Wyeth Pharmaceuticals Inc.
Dear Ms. Devlin:
We have approved your request to supplement your biologics license application (BLA) for Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM197 Protein) to include the prevention of pneumonia and invasive disease caused by S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F in persons 50 years of age or older according to the regulations for accelerated approval of biological products (21 CFR 601.40 and 21 CFR 601.41) effective this date. The evaluation of effectiveness of immunization with Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM197 Protein) was based on serological endpoints that are accepted as being reasonably likely to predict protection from pneumonia and invasive disease caused by S. pneumoniae. The effectiveness of Prevnar 13 in preventing pneumonia and invasive disease has not yet been demonstrated in controlled clinical studies.
The review of this product was associated with the following National Clinical Trial (NCT) number(s): NCT00427895, NCT00488852, NCT00774410, NCT00521586, NCT00546572, NCT00492557, NCT00574548, NCT00500357, NCT00269672, and NCT00500266.
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.
Please note that the accelerated approval regulation concerning promotional materials (21 CFR 601.45) stipulates that all advertising and promotional labeling items that Wyeth Pharmaceuticals Inc. wishes to distribute in the first 120 days following approval, must have been received by FDA prior to the approval date. After approval, promotional items intended for dissemination after the first 120 days following approval should be submitted to the FDA 30 days prior to the anticipated distribution date. Please submit these materials with Form FDA 2253 to the Center for Biologics Evaluation and Research, Advertising and Promotional Labeling Branch, HFM-602, 1401 Rockville Pike, Rockville, MD 20852-1448. Two copies of all final advertising and promotional labeling materials should be submitted at the time of initial dissemination, accompanied by Form FDA 2253.
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.
ACCELERATED APPROVAL REQUIRED STUDY
Products approved under the accelerated approval regulations, 21 CFR 601.41, require further adequate and well-controlled confirmatory clinical studies to verify and describe clinical benefit. We remind you of your post-marketing study commitment specified in your submission dated December 22, 2011. This commitment, along with the agreed upon date for submitting the final study report, is listed below.
You agree to conduct a study to assess the efficacy of the Prevnar 13 in adults ≥65 years of age in preventing community acquired pneumococcal pneumonia caused by the pneumococcal serotypes in the vaccine. A study entitled “A Phase 4, Randomized, Placebo-Controlled Clinical Trial of 13-Valent Pneumococcal Conjugate Vaccine Efficacy in Prevention of Vaccine-Serotype Pneumococcal Community-Acquired Pneumonia and Invasive Pneumococcal Disease” (CAPITA)was begun in the fall of 2008. The original protocol for this study was submitted on April 8, 2008. The final clinical study report will be submitted by December 31, 2013.
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 in children from birth through 16 years of age for this application because the necessary studies to demonstrate the efficacy of Prevnar 13 for the prevention of pneumococcal pneumonia in the pediatric population are impossible or highly impracticable.
AGREED UPON POSTMARKETING COMMITMENTS
Postmarketing Studies Subject to Reporting Requirements of 21 CFR 601.70.
We acknowledge your written commitment as described in your submission of December 22, 2011, as stated below:
You agree to conduct a study to evaluate concomitant use of Prevnar 13 and a U.S. licensed inactivated influenza vaccine in subjects ≥ 50 years of age, pre-immunized with 23-valent pneumococcal polysaccharide vaccine (23vPS). The study will be titled: “A Phase 4, Randomized, Double-Blind Trial to Evaluate the Safety, Tolerability, and Immunogenicity of A 13-Valent Pneumococcal Conjugate Vaccine (13vPnC) When Administered Concomitantly with Trivalent Inactivated Influenza Vaccine in Adults 50 Years and Older Who Received 1 Dose of 23vPS Prior to Study Enrollment.” A final protocol will be submitted by September 30, 2012, and the study will begin by September 30, 2013, and be conducted during the 2013-2014 and 2014-2015 influenza seasons. The study will be completed by March 31, 2015. The final study report will be submitted by December 31, 2015.
Please submit clinical protocols to your IND, with a cross-reference letter to this biologics license application (BLA), STN BL 125324/262. Submit all study final reports to your BLA STN BL 125324/262. 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 also may 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 as 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).
When you have fulfilled your commitment, submit your final report as PMC Submission – Final Study Report or Supplement Contains Postmarketing Study Commitment – Final Study Report.
We will include information contained in the above-referenced supplement in your biologics license application file.
Wellington Sun, MD
Division of Vaccines and
Related Product Application
Office of Vaccines
Research and Review
Center for Biologics
Evaluation and Research