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COVID-19 Vaccine (BNT162, PF -07302048)
BLA STN 125742/45
Module 1.11.3 Response to FDA Request for Information
PFIZER CONFIDENTIAL
Page 1BNT162b2 (COMIRNATY)
BLA STN 125742/45
Response to CBER Comments Received on 1 9January 2022Regarding Datasets for
Adolescents 12 Through 15 Years of Age
02February 2022
090177e199402cef\Approved\Approved On: 02-Feb-2022 14:19 (GMT)
FDA-CBER-2022-5812-0235485
COVID-19 Vaccine (BNT162, PF -07302048)
BLA STN 125742/45
Module 1.11.3 Response to FDA Request for Information
PFIZER CONFIDENTIAL
Page 21.INTRODUCTION
On 19 January 2022, Pfizer/BioNTech received the following requestfrom the FDA
regarding Stud y C4591001 submitted to STN125742/45 from Captain Mike Smith, PhD
(CBER).
The FDA’s request in bold italics is followed by Pfizer/BioNTech’s respon se below.
2. CBER RESPONSE
The review team has the below information request for STN 125742/45 IR RE the datasets
for adolescents 12 through 15 Years of Age
2.1.Item 1
There are 2 subjects (10961068 and 11631062) with AE records that have AEACN =
DRUG WITHDRAWN, but they only have COMPLETED records in DS. Please explain.
Sponsor Response
TheAEACN = DRUG WI THDRAWN listed for both 10961068 and 11631062 refers to the
action taken with the investigational product ( IP)following a reported medication error for
both subjects . Subject 10961068 received Vax 1 and Vax 2 on 19 August 2020 and 10
September 2020 respectively . They were contacted for revaccination following the initial
EUA for administration of BNTb2162b in those aged 16 years and older (12 December 2020)
on 21January 2021 and were confirmed to have received placebo. Therefore, the participant
was vaccinated with active BNT162b2 on 26 January 2021 and 26 February 2021, it is on 26
February 2021 that a medication error was reported as the participant was dosed with I P that
had a temperature excursion, once identified the IP waspermanentl y discontinued. There
were no AEs associated with this medication error and the participant continued the study.
Subject 11631062 received Vax 1 and Vax 2 on 07August 2020 and 26 August 2020
respectivel y. A medication error was retrospectively reported as occurring on 13 August
2020 for “unknown study intervention administered (drug therapy )”due to site staff errors in
retaining source documentation . The IP prep form for this vaccination was no longer present
in source, so the data could not be verified, and this was logged on 25 February 2021. There
were no AEs associated with this medication error and the participant continued on the study .
They were cont acted for revaccination following the initial EUA for administration of
BNTb162b2in those aged 16 y ears and older (12 December 2020) on 26 February 2021 and
were confirmed to have received placebo. Therefore, the participant was vaccinated with
active BNT 162b2 on 30 March 2021 and 20 April 2021.
The tabulation and analysis package submitted to FDA on 16 December 2021 (Sequence
number 0211) included the data to support the review for participants 12 -15 years of age.
Neither of these subjects (10961068 nor11631062) are adolescent participants 12 through
15years of age, therefore, they are appropriately excluded from the dataset.
090177e199402cef\Approved\Approved On: 02-Feb-2022 14:19 (GMT)
FDA-CBER-2022-5812-0235486
COVID-19 Vaccine (BNT162, PF -07302048)
BLA STN 125742/45
Module 1.11.3 Response to FDA Request for Information
PFIZER CONFIDENTIAL
Page 32.2.Item 2
We have found that subject 11311279 was included in SDTM DM but not ADSL. Please
explain
Sponsor Response
Participant 11 311279 was 15 years of age at the time of enrollment but turned 16 y ears of
age at the time of vaccination, therefore, this participant was not included in the ASDL . This
is also noted in the Analysis Data Reviewer’s Guide, (Module 5.3.5.1 Analy sis Data
Reviewers Guide -12- 15 years 6-Month Follow -UpSequence number 0211)that was
provided to the FDA.
2.3.Items 3a-3e
As previously communicated and discussed under BLA 125742 and other BLAs/INDs
reactogenicity events that begin within the prespecified assessment period should have
been reported in FACE and summarized with the subject diary data in CE. Since this was
not implemented, we request that:
a. reactogenicity events that begin within the prespecified assessment period that are
currently reported in the AE dataset be included in FACE, and then be flagged in AE
so that we know that it is being included in the FACE dataset .
b.Include all individual supporting assessments (daily e- diary and any unplanned
assessments) and the assessor for each finding (identified using FAEVAL=STUDY
SUBJECT or INVESTIGATOR) in the FACE domain.
c.Maintain one row per subject/vaccination/symptom in the CE domain, with CE
summarizing the duration of the event and maximum severity. Maximum severity
(CESEV) should be based on the highest -level severity reported by the subject (via e -
diary) or investigator (in the unplanned assessment CRF).
d. Use SUPPCE CESEV1 and CEDIFFRS to show assessment of severity by study
subject and reason investigator’s assessment of severity differed from study subje ct as
needed for events reported in CE.
e.Update the analysis dataset(s) with records covering the entire event duration (which
could go beyond the protocol- defined assessment period) with start/end dates and
durations (based on first and last days the sympt om was present as recorded in the e -
diary and/or Symptom Resolved Dates CRF) derived from both the e -diary and CRF
data.
Sponsor Response to Items 3a –3e:
The tabulation and analysis package submitted to FDA on 06 May 2021(Sequence
number0001) includedthe datato support the review for participants 12- 15 years of age.
With this response , Pfizer/BioNTech are providing additional documents in Module 5.3.5.1
that address FDA’s request 3a to 3e as follows:
Appendix 1: Roadmap
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FDA-CBER-2022-5812-0235487
COVID-19 Vaccine (BNT162, PF -07302048)
BLA STN 125742/45
Module 1.11.3 Response to FDA Request for Information
PFIZER CONFIDENTIAL
Page 4Appendix 2: Supplemental A nalysis Reviewer Guide
Appendix 3: Reactogenicity Tables with Track edChanges
Appendix 4: Summary of Differences Between CSR and Updated Reactogenicity Data
Appendix 5: Reactogenicity Supplemental TLFs
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