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March 24, 2011 Approval Letter - Zostavax
Our STN: BL 125123/734
Merck Sharp & Dohme Corp.
Attention: Alison Fisher, Ph.D.
P.O. Box 1000
North Wales, PA 19454-1099
Dear Dr. Fisher:
We have approved your request to supplement your biologics license application (BLA) for Zoster Vaccine Live (ZOSTAVAX®), to include safety and efficacy data to support a label change for the use of ZOSTAVAX in individuals 50 to 59 years of age.
We have received your request under 21 CFR 201.58 of March 09, 2011, for a waiver of the requirement in 21 CFR 201.57(c)(9)(i)(A) to describe teratogenic effects by a letter classification (A, B, C, or X). We grant this waiver, but note that you will continue to be required to appropriately describe the risks associated with the wild virus in the labeling.
The review of this product was associated with the following National Clinical Trial number: 00534248.
Under 21 CFR 201.57(c)(18), patient labeling must be reprinted at the end of the package insert. We request that the text of information distributed to patients be printed in a minimum of 10-point font.
Please provide your final content of labeling in Structured Product Labeling (SPL) format and include the carton and container labels. In addition, please submit three original paper copies for carton and container final printed labeling. All final labeling should be submitted as Product Correspondence to this BLA at the time of use (prior to marketing) and include implementation information on FDA Form 356h.
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
You may submit two 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)).
Please submit an amendment to all pending supplemental applications for this BLA that include revised labeling incorporating a revised content of labeling that includes these changes.
AGREED UPON POSTMARKETING COMMITMENTS
Postmarketing Studies subject to reporting requirements of 21 CFR 601.70
We acknowledge your written commitment as described in your amendment of March 9, 2011, as outlined below:
- To conduct a large scale observational study of US subjects 50 to 59 years of age vaccinated with ZOSTAVAX to assess the long-term effectiveness of the vaccine and better characterize the duration of protection against herpes zoster (HZ).
- Concept Protocol Submission Date: March 14, 2011
- Final Protocol Submission Date: December 31, 2011
- Study Initiation Date: June 2012
- Interim Study Report Submission Date: The first interim study report is anticipated to be submitted in December 2016 or approximately 5 years after ZOSTAVAX is recommended by the ACIP (assumed to be in June 2011). A second interim study report is anticipated to be submitted in December 2020.
- Study/Trial Completion Date: Either follow-up to June 2023 or follow-up of approximately 5000 subjects 50-59 years of age for 10 years, whichever comes first. The duration of the study will be dependent upon several factors including the retention rate at the study institution and uptake of ZOSTAVAX. Vaccine uptake is influenced by multiple factors including, but not limited to, ACIP recommendations for 50-59 year olds, vaccine supply availability, and healthcare provider and patient attitudes and decisions.
- Final Report Submission Date: December 2024
Please submit clinical protocols to your IND -(b)(4)-, with a cross-reference letter to this supplement to your BLA, STN 125123/734. Submit nonclinical and chemistry, manufacturing, and controls protocols and all study final reports to your BLA, STN 125123/0. 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 commitments as appropriate:
- Postmarketing Study Commitment Protocol
- Postmarketing Study Correspondence
- Postmarketing Study Commitment – Final Study Report
- Supplement Contains Postmarketing Study Commitments – 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 Commitments.” The status report for each study should include:
- information to identify and describe the postmarketing commitment,
- the original schedule for the commitment,
- the status of the 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.
We will include information contained in the above-referenced supplement in your biologics license application file.
Wellington Sun, M.D.
Division of Vaccines and
Related Products Applications
Office of Vaccine
Research and Review
Center for Biologics
Evaluation and Research