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Pfizer Global Regulatory Affairs
Pfizer Inc.
400 Arcola Road Collegeville, PA 19426
Global Product Developm ent
06May2021
Marion Gruber, Ph.D.
Director
Office of Vaccines Research and Review
Food and Drug Administration
Center for Bi ologicsEvaluation and Research
DocumentControl Center
10903 New Hampshire Avenue
WO71, G112
Silver Spring, MD 20993 -0002THIS DOCUMENT CONTAINS CONFIDENTIAL
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THAT IS DISCLOSED ONLY IN CONNECTION
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OTHER PURPOSE WITHOUT THE PRIOR
WRITTEN CONSENT OF PFIZER INC.
Re:BLA 125742
COVID-19 mRNA Vaccine ( BNT162/PF-07302048)
Part 1 of the Origin al Submission – Rolling Biologics License Application (BLA)
Request for Prior ity Review Designation
Dear Dr. Gruber ,
Please find enclosed Part 1 of the Original Submission of the rolling Biol ogics License
Applicatio n (BLA) for the BNT162b2 vaccine candidate developed by BioNTech and Pfizer
under BB -IND 19736 for the prevention of COVID -19caused by SARS-CoV-2in
individuals ≥16 years of age. This vaccine was granted Fast Track D esignation for
individuals >18 years of age on 07July2020.The Grant Fast Track D esignation Letteris
provided in Module 1.7.4. Submission of this BLA as a rol ling application was agreed during
the telecon ference of 16 April 2021.
BioNTech and Pfizer are requesting Priority Review Desig nationfor this BLA. It meets the
criteria for P riority Review Designation, as outlined i n the 2014 Guidance for Industry :
Expedited Programs for Serious Conditions –Drugs and Biologics because BNT162b2
preventsaserious and life -threatening condition (COVID-19)and, if approved, would
provide a significant improvement in sa fety andeffectiveness because there are currentl y no
vaccines licensed for the prevention of COVID-19 in the US. The PriorityReview
Designation Requestis provided in Module1.2.
Awire transfer for $2,875,842.00 was made to the U.S. Department of Treas ury (TREAS
FDA-CBER-2021-5683-0013742
Marion Gru ber, Ph.D. , Director Page 2of 6
BLA125742 06May2021
Pfizer Confid ential
Page 2NYC 33 L iberty Street, New York , NY 10045) on 05May2021(User Fee ID#
PD3017966) for the user fee for this application. A copy of the user fee cover sheet ( Form
3397) is providedin Module 1.1.
The purpose of this submissi on is toprovide the complete non -clinicaland clinical contents
of theapplication. This submission is provided in electronic Common Technical Document
(eCTD) for mat. The Table of Contents isattached. Part2 of the Original Subm ission of the
BLA containing the rest of the BLA contents will be submitted on 21May2021.
Additionally , as agreed during the te leconference of 16 A pril 2016, sequencing data
requested b y the Agency on 09 March 2021 will be provide d by 07June 2021.
Any reference not included with thi s submission is available upon requ est.
In addition, via email on 10August 2020 ,it was agreed that BioNTech could be provided
their US L icense Number upon submission of the BLA (as opposed to at approval ). We
kindly request the US L icense Number for BioNTech at this time with agreement that they
will not use it until after the BLA is approved.
Should you have any questions re garding this submission, or requi re additionalinformation,
pleasecontact me vi aphone at 215-280-5503; via facsimile at 845-474-3500; or via e-mail at
elisa.hark [email protected] .
Sincerely,
Elisa Harkins
Global Regulatory Lead
Global Regulatory Affairs –Vaccines
CC: Ramac handra S. Naik, Ph.D.
