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RPM Filing Checklist STN 125742/0
*** For Internal CBER Use Only *** Page 1of 18Application Information
BLA STN# 125742/0
Proprietary Name:
NOTE : If a primary and alternate are
proposed, specify both names, identifying which is primary and which is alternateCOMIRNATY
Established/Proper Name: COVID-19 mRNA Vaccine
Dosage Form/Strength, if applicable:Suspension for injection. After preparation, a sin
gle dose is 0.3 mL (30 mc g)
Applicant: BioNTech Manufacturin g GmbH
License No.: 2229
If foreign applicant, is a U.S. A
gent identified?Yes
Date of Application: May 18, 2021
Date of Receipt: May 18, 2021
Date clock started after Refusal to Accept for Filin
g (UN): N/A
PDUFA Goal Date: Januar y 16, 2022
Action Goal Date (if different ): September 30, 2021
Date of Filin g Meetin g: June 29, 2021
Filing Date: July 17, 2021
Proposed indication: Active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severeacute respiratory syndrome coronavirus 2(SARS-CoV-2) in individuals 16 years of age andolder.
Submission Type:Refer to the CDER web site for more
information on 505(b)(2)
assessments .Indicate by using Bold the type of submission :
BLANDAEfficac
y Supplement
Review Classification: Indicate by using Bold the type of review
classification
Standard
Priorit y
Resubmission after withdrawal
Resubmission after refuse to file
FDA-CBER-2021-5683-1024801
RPM Filing Checklist STN 125742/0
*** For Internal CBER Use Only *** Page 2of 18Application Information
Part 3 Combination Product?
Note 1: Verify whether the applicant
accurately designated the product as a combination product or not. If designated as a combination product, verify whether the type selected (e.g., CPN, CP1, CP2, etc.) is accurate. If RPM disagrees with the applicant’s designation or the type of combination, consult with the file Chair and appropriate management and notify the applicant immediately of CBER’s assessment and request a corrected form 356h.If yes, indicate by using Bold which type of
combination product and contact the Office of Combination Products (OCP) and copy them on all Inter-Center consults (if applicable).
Note 2 : Notification of OCP should only be done
after verification and applicant notification as
explained in Note 1.
CPN - Not a Part 3 Combination Product
CP1 - Convenience Kit of Co-packa ge
CP2 - Prefilled Drug Delivery Device/System
(syringe, patch, etc. )
CP3 - Prefilled Biologic Delivery Device/System
(syringe, patch, etc. )
CP4 - Device Coated/Impregnated/Otherwise
Combined with Dru g
CP5 - Device Coated/Otherwise Combined with
Biolo gic
CP6 - Dru g/Biolo gic Combination
CP7 - Separate Products Requiring Cross-
Labelin g
CP8 - Possible Combination Based on Cross
Labelin g or Separate Products
CP9 - Other Type of Part 3 Combination Product
(e.g. Dru g/Device/Biolo gic Product )
What is the Application T ype? Indicate the t ype by using Bold
Fast Track
Rollin g Review
Orphan Desi gnation (for this indication )
Rare disease
Breakthrou gh Therap y Desi gnation
Triggers PREA
Other:
PMR response: Indicate by using Bold the type of PMR
response
FDAAA [505 (o)]
PREA deferred pediatric studies [21 CFR 314.55
(b)/21 CFR 601.27 (b)]
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RPM Filing Checklist STN 125742/0
*** For Internal CBER Use Only *** Page 3of 18Application Information
Accelerated approval confirmatory studies [21
CFR 314.510/21 CFR 601.41]
Animal rule postmarketing studies to verify clinical benefit and safety [21 CFR 314.610/21 CFR 601.42]
PMC response: Indicate by using Bold the type of PMC
response
Clinical Safet y [506B PMC]
Clinical Efficac y [506B PMC]
Clinical Pharmacolo gy [506B PMC]
Non-Clinical Toxicolo gy [506B PMC]
CMC or Stabilit y related [non-506B PMC]
Has the Office PMR/PMC Coordinator been notified that submission is in response to PMC or PMR?Indicate by using Bold either yes or no.
