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From: Naik, Ramachandra < [email protected] >
Sent: Monday, August 9, 2021 9:03 AM
To: Rohlfing, Paul < [email protected]>; Smith, Michael (CBER) < [email protected] >;
Harkins Tull, Elisa <[email protected] >; Aghajani Memar, Neda
<[email protected] >; Devlin, Carmel M < [email protected] >
Cc: Gottschalk, Laura < [email protected] >
Subject: RE: STN 125742.0: Questions regarding valida tion of assay methods and lot release
Dear Mr. Rohlfing, Please see FDA’s clarification response below.
Please confirm receipt of this email and let us know if you have any questions or need additional
information. Regards, Ram
From: Rohlfing, Paul < [email protected] >
Sent: Tuesday, August 3, 2021 5:49 PM
To: Smith, Michael (CBER) < [email protected] >; Harkins Tull, Elisa
<[email protected] >; Aghajani Memar, Neda < [email protected] >; Devlin,
Carmel M <[email protected] >
Cc: Naik, Ramachandra < [email protected] >; Gottschalk, Laura
<[email protected] >
Subject: [EXTERNAL] RE: STN 125742.0: Questio ns regarding validation of assay methods and lot release
CAUTION: This email originated from outside of the organizatio n. Do not click links or open attachments unless you
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Dear Mike,
So that we can provide a more clear and a ccurate response to item number 5, could
you provide some clarificati on and context regarding some of the details of that item?
Pfizer is clear about the general requirement s for \amples and Lot Release Protocols
(LRPs) for vaccines, however we are also aw are that since March 20, 2020 CBER has
suspended the receipt of lot release samp les. It was confirmed in early June for
another program that CBER was still operating under this alternate COVID pandemic
process and we are not aware that this suspension has been lifted.
By CBER’s statement “ We recommend submitting LRPs and 20 vials of final DP for
launch lots as soon as possible” , should we interpret that:
xCBER intends to resume receipt of lot release sa mples imminently for all
vaccines?
xCBER intends to resume receipt of lo t release samples for COVID-19 vaccines
only? Michael J.
Smith -S4Digitally signed by Michael J. Smith -S4 DN: c=US, o=U.S. Government, ou=HHS, ou=FDA, ou=People, 0.9.2342.19200300.100.1.1=0014080934, cn=Michael J. Smith -S4 Date: 2021.08.12 09:51:36 -04'00'
FDA-CBER-2021-5683-1150231
xOr is this an inadvertent request bas ed on the normal procedure, but which
would not be applicable until such time as CBER resumes routine receipt of lot
release samples?
CBER’s response:
While CBER suspended receipt of samples for most products, we continue to receive
samples for vaccines considered essential fo r public health during the pandemic. This
includes influenza vaccines and the C OVID-19 vaccines once they are approved. A
notification will be sent to manufacturers when we resume normal business operations and are ready to receive samples for other products.
Additionally, for a period of time immediatel y after the BLA is appr oved, Pfizer will have
been manufacturing lots with t he EUA labelling, and in some instances under conditions
which are authorized by the EU A, but which will not be in full compliance with the BLA
(for example vials filled at Pfizer McPherson) until we are able to file a catch-up
supplement and it is approved (we will provide an outline of how we propose to amend the BLA for these items in the next severa l days). For these recently produced, EUA-
labelled lots, we plan to continue to provide a CofA (and not a Lot Release Protocol or
lot release samples) for lots intended for US and WHO distribution, as we have been
doing, until such time as we are ready to release lots with BLA labelling and in
compliance with the provisio ns of the BLA? Is CBER aligned with this approach?
CBER’s response:We are discussing internally and plan to provide our clarifica tion in a separate
communication as soon as possible.
Please confirm receipt of this message and let me know if you need further information
about these points fo r clarification.
Regards,
Paul Rohlfing
Executive Director GCMC VaccinesPfizer
- mobile
(919) 566-4927 - [email protected]
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FDA-CBER-2021-5683-1150232
From: Smith, Michael (CBER) < [email protected] >
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] >; Gottschalk, Laura
<[email protected] >
Subject: [EXTERNAL] STN 125742.0: Questions regarding va lidation 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 the information provided in your BLA STN 125742/0 for COMIRNATY
(COVID-19 Vaccine, mRNA), for active imm unization 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 dr ug substance (VAL100136648),
the accuracy study report includes a calcul ation of
. Please ex plain how you obtain ed the
values in attachment 8.
2. Regarding the dynamic light scattering (D LS) method to determine lipid size and
polydispersity of drug product (DP): pleas e 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 bas ed on vial and DP . Please
describe how the 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-K ZO 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 sa me 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 Int egrity method:
a. a. Your response includes the integrity results at
for the DP and DS. Please calculate the accuracy at each
of the accordingly ( integrity
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FDA-CBER-2021-5683-1150233
values). It appears that you did not include predetermined acceptance criteria for
assay accuracy in your validation protoc ol; therefore, we assume the accuracy
established in this validation study will be used to support assay transfer or
revalidation studies. Please confirm by st ating the accuracy acceptance criteria
for integrity measurements of both t he DP and DS in the integrity assay.
b. In your response to query 2, it appears t hat the validation results for the DS RNA
integrity range evaluation could not meet the pre-specified a cceptance criterion
at the higher end ( of product spec ification corresponding to a RNA
integrity). Please re-evaluate the DS RNA integrity rang e using available
batches that are able to achieve the RNA integrity level of . Alternatively,
please adjust your validation accept ance criterion based on the available
qualification/validation results should a re-validation and/or assay transfer beperformed.
5.Under 21 CFR 610.2(a), manufacturers may be required to submit samples from all
lots of a licensed biological product toget her 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 offi ce. 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 te mplate within the next two weeks.
Please state how many launch lots you plan to submit and let us know if you need additional information to submit the samples and LRPs.
Please provide your response in an Amendm ent to STN 125742/0 by Tuesday, August
9, 2021. If you have any questions about this co mmunication, please feel free to contact
us.
Regards,
Mike
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FDA-CBER-2021-5683-1150234
-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 & ResearchOffice of Vaccines Research & Review
Division of Vaccines and Related Products Applications
Tel: 301-796-2640
michael.smith2 fda.hhs.gov
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FDA-CBER-2021-5683-1150235