Failure mode Effect Analysis

)FMEA(
Failures in process in sterile liquid area

Process Failure Cause Effect S O D RPN Control S O D RPN

Gowning procedures
IF untrained person enter Contamination for raw Only trained person s are authorized to
not followed for 5 2 4 40 5 1 2 10
to dispensing area material enter in dispensing area
dispensing

Affect the property of RM &

Temp. and RH out of Failure in HVAC system due to increase RH it can Qualified HVAC System is used*
limit during or unqualified AHU in create moisture that may 5 3 3 45 Control and frequent monitoring for RH * 5 1 1 5
dispensing use cause microbial .& Temp
contamination
No proper maintenance*
for Booth There may be chance of
Raw Material -1 Malfunctioning of Qualified dispensing Booth is being used*
Unqualified dispensing * contamination of raw 5 3 3 45 5 1 1 5
Dispensing Dispensing Booth Maintenance plan*
Booth material

SOP for cleaning not *

Written procedure are available for *
No proper cleaning followed There may be chance of
cleaning processes
during dispensing No training provided to* contamination of raw 5 3 4 60 5 2 2 20
QA person daily verify the cleaning of *
process person material
dispensing room
It can be cause of variation
Inaccuracy of in weight of RM during Calibration of weighing balance is done
Due to out of calibration
weighing balance weighing and also cause 3 2 2 12 on daily verification of weighing balance is 3 1 1 3
of weighing balance
during dispensing variation in assay of .done to check its accuracy
.product
Transfer of -2 After dispensing all materials are kept in *
dispensing double dispensing bags and closed with
Material spillage* No proper handling *
material from Cross contamination cable tie with a specific identification for
Material misplace * during transferring of 4 2 2 16 4 1 1 4
the store to between different materials each material
during transfer Material
manufacturing All dispensing materials are transferred in*
area a closed SS cage

S = Severity *
O = Occurrence *
D = Detectability *

Prepared by Approved by

Page 1 of 10
QA-SF-08-700801
Rev ( 3 ) 18/08/2021
 Failure mode Effect Analysis
)FMEA(
Failures in process in sterile liquid area
Process Failure Cause Effect S O D RPN Control S O D RPN

Cleaning not done

SOP for cleaning *
for manufacturing
(CIP) not followed There may be chance of proper training for operators*
tank before 5 2 3 30 5 1 1 5
no training provided* contamination of the CIP system is available for cleaning *
manufacture
to person product
process

SOP for *
Sterilization not Sterilization (SIP) not proper training for operators*
Microbial contamination
done for followed 5 2 3 30 SIP system is available for * 5 1 1 5
-3 increase in tank
manufacturing tank no training provided* sterilization
Manufacturing
Process to person
WFI not meet its *
predetermined There may be chance of
Before Manufacturing WFI sample
WFI failed during specification contamination of the
5 2 3 30 should be send for LAL, conductivity, 5 1 1 5
testing sampling and testing* product
pH & micro. testing
of WFI not done in
correct manner
There may be chance of *
SOP for gowning * contamination of the
Improper gowning procedures not product proper training for operators*
in manufacturing followed cross-contamination * 4 2 3 24 double check for proper gowning is * 4 1 1 4
area no training provided* may occur between diff. done by trained supervisor
to person products

S = Severity *
O = Occurrence *
D = Detectability *

Prepared by Approved by

Page 2 of 10
QA-SF-08-700801
Rev ( 3 ) 18/08/2021
 Failure mode Effect Analysis
)FMEA(
Failures in process in sterile liquid area
Process Failure Cause Effect S O D RPN Control S O D RPN
filter use more than * filter use as pre recommended cycle & -
recommended cycles Product contamination maintained in log book for cycles
Integrity test failure 5 2 4 40 5 1 2 10
filter use without * High bio-burden results final filter integrity done before & after -
integrity testing filtration process
Product filter sterilized with tank & *
Aseptically not
On line product filtration line, after that no any manual
handling after Directly impact the product
sterilization facility not 5 3 4 60 interference 5 1 1 5
sterilization of the sterility & quality
available proper training on aseptic behavior *
product
procedure are done

