Document text
Pfizer Andover Response to the FORM FDA 483 PAI BLA 125742 (COVID -19 mRNA Vaccine)
This document contains Confidential Commercial and Trade Information not authorized for public disclosure .
Page 1 of 36
Observation 1:
There is insufficient data to support product quality prior to the release of BNT162b2 drug
substance (DS) batch FA8057 manufactured at Pfizer Andover on
was derived from batch , and a devi ation (
was initiated due to the multiple control limit excursions during the of
The were below the control limits and the
between and overall bot h 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
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 .
Response to Observation 1
The Pfizer , Andover site has a robust, well documented batch release process to ensure that drug
substance batches meet specification . Quality Assurance (QA) reviews the data supporting the
release of each individual batch, which includes the review of both in -process data and final
release data and confirms that the batch meets all release specifications.
As part of batch release per site procedure
, all data associated with drug substance (DS) batch was reviewed, including
in process critical quality attributes and DS final release results. There is sufficient data to
support the release, namely all release data per
were within specification and all critical quality
attributes were within the expected historical experience . DS batch has been enrolled
on stability to monitor the drug substance over the shelf -life. drug product (DP) lots
were manufactured at from DS batch
and all drug product batches met release specifications. The drug product
lots were released to ex -US markets on .
There are quality reviews performed by Quality Assurance to determine
acceptability of the batch. investigation that is associated with a batch, if
applicable, is assessed for any potential quality impact to that respective batch. Then , as part of
the batch disposition process, a review of all associated deviations is conducted to
determine if there is any impact to product quality . This assessment is performed
pursuant to procedure .
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FDA-CBER-2021-5683-1149879
Pfizer Andover Response to the FORM FDA 483 PAI BLA 125742 (COVID -19 mRNA Vaccine)
This document contains Confidential Commercial and Trade Information not authorized for public disclosure .
Page 2 of 36 The deviation s documented in Investigation did not impact DS batch .
Critical quality attributes specific to the mRNA were reviewed for DS batch and include
the following :
In addition to DS data listed above , Pfizer reviewed the batch release data for the DP
lots associated with DS batch , and all data is within specification and within historical
experience . is the DP critical quality attribute that is most directly linked to the
DS. The for the DP lots is as follows :
Table 2 for DP Lots
Investigation was initiated on to document a deviation to executed
batch record , during for drug
substance batch . During execution it was determined that the re were
deviations that led to the
being outside of the control limit s. A was added to bring the
to within the control limit . The final was
also exceeded. The i mpact of these deviations is described below.
During DS manufacturing, control of
. The range s studied for
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FDA-CBER-2021-5683-1149880
Pfizer Andover Response to the FORM FDA 483 PAI BLA 125742 (COVID -19 mRNA Vaccine)
This document contains Confidential Commercial and Trade Information not authorized for public disclosure .
Page 3 of 36
parameters in the lab qualification studies were focused on manufacturing capability and did not
establish the point of failure or account for all possible deviations. However, the investigation for
this batch shows all performance and quality attributes were within drug substance specification
at release. Results for the batch in question are listed in Table 1.
Investigation determined that there was no product quality impact. All drug
substance release data for the associated drug substance batch are within specification
and all critical quality attributes are also within the expected historical ranges.
Therefore, during the quality review performed in connection with the investigation and again in
connection with the quality review performed as part of batch disposition, it was determined that
the product met specification and there was no impact to product quality .
Pfizer notified FDA of the above discussed deviation associated with DS batch that was
the subject of in writing on . In that communication, Pfizer stated its
intent to release the batch and process it into drug product , as the batch conformed to release
specifications and the investigation determined there was no impact to product quality . Pfizer
acknowledges that , in error, the communication also stated that the DS batch was enrolled on
stability when, in fact, a commitment had been initiated to enroll the batch on stability no later
than 30 September 2021 . Pfizer’s purpose in enroll ing the batch on stability is to monitor the
drug substance over the shelf li fe and not to obtain stability data for purposes of batch release
disposition . Pfizer did not enroll the lot immediately because
. Drug substance batch was enrolled on long -term stability on 22 July 2021.
Pfizer updated its 23 June 2021 communication to FDA on 30 July 2021 to reflect the correct
date that the batch was placed on stability . The i nitial timepoint sample was pulled and submitted
for testing on 22 July 202 1. The initial stability timepoint assay results are pending at the time of
this response.
In addition, manufactured from DS was enrolled on long -term
stability on . The DP lots were released to ex -US markets only on .
Action
Procedure will be revised and made effective to
include the requirement that a drug substance batch be enrolled in a stability program within
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FDA-CBER-2021-5683-1149881
Pfizer Andover Response to the FORM FDA 483 PAI BLA 125742 (COVID -19 mRNA Vaccine)
This document contains Confidential Commercial and Trade Information not authorized for public disclosure .
Page 4 of 36
from the date the determination to enroll is made. Additionally, 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 batch release. Relevant individuals will
be trained per site procedures.
Due Date
15 September 2021
Observation 2
There is inadequate quality oversight in that:
a. The electronic data/reports from associated with the , and
process used in the manufacture of BNT162b2 drug substance are not
reviewed by Quality during batch record review or prior to batch release.
b. During processing of BNT162b2 drug substance lot , the
were , and the operator switched from
The operators performed a calculation for
, and this calculation is not recorded in the batch record. The
printou t from the system documents per
yet the batch record documents were performed . The
record was reviewed and approved by QA on
c. BNT162b2 drug substance lot was manufactured in . The
record was reviewed by Operations in and by Quality on All
were There was no notation in the batch record until
that exceeded the allowable
Response to O bservation 2
The manufacture of BNT162b2 is controlled principally by validated computerized systems:
located in Building of the Andover
Manufacturing Facility; and , located in Building of the
For , phase parameters are required to be input and per
batch record instruction. The control system uses the input parameters to execute phase
parameters as designed. The computerized system record s all entries and actions
performed . Per procedure , the batch summary
report, which includes the batch alarm report and automation manipulation reports , is reviewed
by both Operations and Quality Assurance during executed batch record review.
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FDA-CBER-2021-5683-1149882
Pfizer Andover Response to the FORM FDA 483 PAI BLA 125742 (COVID -19 mRNA Vaccine)
This document contains Confidential Commercial and Trade Information not authorized for public disclosure .
