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U.S. Department of Health and Human Services

Vaccines, Blood & Biologics

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Vaccines

Meeting Minutes, March 11, 2013-Q-Pan

MEETING SUMMARY

Date and Time:          March 11, 2013 12:30 pm – 1:30 pm
Location:                    WOC2 – Room 2330
STN #:                        125419/0
Sponsor:                     ID Biomedical Corporation of Quebec (dba GlaxoSmithKline Biologicals)
Product:                                 Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted              

CBER/FDA Invitees

Attended    Committee Member             Review Assignment                        Supervisor                      
               Carmen Collazo-Custodio    Chair                                                Elizabeth Sutkowski         
                Jeremy Wally                        Lead RPM                                        Elizabeth Sutkowski        
                Kirk Prutzman                      Co-RPM                                           Elizabeth Sutkowski        
                Andrea James                        Clinical                                            Lewis Schrager                
                Hana Golding                        Product CMC                                   Jerry Weir     
                Surender Khurana                 Product CMC                                   Hana Golding                   
                    Nabil Al-Humadi                  Toxicology                                      David Green                     
                Tsai-Lien Lin                        Clinical/Assay Stats                        Dale Horne                        
                Tielin Qin                              Assays Stats                                     Dale Horne                       
                Maryann Gallagher               Advertising/Promotional Labeling          Lisa Stockbridge                   

                        Cheryl Hulme                                  Lot Release                     Joseph Quander III                      
                Yandong Qiang                     Pharmacovigilance                          Wei Hua                           
                    Hector Izurieta                      Epidemiology (Effectiveness)        Richard Forshee
Anthony Hawkins                 BIMO                                               Patricia Holobaugh          
                Randa Melhem                      Facilities/DMPQ                             Chiang Syin                     
Jei He                                    Facilities/DMPQ                             Chiang Syin
James Kenney                       Product Quality                               Rajesh Gupta
                Manju Joshi                          Product Quality                               William McCormick        
                    Lokesh Bhattacharyya          Product Quality                               William McCormick        
                Karen Campbell                    Product Quality                               William McCormick        
David Schwab                       Electronic Integrity Review            Laraine Henchal

 

OTHER ATTENDEES:
Elizabeth Sutkowski
Wellington Sun
Anissa Cheung
Erik Henchal
Richard Forshee
Jerry Weir

1.0 PURPOSE

The objectives of this meeting were:

  1. To update Management on the review progress
  2. To update the review team on the new review timelines including plans to issue a CR letter
  3. To discuss remaining topics that need to be addressed before the Action Due Date

2.0 BACKGROUND

The proposed indication and usage of BLA STN 125419: 

Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted is indicated for active immunization against disease caused by the influenza A virus H5N1 subtype contained in the vaccine.  Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted is approved for use in persons 18 years of age and older at increased risk of exposure to the influenza A virus H5N1 subtype contained in the vaccine.

3.0 DISCUSSION TOPICS

3.1  Milestones and Meetings

Milestones                                                                  Projected Date

  • Application Received                                           February 22, 2012
  • Committee Assignment                                       March 7, 2012 (FDA Tracked Milestone)
  • 1st Committee Meeting                                       March 12, 2012
  • Filing Meeting                                                      April 9, 2012
  • Filing Letter Issued                                              April 22, 2012
  • 1st draft reviews                                                  June 21, 2012
  • Mid-Cycle Review Meeting                                July 20, 2012 (FDA Tracked Milestone)
  • 2nd draft reviews                                                  August 30, 2012
  • Final Reviews (Signed/Uploaded)                       October 14, 2012 (Delayed by Major Amend.)
  • Present to PeRC                                                    September 26, 2012
  • Labeling Comments to Sponsor                          November 9, 2012 (FDA Tracked Milestone)
  • First Action Due                                                  December 22, 2012
  • Final Reviews (Signed/Uploaded)                       February 4, 2013 (Updated due date)
  • Notify GSK of PMC/PMR                                  February 15, 2013
  • Labeling Complete                                              March 5, 2013           
  • Major Amendment Action Due Date                 March 23, 2013

