Sterile & Non-sterile products need control of micro-organisms throughout the manufacturing process & facility

1. Microbiology; A Critical Area
Sterile & Non-sterile products
need control of micro-orgranisms throughout
the manufacturing process & facility
Obaid Ali, R. Ph. M. Phil., Ph. D.
24 Feb 2019, ICCBS, University of Karachi

2. It reflects the views and understanding of presenter
& may not be construed to represent the views or
policies of organization or association to which
speaker has ties
Documents of US-FDA & Review Scientific
Articles are used to construct presentation
Disclaimer
Reference

3. Product Quality Microbiology

4. Manufacturing
process
Microbial Process
Control
Finished product
quality attributes
Sterility assurance
supporting validation
studies
Sterility, Endotoxin,
Bio-burden, Container
Closure Integrity, Anti-
microbial Effectiveness
Bio-burden Testing,
Filter Integrity Testing,
Environmental
Monitoring

5. Make & keep it easy to understand,
logical & simple to assess
Tell them how your
validation data
supports commercial
production

6. Common Deficiencies
1. Validation of Pre-Sterilized Equipment
2. Media fill Process Simulation
3. Drug Product Endotoxins Testing
4. Extended Storage Time after reconstitution

7. Common Deficiencies
Validation of Pre-Sterilized
Equipment
Lack of sterilization validation for pre-
sterilized, commercially available filling or
filtration components for e.g. holding bags,
filters
Issue

8. Common Deficiencies
Validation of Pre-Sterilized
Equipment
Clearly indicate who is responsible for
sterilization of system
Indicate you or cross refer to DMF
Consideration

9. Common Deficiencies
Validation of Pre-Sterilized
Equipment
Avoid deficiencies concerning the content
of equipment loads
“Worst case load” is not descriptive enough
Why

10. Common Deficiencies
Media Fill Process Simulation
Comparison of media fill simulation
conditions to production conditions missingIssue

11. Common Deficiencies
Media Fill Process Simulation
Describe how media fill conditions
simulate production/ worst case processConsideration

12. Common Deficiencies
Media Fill Process Simulation
Avoid simple deficiencies requesting
Maximum filling duration
Filling speed
Routine, non-routine interventions
Container size & type
Why

13. Common Deficiencies
Drug Product Endotoxins Testing
Pooling samples results in additional
dilution equal to number of pool samples
should only one sample exceed the
endotoxins limit
Issue

14. Common Deficiencies
Drug Product Endotoxins Testing
Pooling is acceptable but should
be justifiedConsideration

15. Common Deficiencies
Drug Product Endotoxins Testing
Ensure test method ability to overcome
potential product related interference or
enhancement
Why

16. Common Deficiencies
Extended Storage Time after
reconstitution
Lack of microbiological studies in support
of post constitution/ post dilution storage
time specified on label
Issue

17. Common Deficiencies
Extended Storage Time after
reconstitution
Provide risk assessment including
microbiology challenge study data to
support the post penetration holding
parameters to demonstrate that final solution
do not support microbial growth during
storage
Consideration

18. Common Deficiencies
Extended Storage Time after
reconstitution
Add challenging organism (< 100 cfu/ml)
Incubate at specified storage temperature
Collect the sample at specified storage time,
intermediate time & extended storage time
Study Design

19. Common Deficiencies
Extended Storage Time after
reconstitution
Understand the risk associated with product
labeling with regard to in-use stability and /
or diluent compatibility claim
Why

20. Thank You