FDA-CBER-2021-5683-0013743
Marion Gru ber, Ph.D. , Director Page 3of 6
BLA125742 06May2021
Pfizer Confid ential
Page 3BLA 125742 Part 1 Table of Cont ents
MODULE 1
1 Administrative Information and Prescribing Inform ation
1.1 Forms
FDA 356h Form: Application Form
FDA 3397 Form: User Fee Cover Sheet
FDA 3674 Form: Certification of Compliance with ClinicalTrials.gov
1.2 Cover Letters
CoverLetter
Priority Review Designation Request
1.3 Administrative Inform ation
1.3.1 Contact/Sponsor/Applicant Inform ation
1.3.1.4 Transfer of Obligation
Transfer of Obligation
1.3.3 Debarment Certification
Debarment Certification
1.3.4 Financial Certification and Disclosure
Financial Cer tification and Disclosure -Summary Note
Financial Certification and Disclosure -Bias Statement
Financial Certification and Disclosure -Form FDA 3454
Financial Certification and Disclosure -Form FDA3455
1.3.5 Patent and Exclusivity
1.3.5.3 Exclusivity Claim
Notice of Claimed Exclusivity
1.4 References
1.4.3 List of authorized persons to incorporate by reference
Letter of Authorization to Appoint US Agent
1.6 Meetings
1.6.3 Correspondence Regarding Meetings
Correspondence Regarding Meetings
1.7 Fast Track
1.7.4 Correspondence regarding fast track/rolling review
Grant Fast Track Designation Letter
1.9 Pediatric Administrative Inform ation
1.9.2 Request for Deferral of Pediatric Stud ies
Request for Deferral of Pediatric Studi es
1.9.4 Proposed Pediatric Study Request and Amendments
Agreed initial Pediatric Study Plan
1.9.6 Other Correspondence Regarding Pediatric Exclusivity/Study Plans
Letter of FDA Agreement with initial Pediatric Study Plan
1.12 Other Correspondence
1.12.5 Request for Waiver
FDA-CBER-2021-5683-0013744
Marion Gru ber, Ph.D. , Director Page 4of 6
BLA125742 06May2021
Pfizer Confid ential
Page 4Waiver Request for FDA -Designated Suffix for Biologics
MODULE 2
2 CTD SUMMARIES
2.2 Introduction to Summary
2.4 Nonclinical Overview
2.5 Clinical Overview
2.6 Nonclinical Written and Tabulated Summaries
2.6.1 Introduction
2.6.2 Pharmacology Written Summary
2.6.3 Pharmacology Tabulated Summary
2.6.4 Pharmacokinetics Written Summary
2.6.5 Pharmacokinetics Tabulated Summary
2.6.6 Toxicology Written Summary
2.6.7 Toxicology Tabulated Summary
2.7 Clinical Summary
2.7.1 Summary of Biopharmaceutic Studies and Associated Analytical Methods
2.7.3 Summary of Clinical Efficacy
2.7.4 Summary of Clinical Safety
2.7.5 References
2.7.6 Synopses of Individual Studies
MODULE 4
4 NON-CLINICAL STUDY REPORTS
4.2 Study Re ports
4.2.1 Pharmacology
4.2.1.1 Primary Pharmacodynamics
R-20-0085-COVID-19:Immunogenicity Study of the LNP -Formulated Modrna Encoding the
Viral S Protein -V9
R-20-0112-Characterizing the Immunophen otype in Spleen and Lymph Node of Mice Treated
with SARS -COV-2 Vaccine Candidates
R-20-0211-In vitro Expression of BNT162b2 Drug Substance and Drug Product
VR-VTR-10671-BNT162b2 (V9) Immunogenicity and Evaluation of Protection against S ARS-
CoV-2 Challenge in Rhesus Macaques
VR-VTR-10741-Structural and Biophysical Characterization of SARS -CoV-2 Spike Glycoprotein
(P2 S) as a Vaccine Antigen
4.2.2 Pharmacokinetics
4.2.2.2 Absorption
PF-07302048_06Jul20_072424 -A Single Dose Rat Pharmacoki netic Study of ALC -0315 and
ALC-0159 Follow ing Intravenous Bolus Injection of PF -07302048 Nanoparticle Formulation in
Wistar Han Rats
4.2.2.3 Distribution
R-20-0072 -Expression of Luciferase -Encoding ModRNA After I.M. Application of GMP -Ready
Acuitas LNP Formulation
185350-A Tissue Distribu tion Study of a [3H] -Labelled Lipid Nanoparticle -mRNA Formulation
Containing ALC -0315 and ALC-0159 Follow ing Intramuscular Administration in Wistar Han Ra ts
4.2.2.4 Metabolism
FDA-CBER-2021-5683-0013745
Marion Gru ber, Ph.D. , Director Page 5of 6
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Page 501049-20008 -In Vitro Metaboli c Stability of ALC -0315 in CD -1/ICR Mouse, Sp rague Dawley
Rat, Wistar Han Rat, Cynomolgus Monkey, and Human Liver Microsomes
01049-20009 -In Vitro Metabolic Stability of ALC -0315 in CD -1/ICR Mouse, Sprague Daw ley
Rat, Cynomolgus Monkey, and Human Liver S9 Fractions
01049-20010 -In Vitro Metab olic Stability of ALC -0315 in CD -1/ICR Mouse, Sprague Daw ley
