STANDARD OPERATING PROCEDURE
DEPARTMENT QUALITY ASSURANCE
AREA GENERAL
DESCRIPTION OF PROCESS SIMULATION STUDY
SUBJECT
MEDIA FILL
SOP NO. QA 0181-5
WRITTEN BY CHECKED BY APPROVED BY PAGE NO. 1 of 5
SIGNATURE EFF. DATE 02/04/2024
NAME REVIEW DT. 01/04/2026
DATE SUPERSEDED QA 0181-4
1.0 OBJECTIVE:
To lay down a procedure for description of process simulation study media fill.
2.0 SCOPE:
This SOP is applicable for process simulation study (media fill) in aseptic area.
3.0 RESPONSIBILITY:
Head – QA
Head – Production
Head – Quality Control/Microbiology
Executive - Engineering
4.0 PROCEDURE:
4.1 Process simulation study (Media fill) is carried out to simulate the whole aseptic process in order to
evaluate the sterility confidence of the process.
4.2 During the course of process simulation study (media fill) the documentation system, laboratory
controls, in process checks and filled vials shall be evaluated.
4.3 The process simulation study (media fill) methodology consists of following basis parts:
4.4 Media fill validation shall be done at the time of start up of production and then on- going runs. During
start up atleast three consecutive separate successful runs of different vials sizes shall be taken and
during ongoing simulation test single run twice in year shall be taken.
4.5 Media fill validation shall be done for one shift which shall not be less than 5 hrs.
4.6 The batch size of process simulation study (Media fill) shall not less then 5,500 Vials, during each run.
4.7 Line speed: Machine shall be run on following speeds during media fill activity;
First process simulation study (media fill) with slow line speed,
Second process simulation study (media fill) with optimum line speed and
Third Process simulation study (media fill) with fast line speed.
During periodic qualification, Media fill run shall be done at slow line speed and fast line speed.
4.8 Media selected shall be sterile soyabean casein digest media and sterile Lactose.
4.9 Preparation of Media shall be done by 3% w/v solution of SCDM and WFI is prepared by mixing 30 g of
SCDM in 1000 ml of WFI.
4.10 Following interventions shall be included during media fill for carrying out worst case study.
STANDARD OPERATING PROCEDURE
DEPARTMENT QUALITY ASSURANCE
AREA GENERAL
DESCRIPTION OF PROCESS SIMULATION STUDY
SUBJECT
MEDIA FILL
SOP NO. QA 0181-5
WRITTEN BY CHECKED BY APPROVED BY PAGE NO. 2 of 5
SIGNATURE EFF. DATE 02/04/2024
NAME REVIEW DT. 01/04/2026
DATE SUPERSEDED QA 0181-4
Routine intervention:
Machine parts assembly.
Transferring of material to filling room.
Open the entry door of powder filling room approx. for 02 minute.
Transfer the material to aseptic area through mobile LAF i.e. sterile lactose, sterile media solution,
RFU and RFS rubber bung.
Transferring of sterile lactose into hopper.
Transfer the RFU rubber bung into stopper bowl.
Transfer the RFS rubber bung into stopper bowl.
Fill weight adjustment.
Fill volume adjustment of SCDM during filling.
Compressed air dosing pressure adjustment.
Adjustment of line speed.
Removals of tilted/fallen vials from infeed turntable.
Removals of tilted/fallen, filled/unfilled vials from the out feed turntable.
Filled vials fallen & spillage of media.
Cleaning of infeed and out feed conveyor by stopping the filling machine.
Open the cabinet of vial filling machine.
Rubber stoppers chute adjustment.
Pushing of stopper in the stopper chute by sterile forceps.
Sterile gasses air sampling shall be done during the filling operation.
Improper gowning.
Changing of gloves during the filling operation.
Use of single gloves by the operators.
To perform minor maintenance job.
To perform in- process sampling.
Presence of maximum person in vial filling room i.e. 1 operators, 2 helper, 1 micro biologist, 1
production and 1 IPQA.
Tea break shall be simulated during the filling operations.
Lunch break shall be simulated during the filling operations.
STANDARD OPERATING PROCEDURE
DEPARTMENT QUALITY ASSURANCE
AREA GENERAL
DESCRIPTION OF PROCESS SIMULATION STUDY
SUBJECT
MEDIA FILL
SOP NO. QA 0181-5
WRITTEN BY CHECKED BY APPROVED BY PAGE NO. 3 of 5
SIGNATURE EFF. DATE 02/04/2024
NAME REVIEW DT. 01/04/2026
DATE SUPERSEDED QA 0181-4
Shift change over shall be simulated during media fill operations.