Page 5 of 36
is a recipe -based system for which the recipes are reviewed and approved by Subject
Matter Expert s (SME s) and Quality Assurance per procedure
Operators load
approved recipes per batch record instruction. For , per procedure
Operations
reviews manipulations (such as temporary change s to running batch active steps as
per
, the event log , and the batch alarm report. Per procedure
Quality Assurance also reviews the associated manipulations , the
event log , and the batch alarm report, as part of the executed batch record review. The
Batch Summary Report is not reviewed as part of the Quality Assurance executed batch
record review in all instances . Rather, Quality Assurance reviews the Batch Summary Report by
exception (as applicable in connection with investigation and impact assessment reviews ).
Observation 2a
The electronic data/reports from associated with the , and
process used in the manufacture of BNT162b2 drug substance are not reviewed
by Quality during batch record review or prior to batch release.
Response to Observation 2a
Executed batch record review per procedure
governs QA review of batch related
operating parameters and monitoring data. The batch alarm report is attached to the
executed batch record. Any manipulation , the event log , and the batch
alarm report that is generated during a batch is documented in the executed batch record for QA
review. QA is also part of the review and approval process for the recipe build, which
includes the review and approval of alarm setpoints and alarm criticality . The established batch
record review program ensures full QA oversight of batch execution and any associated eventful
operations , such as deviations and alarms. As an enhancement, QA batch record review procedure
will be revised to include a full review of t he batch summary report.
Actions
Procedure
will be revised and made effective to include additional instructions for
automation system review as part of the executed batch record review process, which will include
the Batch Summary Report. Relevant i ndividuals will be trained according to site
procedures.
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FDA-CBER-2021-5683-1149883
Pfizer Andover Response to the FORM FDA 483 PAI BLA 125742 (COVID -19 mRNA Vaccine)
This document contains Confidential Commercial and Trade Information not authorized for public disclosure .
Page 6 of 36
Completion Date
30 September 2021
Observation 2b
During processing of BNT162b2 drug substance lot , the
were , and the operator switched from for
. The operators performed a calculation for , and this calculation is
not recorded in the batch record. The printout from the system
documents yet the batch record documents
were performed . The re cord was reviewed and approved by QA on 7/15/2021.
Response to Observation 2b
For BNT162b2 drug substance lot were performed in the
. During processing, were and operators accordingly switched
from per site procedure
in To account for the , the operators and
engineering determined an appropriate amount for . This calculation was not
documented in the batch record. Investigation was initiated on to address
the documentation discrepancy. Although not documented in the batch record , the
calculation that is missing from the batch record was reconstructed using data documented in
(data for and the executed batch record at the time of execution. During Operations
and Quality Assurance batch record review per
the correct was confirmed using the data and the executed batch record
for have been confirmed to meet all acceptance
criteria as documented in the executed batch record as part of batch record review .
The for was documented in the executed batch record .
In operation mode , remains running in the background but is not controlling the
additions. While therefore continu ed to log data for additions , that
data is rendered extraneous data in Once operators take manual control of the ,
the primary GMP source data is the executed batch record .
Action
Procedure in will be revised and made effective to
further clarify instructions for implementing operations and to document the
calculation within the batch record . Relevant colleagues will be trained per site procedures.
Completion Date
15 September 2021
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FDA-CBER-2021-5683-1149884
Pfizer Andover Response to the FORM FDA 483 PAI BLA 125742 (COVID -19 mRNA Vaccine)
This document contains Confidential Commercial and Trade Information not authorized for public disclosure .
Page 7 of 36
Action
Manufacturing batch record will be revised and made
effective to clarify that once switching to data documented in the
batch record , and not the data in , is the data to be evaluated for acceptance criteria.
Completion date
15 September 2021
Action
Investigation was initiated on for the documentation discrepancies noted
above. Th is investigatio n was closed on .
Completion Date
Complete
Updated Action as of 17 August 2021
As discussed with the Agency, Pfizer will conduct an evaluation to determine whether the
has the ability to document within its system change s made from
. The evaluation will be completed by 17 September 202 1. Based on the outcome
any required updates will be made.
Completion Date
17 September 2021
Observation 2c
BNT162b2 drug substance lot was manufactured on . The record was
reviewed by Operations in and by Quality on . All
were . There was no notation in the batch record until that
exceeded the allowable duration.
Response to Observation 2c:
Drug substance Batch , the first batch of BNT162b2 produced in was
manufactured in per master batch record 513AM version 2.0. The executed batch record
was reviewed by Operations in and reviewed by Q uality Assurance in
At the time of batch execution, the was a target and not a control limit per
the bat ch record , and therefore no further action was taken for the exceeded value .
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FDA-CBER-2021-5683-1149885
Pfizer Andover Response to the FORM FDA 483 PAI BLA 125742 (COVID -19 mRNA Vaccine)
This document contains Confidential Commercial and Trade Information not authorized for public disclosure .
Page 8 of 36
As part of the continuous process monitoring verification program, to provide ongoing assurance
that during routine production the process remains in a state of control , per
the target was
changed to a control limit in master batch record 513AM version 3.0 , effective date ,
. As part of the process verification monitoring , the parameter was noted as
. Investigation was initiated on
to assess and document impact and on a notation was made in the
executed batch record for , referenc ing the investigation . The investigation was
closed on .
Pfizer will continue to monitor BNT162b2 drug substance manufacturing process through its
process monitoring verification program and manage validated parameter changes
through the change control process.
Action
No action is required .
Completion Date
Not applicable
Observation 3:
The following deviation investigations were found deficient. Deviation
(COVID): and (COVID):
was found in during
its visual inspection . On both occasions the was cleaned and
released into manufactu re. No sampling of and no cleaning
verification was performed or is required after re -cleaning.
Response to Observation 3
Procedure defines the
proce ss by which vis ual inspection of the wetted surfaces of process equipment for cleanliness is
conducted. All visual inspection outcomes are assessed as described in the procedure. As per
the procedure, identification of observed in equipment” results in a failed visual
inspection. If the visual inspection fails due to the presence of an investigation is
initiated per procedure and a team of Subject
Matter Experts (SMEs) consisting of Quality Assurance (QA) , EMU (Engineering, Maintenance
and Utilities) and Operations are notified. This SME team conducts a preliminary assessment
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FDA-CBER-2021-5683-1149886
Pfizer Andover Response to the FORM FDA 483 PAI BLA 125742 (COVID -19 mRNA Vaccine)
This document contains Confidential Commercial and Trade Information not authorized for public disclosure .