Meetings

  • First Committee Meeting:                                               March 6, 2012
  • Filing Meeting:                                                    April 9, 2012
  • Monthly Team Meetings:                                                May 8, 2012

June 11, 2012
July 9, 2012
August 3, 2012 (revised date)
August 31, 2012 (revised date – Sept. Meeting)
October 5, 2012 (revised date)
November 6, 2012 (revised date)
December 10, 2012
January 7, 2013
February 11, 2013
March 11, 2013

  • Mid-Cycle Review Meeting:                              July 20, 2012
  • PeRC:                                                                    September 26, 2012
  • VRBPAC:                                                             November 14
  • SWG:                                                                    Not Scheduled
  • Labeling Meetings:                                               October 22, 2012, October 25, 2012, November 2, 2012, December 14, 2012, December 20, 2012, January 7, 2013, February 5, 2013, February 8, 2013

3.2 Team Reports:

3.2.1    Chair
The chair informed that team that a CR letter will be issued for this BLA and is in the process of being drafted.  The chair asked the review team members if there are any additional items that need to be included in this CR letter (other than those described below) and no other items were identified.  The chair noted that currently the only outstanding Information Requests relate to our comments on the package insert.  Finally, the chair stated that the language for the proposed agreements, PMRs and one PMC is still being finalized.

3.2.2    Clinical
The clinical reviewer stated that issues with the datasets submitted to the BLA for the pivotal study were recently identified during labeling negotiations, and after discussion with GSK on March 8, 2013, it was agreed that the final datasets need to be submitted along with additional relevant information.  It was necessary to issue a CR Letter because a thorough review of the updated, final datasets could not be completed by the March 23, 2013 action due date.  The clinical reviewer discussed that the details of how this additional information will be submitted to the BLA are still being worked out with GSK.  The clinical reviewer further noted that labeling negotiations are still ongoing and may potentially be impacted by the new information that will be submitted in response to the CR letter.  Finally, the clinical reviewer indicated that a revised Request for Deferral of Pediatric Studies was recently submitted to the BLA.  GSK revised the timeline for the proposed pediatric clinical studies.  This revision is adequate.

3.2.3    Statistical
The statistical reviewer noted that finalization of the clinical statistical review will not be possible until GSK submits the information described above.

3.2.4    CMC/Product
The CMC reviewer noted that GSK has submitted reports for stability studies in response to the extractable/leachable Information Request sent to GSK on February 20, 2013, and that the reviewer is satisfied with the results of these studies.  No further comments on this issue are forthcoming.

3.2.5    Facilities/DMPQ
Review Uploaded to EDR

3.2.6    Pharmacovigilance
The Pharmacovigilance reviewer noted that the details of a potential PMC (pregnancy Registry) and a request for expedited reporting time frame of AIH and Narcolepsy are still being discussed by OBE management and that they should be providing final language to the review team in a few days.

3.2.7    DBSQC and Lot Release
Review Uploaded to EDR

3.2.8    Toxicology
Review Uploaded to EDR

3.2.9    Epidemiology (Effectiveness Study)
Review Uploaded to EDR

3.2.10  BIMO
Review Uploaded to EDR

3.2.11  APLB
Review Uploaded to EDR


4.0
Information Requests / Amendments

 

Request Date

CBER Rep(s)

Request

CBER Requester for Info

BLA Amendment Response

Review Pending?

