The document discusses the pressure of real-world evidence on pharmaceutical regulatory science. It mentions the author's experience interacting with international regulatory agencies like the FDA, EU, Health Canada, and MHRA. It lists some references on topics like continuous manufacturing and real-time dissolution prediction. The document emphasizes that improving individual parts of a system will not improve the overall system, and that a systems approach to quality is needed.

1. Roohi B. Obaid
Alumni International Regulatory Forums,
CDER-US-FDA & HPFB, Health Canada
Measure the Pressure of Real World Evidence on
Pharmaceutical Regulatory Science

2. Disclaimer
We discuss science with reproducible evidence
nothing more, nothing less
It is experience based learning expression received during
last 25 years while dealing hundreds of foreign & domestic
inspections, regulatory compliance & enforcements, dozen
of meetings with international experts (FDA, EU, Japan,
Canada, MHRA) etc. etc.
Thoughts represent the current thinking of
Centre for Quality Sciences
Obaid Ali & Roohi B. Obaid

3. Evolving real-time dissolution prediction and product
release (europeanpharmaceuticalreview.com)
Continuous manufacturing for oral solid dosage forms -
European Pharmaceutical Manufacturer
Integrated Continuous Pharmaceutical Technologies—A
Review | Organic Process Research & Development
(acs.org)
Continuous Manufacturing: A Changing Processing
Paradigm (biopharminternational.com)
References

4. We are lucky …. Just imagine for a while …..

6. 1
It might be you
or your son or
daughter

7. 1 2
It might be you
or your son or
daughter
It might be your
loved one or
close relative

8. 1 2 3
It might be you
or your son or
daughter
It might be your
loved one or
close relative
It might not be
your known but
your society

9. 1 2 3
It might be you
or your son or
daughter
It might be your
loved one or
close relative
It might not be
your known but
your society
Don’t please
be a machine
Have a heart
always

10. Dark Room or Blindness
What happen? what may happen? why happen? why may
happen? why it will not reoccur?

12. Dark Room Blindness
What do you choose?

17. Why I describe it?

18. Systems approach to quality is
the foundation of culture of
quality.
A system is the product of
interacting parts. Improving
the parts taken separately will
not improve the system.

19. Is pharmaceutical quality
like an Elephant in the
Dark or is it about our
blindness

20. About 50
people reported
loss of vision in
a week

21. Dark Room or Blindness
What went wrong? Why it happened? How did it happen?
Why it was not caught? Why will it not reoccur?
Blind Spot

22. Dangerous interactions
with some of the most common
medications for cardiovascular disease,
including certain statins and heart
failure therapies

23. Dark Room or Blindness
What went wrong? Why it happened? Why it was not
known earlier? Why will it not reoccur?
Blind Spot

24. Unknown debris
Potential
Contamination
Manipulation in
records

25. Dark Room or Blindness
What went wrong? Why it happened?
Why will it not reoccur?
Blind Spot

26. Deaths & Deaths
1937 – 2022
Its 85 years of
blindness

27. Dark Room or Blindness
What went wrong? Why it happened?
Why will it not reoccur?
Blind Spot

33. Blind
Spot
NDMA
Valsartan, Metformin, Ranitidine etc.
Huge Recall Series
• April 2020: 8 lots of
tetracycline capsules 250 & 500
mg – Dissolution failure - Avet
Pharmaceuticals
• Anagrelide Capsules 1 mg–
Dissolution Failure - Torrent
Pharmaceuticals

34. Blind
Spot
Thyroids
• May 2020 – 13 lots - Super
potent – Acella
Pharmaceuticals
• Sep 2020 – 483 lots – Sub
potent – RLC Labs

35. Clinical Studies

36. Clinical Studies
Bio Studies

37. Clinical Studies
Bio Studies

38. Clinical Studies
Bio Studies
Dissolution
Profiling

39. Clinical Studies
Bio Studies
Dissolution
Profiling

40. Clinical Studies
Bio Studies
Dissolution
Profiling
Dissolution
Testing

41. Clinical Studies
Bio Studies
Dissolution
Profiling
Dissolution
Testing

42. Clinical Studies
Bio Studies
Dissolution
Profiling
Dissolution
Testing
BRIDGING

43. Clinical Studies
Bio Studies
Dissolution
Profiling
Dissolution
Testing
BRIDGING

44. • Bioequivalence is burden
both on company &
regulator
• Unnecessary exposure of
drug to healthy humans

45. Factors affecting Dissolution

46. API ….
• Solubility
• Wettability
• Particle size
• Surface area
• Morphology
• Polymorphs

47. API ….
• Solubility
• Wettability
• Particle size
• Surface area
• Morphology
• Polymorphs
Composition &
Characteristics ….
• Excipient
• Hardness
• Manufacturing
process
• Manufacturing
conditions

48. API ….
• Solubility
• