Document text
CMC Review Memorandum
Date: August 12, 2021
To: The File
From : Anissa Cheung, DVP , Product Specialist
Through: Jerry Weir, DVP
CC: Ramachandra Naik , DVRPA , Chair ;
Michael Smith , DVRPA, RPM ;
Laura Gottschalk , DVRPA, RPM ;
Kathleen Jones , DMPQ, Lead Inspector
Applicant n ame: Wyeth BioPharma Division of Wyeth Pharmaceuticals, LLC.
STN : STN 125742/0 Amendment #25
COVID-19 mRNA Vaccine (BNT162/PF-07302048)
Subject: Original BLA submission
Short summary: Applicant’s response to observations issued during the FDA Pre -License Inspection
A Pre -License Inspection at Wyeth BioPharma Division of Wyeth Pharmaceuticals, LLC. at Andover,
MA for the manufacture of COVID- 19 mRNA Drug Substance (DS) was performed between July 19
and July 23, 2021 for COMIRNATY Biological License Application. At the end of the inspection,
thirteen inspectional observations were identified. In this submission, the applicant provides response
including follow up actions to address these observations and to assure that their product is safe and effective.
My review covers applicant’s response on observation 1. Observation 1
There is insufficient data to support product quality prior to the release of BNT162b2 drug substance (DS) batch manufactured at Pfizer Andover on . was derived
from batch and a deviation ( ) was initiated due to the
multiple control limit excursions during the of The
were below the control limits and the between and overall
both exceeded the control limits. The affected batch was manufactured with a process
that deviated from the validated process parameters, and your firm planned to put this batch on stability
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150414
2
to further assess product quality. However, DS batch was not put on stability until July 22,
2021. The affected DS batch was released on and formulated into drug product (DP)
lots ( ) at on . All DP lots were released on
.
Appl icant’s response:
The firm acknowledges that they did not enroll the affected DS lot immediately. In addition, an error was made when they notified FDA in writing on about the deviation associated with DS
batch . In that communication, Pfizer stated that the affected DS batch was enrolled on stability, but, in fact, they only commit to enroll the batch on stability no later than September 30, 2021. For the release of the DS batch, Pfizer ’s Quality Assurance (QA) reviewed all data associated with this affected
batch including in process critical quality attributes and DS final release results. All release data were within DS specifications and all critical quality attributes (
were within expected historical experience. QA performed a holistic review of all
deviations associated to this DS batch , and they concluded that there was no impact to product quality.
drug product (DP) lots ( ) were manufact ured at Pfizer
from DS batch . Pfizer reviewed the batch release data for these DP batches and all results are within release specifications and within historical experience.
Pfizer proposes the following action to be implemented to prevent the recurrence of delaying the enrollment of DS lots in a stability program:
• Procedure will be revised and made effective to
include the requirement that a drug substance batch be enrolled in a stability program within
from the date of determination an enrollment is made.
• The procedure will include a requirement for a justification as to why the batch is being enrolled on stability, including whether the stability data is required for drug substance bat ch release.
• Relevant individuals will be trained per site procedures.
The committed deadline for this action is September 15, 2021.
Reviewer’s Comments:
The applicant provides adequate response to address the above observation.
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (7)(E), (b) (5)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150415