Document text
Center for Biologics Evaluation and Research
Laboratory Quality System
COMIRNATY (BioNTech Manufacturing GmbH) COVID -19 mRNA Vaccine
Document ID: 1 25742 Revision Level: 01
Revision Date: Effective Date:
Total Pages: 5 (including this cover page)
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Author Approval: _______________
- 1 - WARNING: The information contained in this document is CONFIDENTIAL and should not be released. See FOIA exemption
regarding circumvention.
Product Testing Plans document how CBER currently anticipates regulating licensed products including the circumstances under
which CBER testing may be used to evaluate a lot of licensed product. It is the responsibility of each Product Office to dev elop
Product Testing Plans for the licensed products under its purview.
Product Trade Name: COMIRNATY
License Product Name
(Proper Name): COVID -19 mRNA Vaccine
Product ID (LQDB): 2501
License Number: 2229
STN (RMS -BLA): 125742
Applicant (Supplier): BioNTech Manufacturing GmbH
Signatures Required to Approve or Update this Product Testing Plan
Product Office Director
(or designee): Marion Gruber, PhD
Product Division Director : Jerry P. Weir, PhD
Testing Division Director : Maryna Eichelberger, PhD
Director, DMPQ/OCBQ: John A. Eltermann, Jr., MS, RPh
Center Lab Quality Mgr: Suzanne Carter
Mode of Product Regulation
Based upon Product Office assessment of the product,
including relevant manufacturing, safety, clinical and other
considerations, determine which form of CBER review and or release of manufactured product lots is necessary. Lot Release – Manufacturer may not distribute product until
receiving lot -specific release from CBER.
Surveillance – Manufacturer may distribute product without
lot-specific release from CBER. Manufacturer is required,
according to the terms of the license, to periodically provide
CBER with lot -specific testing information and possibly
samples.
Exempt – Manufacturer is free to distribute product post-
licensure without supplying any additional information or
samples to CBER. Lot Release
Protocol Review
Protocol Review and
Confirmatory CBER Testing
----------------------------------------
Alternative to Lot Release
Surveillance
Exempt
FDA-CBER-2021-5683-1150324
Title: COMIRNATY (BioNTech Manufacturing GmbH) COVID -19 mRNA Vaccine
Document ID: 125742
Revision Level: 0 1
Effective Date: Page 2 of 5
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Justification for Mode of Regulation:
Briefly, describe how the indicated Mode of Regulation supports CBER’s mission to ensure the purity, potency, safety, efficacy,
and availability of this biological product including justification for any confirmatory CBER product testing, per 21 CFR 610.2(a ).
Additionally, for products on Surveillance, summarize the requirements for submission of lot -specific information and sample (if
required) as described in the license.
Brief Description: COMIRNATY is a vaccine indicated for active immunization to prevent
coronavirus disease 2019 (COVID -19) caused by severe acute respiratory syndrome
coronavirus 2 (SARS CoV 2) in individuals 16 years of age and older.
COMIRNATY is supplied as a frozen suspension in multiple dose vials; each vial must be diluted
with 1.8 mL of sterile 0.9% Sodium Chloride Injection, USP prior to use to form the vaccine. Each dose of COMIRNATY contains 30 mcg of a nucleoside-modified messenger RNA (modRNA) encoding the viral spike (S) glycoprotein of SARS -CoV-2.
Each dose of the COMIRNATY also includes the following ingredients: lipids (0.43 mg (4 -
hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), 0.05 mg 2[(polyethylene
glycol)-2000] -N,N-ditetradecylacetamide, 0.09 mg 1 ,2-distearoyl-sn -glycero-3-phosphocholine,
and 0.2 mg cholesterol), 0.01 mg potassium chloride, 0.01 mg monobasic potassium
phosphate, 0.36 mg sodium chloride, 0.07 mg dibasic sodium phosphate dihydrate, and 6 mg
sucrose. The diluent (0.9% Sodium Chloride Injection, USP) contributes an additional 2.16 mg
sodium chloride per dose.
COMIRNATY does not contain a preservative. The vial stoppers are not made with natural
rubber latex.
Dosage and Administration: COMIRNATY multiple dose v ial contains a volume of 0.45 mL,
supplied as a frozen suspension that does not contain preservative (p rior to dilution) . Each vial
must be thawed and diluted prior to administration.
Dilution
• Dilute the vial contents using 1.8 mL of 0.9% Sodium Chloride Injection, USP to form COMIRNATY. Do not add more than 1.8 mL of diluent.
• ONLY use 0.9% Sodium Chloride Injection, USP as the diluent. Do not use bacteriostatic 0.9% Sodium Chloride Injection or any other diluent.
• After dilution, 1 vial contains 6 doses of 0.3 mL.
COMIRNATY is a suspension for injection. After preparation, a single dose is 0.3 mL. It is
administered intramuscularly as a series of 2 doses (0.3 mL each) three weeks apart.
