12-1-2022 IMA 4 For Normal Amp. Filling Line UNIT 4

EGYPTIAN INTERNATIONAL PHARMACEUTICAL INDUSTRIES COMPANY (EIPICO)
Validation Title: Media Fill test Protocol No.: SST-I4U4-6-22

Line: IMA 4 for normal ampoules filling line Issue/Rev.: 1.0
Issued by: Issue date: Effective date: Supersedes No.: SST-I4U4-1-
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Media Fill Protocol
IMA 4 for normal ampoule

filling line
Location: unit 4 sterile liquid department
i Document Approval
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INITIAL DOCUMENT APPROVAL

Approval signifies that this document has been reviewed and has been
What's initial
found accurate and complete.
approval means?
This document is valid as from the date of the last approver's signature.
Function Name Signature Date
Production Manager Dr. Maher Rasmy
Validation Manager Dr. Fathy El-Abd
QC manager Dr. khaled salah
QA manager Dr. Amira Nasr El-Din
ii Validation Team Signature List

All persons involved in the performing of the qualification protocols have to fill out the list ensuring that
each individual has understood the protocol execution procedures, result compiling and reviewing.
Function Name Signature Date

Microbiology
Haitham Mohamed
Department head
QA department head Mohamed Hossam
Engineering ziad
Microbiology specialist A.Magdy
Production Hani Abo Bakr
Validation unit head Mohamed Abdel-Salam
iii Revision Control
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Revision Issue Date Cause of revision Author
1 MEDIA FILL PROTOCOL GENERAL INFORMATION
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1.1 OBJECTIVE
This protocol is designed to establish sufficient data to assure that the aseptic filling process
is adequate and drug product thus produced remains sterile according to batch record issue
date: 20/07/2019
This protocol provides a standard procedure for the validation of aseptic filling process,
environmental conditions and practices to confirm its acceptability in protecting the product
from microbial contamination.
Aseptic processing should include a process simulation test using a nutrient medium (media
fill).
1.2 SCOPE
The protocol describes the procedure for the total Process Simulation (Media Fill) for
ampoule filling line (6U4) ,IMA 4 Filling Line to ensure 100% testing at least on a limited
quantity of ampoules; Aseptic media fill in considered to be the best way to evaluate the
product from microbial contamination.
1.3 ABBREVIATIONS
Abbreviation Description
MF Media Fill N Normal Solution
S Suspension WFI Water for Injection
TSB Tryptic soy broth EC Environmental Control
QA Quality Assurance RM Raw Material
1.4 RESPONSIBILITY MATRIX
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1.4.1 Manufacturing departments will be responsible for the following:
1. Conducting the outlined procedure.

2. Ensuring that requirements outlined in this procedure are met prior to ending a
media fill run.
3. All events are completely and clearly documented on the appropriate SOP.
4. Providing machine operators and supervisory staff.
5. Sterilization of media.
6. Provide materials to be used.
7. Providing samples wherever necessary.
8. Carrying out the aseptic filling process.
9. Checking the damaged Ampoules after filling and SEALING.
10. Cleaning and sanitization of area and equipment after media fill.
1.4.2 The Microbiology and Environmental Control department will be

responsible for the following:
1. Microbiological Environmental monitoring for filling room will be carried out daily
as required per current SOP.
2. Microbiological Environmental monitoring of the manufacturing area and
personnel gown and finger print test.
3. Incubation and ensuring security of media filled ampoules.
4. Observation of incubated filled Ampoules after 7 and 14 days by the aid of
qualified operators from production).
5. Immediately reviewing the non-viable particle counts and notifying management if
alert and/or action levels are exceeded before and during media fill.
6. Participate in investigations in case the media fill trial fails.
7. Ensuring that the Microbiological acceptance criterion per this procedure has
been met (bioburden, sterility testing, Growth promotion and Microbiological
environmental monitoring).
8. Getting rid of media filled Ampoules after evaluation and authorization from Q.A
manager.
9. Performing growth promotion, bioburden and sterility tests according to SOP.
10. Identifying microbial contamination if any turbidity appeared.
1.4.3 Qualified operators from production are responsible for:
1.4.3.1 The visual inspection of the media filled Ampoules after incubation period.
1.4.4 The validation department is responsible for:

1. Initiate protocols and review with concerned departments.
2. Review batch documents.
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3. Compile final report.
1.4.5 The Quality assurance Department shall be responsible for:
1.4.5.1 Approving requirements for all media fill prior to fill, the requirements
will be documented.
1.4.5.2 Give final approval on the protocol.
1.4.6 The Engineering Department shall be responsible for the following:
1.4.6.1 Carrying out the repairs/modifications (if required) prior to revalidation runs
and be present during engineering intervention.
1.4.7 The QC sampling department will be responsible for the following:
1. Submitting samples for growth promotion, bioburden and sterility to microbiology lab.
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1.5 REFERENCES
SOPs  Validation for aseptic filling procedure with media fills SOP.
 USP General Chapter (797), pharmaceutical compounding, sterile

preparations.
 FDA guidance on Sterile Drug Products Produced by Aseptic Processing
Rules and
 Abstract for Overview of Aseptic Fill/Finish Manufacturing Douglas Stockdale
guidance
President, Stockdale Associates, Inc.
 Good manufacturing practices for sterile pharmaceutical products, WHO,
2009, Annex 6.
1.6 REVALIDATION
Three consecutive separate successful media fill runs prior to

Initial validation
approval of a new aseptic processing operation.
Scheduled revalidation Once Bi-annually.
a. After any significant changes: Facility and equipment
modifications, line configuration changes, extended shutdowns,
or end product sterility testing failure may all indicate an
immediate need to implement a full process validation protocol
Unscheduled revalidation (minimum of 3 consecutive successful media-fill runs).

b. After maintenance of Filling Machine or Sealing Machine or
after major significance in HVAC system.
c. Change in the Ampoules Filling Machine and Sealing machine
itself or their critical parts or change in personnel.
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1.7 ACCEPTANCE CRITERIA
1.7.1 The duration of filling will be three days 30,000 in total .(10,000) Ampoules every day.
Qualification of the area should be considered as appropriate. Sterility testing of the media
should be passed. Positive control units must exhibit growth of the specified growth
promotion organisms at the specified incubation parameters.
1.7.2 Ideally the contamination rate should be zero. However, in case of filling 10,000 units
or more:
-One contaminated unit should result in investigation.
-Two contaminated units are considered cause of revalidation following investigation.
1.8 QUALIFICATIONS REQUIRED BEFORE STARTING THE TEST
- HVAC qualification.
- Qualification for Autoclave.
- Qualification for the oven.
- Compressed air for:
1- Preparation Tank.
2- Receiving Tank.
3- The compressed air replacing nitrogen in the ampoule filling stage.
-Integrity test for used filters:
1- Filter used in the media filtration.
2- Vent Filter.
3- Filter used just before filling (Second filtration) N.A. as worst case.
4- Filter used in disinfectant filtration.
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COMPARISON BETWEEN NORMAL OPERATION AND MEDIA

1.9
FILL
ITEM NORMAL PROTOCOL MEDIA FILL

Size container 2 ml , 3 ml , 5 ml 3 ml
Fill volume 2 ml 2 ml
Minimum: 14,000/hr Minimum: 14,000/hr

Normal: 15,000/hr Normal: 15,000/hr
Line speed
Maximum: 15,500/hr Maximum: 15,500/hr
Batch size 160000 30000
Operator 2 2 to be increased
E.C. All E.C. activities All E.C. activities
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GENERAL PROCESS FLOW CHART FOR AMPOULE

2
FILLING OPERATION
Start
Bulk Preparation in a suitable

preparation tank
Sterilizing filtration by using

membrane filter
Receiving of filtered solution

in a suitable receiving tank
De-packing of ampoules
Sterilization of the empty

ampoules in the oven
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Normal
filling
sealing of the
ampoules
Labelling of ampoules by
numerating the racks.
Inspection
Read (Results)
+ve control
End
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PROCESS DESCRIPTION FOR AMPOULE

3
FILLING OPERATION
3.1 Ampoule sterilization
4.1.1 Approved Ampoules are de packed .

4.1.2 The ampoules are placed into stainless steel boxes.
4.1.3 The ampoules are placed into the oven for sterilization. (Cycle charts is attached)
3.2 Raw material transfer and preparation
4.2.1 Approved RM (Tryptic soya Broth) is transferred from stores.