Page 9 of 36
which typically includes a review to: (1) confirm that the qualified cleaning cycle ran as
expected; (2) determine if any mechanical failures occurred; (3) determine the duration between
the completion of the cleaning cycle and identification of the ; and (4)
qualitativ ely determin e the Based on the review of data collected
above, QA will document in the investigation if operations can proceed or not.
Investigations (initiated ) and (initiated )
were initiated per procedure following the detection of . SME preliminary
assessments were performed for both investigations resulting in QA endorsement to proceed with
manufacturing operations. Documentation of the preliminary assessment was deficient a nd
procedure will be updated to provide a more standard approach for both performing
and documenting the SME preliminary assessment.
The dirty hold time established as part of the cleaning performance qualification (CPQ) was
reviewed. In both occurrence s of , the amount of time the was in
the system was than the maximum dirty hold time. As a result, sampling of the
was not deemed a requirement by the SME team . For investigation
(initiated ) recleaning of the was performed beca use the amount of time the
was present in the system was . Procedure
states that stored is given a
expiration from the date it is dispensed. While this instruction is specific to dispensed
, the SME team performing the preliminary assessment leveraged this
instruction and directed Operations to reclean the . A cleaning verification was not
considered a requirement because the amount of time the was in the was
than the qualified maximum dirty hold time established for the . For the occurrence
documented in investigation (initiated ), recleaning of the was not
considered a requirement as the amount of time the was present in the system was
. was again leveraged by the SME team to make this
determination. A , approximately , was observed in the ,
which was prior to commencement of manufacturing operations.
Action
Procedure will be revised
and be made effective to provide a more standardized approach to the preliminary assessment
that SMEs are required to perform when determining potential impact to manufacturing
equipment post identification of a . Specifically , the revision will
include the requirement to assess and document the assessment of
Completion Date
31 August 2021
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FDA-CBER-2021-5683-1149887
Pfizer Andover Response to the FORM FDA 483 PAI BLA 125742 (COVID -19 mRNA Vaccine)
This document contains Confidential Commercial and Trade Information not authorized for public disclosure .
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Action
A study will be conducted to determine the conditions under which cleaning verification will be
required following identification of . The study will include an evaluation of the
potential impact of the contribution to and
therefore on the requirement for performing cleaning verification.
Completion Date
30 November 2021
Action
Based on the outcome of the study, procedure
will be revised and be made effective to ensure the key factors that
must be considered as part of th e assessment are documented and to include additional
instructions on how to perform and document the assessment of risk when a visual failure for
is identified. Relevant individuals will be trained according to site procedures.
Completion Date
30 December 2021
Observation 4
Per cleaning validation has
not been performed on the (Building The is
stored in a and as a result, a trend occurred in
( noted by identification of
Response to Observation 4
The design and use of the Building requires storage of
both the in
between manufacturing batches. As such, the opportunity to collect samples for
is limited .
Additionally, the ability to collect from the surface of the is
impractical as the would need to be dismantled . As a result, the system is
subjected to cleaning verifi cation via in -process monitoring rather than the cleaning cycle being
validated via execution of a cleaning performance qualification protocol .
The is subject to routine process monitoring
controls which ensure, among other things, detection of . As per these
controls, a trend for was noted and investigation was initiated
on . The investigation determined that the most probable root cause for the
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FDA-CBER-2021-5683-1149888
Pfizer Andover Response to the FORM FDA 483 PAI BLA 125742 (COVID -19 mRNA Vaccine)
This document contains Confidential Commercial and Trade Information not authorized for public disclosure .
Page 11 of 36
trend was that certain areas of the were not being
The root cause for this inadequate
of the with was identified to be an
which resulted in a being
unexposed to the . The storage in was not fully effective
because of the lack of . Additionally, because of the
. Investigation which was closed on
, contained corrective and prevent ative actions includ ing:
•
•
The above actions were implemented on and documented within change control
Following the implementation of the above actions, a supplemental validation protocol
was executed to demonstrate the effectiveness of the corrective and
preventative actions taken. The protocol monitored the BNT162b2 drug substance
batches that were manufactured post -remediation. Results of the monitoring are summarized in
validation report
The summary concluded t hat the manufacturing
process steps in scope of the study effectively maintained control following mitigation
and determined that no additional mitigation was warranted. The results for all
samples from the batches in scope of the suppl emental validation protocol were .
As of 12 July 2021, data from operations is available for batches of
BNT162b 2 drug substance manufactured in since implementation of the corrective and
preventative actions identified. The data from these batches demonstrates that the
equipment continues to operate as expected and that no indication of a trend has
been observed since implementation of the corrective and preventativ e actions.
The ability to perform cleaning performance qualification on manufacturing equipment is
directly related to how the equipment is used in the drug substance manufacturing process. In
instances where the manufacturing process requires equipme nt to be stored in a
between batches, the ability to execute cleaning performance qualification testing is
diminished and additional controls are evaluated and/or implemented in order to verify that the
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manufacturing equipment is ma intained in a clean state. In -process analytical testing is built into
the manufacturing process to monitor the effectiveness of the batch -to-batch storage operation
with the storage solution.
Because the equipment design and manufacturing process requires to be stored in
, typical cleaning performance
qualification analysis cannot be obtained. Instead, the manufacturing process includes a series of
samples that are obtained to ensure the equipment is maintained in a state of control regarding
cleaning status.
Following manufacturing operations, the
Action
An effectiveness check (child action record to was initiated on 28 July
2021 to document the effectiveness of the mitigation strategy implemented per change
control Sample results from operations of BNT162b 2 batches
manufactured from were reviewed.
The data confirms the processing step is appropriately stored, effectively monitored, and is
operating as expected.
Completion Date
Complete
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Observation 5
Cleaning of reusable product -contact parts using is not validated. Cleaning
verification of such parts is inadequate as it is limited to testing of
. Verification of surface and
testing is not performed routinely .
Response to Observation 5
Andover Cleaning Master plan takes into
consideration that operator dependent processes like are less controllable and
repeatable than equipme nt system parameter dependent processes and therefore are to be verified
and not validated as a cleaning procedure. The Cleaning Master Plan highlights that where
cleaning by does occur, the strength of the process requires a combination of st ringent
development studies, specific procedural instructions including disassembly of equipment,
operator training and assessment, and inclusion of analytical and visual verification of acceptable
cleanliness.