Mode of Lot Release : Protocol review and c onfirmatory CBER testing
The following discussion forms the rationale for the testing plan for release of this vaccine.
Safety and Purity – The safety and purity of the vaccine will be evaluated from information
provided in the lot release protocols for te sts performed on the fi lled vaccine and BNT162b2
FDA-CBER-2021-5683-1150325
Title: COMIRNATY (BioNTech Manufacturing GmbH) COVID -19 mRNA Vaccine
Document ID: 125742
Revision Level: 0 1
Effective Date: Page 3 of 5
Document Uncontrolled if Printed
drug substance . Refer to the appendices at the end of this document for a description of the
items to review on the lot release protocol.
Potency and Identity – The potency and identity of the vaccine will be evaluated from
information provided in the lot release protocol for tests performed on the t filled vaccine and
BNT162b2 drug substance. Refer to the appendices at the end of this document for a
description of the items to review on the lot release prot ocol.
Anticipated CBER product testing:
List laboratory evaluations to be performed at CBER.
Document
ID number Test Method Test
Specifications Testing
Frequency1
NOTE: Testing will be added as testing methods are brought on -line.
Lot Testing algorithm(s):
For each Test Method listed above describe how the indicated frequency of testing supports the assurance of product quality.
For each method with testing frequencies other than 100%, describe how lots are pre -selected for testing, i.e. random number
table, every nth lot submitted, first X lot(s) submitted per time period, decision tree, etc.
1 Testing may be performed any time an atypical observation is made during lot release protocol review.
2 The lots received, then
Conditions anticipated to require temporary over -ride of algorithm:
Specify conditions justifying algorithm over -ride; i.e. Public Health Considerations (e.g. temporary product shortage, sudden
increase in demand), Operational Considerations (e.g. temporary unavailability of resources), Lot -specific Compliance
Considerations (e.g. questions raised during lot release protocol review).
• Public Health Considerations (e.g., temporary product shortage, sudden increase in demand)
• Operational Considerations (e.g., temporary unavailability of resources
• Lot-specific Compliance Considerations (e.g., questions raised during lot release protocol review)
(b) (5), (b) (7)(E)
(b) (5),
(b) (7)(E)
(b) (4), (b) (5), (b) (7)(E)
FDA-CBER-2021-5683-1150326
Title: COMIRNATY (BioNTech Manufacturing GmbH) COVID -19 mRNA Vaccine
Document ID: 125742
Revision Level: 0 1
Effective Date: Page 4 of 5
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Specifications for Review of Lot Release Protocols
Note: The LRS code – Action/Test indicates under which category this test result will be reviewed. All
tests included in this category for the division indicated will be reviewed and found acceptable prior to
protocol sign off for this category.
Appendix 1: Specifications for tests o n Filled Vaccine
Test Specifications LRS code - Action/Test
These tests are reviewed by personnel in Division of Biological Standard and Quality Control (DBSQC )
Appearance White to off -white suspension Appearance/Volume
Appearance (Visible
Particulates) May contain white to off -white opaque
amorphous particles Appearance/Volume
Subvisible Particles Appearance/Volume
pH 6.9 - 7.9 Chemical Assay
Osmolality Chemical Assay
Lipid nanoparticles (LNP) Size LNP
LNP Polydispersity LNP
RNA Encapsulation RNA
content/encapsulation
RNA content RNA
content/encapsulation
ALC-0315 content Lipid content/identity
ALC-0159 content Lipid content/identity
DSPC content Chemical Assay
Cholesterol content Chemical Assay
Vial content Appearance/Volume
Lipid identities Retention times consistent with
references (ALC- 0315, ALC-0159,
Cholesterol, DSPC) Lipid content/identity
Identity of encoded RNA
sequence Identity
In Vitro Expression In vitro expression
RNA Integrity RNA integrity
Bacterial Endotoxin Purity -LAL
Sterility No growth observed Sterility
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150327
Title: COMIRNATY (BioNTech Manufacturing GmbH) COVID -19 mRNA Vaccine
Document ID: 125742
Revision Level: 0 1
Effective Date: Page 5 of 5
Document Uncontrolled if Printed
Appendix 2: Specifications for tests on BNT162b2 Drug Substance
Test Specifications LRS code - Action/Test
These tests are reviewed by personnel in DBSQC
Clarity Appearance/Volume
Coloration Appearance/Volume
pH Chemical Assay
Content (RNA Concentration) RNA
content/encapsulation
Identity of Encoded RNA
Sequence Identity
RNA Integrity RNA integrity
5’- Cap
Poly(A) Tail
Residual DNA Template Residual n ucleic acid
Residual dsRNA Residual nucleic acid
Bacterial Endotoxin Purity -LAL
Bioburden Sterility
Changes since the last revision
• N/A New document
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150328