Media Fill
Media Fill
Media Fill
(VALIDATION OF ASEPTIC
PROCESSES)
REFERENCES
Introduction.
Importance of Media Fill.
Process Simulation Test Procedures.
Process Simulation Test Conditions.
Interpretation of Data.
Environmental and Personnel Monitoring.
Staff Training.
Important Factors in Validation of Aseptic Manufacturing.
What is Media Fill
The more manual the aseptic process, the higher the risk.
Minimizing contamination
Items What we do to prevent microbial contamination
Vials Sterilized and depyrogenated with dry heat oven or tunnel
Rubber Closures / Caps Sterilized by autoclave
Chemicals Tested to be sure microbial contamination is within specification.
Water for Injection Held at high or low temperature and ozonated
miscellaneous small Sterilized by autoclave / Hot Air Oven
items (scissors, scoops.
Tweezers, etc)
Air Supply Air is especially filtered to reduce chances of microbial problems.
HEPA filters are tested regularly to verify efficiency.
Room and
HVAC Environmental
integrity Controls
“Aseptic
Processing and
Sterility Assurance"
Incident Processing
responsiveness Line
Integrity
Sanitation Product
Procedures Filtration
Media Fill
Validation
People & Aseptic Processing
People continuously shed microbes & particles into their
surroundings; cleanroom garments do not contain all of the
organisms present on human skin.
Principle:
Avoid interventions,
Where they are unavoidable, minimize their
impact.
Critical Surface or
5 aseptic connection Very High Every Fill Yes
Proximity to an open
4 container High Every Fill Yes
Principle:
Minimum: three (3) to qualify the line initially
Maximum: Enough to ensure that results are
consistent and meaningful.
Routine re-validation: each processing line every 6
months.
All personnel who are authorized to enter the aseptic
processing room during manufacturing should
participate at least once a year.
Participation should be consistent with the nature of
each operator’s duties during routine production.
Duration of a Media Fill?
The duration of the run should:
Simulate the expected maximum time for routine
manufacture
Include all production shifts.
Be dictated by the time needed to fill the required
number of units
Ensure that the necessary number of units and
activities are included.
The validated maximum run tome should be included in
batch records
Simulation Conditions - Media
Principle:
Optimize detection of any microbiological contamination.
Soybean casein digest medium (SCDM), should be used as it
promotes growth of gram-.positive and gram- negative bacteria,
and yeast and mold
Consider inclusion of anaerobic growth media (e.g., fluid
thioglycollate medium) if there is a relevant risk factor.
Need to consider production related isolates (use own
isolates).
Media must contact all of each unit (container and closure)
Incubation of Media-Filled Units
Principle:
Principle:
Optimize detection of any microbiological
contamination.
Soybean casein digest medium (SCDM), should be
used as it promotes growth of gram-.positive and
gram- negative bacteria, and yeast and mold
Consider inclusion of anaerobic growth media
(e.g., fluid thioglycollate medium) if there is a
relevant risk factor.
Need to consider production related isolates (use
own isolates).
Media must contact all of each unit (container
and closure)
Examination of Media-Filled Units