A development cleanability assessment was executed using BNT162b2 Vaccine process residues
to understand both the characteristics of the process residues that are intended to be cleaned as
well as determine the cleaning capabilities of the procedure used by operations
personnel. The assessment concluded that the operation was capable of cleaning the
process residues from equipment surfaces and that the BNT162b2 Vaccine process residues are
able to be visually detected on processing equipment within the . The
development cleanability assessment included representative materials of construction (MOCs)
for equipment used in BNT162b2 Vaccine manufacturing and used worst -case cleaning
conditions to appropriately challenge the procedure used by operations personnel.
Procedure governs execution of
activities within the manufacturing suite and is used by operations to .
Procedure requires operations personnel to collect
testing performance of a cleaning to a specified
acceptance criterion of , the procedure requires a visual inspection
of all parts that have been following procedure
to an acceptance criterion of . If the
is not within specification and/or the visual inspection fai ls per
procedure an investigation is initiated per site procedure
All personnel performing analysis and visual
inspection are required to complete and pass a skills -based training for these operations and
retrain on any modifications to the governing procedure as necessary.
Lastly, verification of the effectiveness of the operation, including
testing, is pe rformed on a basis. Periodic monitoring is
performed on equipment cleaned via under the formal cleaning monitoring program
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governed by standard operating procedure
Cleaning monitoring provides ongoing
assurance that the cleaning process is operating as expected to predetermined
accep tance criteria. Cleaning Monitoring includes
, as well as visual inspection. The acceptance criteria are pre-established and
includes
.
Cleaning monitoring of the operation was executed in March 2021. All results
obtained from this monitoring activity, including analysis, were within
the specified acce ptance criteria.
Action
A pre -approved protocol will be executed to generate a larger data set, inclusive of
sampling, to further support verification of the operation performed in
. The protocol will verify cleaning operations performed on
equipment used in using all testing , as required , in the verification. The
results obtained from the executed protocol will be summarized in a formal summary report by
the completion date. If the data from the study indicates a change in cleaning monitoring
frequency is needed, then a subsequent commitment will be initiated.
Completion Date
The study will be completed by 30 November 2021 .
Observation 6
Cleaning efficacy studies are inadequate (Building in that the firm has not
demonstrated consistent efficacy with and a contact time of .
(Building
demonstrates efficacy on all surfaces, however,
(Building demonstrates a lack of efficacy on all surfaces
except with a contact time of .
Response to Observation 6
disinfectant efficacy studies were performed to qualify disinfectants for use in
facilities, including These are summarized in r eport
The studies include
surfaces and that are representative of Building and support the
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contact times applied to Building The independent studies , which included
different surfaces and challenged different , showed that a greater than a
reduction could be achieved with a contact time for .
A comprehensive review of the Building including disinfectant efficacy program was
conducted ove r the last several years and as a result a contemporaneous study employing
improved study design and methodologies was executed and is summarized in report
This study was executed including
surfaces and that are representative of Building This study also
demonstrated efficacy of a contact time for , consistent with the studies
supporting the same for Building Comb ined data from multiple reports support a
contact time for for both facilities.
Actions
No action required.
Completion Date
Not applicable
Observation 7
The ISO - are not monitored to the ISO standards.
Specifically,
a. monitoring is not routinely performed.
b. monitoring limit is set a instead of .
c. (Building ) is within an ISO room.
Response to Observations 7a, 7b , and 7c
The Building Andover
were classified and qualified as ISO during the execution of the Environmental
Monitoring Qualification (EMQ) per validation protocol The objective of the
EMQ was to classify and qualify that each of the current Clean Environmental Areas (CEAs) of
the can meet and maintain the air and surface environmental quality levels for Good
Manufacturing Practices (GMP) based on use for a drug substance facility. The
EMQ was designed to demonstrat e that the facility met United States Pharmacopeia (USP) and
International Organization for Standardization (ISO) requirements. Per ISO
, ISO - in met the air quality levels requirement for
that includes monitoring for
conditions. quality levels are not specified per ISO
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quality levels for are not applicable to a drug substance facility.
The are routinely monitored for and meet the air quality levels
of ISO requirements.
Actions for 7a, 7b, and 7c
All ISO - in the will be classified as , removing the ISO designation .
Procedures
and
will be revised and made effective to reflect the classification for a
drug substance facility. Relevant individual s will be trained according to site
procedures.
Completion Date
15 September 2021
Observation 8:
Routine monitoring of the compressed air of Building does not adequately
represent all points of use. Only , specifically
, listed in
are routinely monitored.
Resp onse to Observation 8
At the present time, there are no specific regulatory guidance or requirements around the number
of compressed air points of use to be sampled or the frequency of sample s, but there are
recommendations. For example, the ISPE Good Practice Guide recommends testing every
on a rotating basis from representative sample locations.
Procedure
, describes the routine monitoring program for the compressed air system. As
part of the routine monitoring program, are representative
sample locations of the compressed air system with a sampling frequency of which is
based on Validation Protocol
.
Per Validation Protocol Section 5.1, the sample site selection followed a
approach. The approach was based on
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Representative sample location were selected as the routine
monitoring points after performance qualification based on being at the
beginning of the compressed air distribution and being at the end of the
distribution as described in Procedure
Table 1 contains the action quality levels for compressed air. Table 2 contains
the results from sample from routine
monitoring that started after the performance qualification and indicates that the compressed air
system is in a state of control. The data results show that sample
met quality levels.
Table 1 Quality Levels for Compressed Air
ISO
Class Water / Oil
Detection TAP Action Level Active Air
Action Level 0.5µm
5.0µm
Particles/
m3 Particles/
m3 cfu/m3
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Action
Procedure
, will be revised and made effective to require that all
locations are tested each . Relevant individuals will be trained according to site
procedures.
Completion Date:
31 August 2021
Observation 9
The environmental program (EM) program in is deficient in ensuring that the
cleanrooms are operating in a state of environmental control:
a. No prospective EM performance qualification (PQ) of classified areas or PQ of
was performed to ensure EM specifications in operation are met.
b. Routine monitoring of ISO area is performed o n a basis.
c. During a walkthrough on 7/22/2021, the door to the Control Room was
observed opened to manufacturing (ISO through the duration of
the walkthrough. Room is classified as controlled not classified and is not
moni tored.
Response to Observation 9
Observation 9a
No prospective EM performance qualification (PQ) of classified areas or PQ of was
performed to ensure EM specifications in operation are met.
Response to 9a
The environmental monitoring performance qualification (EMPQ) of was performed per
procedure
which includes the
sample locations, the action levels , as well as the required identifications . EM
results were documente d on form All results met
criteria of no action level excursions and were approved by Quality Assurance on 24 December
2020, prior to performing GMP operations.