Cleaning not done of There may be a chance SOP for CIP not followed * written procedures are available for *
filtration tank before for contamination of the improper personnel * 5 3 2 30 cleaning process of filtration tank 5 1 1 5
filtration process product training training on SOP of cleaning*

product -4 SOP for cleaning, *

Sterilization not done
Filtration sterilization not written procedures are available for *
of filtration tank Microbial contamination
followed 5 3 3 45 sterilization process of filtration tank 5 1 1 5
before filtration increase in filtration tank
no training provided to* training on SOP of cleaning*
process
person
Pre and post filter integrity before and *
Integrity failure of 0.22u after filtration process to ensure integrity of
Availability of non- There may be chance of
sterile filter and / or use 0.22u filter
sterile solution for contamination of the 5 2 3 30 5 1 1 5
of unsterilized tools ensure sterilization of all tools before *
aseptic filling product
during filtration process filtration process by reviewing sterilization
.chart before filtration process
The material and type of Low assay found in final *
Filter is not
filter (hydrophilic or .product The same filter is used for validation
compatible with the 4 2 2 16 4 1 1 4
hydrophobic) is not High chances of impurities* batches and product stability is conforming
.product
compatible with product

S = Severity *
O = Occurrence *
D = Detectability *

Prepared by Approved by

Page 3 of 10
QA-SF-08-700801
Rev ( 3 ) 18/08/2021
 Failure mode Effect Analysis
)FMEA(
Failures in process in sterile liquid area
Process Failure Cause Effect S O D RPN Control S O D RPN

Written procedure for Cleaning of machine parts is done as per *

Cleaning not machine parts cleaning Directly impacted the respective SOP. * After cleaning all
5 2 2 20 5 1 1 5
properly done not available to product details recorded in batch manufacturing
.record & cleaning log with double check

Unqualified autoclave *
used for sterilization
Autoclave qualification has been done *
process
and a validated load pattern is provided to
Machine -5 Un-qualified load *
machine parts are .production
parts & patterns used
not sterilized by .Maintenance is done as per schedule *
Filling Mechanical problem in * Machine parts not
utilizing the 4 2 2 16 Trained Person handles the all * 4 1 1 4
Assembly autoclave. Working sterilized properly
validated .autoclave processes
*personnel lack of
parameters Pure Steam Generator is qualified and *
adequate training
produces a quality & pure steam for
Impure steam provided *
autoclaving process
from Pure Steam
Generator
Carry and kept without *
Aseptically not
laminar air Product Machine parts carry in Mobile LAF and
handling after 5 2 2 20 5 1 1 5
Use over the holding * contamination assembled under LAF
.sterilization
.period of sterilization

S = Severity *
O = Occurrence *
D = Detectability *

Prepared by Approved by

Page 4 of 10
QA-SF-08-700801
Rev ( 3 ) 18/08/2021
 Failure mode Effect Analysis
)FMEA(
Failures in process in sterile liquid area
Process Failure Cause Effect S O D RPN Control S O D RPN
Unqualified *
autoclave used for
sterilization
process Garments for aseptic * Autoclave qualification has been done *
Garments are not Un-qualified * area not sterilized and a validated load pattern is provided to
sterilized by utilizing load patterns used. properly .production
4 2 2 16 4 1 1 4
the validated *Mechanical contamination of the * maintenance is done as per schedule *
parameters problem in aseptic area and the Trained Person handles the all autoclave *
autoclave product process
Working *
personnel lack of
Garment -6 adequate training
sterilization Sterilized garments * Sterile garment storage in sterile *
No specific place * can get contaminated area and transfer under mobile
provided for by exposing and stored LAF
Garments stored in *
storing the sterile for more than specified
unclassified &
garments. holding time in outer Garment hold time study is *
unqualified place
*Garments holding .area established and a specified hold
*Garments hold up in 4 2 2 16 4 1 1 4
time duration not Contaminated * time period is recommended in
same place for more
specified. garment can also respective SOP. & label written
than specified holding
*Working contaminate the aseptic
. time
personnel lack of area. *Product can get
with date of sterilization and due
adequate training easily contaminated .date of sterilization
garment .Training provided for person*
S = Severity *
O = Occurrence *
D = Detectability *

