• Decrease font size
  • Return font size to normal
  • Increase font size
U.S. Department of Health and Human Services

Vaccines, Blood & Biologics

  • Print
  • Share
  • E-mail

November 22, 2013 Approval Letter- Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted

Our STN: BL 125419/0

 
ID Biomedical Corporation of Quebec
dba GlaxoSmithKline Biologicals
Attention: Michael P. Schwartz, Ph.D.
GlaxoSmithKline Biologicals
2301 Renaissance Boulevard, P.O. Box 61540
King of Prussia, PA 19406-2772
 
Dear Dr. Schwartz:
 
We have approved your biologics license application (BLA) for Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted effective this date. You are hereby authorized to introduce or deliver for introduction into interstate commerce, Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted under your existing Department of Health and Human Services U.S. License No. 1739. However, we acknowledge the statement in your submission of November 11, 2013, that ID Biomedical Corporation of Quebec (dba GlaxoSmithKline Biologicals) does not intend to market this product for commercial distribution in the U.S. since it will be produced and distributed under contract to the U.S. Government as part of national pandemic preparedness initiatives. In addition, we acknowledge that you intend to collaborate with the Food and Drug Administration (FDA) and other governmental agencies in the U.S. on plans to collect additional safety and effectiveness data in the U.S., when Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted is used. Furthermore, if Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted is used in another country and additional safety and effectiveness data are obtained, you will provide these data to the FDA.
 
Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted is indicated for active immunization for the prevention of 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.
 
The review of this product was associated with the following National Clinical Trial (NCT) numbers: NCT00510874, NCT00616928, NCT00695669, NCT00719043, NCT00771615 and NCT00309634.
 
Under this license, you are approved to manufacture Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted. The H5N1 antigen component of the vaccine will be manufactured and filled by ID Biomedical Corporation of Quebec (dba GlaxoSmithKline Biologicals) located in Quebec, Canada. The AS03 adjuvant component of the vaccine will be manufactured and filled by GlaxoSmithKline Biologicals S.A., located in Rixensart, Belgium. The AS03 adjuvant component will be labeled by GlaxoSmithKline Biologicals S.A., located in Wavre, Belgium. 

Final packaging of Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted will be performed by ID Biomedical Corporation of Quebec (dba GlaxoSmithKline Biologicals) located in Quebec, Canada. You may label your product with the name Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted. The vaccine will be supplied in a kit consisting of one package containing 50 multidose vials of H5N1 antigen and two packages each containing 25 multidose vials of AS03 adjuvant.
 
The dating period for the H5N1 antigen component of Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted shall be 36 months from the date of manufacture when stored at 2 °C to 8 °C. The date of manufacture of the H5N1 antigen component shall be defined as the date of filling into final containers. The dating period for AS03 adjuvant component shall be 60 months from the date of manufacture when stored at 2 °C to 8 °C. The date of manufacture of the AS03 adjuvant component shall be defined as the date of filling into final containers. The expiration date for the packaged product, H5N1 antigen component plus AS03 adjuvant component, shall be dependent on the shortest expiration date of any component.
 
Please submit samples from formulated monovalent H5N1 antigen bulk together with protocols showing results of all applicable tests. You may not distribute any lots of product until you receive a notification of release from the Director, Center for Biologics Evaluation and Research.
 
You must submit information to your biologics license application for our review and written approval under 21 CFR 601.12 for any changes in, including but not limited to, the manufacturing, testing, packaging or labeling of Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted, or in the manufacturing facilities.
 
You must submit reports of biological product deviations under 21 CFR 600.14. You should identify and investigate all manufacturing deviations promptly, including those associated with processing, testing, packing, labeling, storage, holding and distribution. If the deviation involves a distributed product, may affect the safety, purity, or potency of the product, and meets the other criteria in the regulation, you must submit a report on Form FDA-3486 to the Director, Office of Compliance and Biologics Quality, Center for Biologics Evaluation and Research, HFM-600, 1401 Rockville Pike, Rockville, MD 20852-1448.
 
Please provide your final content of labeling in Structured Product Labeling (SPL) format and include the carton and container labels. All final labeling should be submitted as Product Correspondence to this BLA at the time of use and include implementation information on FDA Form 356h and FDA Form 2567, as appropriate.
 
In addition, please submit the final content of labeling (21 CFR 601.14) in SPL format via the FDA automated drug registration and listing system, (eLIST), as described at
http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Information on submitting SPL files using eLIST may be found in the guidance for industry titled, “SPL Standard for Content of Labeling Technical Qs and As” at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM072392.pdf.
 
Since, as stated in your November 11, 2013, submission, you do not intend to market this product for commercial distribution, we understand that you will not be distributing promotional advertising or promotional labeling materials. However, should you develop any advertising and/or promotional labeling related to this product (for example, educational brochures), please submit draft copies of the proposed introductory advertising and promotional labeling with an FDA Form 2253 to the Center for Biologics Evaluation and Research, Advertising and Promotional Labeling Branch, HFM-602, 1401 Rockville Pike, Rockville, MD 20852-1448.  You must submit copies of your final advertisement and promotional labeling at the time of initial dissemination or publication, accompanied by Form FDA 2253 (21 CFR 601.12(f)(4)).
 
All promotional claims must be consistent with and not contrary to approved labeling. You should not make a comparative promotional claim or claim of superiority over other products unless you have substantial evidence or substantial clinical experience to support such claims
(21 CFR 202.1(e)(6)).
 
ADVERSE EVENT REPORTING
 
You must submit adverse experience reports in accordance with the adverse experience reporting requirements for licensed biological products (21 CFR 600.80), and you must submit distribution reports as described in (21 CFR 600.81). You should submit these reports to the Vaccine Adverse Event Reporting System (VAERS), P.O. Box 1100, Rockville, MD 20849-1100, using the pre-addressed form VAERS-1 (http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation
/Guidances/Vaccines/UCM164319.pdf
). 
 