Reviewed by and Date Reviewed

4/30/2012a

Carmen Collazo-Custodio

IR for Pediatric Plan, stability data, clinical assay validation,  HA content by SRID validation, other assay validation, facilities information, pharmacovigilance

Andrea James, Hana Golding, Surender Khurana, Tsai-Lien Lin, Tielin Qin, Manju Joshi Lokesh Bhattacharyya, Yandong Qiang, Randa Melhem

125419/0.3
125419/0.4
125419/0.5
125419/0.11

Yes

Surender Khurana – 125419/0.4
Hana Golding – 125419/0.4
Lokesh Bhattacharyya – 125419/0.4, 125419/0.11
Manju Joshi – 125419/0.4
Randa Melhem – 125419/0.3, 125419/0.4

4/30/2012b

Carmen Collazo-Custodio

Revised 356h form, SRID testing reagents and results

Carmen Collazo, Karen Campbell

125419/0.1
125419/0.2

Yes

Collazo – 125419/0.1 (memo pending)
Manju Joshi – 125419/0.2 (test results)

6/15/2012

Carmen Collazo-Custodio

Questions about location of information in the submission.

---

---

No

 

6/21/2012

Carmen Collazo-Custodio

Adjuvant lots and SRID calculation spreadsheet

Karen Campbell

---

No

 

7/30/2012

Carmen Collazo-Custodio

Product Manufacturing Questions

James Kenney, Hyesuk Kong, Karen Campbell, Surender Khurana, Randa Melhem

125419/0.6
125419/0.9
125419/0.10

No

Surender Khurana – 125419/0.9, 125419/0.10
Karen Campbell – 125419/0.6 (LRP)
James Kenney – 125419/0.9 (11/16/2012 Memo)
Manju Joshi – 125419/0.10

8/10/2012

Kirk Prutzman

AS03 Manufacturing Quality

Randa Melhem

125419/0.8

No

Hana Golding – 125419/0.8
Randa Melhem – 125419/0.8

8/15/2012

Kirk Prutzman

Follow questions to GSK’s responses to questions 16, 17d, 18, 21, 22 from the 4/30/2012 IR

Lokesh Bhattacharyya

125419/0.11

No

Lokesh Bhattacharyya – 125419/0.11

8/16/2012

Carmen Collazo-Custodio

IR Regarding GSK’s SRID Results

Manju Joshi, Rajesh Gupta, Karen Campbell

125419/0.7
125419/0.10

No

Manju Joshi – 125419/0.7, 125419/0.10 (12/6/2013 memo)

9/10/2012

Jeremy Wally

Response on Timing of Amendment Submission

---

---

No

 

9/25/2012

Jeremy Wally

IR regarding SRID assay and additional comments on VRBPAC and Proper Name

Manju Joshi
Carmen Collazo-Custodio

125419/0.10

No

Manju Joshi – 125419/0.10 (12/6/2013 memo)

Request Date

CBER Rep(s)

Request

CBER Requester for Info

BLA Amendment Response

Review Pending?

Reviewed by and Date Reviewed

9/26/2012

Jeremy Wally

September 25, 2012, IR/Comments Follow-Up

---

---

No

 

9/28/2012

Carmen Collazo-Custodio

Comments regarding the Pharmacovigilance Plan for Influenza A (H5N1) Virus Monovalent Vaccine (Version 2: July 2012*) provided in the submission of July 18, 2012.

Yandong Qiang

125419/0.17

Yes

 

10/2/2012

Kirk Prutzman

IR for qualification test reports for the AS03 Adjuvant

James Kenney

125419/0.12

No

James Kenney – 125419/0.12
Hana Golding – 125419/0.12

10/10/2012

Carmen Collazo-Custodio

IR regarding the PVP

Yandong Qiang

125419/0.17

Yes

 

10/15/2012

Kirk Prutzman

IR Regarding Clinical Items

Andrea James

125419/0.15

Yes

 

10/16/2012

Carmen Collazo-Custodio

IR Regarding Lot Release Protocol

Karen Campbell

125419/0.13

No

Karen Campbell – 125419/0.13

10/17/2012

Carmen Collazo-Custodio

IR comments: clinical (subgroup analyses) and clarification on filling of AS03 (-------------------(b)(4)--------------------- )

Andrea James
Tsai-Lien Lin
Randa Melhem

125419/0.16
125419/0.18

Yes

Randa Melhem – 125419/0.18

10/18/2012

Kirk Prutzman

IR Regarding Anti-Microbial Effectiveness Testing

James Kenney

125419/0.14

No

James Kenney – 125419/0.14

10/22/2012

Carmen Collazo-Custodio

IR comment on GSK’s PVP

Yandong Qiang

125419/0.17

Yes

 