As part of EMPQ, days of sampling Room and under
conditions were performed from per site
procedure
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This was followed by of sampling Room and under
conditions from per site procedure
conditions were achieved in the ISO production room by allowing
personnel into the room to
operational equipment.
Additional sampling of Room and under conditions was performed
between 28 December 2020 – 02 January 2021 per site procedure
Although EMPQ , and additional sampling was performed in , the site
acknowledges that there was no activity in the at the time of sampling; therefore, EMPQ of
was not performed under true conditions.
The E MPQ was performed per effective start -up and environmental monitoring procedures. All
results were below action levels and one result was above the alert level. Release of for
GMP use was documented in change control
As part of the r eview of change control it was noted by the site that the EMPQ was
not executed via a pre-approved protocol , as required in procedure and a summary
report was not written. However, all elements of EMPQ were completed per site procedure and
all samples met acceptance criteria of no action levels as required by site procedure
Investigation was initiated on 30 June 2021 to document and investigate this
deviation from site procedure The investigation concluded a root cause related to an
isolated human error for not performing the EMPQ via a preapproved protocol . There was no
impact as all EM sampling requirements were performed per effective cGMP procedures . A
summary report,
was written and approved on 23 July 2021.
There is no product quality impact resulting from the failure to perform the EMPQ of per
protocol as all required performance qualification elements were met.
Action
A summary report,
was written and approved on 23 July 2021.
Completion Date
Complete
Action
Procedure
will be revised and made effective to define
conditions under which to execute the portion of
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EMPQ and require appropriate documentation of activities within the EMPQ
Protocol and Final Report. Relevant individuals will be trained according to site procedures.
Completion Date:
31 August 2021
Action
An environmental monitoring qualification of and will be performed in
under predefined conditions.
Completion Date:
15 September 2021
Observation 9b
Routine monitoring of ISO area is performed on a basis.
Response to 9b
The Environmental Monitoring Performance Qualification (EMPQ) for controlled
classified production areas was executed from 16 December 2020 to 21 December 2020 and
followed by increased sampling from 28 December 2020 to 02 June 2021. Routine EM began on
04 January 2021 at a frequency defined in procedure
Routine EM data from 04 January 2021 to 30 June 2021 was assessed and found all samples
reported r esults within quality levels (below alert or action levels) for all test types
collected from ISO areas :
• Total samples collected:
• Count of Alert Level Results: 0
• Count of Action Level Results: 0.
To evaluate the current sampling frequency for the ISO classification, increased
sampling will be executed at a frequency of for a period. The data will be
evaluated and an appropriate sa mpling frequency for the ISO areas will be determined
and implemented as applicable.
Action
Implement protocol for increased sampling to period of
ISO areas. The data will be evaluated and an ap propriate sampling frequency for the
ISO areas will be determined and implemented as applicable.
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Completion Date
The study protocol will be developed, and the study execution will be completed by 15
December 2021 .
Observation 9c
During a walkthrough on 7/22/2021, the door to the Control Room was observed
opened to manufacturing (ISO through the duration of the walkthrough.
Room is classified as controlled not classified and is not monitored.
Response to Observation 9c
During the inspection, it was communicated in error that the control room was
classified as Controlled Not Classified (CNC). Control room is classified as an ISO
area.
control room and adjacent room have the same ISO classification and a
neutral pressure differential; therefore, the room air cascade and air quality should not be
impacted. Pfizer acknowledges is that the ancillary room doors should not be left open.
Environmental monitoring of control room will be performed at a frequency of
for a period. The data will be evaluated, and an appropriate sampling
frequency will be determined and implemented as applicable.
Action
A protocol for increased sampling to will be implemented for a
period of control room. The data will be evaluated and an appropriate sampling
frequency for the ISO areas will be determined and implemente d as applicable.
Updated Action as of 17 August 2021
As discussed with the Agency, an appropriate routine EM strategy for all ancillary ISO rooms
in including room , will be established. A protocol for increased sampling to
will be implemented for a period of the ISO ancillary
room s. The data will be evaluated and sample type and sampling frequency for the ISO
areas will be determined and implemented , as applicable.
Completion Date
The study protocol will be developed, and the study execution will be completed initiated by 15
December 2021 .
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Action
Procedure
will be revised and made effective to ensure all doors to ancillary
rooms, including , are not left open. Additionally , attention activator s will be applied to
doors within to remind personnel to close doors behind them. Relevant individuals will be
trained according to site procedure.
Completion Date
31 August 2021
Observation 10
On the HVAC supplying was shut down for preventative maintenance,
which resulted in pressure differential of room to drop to
relative to the outside non -controlled non -classified corridor at 2:25 AM. The room wa s not
cleaned until and environmental monitoring (EM) of the room was not
performed to ensure that the room returned to ISO state until . Between
the room was used for processing of drug substance batches
, all of which were processed into drug product and
released to US and international markets.
Clean status of the room is not verified or documented in the batch record. The firm allows
up to of HVAC shutdown tim e until an additional cleaning needs to be performed.
There is no data to support that room continuously meets its EM specification for
any time after HVAC shutdown. No product impact assessment was performed.
Response to Observation 10
Heating, ve ntilation, and air conditioning (HVAC) systems that supply the cGMP manufacturing
areas are qualified per procedure
During the initial HVAC qualification , each
HVAC unit is required to undergo multiple tests per Standard ISO-
, which includes a test. This test is
designed to identify the time frame required for each HVAC unit to reduce the
concentration by after being exposed to a source of
challen ge. HVAC , serving , passed the particulate testing in under ,
and all other HVAC qualification tests demonstrating ISO standards were achieved.
Based on historical data documented in assessment
allowance is made
for a loss of air flow for up to prior to requiring an additional facility sanitization .
090177e197d7c0a1\Approved\Approved On: 18-Aug-2021 16:13 (GMT)
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FDA-CBER-2021-5683-1149901
Pfizer Andover Response to the FORM FDA 483 PAI BLA 125742 (COVID -19 mRNA Vaccine)
This document contains Confidential Commercial and Trade Information not authorized for public disclosure .
Page 24 of 36
A Closure Risk Assessment (CRA) was performed (and was effective 31 December 2020) per
with the purpose to
document and understand the operational details and environmental controls around the final
unit operations and related processing steps performed within
In-process monitoring is employed to detect the entry of contaminants into the
manufacturing process. During the production of each batch, samples are taken at pre -defined
points from
.
