Week 2 of Course on Regulatory Science of Sterile Manufacturing Process

1. Regulatory Science of Sterile Manufacturing Process
RSSMP- Week – Two
(1/4)
Roohi B. Obaid & Obaid Ali
29 July 2018 at Karachi

3. This presentation discusses Regulatory Science,
nothing more & nothing less
Reference: US-FDA Documents / Scientific Articles/
Real time hands on experience of Compliance & Enforcement
Personal point of view & nothing to disclose
Disclaimer

4. Discussion
• Science & good
science
Sharing
• Current
Knowledge &
Experience
Navigation
• Towards mutual
goal & Future
directions
Knowledge Sharing Exercise
To Learn through Debate, Discussion & Experience of others
Acknowledgement: Documents of US-FDA & PDA consulted

5. Lets think
How and up to what extent
Regulatory Authority will react?

6. Background
Sterile manufacturing facility
Working w/o terminal sterilization
Aseptic manufacturing was approved
Product was coming in market
There was no complaint
Regular inspection revealed ...

7. Findings
31 Contaminated units in one
MF
+1 … Units in another line on
MF
++ Sterility tests …

8. Findings
Repeat test & found result negative
Evaluated the entire video of MF
Various breaches identified …
Set up, Filling & Changing of tank
Investigation was closed Your job starts …

9. Concluded
Organisms not identified
Investigation declared insufficient
Identification is crucial to determine …
Source Potential Risk

10. Concluded
The investigation of +ve sterility test
was also considered
Insufficient

11. Concluded
Company did not adequately assess
the hazards for aseptic filling
operation
Company did not determine whether
other batches made on the same filling
line were affected

12. Concluded
Several + ve sterility results were
invalidated during batch
release testing.
Criticized

13. End up …
A comprehensive
review & assessment
of all + ve sterility tests & MF failures
Expectations

14. End up …
Review & Assessment
of root causes, corrections,
conclusions with regard to sterility of
marketed commercial batches
Expectations

15. End up …
Revise SOP
of MF with regard to the identification
of microorganism from each
contaminated MF
Expectations

16. End up …
Revise SOP
of sterility failure investigation
Expectations

17. End up …
Retrospective Evaluation
of all videos of the aseptic
manufacture of batches released for
human consumption
Expectations

18. End up …
Adequacy Assessment
of facility, equipment, process &
CAPA plan
Expectations

19. End up …
CAPA Plan
Capable to fully identify microbial
contamination risk throughout
the filling operation
Expectations

20. End up …
Description of Improvements
to assure high confidence in the
Product Sterility
Expectations

21. As a matter of fundamental fact
Be clear

22. is not a controlling
mechanism
But
A system of
It s a proof of contamination
in the product
Monitoring
Alarming

23. So, be focused on microbial
control through proper design
and operating procedures

24. It is essential to keep facility
clean and as dry as possible all
the time
Detection of mold
is a catastrophic
event

25. Complete absence of particles
in all injection types is
desirability and has no dispute
on it
Particles in Injection