Our STN: BL STN 125300/95
Novartis Vaccines and Diagnostics, Inc
Attention: Christopher Webster, Ph.D.
350 Massachusetts Avenue
Cambridge, MA 02139-4182
Dear Dr. Webster:
We have approved your request to supplement your biologics license application (BLA) for Meningococcal (Groups A, C, Y, and W-135) Oligosaccharide Diphtheria CRM197 Conjugate Vaccine (MENVEO ®) to include safety and immunogenicity data to support use in children 2 through 10 years of age.
The review of this product was associated with the following National Clinical Trial (NCT) number(s): 00310817, 00262028, 00329849 and 00616421.
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/
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.
In addition, you agreed to provide expanded adverse experience reporting to the Vaccine Adverse Reporting System for one year as follows:
- In addition to complying with the requirements under 21 CFR 600.80, you have agreed to submit as 30 day (monthly) reports for one year the following events reported in persons 2 through 10 years of age: all allergic events, including anaphylaxis and urticaria, not reported as 15 day reports; neurological events not reported as 15 day reports, including Bell's palsy, Guillain-Barre syndrome, encephalitis, encephalopathy, brachial neuritis, optic neuritis, other neuropathy, myelitis including transverse myelitis, ptosis, ataxia, multiple sclerosis, acute disseminated encephalomyelitis, cerebrovascular accidents or transient ischemic attacks; all cases of intentional and non-intentional injury; and all cases of new-onset autoimmune disease, including ITP, Kawasaki's disease, myasthenia gravis, vasculitis, thrombocytopenia, arthritis, hemolytic anemia, and collagen-vascular disease not reported as 15 day reports.
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.
Study V59P20 fulfills the pediatric requirement to evaluate the safety and immunogenicity of MENVEO when administered to healthy children 2 through 10 years of age as stated in requirement number 6 of the February 19, 2010, approval letter.
This product is appropriately labeled for use in ages 2 through 16 years for this indication.
AGREED UPON POSTMARKETING COMMITMENTS
Postmarketing Studies subject to reporting requirements of 21 CFR 601.70.
We acknowledge your written commitments as described in your amendments of January 24, and January 25, 2011, as outlined below:
- To conduct acomparative trial to further evaluate the safety, immunogenicity and antibody persistence of two doses of MENVEO versus one dose of MENVEO in children 2 through 10 years of age.
- Concept Protocol Submission Date: May 2011
- Final Protocol Submission Date: September 2011
- Study Initiation Date: March 2012
- Interim Study Report Submission Date: June 2013
- Study/Trial Completion Date: February 2013
- Final Report Submission Date: December 2013
- To conduct an open label, descriptive, epidemiological safety surveillance study of MENVEO vaccine in subjects 2 through 10 years of age. The study will include two parts. Part I of the study will begin with the first administration of MENVEO vaccine to a child 2 through 10 years of age (inclusive) 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 MENVEO vaccine in at least one birth cohort within the 2 through 10 year 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. The final study report for Part I will be submitted 1 year after the last subject has completed study Part I. 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.
Study Milestones for PART I
- Concept Protocol Submission Date: May 2011
- Final Protocol Submission Date: September 2011
- Study/Trial Completion Date: December 2014
- Final Report Submission Date: December 2015
Please submit clinical protocols to your IND, with a cross-reference letter to this supplement to your BLA, STN BL 125300/95. 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 BLA file.
Wellington Sun, M.D.
Division of Vaccines and
Related Products Applications
Office of Vaccine
Research and Review
Center for Biologics
Evaluation and Research
Attachment: Approved Final Draft Labeling