Document text
From: Smith, Michael (CBER)
Sent: Monday, August 2, 2021 7:05 PM
To: Harkins Tull, Elisa <[email protected]>; Aghajani Memar, Neda
<[email protected]>; Devlin, Carmel M <[email protected]>; Rohlfing, Paul
<[email protected]>
Cc: Naik, Ramachandra <[email protected]>; Gottscha lk, Laura
<[email protected]>
Subject: STN 125742.0: Questions regarding validation of assay methods and lot release
Elisa,
The review team has the below questions for you regarding validation of assay
methods and lot release.
Our review of t he information provided in your BLA STN 125742/0 for COMIRNATY
(COVID-19 Vaccine, mRNA), for active immunization to prevent COVID -19 caused by
SARS-CoV -2 in individuals 16 years of age and older, is ongoing. We have the
following comments and requests for additional information.
1. In your validation report for the 5’ -cap assay for drug substance (VAL100136648),
the accuracy study report includes a calculation of
Please explain how you obtained the
values in attachment 8.
2. Regarding the dynamic light scattering (DLS) method to determine lipid size and polydispersity of drug product (DP): please state whether this DLS method can
LNPs. Please provide data to support your claim and, if the method does not
LNP provide information describing resolution of
and explain how the is evaluated.
3. For container content of DP:
a. You calculate volume of each vial based on vial and DP . Please
describe how was determined.
b. In the verification report [USP 697 (EP 2.9.17) and USP 788 (EP 2.9. l 9) -PF-
07302048-CMVR-001] from PSG -KZO lab, DP container content was determined
by measuring the total volume after 1.8 mL of sterile 0.9% sodium chloride solution was added. Please confirm that this method will be used for lot release
testing by the PSG -KZO laboratory and that the container volume specification
“Not less than mL” is the same regardless of test site/method.
4. Regarding your response (in STN 125742/0.16 dated July 23, 2021) to our IR dated
July 9, 2021, about the validation of the CGE Integrity method:
a. a. Your response includes the results at
for the DP and DS. Please calculate the accuracy at each
of the accordingly
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FDA-CBER-2021-5683-1150194
values). It appears that you did not include predetermined acceptance criteria for
assay accuracy in your validation protocol; therefore, we assume the accuracy
established in this validation study will be used to support assay transfer or
revalidat ion studies. Please confirm by stating the accuracy acceptance criteria
for integrity measurements of both the DP and DS in the integrity assay.
b. In your response to query 2, it appears that the validation results for the DS RNA
integrity range evaluation could not meet the pre-specified acceptance criterion
at the higher end ( of product specification corresponding to a RNA
integrity). Please re-evaluate the DS RNA integrity range using available
batches that are able to achieve the RNA integrity level of . Alternatively, please adjust your validation acceptance criterion based on the available
qualification/validation results should a re-validation and/or assay transfer be
performed.
5. Under 21 CFR 610.2(a), manufacturers may be required to submit samples from all
lots of a licensed biological product together with the protocols showing results of applicable tests when deemed necessary
for the safety, purity, or potency of the
product. Lots shall not be distributed until released by the Director, CBER. A brief
description of the process follows: samples and Lot Release Protocols (LRPs) must
be submitted to the Product Release Branch (PRB), Office of Compliance and Biologics Quality (OCBQ) via an electronic portal that is different from that used for electronic submissions to the product office. If you need instructions on accessing
the gateway or where to submit samples, please contact Mr. Joseph Quander, Chief,
Product Release Branch, DMPQ, OCBQ at
[email protected] . CBER grants approval to release lots by issuing a
letter from the Center Director or his/her representative, that is sent to the firm’s
representative by email.
If you plan to release lots at the time of approval (launch lots), the LRPs need to be reviewed well before the PDUFA action due date. We recommend submitting LRPs
and 20 vials of final DP for launch lots as soon as possible You will need to use the
LRP template that is currently under review; we anticipate providing a description of
changes that need to be made to this template within the next two weeks.
Please state how many launch lots you plan to submit and let us know if you need
additional infor mation to submit the samples and LRPs.
Please provide your response in an Amendment to STN 125742/0 by Tuesday, August 9, 2021. If you have any questions about this communication, please feel free to contact
us.
Regards,
Mike
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FDA-CBER-2021-5683-1150195
- Please confirm receipt of this e -mail .
Mike Smith, Ph.D.
Captain, USPHS
Senior Regulatory Review Officer
Food and Drug Administration
Center for Biologics Evaluation & Research
Office of Vaccines Research & Review
Division of Vaccines and Related Products Applications
Tel: 301- 796-2640
[email protected]
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FDA-CBER-2021-5683-1150196