Hii,
Can someone help me design and execute a Media Fill Qualification for our dry powder injectable line - line need be ready for operation two to three months from now and I have no experience on this.
Thanks for your help.
J Musumba.
1 Like
where are you from?
This is a comprehensive protocol. You can use it readily.
You have to have your SOP’S, Documents at place and all the controls pertaining to IQ,OQ,PQ of Facility, Equipment. You should have all the training records of the competent technical staff, QA/QC, Engineering should be in place as they participate in this media fill validation.
You can modify this document as per the machine and equipment you use.
Your environmental monitoring methodology should be sound and robust.
Your microbiology lab ought to be well equipped and you should have a competent microbiologist.
Media fill validation or Aseptic fill validation is a team work.
If one element or system or individual has a flaw the entire program will be delayed and at times will have a negative result.
You must have check lists at each and every place.
I expect questions from you folks who use this documents about regulatory issues and interventions.
Questions are always welcome. But please let me know in which continent or country you work from so that my replies are applicable to your case.
Best of luck to you all.
Regards
ASEPTIC MEEDIA FILL.doc (186.5 KB)
CHECK LIST: before media fill
A. WASHING AREA
- Cleaning of compressed air filters.
- Cleaning of DM water storage tank.
- Setting of vials washing machine.
- Fixing of filters of down-flow unit and to check working. Adjust manometer oil to zero.
If HEPA is removed, check PAO test and air velocity. - Keep SS boxes washed with DM water.
- Fix cleaned DM water filters in respective housings.
- Check all tubing, if required, change them.
- Cleaning of split AC filters.
B. RUBBER STOPPERS TREATMENT
- Get the washing machines cleaned thoroughly.
- Check connections of steam and DM water line.
- Clean SS Pall filter, GS filter and fix in-line.
- Clean SS pots and lids.
- Clean distilled water storage tanks and 20 Lt. capacity pressure unit.
- Keep in the area, plastic containers required to soak the stoppers.
- Clean membrane holder assembly and refill it.
- Fix filter of air down-flow unit and check working. If HEP A is removed check DOS test and air velocity.
- Set manometer oil level up to zero.
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Check availability of Benzalkonium Chloride & Hydrochloric Acid in washing area.
C. STERILIZATION
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Clean, dry and connect distilled water storage tank.
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Check working of thermostatic control.
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Run distilled water plant for 2 - 3 hours and discard the collection.
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Check leakages if any during run of distilled water plant. Check water conductivity.
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Get chemical analysis of distilled water done.
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Check rate of distilled water collection per hour.
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Check cleaned SS Pall filter is fixed to the DM water inlet before running the plant.
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Check working of autoclave thermograph. Check inkbottle for sufficient quantity of ink.
If possible,calibrate thermograph timer. -
Normal servicing of autoclave is done by vendor.
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Run autoclave for 30 minutes and observe any leakages through steam valves, door gasket & joints Check working of dial thermometer.
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Check fixing and conditions of air in-let filter.
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Check working of pressure gauges.
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Clean the autoclave with distilled water and Benzalkonium Chloride solution before operating.
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Clean carriage of sterilizer chamber with vacuum cleaner and then with distilled water and sponge.
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Clean carriage of sterilizer with diluted Hydrochloric Acid and then with water.
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DOP test of HEPA filter module and air velocity.
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Run dry sterilizer empty at 300°C for 1 hour to check its heating and cooling functions.
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Check working of thermograph for temperature and time and working of HEP A filter after heating cycle.
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Checks working of inter locking system of autoclave and dry sterilizer.
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Check hot air leakages through door gasket.
D. FILLING ROOM
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PAO test, smoke test for HEP A filter and air currents.
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Cleaning of area with disinfectant solution at least twice. Preferably use 0.5% Cetremide Solution
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Wiping of all equipment surfaces with 70% IPA
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Working of LAF units. Set manometer oil to zero.
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Keep back materials removed from sterile area.
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Replace all UV tubes after noting intensity.
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Provide new slippers for operators.
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Check working of conveyor & filling machine.
- Check grease in filling machine.