YesNoN/A
List referenced IND Number (s): IND 19736 & EUA 27034
IS THE APPLICATION FILEABLE? _X_ Yes / ___ No
FDA-CBER-2021-5683-1024803
RPM Filing Checklist STN 125742/0
*** For Internal CBER Use Only *** Page 4of 18Table 1: Goal Dates/ Product Na mes/ Classification Properties
Goal Dates/ Product Names/
Classification PropertiesYES NO NA Comment
1.PDUFA and Action Goal dates
correct in trackin g system?99
2.Is there a formal communication plan? Have the dates been captured in the appropriate regulatory system?9
9 Non-standard approach (e.g., a Mid-Cycle Communication will be scheduled, but a Late-Cycle Meeting will not be scheduled). Other typical ad-hoc interactions that occur during the review process willoccur.
3.Are the proprietary, established/proper, and applicant names correct in trackin
g system? 99
4.Is the review schedule standard or priority (S or P) and are all classifications/properties entered in the appropriate regulatory system (e.g., workload management, review schedule, STN characteristics)?
If unable to make corrections, contact
CBERRIMS
@fda.hhs. gov99 BLA is a priority review.
Table 2: Application Integrity Policy
Application Inte grity Polic y YES NO NA Comment
5.Is the application affected by the Application Integrity Policy (AIP)? Check the AIP list at:https://www.fda.gov/inspections-
compliance-enforcement-and-
criminal-investigations/compliance-
actions-and-activities/application-
integrity-policy
If yes , explain in comment column
and discuss with immediate supervisor.9
9
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*** For Internal CBER Use Only *** Page 5of 18Application Inte grity Polic y YES NO NA Comment
6.If affected by AIP, has DMPQ &
BiMo been notified of the submission? If
yes, date notified:99
Table 3: User FeesSOPP 8406 CBER Processing of PDUFA Application Payments
User Fees
7.Is Form 3397 (User Fee Cover Sheet) included with authorized signature? [See
SOPP 8406 for details on which products require a coversheet].Indicate by using Bold
YES
NO
N/A
Comment
8.Is the applicant attempting to redeem a
priority review voucher with this application?Notify [email protected] to
confirm payment of priority review voucher fee.NOTE : If the applicant is requesting to
receive a priority review voucher, see Table 12. No
9.User Fee StatusVerify payment status with [email protected] . If a user
fee is required and it has not been paid, the application is unacceptable for filing following a 5-day grace period. Review stops. Send Unacceptable for Filing (UN) letter and contact user fee staff [See SOPP 8406].
Note : CBER PDUFA Staff will monitor
arrears status daily and proactively alert
affected Offices that applications and supplements should not be received if a firm is in arrears.Indicate the payment for this application by using BOLD:
User Fee Paid:
$2,875,842.00
Paid
Exempt (orphan, government )
Waived (e.g., small business, public health
)
Not required
FDA-CBER-2021-5683-1024805
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*** For Internal CBER Use Only *** Page 6of 18Format and Content
Table 4: Overall Format/Content
Overall Format/Content YES NO NA Comment
10.Does electronic submission follow the
eCTD guidance?
Providing Regulatory Submissions
in Electronic Format – Certain
Human Pharmaceutical Product
Applications and Related
Submissions Using the eCTD
Specifications
If not, explain (e.g., waiver granted ).99
11.Index: Does the submission contain
an accurate comprehensive index?
(e.g., table of contents )99
12.Is the submission complete as
required under 21 CFR 314.50
(NDAs/NDA efficacy supplements ) or
under 21 CFR 601.2 ( BLAs/BLA
efficacy supplements ) including:
*RTF issues, a “No” means the
application is unacceptable for filing.
