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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
Silver Spring, MD 20993
CENTER FOR BIOLOGICS EVALUATION AND RESEARCH
OFFICE OF VACCINES RESEARCH AND REVIEW
DIVISION OF VACCINES AND RELATED PRODUCTS APPLICATIONS
DATE: September 24, 2021 PAGES: 4
TO: BioNTech SE/Pfizer., Inc.
Attention: Amit Patel
235 East 42ndStreet
New York, NY 10017
Phone: 214-918-5262
Fax number: 845-474-3500
E-mail: [email protected]
FROM: Ramachandra Naik, Ph.D.
Division of Vaccines and Related Products Applications
Office of Vaccines Research and Review
Center for Biologics Evaluation and Research
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
Phone number: 301-796-2640
Fax number: 301-595-1244
CBER Reference: IND 19736 amendment 434
IND Title: Human Coronavirus mRNA Vaccines (SARS-CoV-2 Spike Protein;
BNT162a1 (uRNA; variant RBL063.3); BNT162b1 (modRNA;
variant RBP020.3); BNT162b2 (modRNA; variant RBP020.2);
BNT162c2 (saRNA; variant RBS004.2)) in Lipid Nanoparticles
(ALC-0315, ALC-0159, DSPC and Cholesterol)
SUBJECT: CBER responses to the Request for Comments and Advice
regarding the supplemental BLA for adolescents 12 through 15
years of age
FDA-CBER-2022-5812-0236379
Page 2 – Mr. Amit Patel IND 19736
Dear Mr. Patel:
Reference is made to amendment 434 (dated August 3, 2021) to your IND 19736 that
contained a Request for Comments and Advice regarding a proposal to submit a
supplemental Biologics License Application (sBLA) to expand the indication to include
use in adolescents 12 through 15 years of age. We have the following responses to the
questions you posed in the Request for Comments and Advice document.
Sponsor Question 1:
Does CBER agree with the proposed clinical safety analyses in the planned sBLA to
?
FDA Response to Question 1:
We have the following additional requests for the clinical safety analyses in the
planned sBLA for individuals :
a. In addition to the listed safety analyses, please include an interim summary of
new or updated safety events that occurred/have been updated since the data
cutoff used for the EUA Amendment submission for individuals 12 through 15
years of age, using the same time periods, and insert a flag into the datasets to
indicate which safety events are new/updated.
b. Please submit the safety data and results for this age group from the dose
ranging portion of Study C4591007, to support the selected dose level for this
age group.
c. In addition to the AE analyses provided as incidence rates to account for
exposure time, please also provide all AE analyses to summarize the
number/percentage of subjects with each AE, regardless of exposure time.
Sponsor Question 2:
Does CBER agree with the proposed criteria for safety narratives in the planned sBLA
for Study C4591001 participants 12-15 years of age?
FDA Response to Question 2:
We have the following additional requests for the proposed criteria for safety
narratives in the planned sBLA for individuals :
a. Please include hyperlinks from the interim study report to the narrative document,
which will identify the specific subject narrative location within the narrative
document.
b. Please include participant listings for all AEs, which include actual study arm,
age, sex and race and time to event from last vaccination.
FDA-CBER-2022-5812-0236380
Page 3 – Mr. Amit Patel IND 19736
c. With regards to the proposed programmed tables summarizing lymphadenopathy
events, please report these by treatment group, include absolute numbers of the
events, and provide narratives for any lymphadenopathy events that meet criteria
as outlined for SAEs, safety-related withdrawals, or any other criteria.
d. Please submit any safety narratives for this age group from the dose ranging
portion of Study C4591007, that also meet the stated criteria.
Sponsor Question 3:
Does CBER agree that the planned sBLA can be comprised of safety and efficacy data
through at least 6-month follow-up for Study C4591001 participants 12-15 years of age?
FDA Response to Question 3:
We agree that updated efficacy analyses of confirmed COVID-19 cases accrued in
the placebo-controlled blinded follow-up period through the sBLA data cutoff will be
sufficient, and additional immunogenicity evaluations will not be requested from
Study C4591001. We have the following additional requests:
a. Similar to the BLA package, please submit the following additional information:
i. for all confirmed COVID-19 cases contributing to the vaccine efficacy
analysis, please provide available viral sequencing information to identify
the SARS-CoV-2 strain for each case and a summary of the variants of
concern and variants of interest, and
ii. a post-hoc analysis of breakthrough cases [i.e., protocol-specified COVID-
19 cases accrued during the current delta variant surge (e.g., during a
defined time period beginning July 1, 2021 and through the data cut-off)]
comparing participants who completed the 2-dose vaccination series early
in the study (i.e., those who were originally randomized to BNT162b2) vs.
those who completed the 2-dose vaccination series later in the study (i.e.,
those who were originally randomized to placebo and then crossed over to
BNT162b2).
b. Please submit the data and immunogenicity results for this age group from the
dose ranging portion of Study C4591007, to support the selected dose level for
this age group.
Sponsor Question 4:
Does CBER agree with the proposal to submit an sBLA with clinical documents limited
to an interim Clinical Study Report and a Module 2.5 Clinical Overview to report 6-
month follow-up data from Study C4591001 participants 12-15 years of age?
FDA Response to Question 4:
We have the following comments regarding the clinical documents for inclusion with
the planned sBLA for individuals :
FDA-CBER-2022-5812-0236381
Page 4 – Mr. Amit Patel IND 19736
a. Please refer to our response to Question 1; this interim summary of safety events
that occurred or have been updated since the data cutoff for the EUA
Amendment can be provided within the interim Clinical Study Report or as a
stand-alone document. Please alert us to the location of this information within
the submission.
b. Because the data, analyses, and your interpretation of the dose-ranging portion
of Study C4591007 are expected to be part of the planned sBLA submission,
please plan to revise your proposal to include an interim Clinical Study Report for
Study C4591007, limited to the 12 through 15 year age group, to describe the
dose-ranging portion of the study. Because the number of subjects 12 through 15
years of age evaluated in Phase 1 of Study C4591007 is small, we agree that
Summaries of Clinical Efficacy and Safety in Module 2 would not be required for
the planned sBLA submission.
Additional FDA Questions/Comments:
1. We also request that the data and analyses from the Postmarketing Required Study
C4591007 substudy to prospectively assess the incidence of subclinical myocarditis
following administration of COMIRNATY in a subset of participants 5 through 15
years of age be submitted to inform the risk benefit analysis of the proposed sBLA
for individuals .
2. We will also provide shell tables specific to this sBLA submission for individuals
years of age.
Please provide your responses in an amendment to your IND 19736. In your reply to
this communication, we recommend that you restate the item and follow it with your
response. Use of this format helps organize the relevant information and provides a
self-contained document that facilitates future reference.
END
FDA-CBER-2022-5812-0236382