4.2.2 Transfer RM to preparation area to be prepared.
4.2.3 Add the TSB slowly to hot water for injection (60-65 °C) in clean sterile
preparation tank (30 gm/1L), and then cool to (25 – 30 ˚C)
4.2.4 Mix for 15 minutes to completely dissolve the powder, and then cool.
4.2.5 Check and record pH, pH Range (7.3 ± 0.2)
4.2.6 Then pass the solution of TSB through 0.22 micron sterile filter, collect the sterile
filtrate in a sterile, particle free tank equipped with vent filter.
4.2.7 Store the receiving tank under LAF at room temp .
3.3 Filling
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4.3.1 The filling machine is located in grade A zone. The machine is provided with door
closures to provide grade A.
4.3.2 The filling machine will start up with installing parts like pistons and needles ,
…….etc. after un-covering them from the autoclave bags under LAF.
4.3.3 Filling machine is operated as per the standard operating procedure.
4.3.4 In process sampling during filling operation is carried out as per the standard
operating procedure.
4.3.5 The run will be NLT 10,000 ampoules
3.4 Filling area
4.4.1 The filling room is grade A. The filling machine is protected by closed doors
suitable for machine operation.
4.4.2 The filling zone is Grade A and the other surrounding area outside the filling zone
is Grade B.
4.4.3 A provision of compressed air instead of nitrogen is provided for media fill
operation.
4.4.4 To simulate the worst case conditions, increase the number of personnel
participating in the media fill operations
3.5 Sealing ampoules
4.5.1 The filled ampoules will be sealed on time .

4.5.2 The sealing of the ampoules carried out as per the standard operating procedure.
3.6 Environmental controls
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4.6.1 Temperature of filling area is maintained 22 0C ±2

4.6.2 Relative Humidity of filling area is maintained not more than NMT 65%
4.6.3 Pressure differential of the filling room is maintained at NLT 10 Pa .
4.6.4 Microbiological monitoring of the filling room is carried out daily for settling
plate, air sampler and contact plates during media fill test, Personnel working in
the area are also monitored for bioburden during media fill test.
4.6.5 Non-viable particulate counts are taken on daily basis to ensure the cleanliness
during media fill test.
3.7 Visual inspection of filled ampoules
4.7.1 After filling and sealing the ampoules are subjected to visual inspection to detect
for the presence of any bad seals (sealing defects), surface defects, cracks on the ampoules
surface, presence of any distinguishable foreign particles in the TSB etc., The rejected
ampoules are collected separately and destroyed.
4 BRIEF PLAN FOR MEDIA FILL
The ampoule filling process described above is simulated by media fill trials. Sterile
TSB is used for filling purpose. Primary packaging material (like ampoules) ,and
equipment for washing, sterilization, filling and sealing of ampoules are same as used
in routine operations. NLT 10,000 ampoules are filled with sterile TSB Media then
sealed. During filling, worst case situations are simulated where possible. Media after
filling is checked for positive (Growth Promotion Test) and checked for negative
control (Sterility Test). Filled ampoules are incubated at (20-25°C)for 7 days followed
by (30-35°C) for further 7 days.
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5 BATCH INFORMATION
5.1 Batch size (L) : 60 L.

