Pfizer Global Regulatory Affairs
Pfizer Inc.
400 Arcola Road Collegeville, PA 19426

Global Product Development
06 May 2021
Marion Gruber, Ph.D.
Director
Office of Vaccines Research and Review
Food and Drug Administration
Center for Biologics Evaluation and Research
Document Control Center
10903 New Hampshire Avenue
WO71, G112
Silver Spring, MD 20993-0002
Re:

THIS DOCUMENT CONTAINS CONFIDENTIAL
AND/OR TRADE SECRET INFORMATIONTHAT IS DISCLOSED ONLY IN CONNECTION
WITH THE LICENSING AND/ORREGISTRATION OF PRODUCTS FOR PFIZERINC OR ITS AFFILIATED COMPANIES. THISDOCUMENT SHOULD NOT BE DISCLOSED ORUSED, IN WHOLE OR IN PART, FOR ANYOTHER PURPOSE WITHOUT THE PRIORWRITTEN CONSENT OF PFIZER INC.

BLA 125742
COVID-19 mRNA Vaccine (BNT162/PF-07302048)
Part 1 of the Original Submission – Rolling Biologics License Application (BLA)
Request for Priority Review Designation

Dear Dr. Gruber,
Please find enclosed Part 1 of the Original Submission of the rolling Biologics License
Application (BLA) for the BNT162b2 vaccine candidate developed by BioNTech and Pfizer
under BB-IND 19736 for the prevention of COVID-19 caused by SARS-CoV-2 in
individuals ≥16 years of age. This vaccine was granted Fast Track Designation forindividuals >18 years of age on 07 July 2020. The Grant Fast Track Designation Letter isprovided in Module 1.7.4. Submission of this BLA as a rolling application was agreed during
the teleconference of 16 April 2021.
BioNTech and Pfizer are requesting Priority Review Designation for this BLA. It meets thecriteria for Priority Review Designation, as outlined in the 2014 Guidance for Industry:
Expedited Programs for Serious Conditions – Drugs and Biologics because BNT162b2
prevents a serious and life-threatening condition (COVID-19) and, if approved, would
provide a significant improvement in safety and effectiveness because there are currently novaccines licensed for the prevention of COVID-19 in the US. The Priority Review
Designation Request is provided in Module 1.2.
A wire transfer for $2,875,842.00 was made to the U.S. Department of Treasury (TREAS

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Marion Gruber, Ph.D., Director
BLA 125742

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NYC 33 Liberty Street, New York, NY 10045) on 05 May 2021 (User Fee ID#PD3017966) for the user fee for this application. A copy of the user fee cover sheet (Form3397) is provided in Module 1.1.
The purpose of this submission is to provide the complete non-clinical and clinical contentsof the application. This submission is provided in electronic Common Technical Document(eCTD) format. The Table of Contents is attached. Part 2 of the Original Submission of theBLA containing the rest of the BLA contents will be submitted on 21 May 2021.
Additionally, as agreed during the teleconference of 16 April 2016, sequencing data
requested by the Agency on 09 March 2021 will be provided by 07 June 2021.
Any reference not included with this submission is available upon request.
In addition, via email on 10 August 2020, it was agreed that BioNTech could be provided
their US License Number upon submission of the BLA (as opposed to at approval). We
kindly request the US License 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 regarding this submission, or require additional information,please contact me via phone at 215-280-5503; via facsimile at 845-474-3500; or via e-mail atelisa.harkinstull@pfizer.com.
Sincerely,
Elisa Harkins
Global Regulatory Lead
Global Regulatory Affairs – Vaccines
CC: Ramachandra S. Naik, Ph.D.