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Check all nitrogen, oxygen and LPG gas lines for working and leakages. Check all gas lines are
correctly identified. -
Check the pressure of room and change rooms.
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Check temperature of filling room.
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Replace old sponge used for wiping foot soles in first change room.
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Calculate air changes per hour from velocity of air through each terminal HEP A filters.
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Open all return air riser dampers.
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Check working of fumigation switch and hot plate.
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Get area cleaned with 0.5% Aarshol again before starting fumigation.
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Check working of down-flow unit, portable laminar including DOP test and air velocity.
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Check working of ampoules filling machine if required.
E. SEALING ROOM
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Run machine without vials for few minutes. Observe any abnormal sound.
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Take trial of2 ml vials sealing.
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Lubricate the machine and keep ready for use.
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Thoroughly wipe and clean vibrator with 70% IP A
F. INSPECTION ROOM
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Keep batch record, in inspection room.
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Remove labels of the product other than those that are under inspection.
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Take trial of machine without vials.
G. LABELLING ROOM
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Keep batch and labels ready for labeling on the first day of the start up.
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Keep about 3.0 Kg. Gum Acacia in container.
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Remove previously labelled products from area.
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Check all accessories required for labeling.
H. PACKING ROOM -
Keep packing materials, batch ready for packing.
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Check all accessories required for packing.
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Confirm line clearance before packing start up.
media qualification annexure
Regulatory Requirements
The key regulatory documents covering these aspects for the aseptic operations are the European GMP, Annex I and the FDA Guidance “Sterile Drug Products Produced by Aseptic Processing,” except 21 CFR part 210 and 211.
However, none of these guides clearly define what the mandatory requirements are in case the campaign approach is used and particularly for specific topics such as maximum accepted duration.
Although there are no specific requirements, some concepts are frequently discussed in these documents and can help to clarify the expectations of the main Regulatory Authorities. FDA recommends that “Factors associated with the longest permitted run on the processing line that can pose contamination risk” are addressed during Media Fill program and “When appropriate, time limits should be established for each phase of aseptic processing”… and these “limits should be supported by data”.
EU GMP (Annex I) similarly states that "The interval between the sterilisation and use of components, containers and equipment should be minimized and subject to a time-limit appropriate to the storage conditions".
Role of Media Fill :
“Aseptic Process Simulation” (also called Media Fill) is considered as the validation of the aseptic process, but actually is more a demonstration of the appropriate capability of the aseptic process through a detailed challenge of all operational conditions that could affect the sterility of the product.
The main focus of the study should be operator’s interventions because contamination is largely personnel activity related, but it’s also important during the process simulation to assess other critical factors such as machine assembly, handling and storage of components, surrounding environment, number of personnel admitted during production and their activities’ length of production.
All the above factors can contribute to the robustness or the weakness of the whole aseptic process and need to be fully investigated prior to the design of the Media Fill and considered and challenged during the study.
Interventions can be categorized as inherent because integral part of the process or corrective to fix problems. Whilst corrective interventions should be avoided during production and accepted as exception only if supported by robust procedures and validation data (e.g. exposed products protected by appropriate Unidirectional Air Flow, interventions successfully tested during Aseptic Simulation, manual/automated rejection of filled units potentially impacted during the intervention), inherent interventions need to be accepted as part of the whole process.
Good one ! Detailed Media fill …really going to be useful for all.
I would like ask, can i only do one batch of media fill every six months after I already initially completed a three-batch media fill for aseptic filling? Thanks a lot!
[b]Media filling is an assurance system protocol that all the systems and processes in the lines are working as per the guidances and with in the ranges that comply the Sterility Assurance Levels (SAL).
You have a predetermined media fill protocol as per your VMP and you will perform the test at such intervals.
In case of sterility failures which are repeating and as per the route cause study if they find in investigation that it might be one of the causes (Might be a lack of a proper handling training in aseptic areas) you woould perform this protocol based on emergency situations to find out the flaws.
So there is no hard and fast rule that it must be performed every 6 months once. Incase of failures it must be performed to evaluate the SAL of production suite, processes and product equipment.[/b]