If any of the following are “no” ,
explain why (i.e., datasets are not in correct format
)99
a.xLegible* 99
b.xEnglish* (or translated into En
glish)99
c.xPagination 99
d.xNavigable hyperlinks* (electronic submissions onl
y)99
e.xDatasets present in software compatible format*9
9
f.xAll sections are present* 99
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*** For Internal CBER Use Only *** Page 7of 18Overall Format/Content YES NO NA Comment
13.Companion application received if a
shared or divided manufacturing arrangement ( BLA only ) or, cross-
reference to Master File received for proprietary information not included with submission.
If yes, insert companion application
BLA # or cross-referenced Master File # If missing, this may be a Refuse to file issue, discuss with review team and mana
gement.99 Cross-reference letters to authorize review information regarding vials and stoppers:IND 19736, DMF 012683, DMF 9543, DMF 15209, DMF 011793, DMF 011820, DMF 011321, DMF 10953
Table 5: Applications in The Program (PDUFA)
Applications in The Program
(PDUFA )YES NO NA Comment
14.Were there agreements made at the applicant’s pre-submission meeting (and documented in the minutes) regarding certain late submission components that could be submitted within 30 days after receipt of the ori
ginal application?99 Strain sequence analysis of all COVID-19 cases will be provided by June 7, 2021.
15.xIf so, were the late submission components all submitted within 30 days? List any late submission components which arrived after 30 days in the comments box.
(This is an RTF issue, discuss with review team and mana
gement. )99 Submitted in amendment 5 (sequence 0006) dated June 7, 2021.
Forms and Certifications
16.Electronic forms and certifications with electronic signatures (scanned, digital, or
electronic) are acceptable. Forms include: user fee cover sheet (3397), application
form (356h), financial disclosure (3454/3455), and clinical trials (3674);Certifications include: debarment certification and pediatric certification on Pediatric
Plan for waived or deferred Pediatric studies.
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*** For Internal CBER Use Only *** Page 8of 18Table 6: Application Form
Application Form YES NO NA Comment
17.Is form FDA 356h included with
authorized signature per 21 CFR 601.2(a) (BLAs) or per 21 CFR 314.50
(a) (NDAs )?99
18. If foreign applicant, has a U.S. agent signed the form [see 21 CFR 314.50(a)(5)]?9
9 BioNTech Manufacturing GmbH is the foreign applicant and the U.S. Agent, Elisa Harkins, Pfizer,Inc. signed the form.
19. Is a comprehensive and readily located list of all clinical sites listed
on the form or attached to the
form? 9
9 Lists of clinical sites are included
in section 5.3.5.1
for each individual study under APPENDICES.Also, sites are listed in FDA form 3454 in section 1.3.4.
20. Are all establishments and manufacturing facilities, along with their registration numbers, listed on the form or attached to the form? 9
9
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*** For Internal CBER Use Only *** Page 9of 18Table 7: Financial Disclosure
Financial Disclosure YES NO NA Comment
21.Are financial disclosure forms FDA
3454 and/or 3455 included with authorized signature per 21 CFR 54.4(a)(1) and (3)?
Forms must be signed by the
APPLICANT, not an Agent [see 21 CFR 54.2(g)].
Note: Financial disclosure is required
for bioequivalence studies that are
the basis for approval.9
9 The Phase 1/2/3 study C4591001 was conducted by Pfizer; therefore, Pfizer submitted the form 3454 (page 1) signed by J. R. Meloro (Pfizer).
The Phase 1/2
study BNT162-01 was conducted by BioNTech SE; they also submitted the form 3454 signed by Dr. Christopher Marshallsay (page 78
).
Table 8: Clinical Trials Database and Study Data
Clinical Trials Database & Study
DataYES NO NA Comment
Is form FDA 3674 included with authorized signature?
If yes, ensure that the application is
also coded with the supporting document category, “C ertification
Form 3674.”
If no, ensure that language
requesting submission of the form
is included in the STN Assignment
Application letter (also called the Acknowled
gement Letter ).99
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*** For Internal CBER Use Only *** Page 10of 18Clinical Trials Database & Study
DataYES NO NA Comment
22.Are National Clinical Trial (NCT)
Numbers included on 3674?