Monitoring of Non-viable particulate count during initial and end of the process.
Transfer of Flip of seal to sealing area by mobile LAF.
Collection of filled vials;
With tunnel high speed
With tunnel low speed
Monitoring of viable particle count;
By settle plate
By active air sampling.
Non routine intervention
Switch off the blower of LAF’s in critical area for 2 minutes during filling and bunging operation.
Power break down for 5 minutes (Maximum time required for generator to supply electricity in
case of power failure).
Temperature of tunnel below 330°c for 3 minutes.
Natural call for operators
4.11 Incubation conditions and examination of Media filled vials:
Incubation temperature should be 20-25 0C for 1st 7 days suitable for fungal growth.
For next 7 days the incubation temperature is 30-35 0C for bacterial growth.
First 7 days the vials shall be incubated in Up- right position and next 7 days vials shall be
incubated at inverted position.
4.12 Acceptance criteria:
4.12.1 When filling fewer than 5000 units, no contaminated units should be detected.
4.12.2 When filling 5,000 to 10,000 units:
a) One (1) contaminated unit should result in an investigation, including consideration of a repeat
media fill;
b) Two (2) contaminated units are considered cause for revalidation, following investigation.
4.12.3 When filling more than 10,000 units:
a) One (1) contaminated unit should result in an investigation.
b) Two (2) contaminated units are considered cause for revalidation, following investigation.
STANDARD OPERATING PROCEDURE
DEPARTMENT QUALITY ASSURANCE
AREA GENERAL
DESCRIPTION OF PROCESS SIMULATION STUDY
SUBJECT
MEDIA FILL
SOP NO. QA 0181-5
WRITTEN BY CHECKED BY APPROVED BY PAGE NO. 4 of 5
SIGNATURE EFF. DATE 02/04/2024
NAME REVIEW DT. 01/04/2026
DATE SUPERSEDED QA 0181-4
4.13 Container closure integrity test (CCIT) of post incubated vials shall be peformed after incubation of 14
days.
4.14 Frequency of validation: The frequency of Periodic Validation for Process Simulation Study (Media Fill)
shall be every six month (±30 days) for existing system.
4.15 Area Cleaning and environmental monitoring:
After completion of media fill activity, production team shall perform the area cleaning as per SOP no.
PR 0105 followed them environmental monitoring shall performed by microbiologist. This entire activity
shall be carried out three continuous days.
4.16 Left over media of pressure vessel and media of rejected vials shall be handle as per SOP no. QC
0424.
4.17 The pressure vessles, hopper, membrane holder and filling nozels shall be neutralize by 70% IPA
solution and sterilized them in autoclave cycle.
4.18 The post incubated media fill vials, rubber bung & seal shall be destroyed as per SOP No. QC 0424.
5.0 REFERENCE:
PR 0105:- Cleaning and sanitization of sterile area.
QC 0424:- Destruction of media fill vials
PIC/S guideline PI 007-6.
6.0 HISTORY OF CHANGE:
S. No. Ref. SOP No. Revised SOP No. Reason for the change Change request Ref. No.
1.0 QA 0181 - NEW -
Subtitles scope and
2.0 QA 0181-0 QA 0181-1 CRF/15/08
abbreviations added
Inclusion of Blending stage and
3.0 QA 0181-1 QA 0181-2 increase in number of CRF/16/15
interventions.
QA 0181-2 QA 0181-3 Media fill frequency revised to
4.0 CRF/19/09
carry out after every six month.
STANDARD OPERATING PROCEDURE
DEPARTMENT QUALITY ASSURANCE
AREA GENERAL
DESCRIPTION OF PROCESS SIMULATION STUDY
SUBJECT
MEDIA FILL
SOP NO. QA 0181-5
WRITTEN BY CHECKED BY APPROVED BY PAGE NO. 5 of 5
SIGNATURE EFF. DATE 02/04/2024
NAME REVIEW DT. 01/04/2026
DATE SUPERSEDED QA 0181-4
S. No. Ref. SOP No. Revised SOP No. Reason for the change Change request Ref. No.
The intervention has been
classified as routine and non-
routine intervention.
5.0 QA 0181-3 QA 0181-4 Procedure has elaborate. CRF/22/07
Typographical error has been
corrected.
6.0 QA 0181-4 QA 0181-5 Periodic Revision --NA--
7.0 LIST OF ATTACHMENT:
S. No. Detail of attachment Ref. No.
- - -
8.0 ABBREVIATIONS:
SCDM Soyabean Casein Digest Media
AHU Air Handling Unit
SWFI Sterile water for injection
QA Quality Assurance
CRF Change Request Form
CCIT Container closure integrity test