10/31/2012

Carmen Collazo-Custodio

Request for CRFs for subjects in study Q-Pan-002

Andrea James

125419/0.15

Yes

 

11/5/2012

Kirk Prutzman

IR regarding ---(b)(4)------- levels in the Adjuvant

Hana Golding

125419/0.19

No

Hana Golding – 125419/0.19

11/8/2012

Carmen Collazo-Custodio

IR regarding further clarification on filling of AS03 (-----(b)(4)---------------------------------- )

Randa Melham

125419/0.18

No

Hana Golding – 125419/0.18
Randa Melhem – 125419/0.18

Request Date

CBER Rep(s)

Request

CBER Requester for Info

BLA Amendment Response

Review Pending?

Reviewed by and Date Reviewed

11/9/2012

Kirk Prutzman

PI, Carton, Container comments to GSK

 

125419/0.20
125419/0.21

Yes

Hana Golding – 125419/0.20, 125419/0.21
Labeling Memo Pending

11/9/2012

Kirk Prutzman

IR regarding HA minimum release acceptance criterion

Tsai-Lien Lin
Hana Golding
Surender Khurana
Manju Joshi

125419/0.20

No

Hana Golding – 125419/0.20

11/16/2012

Carmen Collazo-Custodio

Additional comments on the Package Insert and the Carton Labels

 

125419/0.21

Yes

Hana Golding – 125419/0.21
Labeling Memo Pending

11/19/2012

Kirk Prutzman

IR Regarding Lot Release Protocol in Amendment 13

Catherine Poole

125419/0.19

No

Karen Campbell – 125419/0.19 (LRP)

11/20/2012

Kirk Prutzman

Additional IR item regarding Lot Release Protocol

Catherine Poole

125419/0.19

No

Karen Campbell – 125419/0.19 (LRP)

11/20/2012

Kirk Prutzman

IR regarding Amendment 16 submitted on November 15, 2012

Andrea James

125419/0.19

Yes

 

11/26/2012

Carmen Collazo-Custodio

IR Regarding the Ste. Foy and the Rixensart/Wavre facilities

Randa Melhem

125419/0.22

No

Randa Melhem – 125419/0.22

11/28/2012

Carmen Collazo-Custodio

Conference Call Summary and CBER’s Response to GSK’s Potency Specifications Proposal

---

---

No

 

11/29/2012

Carmen Collazo-Custodio

Characterization of new working seed banks

Surendur Khurana

125419/0.19

Yes

 

11/29/2012

Carmen Collazo-Custodio

Clarification on environmental monitoring qualifications studies performed at the Rixensart facility

Randa Melhem

125419/0.22

No

Randa Melhem – 125419/0.22

11/30/2012

Carmen Collazo-Custodio

IR regarding cleaning validation

Randa Melhem

125419/0.22

No

Randa Melhem – 125419/0.22

Request Date

CBER Rep(s)

Request

CBER Requester for Info

BLA Amendment Response

Review Pending?

Reviewed by and Date Reviewed

11/30/2012

Carmen Collazo-Custodio

Follow-up discussion regarding the telephone conversation held on November 29, 2012, in which CBER requested clarification on discrepancies found on environmental monitoring qualifications studies performed at the Rixensart facility.

Randa Melhem

125419/0.22

No

Randa Melhem – 125419/0.22

11/30/2012

Carmen Collazo-Custodio

Information request regarding the description of a reproductive and developmental toxicity study described in the PI.

Andrea James
Nabil Al-Humadi

125419/0.21

Yes

Nabil Al-Humadi– 125419/0.21

12/3/2012

Carmen Collazo-Custodio

Request to clarify if    ------------------------------------(b)(4)-------------------.

Randa Melhem

125419/0.22

No

Randa Melhem – 125419/0.22

12/5/2012

Carmen Collazo-Custodio

Conference call with GSK to discuss documents/reports translated from French containing inconsistent information.