If yes, enter in the appropriate
regulatory tracking database (RMS/BLA).
If no, request in either the Filing or
Filing Issues (also called the Deficiencies Identified (DI)) letters. The NCT numbers will be referenced in the final action letter. 9
9 NCT04368728 (Study C4591001),and NCT04380701(Study BNT162-01) are entered in RMS-BLA
23.Determine if Study Data Tabulation Model (SDTM), Analysis Data Model (ADaM) data, Standard for Exchange of Nonclinical Data (SEND) or CTD datasets - Module 5 are present.
If yes, notify CBER’s Clinical Data
Interchange Standards Consortium (CDISC) representative and request that a CDISC format validation be performed. [email protected].
Note : CDISC will email validation
reports to the RPM upon completion for upload to the EDR.
Refer to CBER JA 900.18: Study Data
Validation Process .99
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*** For Internal CBER Use Only *** Page 11of 18Clinical Trials Database & Study
DataYES NO NA Comment
24.Is study data acceptable based on the
validation reports? Refer to CBER JA
900.18: Study Data Validation Process.
Note 1 : If there are errors, collaborate
with discipline reviewer(s) and the
CDISC representative to draft an information request for minorcorrections or a refuse to file letter as appropriate.
Note 2 : Review decision regarding
acceptance of data should be
documented in the filing review checklist or memo and in the discipline reviewer’s review memo.9
9 Dataset validation will not be done for this BLA. The included datasets are the same as those in the EUAamendment for adolescents 12 through 15 years of age, which were validated during the review of the EUA 27034 amendment 132.
Table 9: Debarment Certification
Debarment Certification YES NO NA Comment
25.Is a correctly worded Debarment Certification included with authorized signature?
Certification is not required for
supplements if the debarment certification was submitted in the original application. If foreign applicant, both the applicant and the U.S. Agent must sign the certification [per Guidance for Industry: Submitting Debarment Certifications].
Note: Debarment Certification should
use wording in FD&C Act Section 306(k)(1) i.e.,“[Name of applicant] hereby certifies that it did not and will not use in any capacity the services of any person debarred under section 306 of the Federal Food, Drug, and Cosmetic Act in connection with this application..” Applicant may notuse wording such as,
“To the best of m
y knowledge…”99
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RPM Filing Checklist STN 125742/0
*** For Internal CBER Use Only *** Page 12of 18Table 10: Exclusivity
Exclusivit y YES NO NA Comment
26.Does another product (same active
moiety) have orphan exclusivity for the same indication?
Check the Orphan Drug Designations and Approvals list at:http://www.accessdata.fda.gov/script
s/opdlisting/oopd/index.cfm
If yes, consult CBER Jurisdiction Officer. See Jurisdiction intranet site for current CBER contact: http://inside.fda.gov:9003/cber/officeofthedirector/associatedirectorforqualit
yassurance/ucm023543.htm99
27.If another product has orphan exclusivity, is the product considered to be the same product according to the orphan drug definition of sameness [see 21 CFR 316.3(b)(13)]?
If yes, consult CBER Jurisdiction
Officer. See Jurisdiction intranet site for current CBER contact: http://inside.fda.gov:9003/cber/officeof
thedirector/associatedirectorforquality
assurance/ucm023543.htm99
28.Has the applicant requestedreference product designation and
12-year exclusivity? (Applies to first
licensed product under section 351(a) for Original BLAs/BLA supplements only, request protects against biosimilar applications under 351(k)(7) )
If yes, refer to JA 900.11 Determining
Exclusivity Period of Reference
Product Based on First Licensure
Date for procedures and alert CMC
reviewer. 99
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*** For Internal CBER Use Only *** Page 13of 18Exclusivit y YES NO NA Comment
29.Has the applicant requested pediatric
exclusivity under BPCA?
