batches of squalene that were tested by -----------(b)(4)------- (section 4.4.1.), and retested by                      -----(b)(4)--------------.
  2. Please provide the TEQ results obtained for the individual -----(b)(4)-------------------------------------- and describe how the average toxic equivalent of ------(b)(4) was derived for the (b)(4) batches of squalene mentioned in item #1.

Such data will provide important information on the distribution of ----(b)(4)--------------------------- in the squalene batches obtained from --------(b)(4)--------------, and will increase the confidence that even compounds with very low Toxic Equivalency Factors (TEF) are not present in the AS03 adjuvant system at levels above the WHO recommended 1-4 TEQ pg/kg bw.