Pfizer Confidential
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Marion Gruber, Ph.D., Director
BLA 125742

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06 May 2021

BLA 125742 Part 1 Table of Contents
1
1.1

1.2

1.3
1.3.1
1.3.1.4
1.3.3
1.3.4

1.3.5
1.3.5.3
1.4
1.4.3
1.6
1.6.3
1.7
1.7.4
1.9
1.9.2

MODULE 1
Administrative Information and Prescribing InformationForms
FDA 356h Form: Application Form
FDA 3397 Form: User Fee Cover Sheet
FDA 3674 Form: Certification of Compliance with ClinicalTrials.gov
Cover Letters
Cover Letter
Priority Review Designation Request
Administrative Information
Contact/Sponsor/Applicant Information
Transfer of Obligation
Transfer of Obligation
Debarment Certification
Debarment Certification
Financial Certification and Disclosure
Financial Certification and Disclosure - Summary Note
Financial Certification and Disclosure - Bias Statement
Financial Certification and Disclosure - Form FDA 3454
Financial Certification and Disclosure - Form FDA 3455
Patent and Exclusivity
Exclusivity Claim
Notice of Claimed Exclusivity
References
List of authorized persons to incorporate by reference
Letter of Authorization to Appoint US AgentMeetings
Correspondence Regarding Meetings
Correspondence Regarding Meetings
Fast Track
Correspondence regarding fast track/rolling review
Grant Fast Track Designation Letter

1.9.6

Pediatric Administrative Information
Request for Deferral of Pediatric Studies
Request for Deferral of Pediatric Studies
Proposed Pediatric Study Request and Amendments
Agreed initial Pediatric Study Plan
Other Correspondence Regarding Pediatric Exclusivity/Study Plans

1.121.12.5

Letter of FDA Agreement with initial Pediatric Study Plan
Other Correspondence
Request for Waiver

1.9.4

Pfizer Confidential
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Marion Gruber, Ph.D., Director
BLA 125742

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Waiver Request for FDA-Designated Suffix for Biologics
MODULE 22
2.2
2.4
2.5
2.6
2.6.1

CTD SUMMARIESIntroduction to Summary
Nonclinical Overview
Clinical Overview
Nonclinical Written and Tabulated Summaries
Introduction

2.6.2
2.6.3
2.6.4
2.6.5
2.6.6
2.6.7

Pharmacology Written Summary
Pharmacology Tabulated Summary
Pharmacokinetics Written Summary
Pharmacokinetics Tabulated Summary
Toxicology Written Summary
Toxicology Tabulated Summary

2.7
2.7.1
2.7.3
2.7.4
2.7.5
2.7.6

Clinical Summary
Summary of Biopharmaceutic Studies and Associated Analytical Methods
Summary of Clinical Efficacy
Summary of Clinical Safety
References
Synopses of Individual Studies

44.2
4.2.1
4.2.1.1

4.2.2
4.2.2.2

4.2.2.3

4.2.2.4

MODULE 4
NON-CLINICAL STUDY REPORTS
Study Reports
Pharmacology
Primary Pharmacodynamics
R-20-0085 - COVID-19: Immunogenicity Study of the LNP-Formulated Modrna Encoding theViral S Protein-V9
R-20-0112 - Characterizing the Immunophenotype in Spleen and Lymph Node of Mice Treatedwith 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 SARSCoV-2 Challenge in Rhesus Macaques
VR-VTR-10741 - Structural and Biophysical Characterization of SARS-CoV-2 Spike Glycoprotein(P2 S) as a Vaccine Antigen
Pharmacokinetics
Absorption
PF-07302048_06Jul20_072424 - A Single Dose Rat Pharmacokinetic Study of ALC-0315 andALC-0159 Following Intravenous Bolus Injection of PF-07302048 Nanoparticle Formulation inWistar Han Rats
Distribution
R-20-0072 - Expression of Luciferase-Encoding ModRNA After I.M. Application of GMP-ReadyAcuitas LNP Formulation
185350 - A Tissue Distribution Study of a [3H]-Labelled Lipid Nanoparticle-mRNA Formulation
Containing ALC-0315 and ALC-0159 Following Intramuscular Administration in Wistar Han Rats
Metabolism
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Marion Gruber, Ph.D., Director
BLA 125742