If yes, email CBER Pediatric
Exclusivity Board RPM at: CBERIOD-PEB
@fda.hhs.gov99
Table 11: Priority Review Voucher Requests
Priorit y Review Voucher Requests YES NO NA Comment
30.Has the applicant requested a priority review voucher? If yes, notify:
[email protected]
ovthat a voucher request has been
received and select the type below.Note : Follow the job aid and complete
the checklist for the voucher type requested
(see links below ).99
31.Rare pediatric disease (RPD)Follow: JA900.19 RPD PRV
C900.03 RPD PRV Eli gibility Checklist99
32.Material Threat Medical Counter Measures (MCM)Follow: JA900.20 MTMCM PRV
C900.01 MTMCM PRV Eligibility
Checklist99
33.Tropical disease (TD)Follow: JA900.21 TD PRV
C900.02 – TD PRV Eli gibility Checklist99
Table 12: Pediatrics
Pediatrics YES NO NA Comment
34.Pediatric Research Equity Act (PREA)
Does the application trigger PREA?
BLAs/efficacy supplements for new active ingredients, new indications (not change of age range only), new dosage forms, new dosing regimens, or new routes of administration trigger PREA.9
9
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*** For Internal CBER Use Only *** Page 14of 18Pediatrics YES NO NA Comment
a. If yes , has the applicant included or
referenced the agreed upon pediatric
study plan (PSP)? This should have been submitted at least 210 days prior to submission of this application. [ See
JA851.05 Instructions for Processing
PSPs .] If no agreed PSP is included or
referenced in the submission, consider RTF. Discuss with
your Supervisor.99
b. If yes , has the applicant submitted
the pediatric assessment, or provided documentation requesting either a waiver and/or deferral in accordance with their agreed PSP?
Note 1: All waiver & deferral
requests, pediatric plans, and pediatric assessment studies must be reviewed by PeRC prior to approval of the application/supplement.
Note 2: If the applicant deviated
from their agreed PSP discuss with Supervisor and Office representative to CBER Pediatrics Working Group.
Note 3: Pediatric items are looked at
by both the RPM and the Clinical Reviewer.9
9
35.Does the submission include a pediatric assessment in response to a deferred Pediatric study?All pediatric assessment studies must be reviewed by PeRC prior to approval of the supplement.9
9
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RPM Filing Checklist STN 125742/0
*** For Internal CBER Use Only *** Page 15of 18Table 13: Proprietary Name
Proprietar y Name YES NO NA Comment
36.Is a proposed proprietary name submitted?
If yes, ensure that PNR is selected for this
submission in the regulatory system.If no, include missing PNR in an information request. [See SOPP 8001.4:
Review of Proprietary Names for CBER
Regulated Products and JA 910.02
Proprietar y Name Review (PNR ) Processing ]99
a.Are the PDUFA milestones correct for review of proprietar
y name?99
b.Has APLB reviewer been notified? 99
Table 14: REMS
REMS YES NO NA Comment
37Is a REMS submitted? 99
Table 15: Prescription Labeling-1
38.Prescription Labelin g Check all t ypes of labelin g submitted.
a. Packa ge Insert (PI) 99
b. Patient Packa ge Insert (PPI)
c. Patient Oriented Labelin g (POL)
d. Instructions for Use (IFU)
e. Medication Guide (MedGuide )
f. Carton labels 99(BLA includes 25- and 125-dose carton
labels for both Puurs and Kalamazoo packa
ging sites ).
g. Immediate container labels 99(BLA includes vial labels for both Puurs and
Kalamazoo packa ging sites ).