On the HVAC unit serving was shutdown at approximately
to perform planned maintenance. The planned maintenance was performed
to and of terminal HEPA filters. Temperature and relative humidity
inside stayed within specification throughout this period. The HVAC unit was returned to
service and all pressure cascades and air change rates were re -established at . A facility
sanitization was performed at prior to the HVAC shutdown , per
procedure
No personnel were present within the suite and no
manufacturing operation s were occurring during the HVAC shutdown . Closed operations within
began at approximately No additional sanitization was required because of
the loss of airflow on per procedure which allows for a loss of air
flow up to prior to requiring an additional facility sanitization . Subsequent , routine
facility sanitization was performed on
For the reasons noted below, t here is no product impact to batches
Per procedure manufacturing operations occurring with an audible
HVAC alarm require a comment in the executed Manufacturing Batch Record ( MBR ) that is in
process at the time of the alarm. Per procedure
executed MBRs are reviewed by Quality Assurance. Batch records
did not contain comments for loss of air flow as there was no processing at
the time of the loss of air flow.
The associated drug substance batches produced from
met all in process and release specifications, and disposition criteria including as
outlined in procedures and
and were dispositioned with a status of released.
090177e197d7c0a1\Approved\Approved On: 18-Aug-2021 16:13 (GMT)
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FDA-CBER-2021-5683-1149902
Pfizer Andover Response to the FORM FDA 483 PAI BLA 125742 (COVID -19 mRNA Vaccine)
This document contains Confidential Commercial and Trade Information not authorized for public disclosure .
Page 25 of 36
Action
A study to assess the return to environmental specification per procedure
will be initiated following
an HVAC unit Shutdown in . The study will be initiated by 28 October 2021.
Completion Date
28 October 2 021
Action
Based on the results of the study, if required, procedure
, will be revised and made effective to
specify actions, such as facility sanitization and/or environmental monitoring in response to
alarms. Relevant individuals will be trained per site procedures.
Completion Date
25 November 2021
Action
An interim control to assess for product impact following a HVAC shutdown of greater than a
duration until the study has been completed and will be documented per planned
temporary change This interim control was approved on 30 July 2021.
Completion Date
Complete
Action
manufacturing batch records will be revised and made effective to document the
confirmation of the clean status of
Completion Date
15 September 2021
Observation 11
Standard operating procedures are not followed. For example,
a. On 7/22/2021 during observation of operations, cleaning of , and
dispensing of drug substance, the following was observed in deviation from
, and
090177e197d7c0a1\Approved\Approved On: 18-Aug-2021 16:13 (GMT)
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FDA-CBER-2021-5683-1149903
Pfizer Andover Response to the FORM FDA 483 PAI BLA 125742 (COVID -19 mRNA Vaccine)
This document contains Confidential Commercial and Trade Information not authorized for public disclosure .
Page 26 of 36
• An alarm went off due to operator to introduce a
. prohibits work in a if it is in alarm
condition.
• operators were over the of the blocking the
.
• did not cover all surfaces of the and was
contact time required per
b. cleaning of the in was not performed
in the of July 2021 in deviation from
Response to Observation 11
Observation 11a
On 7/22/2021 during observation of operations, cleaning of , and
dispensing of drug substance, the following was observed in deviation from
and
• An alarm went off due to operator to introduce a
. prohibits work in a if it is in alarm
condition.
• operators were over the of the blocking the
.
• did not cover all surfaces of the and was set
contact time required per
Response to Observation 11a
At the time of the alarm conditions on 22 July 2021, no work was being performed in
. All aseptic connections required for the were made by the
operator within prior to the alarm condition created when the were
transferred into the . Per procedure
were
with prior to transfer into the . The alarm condition was
triggered by the operator to introduce the into the and the
alarm cleared once the was . Once the were in the and the
alarm was cleared , the operator followed procedu re by allowing the items
introduced to sit undisturbed for a minimum of within the before
proceeding with putting the .
Investigation was init iated on 26 July 2021 regarding the alarm condition of the
that was observed on 22 July 2021. The r oot cause was determined to be procedure
090177e197d7c0a1\Approved\Approved On: 18-Aug-2021 16:13 (GMT)
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FDA-CBER-2021-5683-1149904
Pfizer Andover Response to the FORM FDA 483 PAI BLA 125742 (COVID -19 mRNA Vaccine)
This document contains Confidential Commercial and Trade Information not authorized for public disclosure .
Page 27 of 36
lacks instru ctions on how to proceed when the needs to be to add/remove items from
a .
As an additional improvement, the site will assess minimizing the number of items transferred
into the to only what is required for open product manipulation. Enabling the
operations portion of the activities to occur outside of the will eliminate the need
to to bring in equipment such as , thus
preventing the triggering of an alarm condition within the .
Investigation was initiated on 27 July 2021 to document the deviations to procedure
pertaining to operator over the of the and
insufficient work surface sanitization of observed on 22 July 2021 .
Colleagues and contractors are trained on training material
as a pre -requisite to open product man ipulations
in critical environments and are requalified by completing training material ,
Both training materials,
, require the learner to demonstra te proper aseptic technique and pre -
use/post -use sanitization of the per procedure The operator who performed the
work surface sanitization of and operations within the was trained on
procedure and training material .
Procedure states “In , do not the . This will disrupt
the .” Based on an interview with the operat or, the root cause of this
observation was human error of omission. The o perator was aware of the requirement to not
the of the and was purposefully keeping his arms up while working
within the ; however , while the w as running , the operator was
. Enabling the activities to occur outside of the will
minimize the time an operator will spend within the , thus reducing the risk of deviation
to procedure the .
For work surface sanitization of the , procedure specifies to saturate unit surfaces
with and leave undisturbed for , however it does not require that the work
surface must remain wet for the full contact time. Additionally, as a control for batch -to-
batch processing, requires a work surface sanitization and
sanitization of the .
The operator who performed the sanitization of the was interviewed regarding the observation
of not covering all surfaces of the with . The operator’s recollection was that
procedure was followed and that all surfaces of the were covered with
. The operator completed re -training on on 29 July 2021 pri or to performing
additional operations within the .
090177e197d7c0a1\Approved\Approved On: 18-Aug-2021 16:13 (GMT)
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FDA-CBER-2021-5683-1149905
Pfizer Andover Response to the FORM FDA 483 PAI BLA 125742 (COVID -19 mRNA Vaccine)
This document contains Confidential Commercial and Trade Information not authorized for public disclosure .
