SOP For media fill run is described in this post which you can follow in the section of the Quality Assurance Department.
INTRODUCTION
Media fill run is simulated filling run for sterile powders and liquid products. The media fill is conducted which is a liquid that promotes microbial growth and the study is designed to provide evidence that all of the numerous factors that affect the sterile environment are under a state of control; such factors include (but are not limited to) environmental system design, operation, and maintenance, component preparation, product preparation and personnel training.
OBJECTIVE
The objectives of this validation study is to
Ensure and justify, through continuous process monitoring, and documentation, the precision and consistency in the output against the already established Acceptance Criteria.
Identify and solve the problem(s), if any, encountered during the process.
Establish confidence on existing sterile filling operation.
Find ways and means to improve quality.
Assure that complete process is under control.
SCOPE
This protocol is intended to prove through documented evidence that the current process for sterile filling is under control and capable of producing reproducible, reliable and consistent quality product.
To describe the phases of validation dealing with various stages of critical process of filling to ensure that the sterilization process is up to the mark.
PRECAUTIONS
The media used in trials is intended to detect very low levels of contamination.
Upon completion of the media fill trials, the filling parts and any media spills in the sterile area to be thoroughly cleaned, which should be confirmed by the microbiologist and production supervisor.
Comply with current Good Manufacturing Practices (cGMP) throughout all phases of the validation
MATERIAL REQUIREMENT
Soybean-Casein Digest Medium ( SDM)
Sterile Polyethylene Glycol (PEG 8000) powder required for the powder fill media trials for dry powder injectables.
A sufficient quantity of containers, stoppers and seals to fill at least 3000 containers (vials) for each trial.
Required microorganisms for growth promotion test.
BULK MEDIA PREPARATION
The SDM medium is to be prepared according to the supplier’s instruction, using either WFI or distilled water for liquid and powder media fill. The liquid media will be sterilized by steam or sterile filtration, the media may be prepared in 15 liter quantities or as required
PREPARATION OF COMPONENTS AND MACHINE PARTS
All processing of the components and parts is to be completed according to current production standard operating procedures. For powder filler trials using polyethylene glycol ( PEG) powder, suitable liquid filler for the disposing of media is to be temporarily installed on line either after (preferred) or prior to the powder filler.
FACILITY AND EQUIPMENT SETUP
The facility is to be properly cleaned and sanitized prior to initiating the trial in accordance with SOPs.
Carefully connect the sterile media to the filler under laminar flow protection. Use special care to prevent contamination of the tube when connecting the bottle to the filler.
The filling line is to be set up in accordance with production standard operation procedures.
For liquid media fills, the fill size is to be based on that used for product (preferred) or at least 10 % of the total capacity of the container.
For powder media fills, the amount of liquid which is used into the containers must represent at least 10% of container volume and a minimum of 100 mg of PEG powder will be used for every one ml of liquid media.
For the powder fill trials using PEG powder, approximately 50 containers of media only (no PEG powder) are to be filled prior to the initiation of the trials. The liquid filled containers will be included with the powder filled containers when calculating the overall percentage. These containers are to be clearly labeled to ensure segregation from the actual trial containers containing media and the PEG powder
CONDUCT THE MEDIA FILL TRIALS
The sterile media fill trials are to be representative of normal production operation and include the following conditions:
Fill sufficient containers to ensure that a minimum of 3000 containers (vials) are available for incubation.
The line speed, used for the media fill will be approx. half the normal production speed.
After filling 1500 containers, an employee break will be observed, i.e. people leave and re-enter the sterile area prior to fill the remainder of the required number of containers.
A line stoppage will be intentionally performed during the second half of the run.
MONITORING
As an added precaution for powder fills, sterility testing may be performed prior to the trials on the 50 gram sample PEG powder that is provided.
A sterile PEG 8000 retains will be kept for investigational purposes.
Observe liquid media for 72 hours.
INCUBATION AND TESTING OF THE MEDIA FILLED CONTAINERS
The media filled containers are to be carefully inverted and rotated so that all surfaces have contacted with media. Container will be incubated upside down so that media remains in contact with the stopper as well.
The media filled containers are to be incubated for 07 days at 30 – 35 °C and 7 days at 20 – 25 °C.
The media filled containers may be examined daily prior to completion of the 14 days incubation period, and placed back in the incubator after examination.
The media filled containers are to be inspected by trained operators by holding the containers up to the light and gently swirling. Presence of turbidity, sedimentation, or flocculation indicates microbial growth.
At the end of 14 days, all of the containers are to be inspected and total count per trial is documented. All the failures are to be documented and growth promotion testing is successfully completed, the media filled containers may be discarded. All positive containers will be sent to the appropriate laboratory to be identified to the species level when possible.
GROWTH PROMOTION TESTING
Growth promotion testing of two (2) media filled containers using required microorganisms is performed. The number of organisms used for each test is to be between 10 to 100 cfu / ml. The media filled containers should be actual samples from the trial that are sterile (non- turbid) after 14 days. The actual growth promotion test is to last a maximum of seven (7) days.
Results of the growth promotion tests: there is to be at least two positive control samples. All failure must be fully investigated to determine the cause of failure.
FOLLOWING
IS THE ACCEPTANCE CRITERIA
|
Trials |
%
contamination |
Results |
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Trial 1 |
Not more than 0.1% More than 0.1 % |
Accepted Go to trial 2. |
|
Trial 2 |
Not more than 0.1% More than 0.1 % |
Accepted Go to trial 3. |
|
Trial 3 |
Not more than 0.1% More than 0.1 % |
Accepted Rejected. |
% of contamination = Number of un-damaged contaminated containers X 100
Total Number of Containers.
NOTE:
A minimum of 3000 containers will be used for each trial.
A minimum of one media fill trial is to be performed every one year for each validated filling operation.
Routine media fills be conducted in such a manner that all production personnel participate in media fill operation.
The sterile media fill trials are conducted based on the manufacturing procedures.
For sterile media fill trials soybean-casein digest media and for sterile powder filling validation, sterile polyethylene glycol 8000 will be used.
FREQUENCY:
INITIAL VALIDATION = ONCE
REVALIDATION = ANNUALLY
APPROPRIATE VALIDATION TEAM WILL PREPARE A VALIDATION REPORT ACCORDING TO THIS PROTOCOL.
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Identification
of Responsible Personnel: |
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Name
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Job Title
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Signature
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Microbiologist |
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Q.C.
Analyst |
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Senior
QA inspector |
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Production
Officer |
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