5.2 Used media : TSB
5.3 Volume of media filled into ampoules (ml) : 2 ml
5.4 Number of intended filled ampoules is 30,000 amp. .
6 VALIDATION METHODOLOGY
6.1 Pre-validation checks
Prior to performing the validation of the aseptic filling, it should be ensured that all
equipment, utilities and processes are validated and all instruments are calibrated.
It should be ensured that the aseptic filling room is at a positive pressure with
respect to the surrounding areas.
6.2 Checks during the run
i. Personnel Monitoring:
Ensure that personnel entering the sterile area have followed the gowning and entry
procedures as per standard Operating Procedure and have been qualified as per standard
Operating Procedure. Personnel should undergo monitoring by gown and finger print test
after completion of the trial.
ii. Environmental Monitoring
-Environmental Monitoring of the clean room should be done as per standard Operating
Procedure.
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-RODAC test for surfaces like walls/floor etc. of the filling room and surfaces of the
filling machine.
-Monitoring of microbial counts in air shall be done by air sampler and settle plate tests.
-Monitor the environmental conditions for temperature, differential pressure, relative
humidity.
-Monitor the Non-viable airborne particle counts.
The area under vertical laminar air flow unit should meet the specifications of grade A.
Environmental and personnel monitoring result should comply with the acceptance limit
as written in Standard Operating Procedure for Environmental Monitoring.
6.3 Duration of media fill shift
Ampoules shall be filled for each run in duration of 9 hours per shift.
6.4 Preparation of Media

Dissolve 30 gm of TSB powder in 1 L. of pyrogen free (Distilled water) in a clean sterile
preparation tank ,mix thoroughly for 15 minutes to completely dissolve the powder and
then cool, check pH (7.3 ±2) then filter the media through 0.22 micron sterile filter
Note:
 Store the sterilized tank filled with media under LAF till it is used. The media
preparation and sterilization will be done in presence of Microbiologist.
6.5 Method of growth promotion test
Objective of the test: To ensure that media used for the media fill test is capable
of microbial growth promotion during and after incubation period.
Test method : according to Sop No . WI-10-038.

Acceptance Criteria: Media inoculated with microorganism should promote growth of
microbes and un-inoculated media should remain sterile.
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6.6 Component preparation
Components i.e. Ampoules, machine parts are washed, sterilized, dried and transferred to
Ampoules filling room under mobile LAF. Following SOPs are applicable:
Operation SOP No
Sterilization and Drying for Ampoules WI-09-027
Cleaning of filling machine parts WI-06-010
Steam Sterilization of Filling Machine Parts and tanks WI-06-013
Washing and sterilization of Garments WI-09-107
Sterilization of Garments WI-09-027
Sterilization Holding time for : amp.s is 7 days , machine parts is 5 days , tanks
is 5 days , garments is 4 days.
6.7 Media fill operations

a. Obtain the line clearance before starting filling operation of the batch as per
Standard Operating Procedure for any leftover Raw Material, Ampoules of
previous batch.
b. Check the area and machine for cleanliness.
c. Check the temperature, Differential Pressure and Relative Humidity of
liquid filling Room.
d. Take 300 ml sample from the bulk before filtration for Bioburden.
e. Take 200 ml media from receiving tank in a sterile conical flask
for sterility test and 300 ml for growth promotion test.
f. Transfer tank-containing media to filling room. Connect volumetric

liquid filling assembly with the tank.
g. Transfer the sterilized machine parts to filling room and assemble the
machine parts
h. Check and ensure that all media filled containers are free from microbial
growth / turbidity.
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i. Adjust the liquid doser.

j. Operate the machine at minimum, maximum and normal production speed.
k. Divide the media filled amp.s in containers and label them. Invert the
ampoules so that the media comes in contact to all the inner surfaces.
l. Following sequence will be followed for normal operation:
 Ampoules from AMPOULE washer Outlet  Oven  TurnTable  Media fill 
SEALING  Visual inspection  invert the Ampoules  Incubation  Ampoules
upright  Incubation.
m. Collect these filled Ampoules in trays identify the trays with number and
time of filling. Invert the Ampoules so that the media comes in contact
with all the inner surfaces.
n. After completion of filling obtain line clearance from In Process QA
chemist.
 Important requirements:
a. Contrary to the regular fills, Ampoules with high and low fills, particles, cap
defects, etc., will be included as part of media fills. Ampoules will not be
discarded unless they are cracked, broken, or not properly filled.
b. The duration of media fill runs should simulate the normal production shift.
c. Sanitize the fill line surfaces such as conveyor belt, and the other machine parts
that are not subject to autoclave, by wiping with 70% Sterile Isopropyl Alcohol or
Ethyl Alcohol.
d. The inspection log sheet in the batch record will list the Ampoules and box
number of media filled Ampoules.
e. Sterility test samples will be pulled after filteration and during filling.
f. Growth promotion samples will be pulled after filteration and at the end of
incubation.
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 Following are the reasons to invalidate the media fill:

a. Failure of growth promotion test of media.
b. Failure of sterility test of media.
c. After the initial qualification, one (1) media fill will perform semi-annually.
This stipulates that there were no changes in normal production procedures
and no action limits were exceeded.
d. The media fill start time, break period start and end time, and media fill
completion time will be recorded.
7 INTERVENTIONS
7.1 Routine interventions
1- Machine set up
2- Initial fill weight adjustment.
3- Operator’s interventions inside grade A machine.
4- Environmental monitoring.
5- Operator shift changes.
6- Stopping of the machine.
7- Simulate the worst case condition in the filling room during media fill by increasing the
number of personnel including (E.C. personnel and engineering personnel)
8- Product sampling.
9- Tank change.
10- Fill needle adjustment.
11- Removal of dropped filled and unfilled Ampoules from the turn table and from the filling
line.
12- Jammed, fallen and broken Ampoules.
13- Ampoules feeding.
7.2 Non-routine interventions
1- Maintenance by engineer.
2- Electrically adjustments (Shut down of HVAC for 60 seconds)
3- Fill pump manifold replacement.
4- Fill needle replacement.
5- Mechanical adjustment (low speed)
6- Mechanical adjustment (fast speed)
7- Holding the door of the filling machine for two minutes, the machine will stop
automatically during this period.
8- Simulate the interlock failure by switch off the interlocking system for 2 minutes.
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8 Media Fill Procedures
-The machines will be stopped in time intervals to cover the shift duration time.
-Ampoules will be removed from the fill line if the following occur:
Ampoules with no media.
Ampoules with no seals or defective seals.
-After the filling & SEALING operation, examine each Ampoules for clarity, glass
defects. Reject the Ampoules found defective. Number the inspected Ampoules with
marking pen with sequential numbers starting from one (1) after inspection and
arrange the Ampoules in boxes. Label the boxes with lot number, number of
Ampoules inside the box, fill date and sequential box serial number. Deliver the
boxes to microbiology laboratory for incubation.
After each fill, remove pistons, tank and needles and sterilize for the next usage & major
cleaning & fumigation to prepare the unit for production work.
The media filled containers will be incubated.
Visual inspection will be performed during incubation period on the last day of each 7-
days period. Inspection will be performed by QA/QC personnel and will be recorded.
9 PERSONNEL INVOLVEMENT
9.1 During Media filling operation 3 persons will be present inside the filling room.
All persons involved in routine initial qualification should be included in any one of
the following critical aseptic operations in the trial:
a. Unloading of machine parts from steam Sterilizer
b. filtrate of RM
c. AMPOULE filling machine assembling and setting
d. AMPOULE filling operation.
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9.2 To simulate the worst case conditions in the filling room during media fills, the
number of personnel to participate during the media fill operations will be increased
more than in the normal operation:
NORMAL OPERATION
Filling room Production Environmental control Engineering max .no.
Grade A Filling Room 2 1 0 3
MEDIA FILL
Filling room Production Environmental control Engineering max .no.
Grade A Filling Room 2 1 1 4
9.3 All persons involved in routine filling operation should involve in media filling
operation over a period of 1 year
9.4 One Microbiologist (QC), qualified to enter into critical area, will enter into critical
area for area monitoring, personnel monitoring and sampling. All microbiologists
involved in sampling and environmental monitoring during normal manufacturing
periods will take part in system simulation run over a period of one year.
9.5 The maintenance personnel, qualified to enter into critical area, shall be required to
enter the critical area.
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9.6 The following are the minimum requirements for operator

Certification of :
 Gowning training.
 Gowning certification.
 Aseptic conditions training.
 Medical checks.
 Operators are required to participate in at least one media fill per year for annual
certification (except initial media fill).
 Operators trained to perform setup of fill line must also perform setup of fill line
for media fill.
 The time required for simulating the fatigue of personnel in the clean room is 3
hours as maximum.
 All the employees entering the filling room will require to be monitored for finger
and growing microbial test.
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10 INCUBATION OF AMPOULES
10.1 Incubation at (20-25°C)
 Ampoules should be put inverted.