Page 28 of 36
There is no impact to product quality for the batch that was processed on 22 July 2021. The drug
substance sample results for the product for batch
passed testing in
Action
Investigation was initiated on 26 July 2021 for the documentation discrepancies
noted above. Th is investigatio n was closed on 29 July 2021.
Completion Date
Complete
Action
The current method used to perform operation will be evaluated to minimize the
type of equipment/materials that are brought into the for this operation .
and batch record s
and
will be revised and made effective , as appropriate , based on the evaluation . Relevant
individuals will be trained according to site procedures.
Completion Date
15 September 2021
Action
Procedure
, will be revised and made effective to clarify section 9.1.6
regarding Alarm Condition and include instructions for what to do if the needs to be
when ad ding/removing materials from . Relevant individuals will be trained according to
site procedures.
Completion Date
31 August 2021
Action
The operator who performed final operation within the and sanitization of the
was retrained on the entirety of procedure
, according to s ite procedures. The
re-training was completed on 29 July 2021.
Completion Date
Complete
090177e197d7c0a1\Approved\Approved On: 18-Aug-2021 16:13 (GMT)
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FDA-CBER-2021-5683-1149906
Pfizer Andover Response to the FORM FDA 483 PAI BLA 125742 (COVID -19 mRNA Vaccine)
This document contains Confidential Commercial and Trade Information not authorized for public disclosure .
Page 29 of 36
Action
Training materials ,
and ,
will be reviewed to ensure all key aseptic technique elements from
,
are included. Training materials will be revised and made effective
to include the instructions for the of the as part
of the proper aseptic technique demonstration . Additional aseptic technique elements will be
added, as needed, based on the review . The revisions to the training material will be completed
by 30 September 2021 and will be used for Aseptic Technique Fundamentals for Manufacturing
Qualification and Requalification moving forward , according to site procedures.
Completion Date
30 September 2021
Observation 11b
cleaning of the in was not performed in
the of July 2021 in deviation from
Response to Observation 11b
Investigation was initiated on 22 July 2021 to document the deviation to procedure
for not performing the cleaning of the outside
surfaces o f the equipment in during of July 2021. The surfaces of equipment
were cleaned upon discovery per procedure on 22 July 2021. Procedure
currently requires log sheet review for completeness and accuracy , as needed. A
retrospective review of the sanitization logbook was conducted to ensure no other
cleanings for had been missed.
There is no potential impact to product quality as in -process controls and environmental
monitoring ensure the bioburden/endotoxin levels stay within limits. There were no
environmental or HVAC alarm excursions reported for during the timeframe in scope.
Action
Procedure
will be revised and made effective to remove the terminology
“as needed” and change the requirement of review of the sanitization log sheets from
. Relevant individuals will be trained on revised procedure according to site
proce dures.
Completion Date
31 August 2021
090177e197d7c0a1\Approved\Approved On: 18-Aug-2021 16:13 (GMT)
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FDA-CBER-2021-5683-1149907
Pfizer Andover Response to the FORM FDA 483 PAI BLA 125742 (COVID -19 mRNA Vaccine)
This document contains Confidential Commercial and Trade Information not authorized for public disclosure .
Page 30 of 36
Observation 12
The following deficiencies were observed within buildings used to produce BNT162b2 drug
substance:
a. In Building preparation area:
• was observed on multiple walls.
• was observed in the hallway.
• were observed with dust and debris on the and
streaking/raised residue down the sides and bottom of multiple .
b. In Bui lding
• was observed on multiple walls inside room .
• was observed in room
c. Residue was observed on the sides and base of multiple sample pass throughs to include
preparation, and .
d. A gap to the outside was observed on the side of the mobile platform at the receiving
dock in Building
Response to Observation 12
Pfizer Andover is committed to ensuring facilities, equipment and utilities are well maintained.
Site procedure
describes the procedures used to perform preventive and corrective
maintenance activities and to manage and document these activities within the Computerized
Maintenance Management System (CMMS). This procedure covers the requirements for
establishing and executing equipment maintenance tasks and schedules applicable to equipment,
instruments, utilities, facilities and systems, and the documentation, review , and approval of
maintenance records in CMMS in accordance with procedure
In addition, periodic self -inspection programs are in place for the GMP manufacturing areas and
associated mechanical spaces as described in responses for 12a and 12b. These inspection
programs include the identification of fac ility defects on walls and floors. Defects identified
during the inspection process are repaired using corrective maintenance. Corrective work orders
to repair surface defects are evaluated and prioritized based on risk. Facility inspection and
maintena nce are continuous processes.
The periodic inspections and corrective maintenance process maintain the facility walls and
floors in a state of control.
Observation 12a
In Building preparation area:
• was observed on multiple walls.
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FDA-CBER-2021-5683-1149908
Pfizer Andover Response to the FORM FDA 483 PAI BLA 125742 (COVID -19 mRNA Vaccine)
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Page 31 of 36
• was observed in the hallway.
• were observed with dust and debris on the and
streaking/raised residue down the sides and bottom of multip le .
Response to Observation 12a
Procedure
provides standard expectations for the self -inspection of the
external condition of the equipment, general physical appearance inside manufacturing spaces
and associated mechanical spaces. Per procedure, the facility self-inspections are executed on a
quarterly basis. In the last self -inspection of this area was performed on 07 Jun 2021 and
documented in report
.
Procedure
requires cleaning of the exterior of all equipment with
disinfectant . After the contact time is achieved, the exterior of equipment is wiped with
ethanol to remove residual cleaning agent. P rocedure
Section 5.8 instructs
operators to perform workspace clearance formulation. Workspace clearance
Action
Repairs of in Building Preparation Area were
documented under work orders 1592463 and 1592462 and completed on 22 July 2021. There
were no defects observed in the drug substance manufacturing .
Completion Date
Complete
Action
Repairs to the in the Clean Not Classified (CNC) corridors ,
were documented under work orders 1593616 and 1593622 and completed on 28 July 2021 .
Completion Date
Complete
Action
Procedure
, will be revised and made effective to include instructions for
personnel to (1) identify any defects/damage that occur or are observed between routine
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FDA-CBER-2021-5683-1149909
Pfizer Andover Response to the FORM FDA 483 PAI BLA 125742 (COVID -19 mRNA Vaccine)
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Page 32 of 36
inspections and (2) how to escalate facility maintenance issues. Relevant i ndividuals will be
trained according to site procedures.
