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LABELING REVIEW MEMORANDUM
To: The File
Date: September 1, 2021
STN: 125742/0
Applicant: BioNTech Manufacturing GmbH (in partnership with Pfizer, Inc.)
Product: COVID -19 Vaccine, mRNA (COMIRNATY)
From : Laura Gottschalk, Ph.D .
OVRR/DVRPA/RRB3
Through: Elizabeth M. Sutkowski, Ph.D.
OVRR/DVRPA/RRB3
Summary :
This memorandum outlines the labeling review of the original BLA (STN 125742/0) from
BioNTech Manufacturing GmbH (in partnership with Pfizer, Inc.) for COVID -19 Vaccine,
mRNA (COMIRNATY) 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 . This BLA was a Rolling Submission and the labeling
information was included in the second (last) roll (STN 125742/0.1) submitted and
received on May 18 , 2021.
The product labeling submitted in this original BLA included carton and container labels and a
proposed Package Insert (PI) incorporating safety and efficacy data that support the licensure
of COMIRNATY for use in individuals 16 years of age and older . Additionally, a Dear Health
Care Provider (HCP) Letter was submitted as part of the labeling to be included with the
packaging of lots considered by CBER to be BLA -compliant.
COMIRNATY is packaged at two sites: Pfizer Manufacturing Belgium NV (Puurs) and
Pharmacia and Upjohn Company LLC (Kalamazoo). Separate carton and container labels for
both Kalamazoo and Puurs were included in the submission. Labels for the following
COMIRNATY cartons and containers were submitted:
• COMIRNATY Multiple Dose Vial Label s (Kalamazoo)
• COMIRNATY Multiple Dose Vial Labels (Puurs)
• COMIRNATY 25 Vial Carton Label s (Kalamazoo)
• COMIRNATY 25 Vial Carton Labels (Puurs)
• COMIRNATY 195 Vial Carton Label s (Kalamazoo)
• COMIRNATY 195 Vial Carton Labels (Puurs)
FDA-CBER-2021-5683-0652379
STN 125742/0 Labeling Review Memo
2 Vials of sterile 0.9% Sodium Chloride Injection, USP will also be provided but shipped
separately for use as a diluent for COMIRNATY. The diluent is supplied by two manufacturers :
Fresenius Kabi USA , LLC and Hospira, Inc. Separate carton and container labels for both
Fresenius Kabi and Hospira were included in the submission. Labels for the following diluent
cartons and containers were submitted:
• Diluent Vial Label (Fresenius Kabi) – 2 mL single dose vial
• Diluent Vial Label (Hospira) – 10 mL single dose vial
• Diluent Carton Label s (Fresenius Kabi) – 25 single-dose vials
• Diluent Carton Label s (Hospira) – 25 single-dose vials
• Diluent Supplemental Carton Stamp ( Fresenius Kabi )
• Diluent Supplemental Carton Sticker ( Hospira)
Revisions to the proposed labels for the cartons and containers , PI and Dear HCP Letter were
communicated to Pfizer/BioNTech, as indicated below in Table 1, and the corresponding
amendments that were received are described in Table 2. The principal reviewers of the PI
were the Clinical Reviewers, the Pharmacovigilance Reviewer, the Biostatistics Reviewer s, the
Advertising and Promotional Labeling Branch Reviewer, the Committee Chair, the RPM s, and
supervisors, with additional advice from DVP, DVRPA and OVRR Immediate Office of the
Director.
Table 1. Labeling Review History
Date Action Labels
PI Cartons &
Containers Dear HCP
Letter
07/28/2021 First set of labeling comments regarding the PI were
sent.
08/04/2021 Internal labeling meeting
08/05/2021 Internal labeling meeting
08/05/2021 Second set of labeling comments regarding the PI
were sent .
08/05/2021 Four questions regarding the diluent were sent .
08/09/2021 Internal labeling meeting
08/09/2021 First set of labeling comments regarding the cartons
and containers were sent .
08/11/2021 Internal labeling meeting
08/13/2021 Internal labeling meeting
08/13/2021 Third set of labeling comments regarding the PI
were sent .
08/16/2021 Two internal labeling meetings: one carton and
container discussion and one PI discussion
08/16/2021 Second set of labeling comments regarding the
cartons and containers were sent.
08/16/2021 Teleconference with Pfizer to discuss identification
of BLA -compliant lots and a draft Dear HCP Letter
08/17/2021 Two internal labeling meetings: one carton and
container discussion and one PI discussion
FDA-CBER-2021-5683-0652380
STN 125742/0 Labeling Review Memo
3 Date Action Labels
PI Cartons &
Containers Dear HCP
Letter
08/17/2021 Two separate set of comments were sent: Third set
of carton and container comments and fourth set of
PI comments .
