October 14, 2010 Approval Letter - Ixiaro
Our STN: BL 125280/19
Intercell USA, Inc.
Attention: Paul J. Wilson
112 Lightship Drive
Mooresville, NC 28117
Dear Mr. Wilson:
We have approved your request to supplement your biologics license application for Japanese Encephalitis Virus Vaccine, Inactivated, Adsorbed, to include long term immunogenicity data in the package insert and the use of a booster dose following the primary series.
The review of this product was associated with the following National Clinical Trial (NCT) number(s): NCT00596102, NCT00595309, and NCT00595270.
We previously approved a Medication Guide for distribution with this product in accordance with 21 CFR Part 208. We approve the revised draft Medication Guide you submitted on December 17, 2009.
Please note that:
- this Medication Guide must be reprinted at the end of the package insert [21 CFR 201.57(f)(2)];
- you are responsible for ensuring that this Medication Guide is available for distribution to every patient who is dispensed a prescription for this product [21 CFR 208];
- the final printed Medication Guide distributed to patients must conform to all conditions described in 21 CFR 208.20, including a minimum of 10 point text; and
- you are responsible for ensuring that the label of each container or package includes a prominent and conspicuous instruction to authorized dispensers to provide a Medication Guide to each patient to whom the drug is dispensed, and states how the Medication Guide is provided.
Under 21 CFR 201.57(f)(2), patient labeling must be reprinted at the end of the package insert and printed in a minimum of 10- point font.
Please submit all final printed labeling and include implementation information on FDA Form 356h and FDA Form 2567. Please provide your final content of labeling in Structured Product Labeling (SPL) format as well as a PDF-format electronic copy and ten original paper copies.
All final labeling should be submitted as Product Correspondence to this BLS at the time of use (prior to marketing).
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 wish to 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, MD 20852-1448. Please submit your final printed advertising and promotional labeling at the time of initial dissemination, accompanied by an FDA Form 2253.
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 waiving the pediatric study requirement for ages 0 months to 12 months because necessary studies are impossible or highly impracticable. This is because insufficient numbers of suitable study subjects exist, because (1) maternally derived JE-neutralizing antibodies are common in infants born in endemic areas and (2) non-travelers in non-endemic regions could not be ethically enrolled in a study from which they could not expect any potential benefit.
We are deferring submission of your pediatric study for ages 12 months to 17 years for this application because this product is ready for approval for use in adults and the pediatric study has not been completed.
Your deferred pediatric study required under 505B(a) of the Federal Food, Drug, and Cosmetic Act is a required postmarketing study. The status of this postmarketing study must be reported according to 21 CFR 601.70 and section 505B(a)(3)(B) of the Federal Food, Drug, and Cosmetic Act. The required study is listed below:
1. IC51-325: Long Term Immunogenicity And Safety With Or Without A Booster Dose Following Primary Vaccination With The Japanese Encephalitis Vaccine IC51 (IXIARO®) In A Pediatric Population In JEV‐Endemic Countries. An open-label, randomized follow-up study to evaluate use of a booster dose of Ixiaro administered to a subset of children who received a primary series of Ixiaro in Study IC51-323.
Final Report Submission: Q2/2015
Submit the final study report to this BLA. For administrative purposes, all submissions related to this required pediatric postmarketing study must be clearly designated “Required Pediatric Assessment”.
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