Rat, Wistar Han Rat, Cy nomolgus Monkey, and Human Hepatocytes
01049-20020 -In Vitro Metabolic Stability of ALC -0159 in CD -1/ICR Mouse, Sprague Daw ley
Rat, Wistar Han Rat, Cynomolgus Monkey, a ndHuman Liver Microsomes
01049-20021 -In Vitro Metabolic Stability of ALC -0159 in CD-1/ICRMouse, Sprague Daw ley
Rat, Cynomolgus Monkey, and Human Liver S9 Fractions
01049-20022 -In Vitro Metabolic Stab ility of ALC -0159 in CD -1/ICR Mouse, Sprague Dawley
Rat, Wistar Han Rat, Cynomolgus Monkey, and Human Hepatocytes
PF-07302048_ 05Aug20_043725 -Investigation of the Biotransformation of ALC -0159 and ALC -
0315 In Vitro and In Vivo in Rats
4.2.3 Toxicology
4.2.3.2 Repeat-Dose Toxicity
38166-Repeat-Dose Toxicity Study of Three L NP-Formulated RNA Platforms Encoding for Viral
Proteins by Repeated Intramuscular Administration to Wistar Han Rats
38166 -SEND Datasets
20GR142 - 17-Day Intramuscul ar Toxicity Study of BNT162b2 (V9) and BNT162b3c in Wistar
Han Rats with a 3 -Week Recovery
20GR142 - SEND Datasets
4.2.3.5 Reproductive and Developmental Toxicity
4.2.3.5.1 Fertility and Early Embryonic De velopment
20256434 - (RN9391R58) -Combined Fertility and Developmental Study (Including
Teratogenicity and Postnatal Inv estigations) of BNT162b1, BNT162b2 and BNT162b3 by the
Intramuscular Route in the Wistar Rat
4.3 Literature References
MODULE 5
5 CLINICAL STUDY REPORTS
5.2 Tabular List ingof All Clinical Studies
Tabular Listing
Listing of Clinical Sites and CVs
5.3 Clinical Study Reports
5.3.1 Reports of Biopharmaceutic Studies
5.3.1.4 Reports of Bioa nalytical and Analytical Methodsfor Human Studies
VR-MVR-10080 -Report on Method Validation of a Cepheid Xpert Express PCR Assay to Detect
SARS-CoV-2
VR-MVR-10081 -Method Validation Report for the Elecsys Anti -SARS-CoV-2 Assay
VR-MVR-10083-Validation Report for the SARS -CoV-2 mNeonGreen Virus Microneutralization
Assay
VR-MQR-10211 -Qualification Report for a Single- plex Direct Luminex Assay (dLIA) for
Quantitation of IgG Antibodies to SARS -CoV-2 S1 Protein in Human Sera
VR-MQR-10212 -Qualification Report for a Sing le-plex Direct Luminex Assay (dLIA) for
Quantitation of IgG Antibodies to SARS -CoV-2 RBD Protein in Human Sera
VR-MQR-10214 -Qualification of the SARS-CoV-2 mNeonGreen Virus Microneutr alization
Assay
VR-TM-10293 -Single-plex Luminex Assay for Quant itation of IgG Antibodies to SARS -CoV-
2S1 Prote in in Human Serum
FDA-CBER-2021-5683-0013746
Marion Gru ber, Ph.D. , Director Page 6of 6
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Page 6VR-TM-10294 -Single-plex Luminex Assay for Quantitation of IgG Antibodies to SARS -CoV-2
RBD Protein in Human Serum
VR-TM-10298 -Manual 96 -well Neutralization Assay for the Detection of Functional Antibodies
to SARS-CoV-2 in Test S erum
VR-TM-10304 -Test Method for the SARS CoV -2 Nucleocapsi d (N) Antigen Detection Assay
VR-SOP-LC-11120 -Data Review Procedures for Direct Luminex Immunoassays in LIMS v6
SHI-SOP-10011 -Manual 96 -well Neutralization Assay for the Detection of Functional Antibodies
to SARS-CoV-2 in Test Serum using Cytatio n 7 Image Reader
5.3.5 Reports of Efficacy and Safety Studies
5.3.5.1 Reports of Controlled Clinical Studies Pertinent to the Claim ed Indicat ion
C4591001 -A Phase 1/2/3, Placebo -Controlled, Randomized, Observer -Blind, Dose-Finding Study
to Evaluate the Safety, Tolerability , Immunogenicity, and Efficacy of SARS -CoV-2 RNA Vaccine
Candidates Against COVID -19 in Hea lthy Individuals
C4591001 - Final Analysis Interim CSR
C4591001 -6-M onth Update Interim CSR
C4591001 - Case ReportForms
C4591001 - ADaM and SDTM Datasets
C4591001 - ADaM and SDTM Supplemental Datasets
BNT162-01 -AMulti-Site, Phase I/II,2-Part, Dose- Escalation Trial Investigating the Safety and
Immunogenicity of Four Prophylactic SARS -CoV-2 RNA Vaccines Against COVID -19 Using
Different Dosing Regimens in Healthy Adults
BNT162-01 -Interim CSR v3.0
BNT162-01 -Case Report Forms
BNT 162 -01 -ADaMand SDTM Datasets
5.3.6 Postmarketing Experience
Cumulative Analysis of Post -Authorization Adverse Event Reports of
PF-07302048 (BNT162b2) Received Cumulatively th rough 28-Feb-2021
5.4 Literature References
FDA-CBER-2021-5683-0013747