Randa Melhem

125419/0.22

No

Randa Melhem – 125419/0.22

12/5/2012

Carmen Collazo-Custodio

CBER’s comments to GSK’s response submitted on November 30, 2012, regarding the proposed Lot Release Protocol.

Karen Campbell

125419/0.23

No

Karen Campbell – 125419/0.23

12/19/2012

Kirk Prutzman

IR Regarding Cleaning Validation information

Randa Melhem

125419/0.23

No

Randa Melhem – 125419/0.23

12/20/2012

Carmen Collazo-Custodio

IR on alternative ---------(b)(4)---- used to storage the H5N1 ----------(b)(4)-----

Randa Melhem
Surender Khurana

125419/0.26

No

Randa Melhem – 125419/0.26

12/21/2012

Carmen Collazo-Custodio

Second Round or Carton/Container comments

 

125419/0.24

Yes

Labeling Memo Pending

1/22013

Kirk Prutzman

IR Regarding LRP

Karen Campbell

125419/0.23

No

Karen Campbell – 125419/0.23

Request Date

CBER Rep(s)

Request

CBER Requester for Info

BLA Amendment Response

Review Pending?

Reviewed by and Date Reviewed

1/14/2013

Jeremy Wally

Second Round of PI Labeling

 

125419/0.25

Yes

Labeling Memo Pending

1/22/2013

Jeremy Wally

Tcon with GSK:  IR regarding shipping validations and shipping protocols

Randa Melhem

125419/0.26

No

Randa Melhem – 125419/0.26

2/6/2013

Jeremy Wally

Discussion of Narcolepsy

---

---

No

 

2/8/2013

Carmen Collazo-Custodio

Extractables and Leachables studies for the ----(b)(4)--- are limited and the data are insufficient to draw any conclusions about the appropriateness of these (b)(4) for ---(b)(4)--- storage.

Randa Melhem
Surender Khurana

125419/0.27

No

Randa Melhem – 125419/0.27

2/11/2013

Carmen Collazo-Custodio

GSK response to CBER comments of Feb. 8, 2013 – GSK decided to remove the information submitted in the BLA regarding the use of  -----(b)(4)----------- for storage of the ---(b)(4)-----  in response to CBER’s comments provided on February 8, 2013.

---

---

No

 

2/12/2013

Carmen Collazo-Custodio

Third round of review on container and carton labels.

 

125419/0.28

Yes

Labeling Memo Pending

2/12/2013

Carmen Collazo-Custodio

GSK-request for clarification carton/container comments – GSK conducted an initial review of CBER comments on the container/carton labels provided on February 12, 2013, and have a question regarding consistency of the use of the word vial(s).

---

---

No

 

2/14/2013

Carmen Collazo-Custodio

Additional comments on third round of review on container and carton labels.

 

125419/0.28

Yes

Labeling Memo Pending

Request Date

CBER Rep(s)

Request

CBER Requester for Info

BLA Amendment Response

Review Pending?

Reviewed by and Date Reviewed

2/20/2013

Carmen Collazo-Custodio

Comments regarding leachables studies

Surender Khurana

125419/0.29

Yes

 

2/20/2013

Carmen Collazo-Custodio

Exemptions from General Safety Testing - CBER's feedback on
GSK's request for exemptions from General Safety Test for both AS03
adjuvant and Quebec H5N1 antigen

---

---

No

 

2/25/2013

Kirk Prutzman

Communication of UNII Code assignments

---

---

No

 

3/1/2013

Kirk Prutzman

Third Round  of PI Labeling

 

 

Yes

Labeling Memo Pending

 

5.0 Amendments

Date/STN

Summary

May 3, 2012
(125419/0.1)

Partial response to 4/30/2012b IR.  Revised 356h form.

May 25, 2012
(125419/0.2)

Partial response to 4/30/2012b IR.  Answers to Item 2.

June 20, 2012
(125419/0.3)

Partial response to 4/30/2012a IR.  Answers to Items 24-34 (facilities).