As stated in your November 11, 2013, submission, you will report all, serious or non-serious, narcolepsy cases (with or without cataplexy) and autoimmune hepatitis cases, following vaccination with Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted, as 15-day expedited reports to the Vaccine Adverse Event Reporting System (VAERS).
 
Postmarketing Studies subject to reporting requirements of 21 CFR 601.70
 
PEDIATRIC REQUIREMENTS
 
Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for new active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of administration are required to contain an assessment of the safety and effectiveness of the product for the claimed indication in pediatric patients unless this requirement is waived, deferred, or inapplicable.
 
We are deferring submission of your pediatric studies for this application because this product is ready for approval for use in adults and the pediatric studies have not been completed.
 
Your deferred pediatric studies required under 505B(a) of the Federal Food, Drug, and Cosmetic Act are required postmarketing studies.  The status of these postmarketing studies must be reported according to 21 CFR 601.70 and section 505B(a)(3)(B) of the Federal Food, Drug, and Cosmetic Act.  These required studies are listed below:
 

1.  Deferred pediatric study Q-Pan H5N1=AS03-021 under PREA to evaluate the safety and immunogenicity of Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted when administered to healthy persons 6 months to < 18 years of age. 

 
Final Protocol Submission:  March 2, 2012
 
Study Completion Date:  September 30, 2014
 
Final Report Submission:  April 30, 2015
 
2.  Deferred pediatric study Q-Pan-023 under PREA to evaluate the safety and immunogenicity of Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted when administered to healthy children 6 months to < 36 months of age. 
 
Final Protocol Submission:  February 28, 2017
 
Study Completion Date:  December 31, 2018
 
Final Report Submission:  June 30, 2019
 
3.  Deferred pediatric study Q-Pan-024 under PREA to evaluate the safety and immunogenicity of Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted when administered to healthy persons 6 months to < 18 years of age.  Study Q-Pan-024 will be conducted only if study Q-Pan-023 identifies a pediatric dose that is different than that evaluated in study Q-Pan H5N1=AS03-021.
 
Final Protocol Submission:  June 30, 2018
 
Study Completion Date:  April 30, 2020
 
Final Report Submission:  October 31, 2020
 
4.   Deferred pediatric study Q-Pan-025 under PREA to evaluate the safety and immunogenicity of Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted when administered to healthy infants < 6 months of age. 
 
Final Protocol Submission:  October 31, 2021
 
Study Completion Date:  July 31, 2022
 
Final Report Submission:  December 31, 2022
 
Submit final study reports to this BLA. For administrative purposes, all submissions related to these required pediatric postmarketing studies must be clearly designated “Required Pediatric Assessments.”
 
AGREED UPON POSTMARKETING COMMITMENT
 
We acknowledge your written commitment as described in your submission of November 11, 2013, as outlined below:
 
5.  To establish a pregnancy registry in the U.S. that is able to prospectively collect data on an actively recruited cohort to study the safety of Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted during pregnancy.  A concept protocol for this pregnancy registry will be prepared under the assumption that the vaccine would be distributed to the general population in the U.S. in an officially-declared H5N1 influenza virus pandemic.  Once the circumstances of the vaccine use in an officially-declared H5N1 influenza virus pandemic are determined by the U.S. Government, you will work with the FDA to finalize the protocol and you will initiate the registry. 
 
Concept Protocol Submission: June 30, 2014
 
Final Protocol Submission:  60 days after notification by the FDA to finalize the protocol and initiate the registry
 
Study Completion Date: 24 months after initiation of the registry
 
Final Report Submission: 12 months after completion of data collection
 
Please submit clinical protocols to your BB-IND 13413, with a cross-reference letter to this BLA, STN BL 125419. Submit nonclinical and chemistry, manufacturing, and controls protocols and all study final reports to your BLA, STN BL 125419. If the information in the final study report supports a change in the labeling, the final study report should be submitted as a supplement. We may also request a supplement if we think labeling changes are needed. Please use the following designators to label prominently all submissions, including supplements, relating to these postmarketing study requirements or commitmentsas appropriate:
 
  • Postmarketing Study Requirement/Commitment Protocol
  • Postmarketing Study Correspondence
  • Postmarketing Study Requirement/Commitment – Final Study Report
  • Supplement Contains Postmarketing Study Requirement/Commitment – Final Study Report
 
For each postmarketing study subject to the reporting requirements of 21 CFR 601.70, you must describe the status in an annual report on postmarketing studies for this product.  Label your annual report an “Annual Status Report of Postmarketing Study Requirements/Commitments.” The status report for each study should include:
 
  • information to identify and describe the postmarketing requirement or commitment,
  • the original schedule for the requirement or commitment,
  • the status of the requirement or commitment (i.e., pending, ongoing, delayed, terminated, or submitted), and
  • an explanation of the status including, for clinical studies, the patient accrual rate (i.e., number enrolled to date and the total planned enrollment).
 
As described in 21 CFR 601.70(e), we may publicly disclose information regarding these postmarketing studies on our Web site (http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Post-marketingPhaseIVCommitments/default.htm). Please refer to the February 2006 Guidance for Industry: Reports on the Status of Postmarketing Studies – Implementation of Section 130 of the Food and Drug Administration Modernization Act of 1997 (see http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM080569.pdf) for further information. 
 
 
Sincerely yours,
 
 
 
Marion F. Gruber, Ph.D.
Director
Office of Vaccines
 Research and Review
Center for Biologics
 Evaluation and Research
 
Attachment: Approved Final Draft Labeling