Professional Documents
Culture Documents
Luisa Stoppa
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:aseptic process
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washing machine
depirogenating tunnel
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stoppering machine
filling machine
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3000
4750
6300
7750
9150
10510
11840
13150
14430
15710
16960
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Health Canada
Contamination
The root cause of a failure (contamination), or at least the most
probable one, must be identified
It is important to be able to isolate and identify (to species level) the
microorganisms
An appropriate corrective action / preventive action plan must be
implemented
The impact of the failure on product lots already released (if any)
must be evaluated
After the corrective actions have been implemented, a new media fill
study is performed to confirm their efficacy
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Contamination
Contamination rate
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Contamination
Contamination rate decreasing during filling
Contamination rate
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Contamination
Contamination spike during filling
Contamination rate
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Contamination
Contamination spike followed by an increase
Contamination rate
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Contamination
Contamination rate
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Contamination
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Contamination
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Conclusion
Even if all media fills are negative in a Company, it does not
necessarily indicate that no products were ever possibly
contaminated because the frequency requirement of media fill testing
is so minimal that it is not statistically significant
A robust media fill programme is a necessary step to validate process
Media fill testing is just one part of a necessary overall quality
assurance program (HVAC qualification, cleaning procedure,
sanitization, personnel training, )
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l.stoppa@aifa.gov.it
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Reference documents
WHO GMP guidelines Technical Report series n. 937
EU GMP guidelines, Part I annex 1 & 15
ICH Q7A or EU GMP Part II chapter 13
FDA Guidance for Industry: sterile drug products produced by
aseptic processing cGMP
PIC/S Recommendations PI 007-5
USP <797> media fill testing / <71> growth promotion test
EP 2.6.1 sterility
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