h. Diluent 99
i. Other (specif y):
Table 16: Prescription Labeling-2
Prescription Labelin g YES NO NA Comment
39Is Electronic Content of Labeling (COL) submitted in SPL, PDF, and Word format?If no, request applicant to submit SPL and Word before the filing date. 9
9
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*** For Internal CBER Use Only *** Page 16of 18Prescription Labelin g YES NO NA Comment
40Is the PI submitted in Physicians
Labeling Rule (PLR) and Pregnancy and Lactation Labeling Rule (PLLR) format?If no, request applicant to submit labeling in corrected format (PLR and PLLR, as applicable) before the filin
g date.99
41Was all labeling (e.g., PI, PPI, MedGuide, POL/IFU, carton and immediate container labels) consulted to APLB?9
9
Table 17: Other Consults
Other Consults YES NO NA Comment
42Are additional consults needed? (e.g., CDER, CDRH)
If yes, specify consult(s) and
date
(s) sent:99
Table 18: IND/Pre- BLA/NDA Meeting Minutes in the EDR
Meetin g Minutes in the EDR YES NO NA Comment
43.End-of Phase 2 meeting(s)?
If yes, reference IND number where
minutes can be found in the filing meeting
agenda and summary.99
FDA-CBER-2021-5683-1024816
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*** For Internal CBER Use Only *** Page 17of 18Meetin g Minutes in the EDR YES NO NA Comment
44.Pre-BLA/Pre-NDA/Pre-Supplement
meeting?
Date: 4/16/2021If yes, reference IND number where
minutes can be found in the filing meeting agenda and summary. For PDUFA BLAs, check for any late components agreed upon during Pre-BLA meeting, if held, and a formal communication plan. All late components mu st be submitted
by day 30 after the initial submission is received from the applicant. 9
9 IND 19736:We provided feedback regarding clinical/nonclinical questions on March 9, 2021 andprovided feedback regarding CMC/facilitiesquestions on March 31, 2021. During the 4/16/2021 teleconference, we discussed all the unresolved issues related to both clinical and CMC/facilitiesdisciplines.
45.Any Special Protocol Assessments (SPAs)?
If yes, reference IND number where
minutes can be found in the filing meetin
g agenda and summar y.99
Append C 905.01.01 here, if submission contains 505(b)(2).
See: http://inside.fda.gov:9003/CDER/OfficeofNewDrugs/ImmediateOffice/UCM027499
for more information on 505(b)(2) and append C 905.01.01: RPM FILING REVIEW
CHECKLIST FOR 505(b)(2) APPLICATIONS (NDA and NDA Supplements only) here
prior to filing review. Access C 905.01.01 here: https://fda.sharepoint.com/sites/CBER-
Review-Resources/SOPPsJAsTemplatesOther References/C-905.01.01.docx
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*** For Internal CBER Use Only *** Page 18of 18RPM FILING REVIEW CONCURRENCE
Application number : STN 125742/0
RPMs (Laura Gottschalk and Mike Smith) Date
I concur with the reviewer(s) recommendation? 9Yes / ___ No If no, provide a
justification.
Branch Chief Date
I concur with the reviewer(s) recommendation? 9Yes / ___ No If no, provide a
justification.
Division Director (or equivalent second line supervisor) Date06/30/2021
06/30/2021
07/01/2021Laura B. Gottschalk -S
2021.06.30 14:01:34 -04'00'Michael J. Smith -S4Dig tally s gned by M chael J Smith S4 DN c=US o=U S Government ou=HHS ou=FDA ou=People 0 9 2342 19200300 100 1 1=0014080934 cn=M chael J Smith S4 Date 2021 06 30 14 37 09 04'00'
Elizabeth M. Sutkowski -SDigitally signed by Elizabeth M. Sutkowski -S DN: c=US, o=U.S. Government, ou=HHS, ou=FDA, ou=People, 0.9.2342.19200300.100.1.1=1300076199, cn=Elizabeth M. Sutkowski -S Date: 2021.06.30 20:36:26 -04'00'
Loris D. Mcvittie -SDigitally signed by Loris D. Mcvittie -S DN: c=US, o=U.S. Government, ou=HHS, ou=FDA, ou=People, 0.9.2342.19200300.100.1.1=1300064781, cn=Loris D. Mcvittie -S Date: 2021.07.01 11:05:07 -04'00'
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