This document discusses two case studies related to stability failures and deficiencies in stability programs. Case Study 1 describes a product where the gelatin source was changed without properly assessing the impact, resulting in stability failures and the recall of hundreds of batches. The factory was shut down for years and people lost their jobs. Case Study 2 describes a fluocinonide cream that failed the 6-month stability testing for 3 out of 24 lots. This calls into question the correctness of the product's 36-month shelf life determination and stability program. The document emphasizes the importance of characterizing natural materials like gelatin given their variability, and having robust stability programs to avoid regulatory issues.

1. Case Studies
Obaid Ali
Civil Service Officer, Member, ISPE, PDA
26 March 2017

2. Not the
view of
DRAP
Current
judgment
No
obligation
on DRAP
Regulatory
experience
D
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References US-FDA WHO ICH NRAs

3. Case
Study 1

4. Lets have a look at
Real Cases
From the personal
experience

5. A very famous product
Everybody knows about it
Millions of capsules/week manufactured since
years and years

6. Stability failed
100’s of batches recalled
Factory shut down for years
Several people lost their jobs
Corporate could not sustain

7. Source of gelatin was changed
Assessment was weak
Change impact was not appropriately studied
Stability program was weak

8. Inspector asked to perform disintegration
test of capsule manufactured a year before
A month old batch found not qualified for
disintegration test
Failed
Failed
Failed Failed Failed

9. Characterization of Gelatin is very difficult
Because it is from natural source
Storage, Transportation and its Handling require narrow
control range for humidity & temperature
A lot of variation potential

10. Lets Understand Gelatin

11. Case
Study 2

12. Fluocinonide Cream 0.05% (36 month shelf life)1
24 Lots
21 Lots Complied
3 lots failed

13. SD RSD
T
M
B
6%
Fluocinonide Cream 0.05% (36 month shelf life)1

14. 6% Uniformity
?
Fluocinonide Cream 0.05% (36 month shelf life)1

15. Fluocinonide Cream 0.05% (36 month shelf life)1
3 6
9 12
15 18
21 24 27 30 33 36

16. Tube
Uniformity
failed
T
M
B
Important
characteristic
failed
Fluocinonide Cream 0.05% (36 month shelf life)1
Shelf life
determination is
not correct

17. Is it not correct to suggest that
Stability Program is Deficient

18. Lets keep catching and walking
together with clarity

19. Commitment on 3 month data
Can a generic product filed with 3 month data and
committed to provide 6 month data in future be accepted?

20. No, 6 month stability data is
required

21. Decommissioning of Commissioning
How long do pilot scale batches need to be stored before
they can be destroyed?

22. At least one year after approval

23. Manual Operations
Can small scale batches be packed by hand?

24. No, always avoid doing
anything which is critical in
process by hand

25. Math with other Science
Can mix and match approach be applied, for e.g. one
batch at 6 month and 2 batches at 3 month

26. No, not at all
Use math with clear understanding