 Transfer the properly identified trays containing media filled
Ampoules into the incubation room.
 Maintain the room temperature at 20-25°C for 7 days.
 After 7 days of incubation at 20-25°C observe each ampoule
visually for any type of growth/Turbidity.
 Identify the Ampoules with growth/turbidity (if any) and send
these to microbiology laboratory for further investigations.
10.2 Incubation at 30-35°C
 Ampoules should be put upright.

 Maintain the temperature of incubation room at 30-35°C for
next 7 days.
 After 7 days of incubation at 30-35°C observe each ampoule
visually for any type of growth/Turbidity
 Identify the Ampoules with growth/turbidity (if any) and send
these to microbiology laboratory for further investigations.
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11 Actions taken in case of system simulation failure
In the event of any one or more trial results out of three trials fails in the test for sterility,
before starting product campaign, following actions will be taken.
Characterisation of microorganisms up to species level, shall be carried out to find out the
source of contamination.
Review of following records prior to system simulation trial failure after the failing batch
processing is carried out:
a. Environmental records for manufacturing and testing area for temperature, relative
humidity, differential pressure and non-viable particulate counts.
b. Microbiological monitoring, reports of manufacturing and testing area for settling
plate, air sampling, surface monitoring and personnel monitoring.
c. Sterilization records for garments, filters, Ampoules, machine parts, media etc.
d. Filter integrity record air supply filters.
e. WFI monitoring records.
f. Cleaning and sanitizing records.
g. Batch records of system simulation trials to find out the sign of any failures or
abnormalities.
h. All other points mentioned in SOP for investigation will be included for
investigation.
Based on the above review, the most likely cause of failure will be identified and an
action plan will be made to avoid such occurrence in future.
The area will be monitored
All three such trials should pass as per the acceptance criteria for sterility.
Note: No commercial production batches will be produced till media fill runs pass as per
acceptance criteria.
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11.1 CORRECTIVE ACTIONS
- If any positive unit (s) is/are identified such that an action level is reached, an investigation will be
performed and documented.
-The investigation will include but not be limited to the following:
a) Microbial environmental monitoring data.
b) Particulate monitoring data.
c) Bio burden data (Prior to pre-filtration and prior to final filtration).
d) Personnel monitoring data (finger impressions, etc.,).
e) Sterilization for media, equipment and commodities.
f) HEPA filter evaluation (airborne particle levels, smoke challenge testing, velocity measurements,
etc).
g) Room airflow patterns and pressures.
h) Operator techniques and training.
i) Unusual events that occurred during the media-fill.
j) Storage conditions of sterile commodities.
k) Identification of contaminants.
l) Calibration of sterilization equipment.
m) Pre- post- filter integrity test data.
n) Product and/or process defects, and/or limitation of inspection process.
o) Documented disqualification of samples for obvious reasons prior to final reading.
A. When action levels are exceeded: The investigation will include a prompt review of all appropriate
records relating to the aseptic production lots between the current media fill and the last successful
media fill. The filling room will immediately placed out of service and an “Out of service” tag will
be placed by the entrance of the filling room. A written notification will be distributed by quality
assurance to management.
B. When action level is exceeded, routine production will not be resumed until acceptable media test
run results are achieved.
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12 Documentations
The following documents shall be maintained in one binder.

