Our STN: BL 125300/226
Novartis Vaccines and Diagnostics, Inc.
Attention: Patricia Stoehr, Ph.D.
350 Massachusetts Ave.
Cambridge, MA 02139
Dear Dr. Stoehr:
We have approved your request to supplement your biologics license application for Meningococcal (Groups A, C, Y, and W-135) Oligosaccharide Diphtheria CRM197 Conjugate Vaccine to include safety and effectiveness data to support use in children 2 months through 23 months of age for active immunization to prevent invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135.
The review of this product was associated with the following National Clinical Trial (NCT) numbers: 00474526, 00806195, 01000311, 00310856, 00626327, 00310817, 00262028, 00329849, 00616421, 01018732, 00329901, 00450437, 00474487, 00518180, 00856297, and 00262002.
We hereby approve the draft package insert labeling submitted on August 1, 2013, to include safety and effectiveness data to support use in children 2 months through 23 months of age for active immunization to prevent invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135, and the draft carton and container labeling submitted on January 30, 2013, to include use in persons 2 months through 55 years of age.
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/UCM072392.pdf.
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.
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 at http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/
Guidances/Vaccines/UCM164319.pdf. Per 21 CFR 600.2(f), please refer to http://www.fda.gov/AboutFDA/CentersOffices/CBER/ucm106001.htm for updated mailing address information.
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.
Studies V59P14, V59P23, V59P21, and V59_33 fulfill the pediatric requirement to evaluate the safety and effectiveness of MENVEO for active immunization to prevent invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 in children 2 months through 23 months of age as stated in requirement numbers 3, 4, 5, and 7 of the February 19, 2010, approval letter.
We note that you have fulfilled the pediatric study requirement for all relevant pediatric age groups for this application.
AGREED UPON POSTMARKETING COMMITMENTS
Postmarketing Studies subject to reporting requirements of 21 CFR 601.70.
We acknowledge your written commitments as described in your amendment dated July 22, 2013, as outlined below:
- To conduct an open label, descriptive, epidemiological safety surveillance study of MENVEO in children 2 months through 23 months of age. The study will include two parts. Part I of the study will begin with the first administration of MENVEO to a child 2 through 23 months of age who receives medical care at the site where the study is being conducted. Part I will continue for 3 years, or until commencement of Part II, whichever occurs first. Part II of the study will be initiated if there is a recommendation by the Advisory Committee on Immunization Practices (ACIP) for routine use of meningococcal conjugate vaccine in at least one birth cohort within the 2 through 23 months age range.
Part II will commence with the effective date of the ACIP recommendation, and will continue until 20,000 children are enrolled, or until 1 year has elapsed, whichever occurs last. If initiated, a final study report for Part II will be submitted 1 year after the last subject has completed study Part II. In the event there is no recommendation for routine use of meningococcal conjugate vaccine in this age group, Part II will be considered fulfilled when Part I is completed.
We acknowledge the timetable you submitted on July 22, 2013, which states that you will conduct Part I of this study according to the following schedule:
- Final Protocol Submission Date: May 31, 2014
- Study Completion Date: November 30, 2017
- Final Report Submission Date: November 30, 2018
- To submit results of completed Study V59_36, in which the safety and immunogenicity of vaccines recommended for routine use in infants, including Prevnar 13, were evaluated when concomitantly administered with MENVEO.
We acknowledge the timetable you submitted on July 22, 2013, which states that you will submit the results from this study according to the following schedule:
- Final Report Submission Date: August 31, 2014
Please submit clinical protocols to your IND, with a cross-reference letter to this biologics license application (BLA), STN BL 125300/226. Submit nonclinical and chemistry, manufacturing, and controls protocols and all study final reports to your BLA STN BL 125300/0. 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