Completion Date
10 September 2021
Action
Remediatio n of observed residues (residual disinfectant) on exterior surfaces for
were documented under work Orders 1593895, 15593897,
1593908 and 1593910 respectively, and completed on 28 July 2021.
Completion Date
Complete
Action
Procedure
will be revised and made effective to provide more robust
instruction for the cleaning of equipment exteriors and removal of disinfectant residue. Relevant
individuals will be trained according to site procedures.
Completion Date
30 September 2021
Action
Procedure
will be revised and made effective to require workspace
clearance upon formulation. More robust instruction for
and surrounding surfaces will be included. Additionally, the procedure will be revised to
require inspe ction of and surrounding area to ensure it is free of dust, debris , and
residual raw material formulation. Relevant in dividuals will be
trained according to site procedures.
Completion Date
10 September 2021
Observation 12b
In Building
• was observed on multiple walls inside room .
• was observed in room
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FDA-CBER-2021-5683-1149910
Pfizer Andover Response to the FORM FDA 483 PAI BLA 125742 (COVID -19 mRNA Vaccine)
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Page 33 of 36
Response to Observation 12b
Procedure ,
provides the standard expectations of self -inspections that are required to ensure issues are
escalated and resolved when observed. Per procedure these self-inspections occur
. In the last self-inspec tion was performed on 14 July 2021 and documented in
work order 1528780. Operations personnel are performing self-inspections as required per
procedure
Action
Repair of a single wall defect observed on a wall in was documented under work order
1593834 and was completed on 29 July 2021.
Completion Date
Complete
Action
Repair to a in was documented under work order 1592483 and was
completed on 23 July 2021.
Completion Date
Complete
Action
Procedure , will be
revised and made effective for the following updates/clarification: Update Andover Production
Operations responsibility section to include the requirement that manufacturing is responsible for
escalating facility/equipment issues when they are observed to ensure issues are resolved in
between GMP100 inspections. Relevant i ndividuals will be trained according to site procedures.
Completion Date
08 September 2021
Action
Preventive maintenance (PM) plans will be implemented in the site maintenance system to assess
the need for repair of wall and floor surface defects in on a basis.
Frequency of assessment will be re -assessed at .
Completi on Date
08 September 2021
090177e197d7c0a1\Approved\Approved On: 18-Aug-2021 16:13 (GMT)
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FDA-CBER-2021-5683-1149911
Pfizer Andover Response to the FORM FDA 483 PAI BLA 125742 (COVID -19 mRNA Vaccine)
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Observation 12c
Residue was observed on the sides and base of multiple sample pass throughs to include
, and .
Response to Observation 12c
Procedure
Sections 9.1.3 and 11.9 requires disinfecting of all sample pass
throughs on a frequency. The residue observed on the inside surfaces of sample pass
throughs was found to be residual disinfectant .
Action
A Special Sanitization Request (SSR) was issued and completed on 27 July 2021
which removed the residu al disinfectant .
Completion Date
Complete
Action
Procedure
will be revised and made effective to provide more robust
instruction for the sanitization of sample pass through interior surfaces and removal of
disinfectant residue. Relevant i ndividuals will be trained according to site procedures.
Completion Date
30 September 2021
Observation 12d
A gap to the outside was observed on the side of the mobile platform at the receiving dock
in Building
Response to Observation 12d
Procedure establishes procedures for the control of insect, bird,
rodent, vermin and wildlife at the Pfizer Andover, MA facilities. Building pest control is
governed by procedure
Section 5.11 (Pest Control Device Inspections and Locations) indicates the pest control provider
is responsible in sub -sections 5, 6, 7, 8 and 9 to “note any adverse conditions observed in the
vicinity of the device.” In addition, under Section 5.11 sub -section 10: “Any conditions and
observations are noted on the inspection report. The IFM (Integrated Facilities Management ) QA
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FDA-CBER-2021-5683-1149912
Pfizer Andover Response to the FORM FDA 483 PAI BLA 125742 (COVID -19 mRNA Vaccine)
This document contains Confidential Commercial and Trade Information not authorized for public disclosure .
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Pest Control Specialist, or designee will initiate and track work orders to address any
deficiencies.”
The last inspection for the control devices associated with location was completed
on 28June2021. The inspection frequency is . No adverse conditions were noted with
respect to the loading dock door at location . No pest control issues were identified
during this inspection and no adverse trends have been identified.
Action
Repair of the gap identified on loading dock door at location was documented under
work order 1591632 and completed on 23 July 2021.
Completion Date
Complete
Action
Procedure will be revised and made effective with the
following update: Update Section 5.11 (Pest Control Device Inspections and Locations) to add a
step for the pest control provider to inspect doors and similar openings for adverse conditions
which may lead to pest infiltration. All adverse conditions will continue to be do cumented in the
pest control report. The Pest Control Specialist or designee will continue to initiate work orders
to address any deficiencies. Relevant individuals will be trained according to site procedures.
Completion Date
31 August 2021
Observa tion 13:
During activities observed on 7/22/2021, an operator was observed to
and subsequently material from a full and previously opened container of
. The previously opened container of had a lid which
was not fully closed, the within the container was not closed, and there was no
documentation as to when the container had been initially opened.
Response to Observation 13:
Per procedure
, partial containers returned to warehouse after sub -division must be
closed, sealed , and contained.
Per procedure ,
each container received will be given a unique reference number (Sub -batch). This allows the
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FDA-CBER-2021-5683-1149913
Pfizer Andover Response to the FORM FDA 483 PAI BLA 125742 (COVID -19 mRNA Vaccine)
This document contains Confidential Commercial and Trade Information not authorized for public disclosure .
Page 36 of 36
Inventory and system to provide full transaction history for each
sub-batch. The system keeps a record of every transaction
performed on a sub -batch and can produce a transaction history report for each container on
when it was opened, and by whom. Review of the transaction history report for the container of
(Batch , Sub -batch ) obse rved on
indicates the container was initially opened for subdivision on The
transaction history provided by the Inventory and system negates
the need for labeling of containers.
Action
An inspectio n of the 23 partial containers stored in the Andover
warehouse was completed on 27 July 2021 to ensure containers were closed and
. All containers were found closed and with . No
additional corrective action is required.
Completion Date
Complete
Action
Procedure
will be revised and made effective to provide clear
instructions for acceptable methods of container closure following sub -division or sampling and
proces s for escalating observations of unexpected conditions . Relevant i ndividuals will be
trained according to site procedures.
Completion Date
31 August 2021
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FDA-CBER-2021-5683-1149914