 Summary report of Media fill trial :
For each media fill qualification, a summary report will be written and reviewed, which will include
the following information:
 Approved Validation protocol.
 The date, time duration, and lot number of the media fill
 The names of the participants in the media fill
 The number and size of Ampoules filled as well as the target volume of media used
 Container/closure type and size
 Type of media filled
 Number of units rejected at inspection and reason
 Number of operators requalified
 Number of shifts
 Number of units incubated
 Number of units positive
 Incubation time for each group of units incubated
 Temperatures during the incubation
 Environmental and personnel monitoring report of the critical area during the trials
 Identification of the micro-organisms from any positive units and investigation of any
contamination events observed during media fills .
 Recommendation for the corrective action [if any] required
 Analysis of experimental results of the trials
 Fumigation certifiate
 Executed Batch Production Record for System Simulation Test ( Media Fill Trials).
 Summary and Conclusion duly approved by Head of the Quality Assurance Department.
The observations during the system simulation test (Media fill trials) should be recorded
in the system simulation test record and its attachments.
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13 CONCLUSION
Acceptable result of all media runs will establish the suitability of Standard Operating
Procedure for area cleaning and disinfection, cleaning and sterilization of component,
aseptic transfer of component, raw material and primary packaging material, Environmental
control system for temperature, Relative Humidity, Differential pressure and viable / non-
viable particulate load and finally the training and practices of person.
14 FINAL APPROVAL
Name/designation Signature Date
Prepared by
Validation dept. head
Checked by
Production dept. head
QC dept. head
Approved by
QA dept. head
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EGYPTIAN INTERNATIONAL PHARMACEUTICAL INDUSTRIES COMPANY (EIPICO)

Validation Title: Media Fill test Protocol No.: SST-I4U4-6-22

Media Fill Protocol

IMA 4 for normal ampoule

Location: unit 4 sterile liquid department

INITIAL DOCUMENT APPROVAL

Production Manager Dr. Maher Rasmy

Validation Manager Dr. Fathy El-Abd

QC manager Dr. khaled salah

QA manager Dr. Amira Nasr El-Din

ii Validation Team Signature List

Function Name Signature Date

QA department head Mohamed Hossam

Microbiology specialist A.Magdy

Production Hani Abo Bakr

Validation unit head Mohamed Abdel-Salam

iii Revision Control

Revision Issue Date Cause of revision Author

1 MEDIA FILL PROTOCOL GENERAL INFORMATION

1.4 RESPONSIBILITY MATRIX

1.4.1 Manufacturing departments will be responsible for the following:

1. Conducting the outlined procedure.

1.4.2 The Microbiology and Environmental Control department will be

1.4.3 Qualified operators from production are responsible for:

1.4.4 The validation department is responsible for:

3. Compile final report.

1.4.5 The Quality assurance Department shall be responsible for:

1.4.6 The Engineering Department shall be responsible for the following:

1.4.7 The QC sampling department will be responsible for the following:

 USP General Chapter (797), pharmaceutical compounding, sterile

Three consecutive separate successful media fill runs prior to

Unscheduled revalidation (minimum of 3 consecutive successful media-fill runs).

1.7 ACCEPTANCE CRITERIA

1.8 QUALIFICATIONS REQUIRED BEFORE STARTING THE TEST

COMPARISON BETWEEN NORMAL OPERATION AND MEDIA

ITEM NORMAL PROTOCOL MEDIA FILL

Minimum: 14,000/hr Minimum: 14,000/hr

Batch size 160000 30000

E.C. All E.C. activities All E.C. activities

GENERAL PROCESS FLOW CHART FOR AMPOULE

Bulk Preparation in a suitable

Sterilizing filtration by using

Receiving of filtered solution

Sterilization of the empty

PROCESS DESCRIPTION FOR AMPOULE

3.1 Ampoule sterilization

4.1.1 Approved Ampoules are de packed .

3.2 Raw material transfer and preparation

4.2.1 Approved RM (Tryptic soya Broth) is transferred from stores.

3.4 Filling area

3.5 Sealing ampoules

4.5.1 The filled ampoules will be sealed on time .

4.6.1 Temperature of filling area is maintained 22 0C ±2

3.7 Visual inspection of filled ampoules

4 BRIEF PLAN FOR MEDIA FILL

5.1 Batch size (L) : 60 L.

6.1 Pre-validation checks

6.2 Checks during the run

6.3 Duration of media fill shift

6.4 Preparation of Media

6.5 Method of growth promotion test

Test method : according to Sop No . WI-10-038.

6.6 Component preparation