4.2.3
4.2.3.2

4.2.3.5
4.2.3.5.1

4.3

Page 5 of 606 May 202101049-20008 - In Vitro Metabolic Stability of ALC-0315 in CD-1/ICR Mouse, Sprague 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 Dawley
Rat, Cynomolgus Monkey, and Human Liver S9 Fractions
01049-20010 - In Vitro Metabolic Stability of ALC-0315 in CD-1/ICR Mouse, Sprague Dawley
Rat, Wistar Han Rat, Cynomolgus Monkey, and Human Hepatocytes
01049-20020 - In Vitro Metabolic Stability of ALC-0159 in CD-1/ICR Mouse, Sprague Dawley
Rat, Wistar Han Rat, Cynomolgus Monkey, and Human Liver Microsomes
01049-20021 - In Vitro Metabolic Stability of ALC-0159 in CD-1/ICR Mouse, Sprague Dawley
Rat, Cynomolgus Monkey, and Human Liver S9 Fractions
01049-20022 - In Vitro Metabolic Stability 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 ALC0315 In Vitro and In Vivo in Rats
Toxicology
Repeat-Dose Toxicity
38166 - Repeat-Dose Toxicity Study of Three LNP-Formulated RNA Platforms Encoding for Viral
Proteins by Repeated Intramuscular Administration to Wistar Han Rats
38166 - SEND Datasets
20GR142 - 17-Day Intramuscular Toxicity Study of BNT162b2 (V9) and BNT162b3c in Wistar
Han Rats with a 3-Week Recovery
20GR142 - SEND Datasets
Reproductive and Developmental Toxicity
Fertility and Early Embryonic Development
20256434 - (RN9391R58) - Combined Fertility and Developmental Study (IncludingTeratogenicity and Postnatal Investigations) of BNT162b1, BNT162b2 and BNT162b3 by theIntramuscular Route in the Wistar Rat
Literature References
MODULE 555.2

CLINICAL STUDY REPORTS
Tabular Listing of All Clinical Studies
Tabular Listing
Listing of Clinical Sites and CVs

5.3

Clinical Study Reports

5.3.1
5.3.1.4

Reports of Biopharmaceutic Studies
Reports of Bioanalytical and Analytical Methods for 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 Single-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 Microneutralization
Assay
VR-TM-10293 - Single-plex Luminex Assay for Quantitation of IgG Antibodies to SARS-CoV2S1 Protein in Human Serum
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5.3.5
5.3.5.1

5.3.6
5.4

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06 May 2021

VR-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 SerumVR-TM-10304 - Test Method for the SARS CoV-2 Nucleocapsid (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 Cytation 7 Image Reader
Reports of Efficacy and Safety Studies
Reports of Controlled Clinical Studies Pertinent to the Claimed Indication
C4591001 - A Phase 1/2/3, Placebo-Controlled, Randomized, Observer-Blind, Dose-Finding Studyto Evaluate the Safety, Tolerability, Immunogenicity, and Efficacy of SARS-CoV-2 RNA Vaccine
Candidates Against COVID-19 in Healthy Individuals
C4591001 - Final Analysis Interim CSR
C4591001 - 6-Month Update Interim CSR
C4591001 - Case Report Forms
C4591001 - ADaM and SDTM Datasets
C4591001 - ADaM and SDTM Supplemental Datasets
BNT162-01 - A Multi-Site, Phase I/II, 2-Part, Dose-Escalation Trial Investigating the Safety andImmunogenicity 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 - ADaM and SDTM Datasets
Postmarketing Experience
Cumulative Analysis of Post-Authorization Adverse Event Reports ofPF-07302048 (BNT162b2) Received Cumulatively through 28-Feb-2021
Literature References

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