The document discusses the investigation of sterility failures, emphasizing the need for a structured approach involving thorough laboratory and process investigations. Key points include preparing an action plan, avoiding assumptions, and documenting observations, while considering laboratory conditions and personnel practices. Factors contributing to sterility failures include compromised container integrity, improper aseptic processing, and environmental monitoring data.

1. Sterility Failure Investigation

2. ● Assessment of whether a
product is free from
contaminated
microorganisms.
Sterility test

3. Sterility test
-Advantages
-Limitations

4. Keys points to be considered for sterility failure
investigation
● Do not panic
● Prepare a sound action plan
● Involve all the stake holders
● Make no assumptions and keep an open mind
● Document everything

5. ● Sterility test observation
● Laboratory investigation
● Process investigation
● Conclusion
Sections:

6. Sterility test observation
● Observation method
● False positive
● Negative control results

7. Sterility Failure Investigation
Laboratory investigation Process investigation

8. Laboratory
investigation:
Initiate OOS (out of specification):
● Verification of negative control data
● Detailed of sterility test method examination
● Interrogation with Analyst
● Cleaning and sanitization records and interrogation
with operator
● Environmental monitoring data
● Identification of isolates
● Reporting of any other abnormalities

9. Laboratory
investigation:
Condition of sample upon receipt
Material and sample handling/transfer from non
classified area to sterility testing area
Analyst qualification (operator history)
Environmental conditions of sterility testing area

10. Laboratory
investigation
Environment monitoring data
review
Trending of EM data:
● Increased number of viable
microorganisms in critical areas
● New or unusual isolates in facility
● Increase in baseline of Microbial
load
● Disinfectact efficacy/resistance
against organisms

11. Laboratory
investigation
Bacterial endotoxin
test results
Bioburden test results

12. Laboratory
investigation
Maintenance work in
sterility testing area
Area physical
condition
CCTV verification

14. Laboratory
investigation:
General causes:
● Cracked Media container
● Personnel practices
● Cleaning and sanitization practices as well as
Transfer of articles/media from non classified area
to classified area

15. Process
investigation
Compromised container integrity
Improper aseptic processing and
facilities
Invalid sterilization processes
Environment monitoring data of
production area
Production personnel training and
history
Cont...

16. Process
investigation
Review of production history
(including media fill)
Review of product Bioburden
Review of API and Excipient source
HEPA filter integrity review
Autoclave records
Factors as the type of product,
container, filling line, equipment
operation, operators involved,
interventions, environmental
sampling

17. Recommendations
Usage of isolator in place of
conventional Laminar air flow
for Sterility test

18. Without knowing the source of contaminating microbes, it is almost
impossible to arrive at a probable or definitive root cause.

19. Thanks!
Tapas Joshi
For Q &A:
Mail to
tapas.joshi86@gmail.com
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asjoshi86