Prepared by Approved by

Page 5 of 10
QA-SF-08-700801
Rev ( 3 ) 18/08/2021
 Failure mode Effect Analysis
)FMEA(
Failures in process in sterile liquid area

Process Failure Cause Effect S O D RPN Control S O D RPN

Non-qualified filling *
machine used for filling
Performance qualification of filling *
During filling operation
machine has been done as per its
operation there is It might be due to *
There might be a problem of .testing parameters
volume variation of piston setting/ dosing 3 2 1 6 3 1 1 3
fill volume variation
solution from set .timing setting problem
Only Trained persons authorized to *
.limit Working personnel *
.access filling & sealing operations
lack of adequate
.knowledge
No Pre and Post In case of absence of
Nitrogen pressure always checked
nitrogen flushing Disconnection of nitrogen, filling will be
with operator during filling, whenever
during filling nitrogen line from filling automatically stopped 4 2 2 16 4 1 1 4
low pressure or no nitrogen available
Filling -7 operation in case of .machine followed by delay in
the filling should be stop
& sealing ampoule filling operation
process periodic validation tests has been *
Non-Sterile nitrogen There might be a chance of done to ensure the quality of nitrogen
Integrity failure of 0.2 µ
is coming in sterile area contamination followed 5 2 3 30 air in sterile area Before filling two 5 1 1 5
sterile filter
.area .by product contamination pre integrity tested 0.2 µ filters are in
place
There might be failure *
of air velocity sensor & During operational qualification all *
.Problem Filling during switch off sensors has been verified.
Failure of LAF
Non-qualified Laminar* condition of LAF will *Performance qualification of LAF
during the filling 5 2 2 20 5 1 1 5
air flow unit used for directly impact the sterility has been completed
.operation
filling operation of the sterility of the product maintenance of LAF done as per *
No preventive * schedule
.maintenance of LAF

S = Severity *
O = Occurrence *
D = Detectability *

Prepared by Approved by

Page 6 of 10
QA-SF-08-700801
Rev ( 3 ) 18/08/2021
 Failure mode Effect Analysis
)FMEA(
Failures in process in sterile liquid area

Process Failure Cause Effect S O D RPN Control S O D RPN

During power failure of LAF all *
Filling during power
Failure of power * .filling operation will stop
failure condition of LAF
supply in aseptic A proper training has been provided *
will directly impact the
During filling power .area to concerned personnel that filling
sterility of the product 4 2 2 16 4 1 1 4
.failure of LAF Failure of UPS * operations shall be done only under
and there might be a
Backup of filling LAF and also background of LAF shall
chance of contamination
.LAF be maintained as per specific grade
.of product
.requirement
Filling line speed of filling machine *
It can lead the *
Filling line speed * has been studied and verified during
variation of extractable
.not verified performance qualification of filling &
Filling line speed and volume for its
Wrong parameters * 3 2 2 12 .sealing machine 3 1 1 3
volume variations .specifications
set in the batch Details of filling machine speed has *
It can be cause of *
manufacturing record been set as per PQ OF m/c and
.batch failure
. checked & verified
Due to low ΔP there
Audio- visual alarm system is *
Filling room Due to insufficiency* might be a risk of area
provided when pressure differential
differential pressure of AHU Performance. contamination with
4 2 2 16 .will go out of limit 4 1 1 4
is out of range during *Non-qualified AHU respect to adjacent room
PQ pressure differential has been *
product filling .used for operation followed by
verified
contamination in product