08/18/2021 A request was sent to submit to the BLA the
information that was emailed to Mary Malark ey on
08/16/2021 regarding identification of BLA -
compliant lots and a draft Dear HCP Letter .
08/18/2021 Internal labeling meeting
08/18/2021 Fifth set of PI comments sent and a request to
submit specific carton and container label versions together in a new amendment for ease of refencing
in the Approval Letter was sent .
08/19/2021 Internal labeling meeting
08/19/2021 Sixth set of labeling comments regarding the PI
were sent.
08/20/2021 Two internal labeling meeting s: one PI discussion
and one Dear HCP Letter discussion
08/20/2021 Seventh set of labeling comments regarding the PI
were sent.
08/20/201 First set of c omments regarding identification of BLA
lots/Dear HCP Letter were sent.
08/21/2021 Internal meeting to discuss the PI , carton and
container labels and Dear HCP Letter
08/21/2021 The Applicant was notified that the carton and
container labels submitted in Amendment 63 on
August 19, 2021 are considered the Final Draft
Labels.
08/21/2021 Eight h set of labeling comments regarding the PI
sent
08/21/2021 Second set of comments regarding the Dear HCP
Letter were sent.
08/21/2021 The Applicant was notified that there are no
additional comments on their Dear HCP Letter.
08/22/2021 The Applicant was notified that the PI submitted in
Amendment 74, dated August 21, 2021 is
considered the Final Draft Label.
Table 2. Labeling Amendments
Date Amendment Summary Labels
PI Cartons &
Containers Dear HCP
Letter
08/02/2021 125742/0.27 Response to July 28, 2021, first
set of labeling comments
regarding the PI.
08/09/2021 125742/0.36 Response to four questions
regarding the diluent from dated
August 5, 2021.
FDA-CBER-2021-5683-0652381
STN 125742/0 Labeling Review Memo
4 Date Amendment Summary Labels
PI Cartons &
Containers Dear HCP
Letter
08/09/2021 125742/0.38 Response to August 5, 2021,
second set of comments on the
PI.
08/13/2021 125742/0.46 Response to August 9, 2021 f irst
set of comments on the c arton
and container label s.
08/16/2021 125742/0.49 Response to August 13, 2021 ,
third set of comments on the PI.
08/17/2021 125742/0.53 Response to August 16, 2021
second set of comments on the
carton and c ontainer label s. This
amendment also contains the full
diluent carton labels and diluent vial labels that were not included
in the original BLA submission.
08/18/2021 125742/0.58 Response to August 17, 2021 ,
fourth set of comments on the PI.
08/19/2021 125742/0.63 Responses to August 18, 2021,
third set of comment on the c arton
and container label s.
08/18/2021 125742/0.64 Response to August 18, 2021,
comments regarding identification
of BLA -compliant lots/Letter to
HCP.
08/19/2021 125742/0.66 Response to August 18, 2021, fifth
set of comments on the PI.
08/20/2021 125742/0.68 Response to August 19, 2021,
sixth set of comments on the PI.
08/20/2021 125742/0.71 Response to August 20, 2021,
seventh set of comments on the
PI.
08/20/2021 125742/0.73 Response to August 20, 2021, first
set of comments regarding
identification of BLA lots/Dear
HCP Letter.
08/21/2021 125742/0.74 Response to August 21, 2021,
eighth set of comments on the PI.
08/21/2021 125742/0.76 Response to August 21, 2021,
second set of comments regarding
identification of BLA lots/Dear
HCP Letter.
08/23/2021 125742/0.77 Final PI
08/24/2021 125742/0.78 Final PI with license number
included .
Regarding Pfizer/BioNTech’s amendments containing revisions to the PI:
Pfizer/BioNTech submitted to CBER eight versions of the PI (as amendments to the BLA) in
response to CBER’s comments in the following amendments: 125742/0.27, 125742/0.38,
FDA-CBER-2021-5683-0652382
STN 125742/0 Labeling Review Memo
5 125742/0.49, 125742/0.58, 125742/0.66, 125742/0.68, 125742/0.71 and 125742/0.74. The
clean copy Word version of the PI submitted on August 21, 2021 (Amendment 74) was
considered the Final Draft PI for approval. Pfizer/BioNTech was notified on August 23, 2021,
that CBER considered the clean version of the PI included in Amendment 74 as the Final Draft
PI for approval.
Two additional versions of the PI were submitted to the BLA after the date of approval . A Final
Version of the PI with an updated version number was submitted in Amendment 77 on August
23, 2021. Pfizer/BioNTech then submitted a revised F inal Version of the PI in Amendment 78
on August 24, 2021 which included the license number that was inadvertently left off previous
versions. Pfizer/BioNTech submitted each of these final versions of the PI in amendments to
the BLA without being requested to do so by CBER.