July 18, 2012
(125419/0.4)

Partial response to 4/30/2012a IR.  Answers to Items 2-23 and 35-36.

July 19, 2012
(125419/0.5)

Partial response to 4/30/2012a IR.  Answer to Item 1.  All responses to IR now submitted.

August 13, 2012
(125419/0.6)

Partial response to 7/30/2012 IR.  Answer to Item 1.  Addition of Robert D. Brobst as secondary POC

August 29, 2012
(125419/0.7)

Response to 8/16/2012 tcon; updated 356h form; updated list of POC’s.

September 10, 2012
(125419/0.8)

Response to 8/10/2012 tcon

September 14, 2012
(125419/0.9)

Response to Questions 2, 3, and 5-18 from CBER’s 7/30/2012 IR.

September 28, 2012
(125419/0.10)

Response to Information Requests dated July 30, 2012, August 16, 2012, and September 25, 2012.

October 10, 2012
(125419/0.11)

Response to Information Requests dated April 30, 2012, and August 15, 2012.

October 18, 2012
(125419/0.12)

Response to IR from CBER dated October 2, 2012

October 26, 2012
(125419/0.13)

Response to IR from CBER dated October 16, 2012 regarding the LRP

November 5, 2012
(125419/0.14)

Response to IR from CBER dated October 18, 2012 regarding the Anti-Microbial Effectiveness Testing

November 6, 2012
(125419/0.15)

Response to 2 IRs from CBER dated October 15, 2012, and October 31, 2012, regarding clinical issues

November 15, 2012
(125419/0.16)

Response to IR from CBER dated October 17, 2012, regarding subgroup analyses of all primary immunogenicity and safety endpoints by age, race and gender in studies Qpan-001, Q-Pan-002 and the ISS analyses.

November 19, 2012
(125419/0.17)

Responses to 3 Information Requests from CBER dated 9/28/2012, 10/10/2012, and 10/22/2012 regarding the PVP.

November 30, 2012
(125419/0.18)

Responses to 2 Information Requests from CBER dated 10/17/2012, and 11/8/2012.

November 30, 2012
(125419/0.19)

Responses to 5 Information Requests from CBER dated 11/5/2012, and 11/19/2012, 2 Irs on 11/20/2012, and 11/29/2012.

December 4, 2012
(125419/0.20)

Response to PI labeling comments from CBER on November 9, 2012.  Response to MRAC IR from CBER dated November 9, 2012.

December 8, 2012
(125419/0.21)

Response to Carton and Container comments from CBER on November 9, 2012 and November 16, 2012.  Response to comments regarding the toxicity study described in Section
8.1, Pregnancy, of the proposed Package Insert from CBER date November 30, 2012.

December 13, 2012
(125419/0.22)

Response to information requests from CBER dated 11/26/2012, 11/30/2012, and 12/3/2012.  Response to questions from telephone-tcons dated 11/29/2012, 11/30/2012, and 12/5/2012.

January 21, 2013
(125419/0.23)

Response to information requests from CBER dated 12/5/2012, 12/19/2012, and 1/2/2013. 

January 24, 2013
(125419/0.24)

Response to Carton and Container comments from CBER on December 21, 2012. 

February 1, 2013
(125419/0.25)

Response to 1/14/2013 Second round of PI labeling comments.  Additional rationale for PI Sections 6.1 and 5.2 are included.

February 1, 2013
(125419/0.26)

Response to information requests from CBER dated 12/20/2012 and 1/22/2013. 

February 18, 2013
(125419/0.27)

Response to information requests from CBER dated 2/8/2013.

February 22, 2013
(125419/0.28)

Response to Carton and Container comments from CBER on February 12, 2013. 
FINAL/ACCEPTABLE VERIONS OF CARTON AND CONTAINER LABELS

February 27, 2013
(125419/0.29)

Response to information request from CBER dated 2/20/2013.

March 1, 2013
(125419/0.30)

Response to information request from CBER dated 2/6/2013.  New Pediatric Plan