S = Severity *
O = Occurrence *
D = Detectability *

Prepared by Approved by

Page 7 of 10
QA-SF-08-700801
Rev ( 3 ) 18/08/2021
 Failure mode Effect Analysis
)FMEA(
Failures in process in sterile liquid area
Process Failure Cause Effect S O D RPN Control S O D RPN
Filling room
Due to inefficiency There might be an
temperature & RH is Frequent temp. & RH measure during
of chiller & heater of impact on inprocess 4 2 3 24 4 1 2 8
out of range during filing
that particular AHU product
product filling
Filling process is covered by media *
Operators not It can be a cause of * fill study and all operators has been
Routine filling involved & qualified in each
qualified in each producing a non -sterile
interventions occurs intervention & training on aseptic
interventions and it product. *Product safety 4 2 2 16 4 1 1 4
due to any behavior
can lead the chance of and quality problem
.mechanical problem Media fill report covers the container *
.human error occur
.size and filling interventions
There is a high degree of
Unawareness of Only trained and authorized personnel *
chances to increase the
Area cleaning not operator and staff can enter & work in the aseptic area
chemical & microbial
done after batch members. Working 4 2 2 16 and they all are trained in their work. 4 1 1 4
growth in the area that
.completion personnel lack of *After completion of every batch the
can lead product
adequate training .cleaning has been done
Area -8 .contamination
Cleaning Disinfectant using *
area cleaning not
Microbial growth Disinfectant validation has been done
validated.
increases in aseptic Product get contaminated 5 2 3 30 and only validated disinfectant has 5 1 1 5
*Effectiveness of
area been used for cleaning of aseptic area
disinfectant not meet
specification

S = Severity *
O = Occurrence *
D = Detectability *

Prepared by Approved by

Page 8 of 10
QA-SF-08-700801
Rev ( 3 ) 18/08/2021
 Failure mode Effect Analysis
)FMEA(
Failures in process in sterile liquid area
Process Failure Cause Effect S O D RPN Control S O D RPN
There are separate entry procedures *
.for personnel & material
personnel& *
All materials for aseptic area has *
material entry not
been transferred through Dynamic pass
properly segregated
personnel & -9 personnel & There are high chances box, and all personnel have been
for entering in
material entry in material entry of cross contamination. It 4 2 2 8 entering in the aseptic area through 3 4 1 1 4
aseptic area. *Entry
aseptic area not specified can cause product change room system as per the entry &
& exit procedure
exit procedure for aseptic area
for aseptic area not
gowning procedure training & *
.specified
aseptic behavior training done for all
.personnel enter to aseptic area
The performance of all wash station *
Water (PW& , WFI verified at the time of washing
) & Compressed air operation
quality may not Performance washing machine is *
Dirty ampoules
comply with its There might be a chance qualified and run as per its set
ampoule -10 are coming at the
specification . of product 4 2 2 16 .parameters 4 1 1 4
washing outlet of washing
*Pressure of WFI .contamination Maintenance of washing machine is *
machine
& compressed air .done as per schedule
may not comply Filter integrity of filter installed on *
with set parameters compressed air & WFI has been done
as per SOP

S = Severity *
O = Occurrence *
D = Detectability *

Prepared by Approved by

Page 9 of 10
QA-SF-08-700801
Rev ( 3 ) 18/08/2021
 Failure mode Effect Analysis
)FMEA(
Failures in process in sterile liquid area
Process Failure Cause Effect S O D RPN Control S O D RPN
Inefficiency of
It can cause
filters due to
contamination for Integrity of filter had been done at *
excess air
Leakage in filters ampoule by generating the time of performance qualification
pressure from 4 2 3 24 4 1 2 8
of oven particulate matters, .of oven
blower, might
which are ready for .periodic oven qualification is done *
damage any
.filling process
filter
Sterilization -11 Insufficient *
& exposure of
depyrogenation temperature & It can cause a serious *
of container time provided for contamination on Depyrogenation test with at least 3 log
oven not ampoules. * .product reduction challenge test has been
depyrogenating the Heating zone Product filling shall be * 5 2 1 10 confirmed at the time of performance 5 1 1 5
ampoules didn’t have a done in pyrogenated .qualification of oven
sufficient containers imposing risk
temperature to .to final product
depyrogenate
.ampoule

S = Severity *
O = Occurrence *
D = Detectability *

Prepared by Approved by

Page 10 of 10
QA-SF-08-700801
Rev ( 3 ) 18/08/2021