Regarding Pfizer/BioNTech’s amendments containing revisions to the carton and
container labels:
Pfizer/BioNTech submitted to CBER three versions of the revised carton and container labels
in response to CBER’s comments in the following amendments: 125742/0.46, 125742/0.53
and 125742/0.63. Pfizer/BioNTech was notified on August 21, 2021, that the carton and
container labels submitted in Amendment 63 on August 19, 2021 were considered the Final
Draft Labels.
Regarding Pfizer/BioNTech’s amendments containing revisions to the Dear HCP Letter:
In response to CBER ’s inquir y about BLA -compliant EUA -labeled lots that may be available for
use upon licensure of COMIRNATY, Pfizer submitted information listing which lots they considered to be manufactured according to the BLA. To address the issue of these lots not
bearing the vial label associated with BLA-approval, CBER worked with Pfizer to develop a
Dear HCP letter to be included with lots considered by CBER to be BLA -compliant. This letter
explained that some lots labeled for EUA use were also considered BLA -compliant and refers
HCP to a website for additional information. CBER requested and Pfizer agreed that only EUA -
labeled lots that had also undergone CBER lot release according to the BLA would be considered BLA -compliant and listed at the website included in the Dear HCP letter.
Pfizer/BioNTech submitted to CBER two versions of the revised Dear HCP Letter in response
to CBER’s comments in the following amendments: 125742/0.73 and 125742/0.76.
Pfizer/BioNTech was notified on August 21, 2021, that CBER has no additional comments on
the Dear HCP Letter provided in Amendment 76 on
August 21, 2021.
Review of National Drug Codes (NDCs) :
A review of the N DCs on the COMIRNATY and diluent carton and container labels w as
conducted according to the Job Aid JA 900.08.
Table 3. NDC assignments for COMIRNATY and diluent carton and container labels
Label NDC#
COMIRNATY Vial Label ( Kalamazoo and Puurs ) 0069 -1000 -01
COMIRNATY 25 Vial Carton Label ( Kalamazoo and Puurs ) 0069 -1000 -03
COMIRNATY 195 Vial Carton Label ( Kalamazoo and
Puurs ) 0069 -1000 -02
FDA-CBER-2021-5683-0652383
STN 125742/0 Labeling Review Memo
6 Diluent Vial Label (Fresenius Kabi ) – 2 mL single dose vial 63323 -186-04
Diluent Carton Label (Fresenius Kabi) – 25 single -dose
vials 63323 -186-02
Diluent Vial Label ( Hospira ) – 10 mL single dose vial 0409 -4888 -02
Diluent Carton Label ( Hospira ) – 25 single -dose vials 0409 -4888 -10
The first segment s (NDC labeler code) w ere verified using the NDC/NHRIC Labeler Code sit e.
The first segments are correct and appropriately assigned.
Table 4. Search Results for NDC Labeler Codes
NDC Labeler
Code Firm Name
0069 Pfizer Laboratories Div Pfizer Inc
63323 Fresenius Kabi USA, LLC
0409 Hospira, Inc.
The second segments (the product code that identifies a specific strength, dosage form, and formulation) are different (unique) for COMIRNATY labels (-1000-) and diluent labels (-186-
[Fresenius Kabi] and -4888- [Hospira] ).
The third segments (the package code that identifies package sizes and types) are different (unique) for labels of cartons containing 25 (-03) and 195 (-02) vials of COMIRNATY and for
the individual vials (-01) of COMIRNATY. Additionally, the third segments are also distinct for
the two diluent cartons (-02 [Fresenius Kabi] and -10 [Hospira] ) and the two diluent vials (-04
[Fresenius Kabi] and -02 [Hospira]) .
2D Bar Code Review Under the Drug Supply Chain Security Act (DSCSA):
During the COVID -19 public
health emergency, FDA interprets the exemption and exclusion
from certain requirements of the DSCSA to cover the distribution of prescription drug products
either (a) issued an emergency use authorization under section 564 of the FD&C Act (21 U.S.C. 360bbb-3) to combat COVID -1917 or (b) approved by FDA to diagnose, cure, mitigate,
treat, or prevent COVID -19. Therefore, COMIRNATY is exempt from the product identifier
requirements, including serialization.
Additi onal
information can be found in the Guidance for Industry: Exemption and Exclusion
from Certain Requirements of the Drug Supply Chain Security Act During the COVID -19 Public
Health Emergency (April 2020).
Recommendation:
The discipline reviewers mentioned above have reviewed the relevant labeling documents and
found them to be acceptable as Final Draft Labeling for approval. As the Regulatory Project Manager, I concur with their recommendation. The Final Draft PI will be p rovided to the Office
of Communication, Outreach and Development as part of the approval package for web posting.
FDA-CBER-2021-5683-0652384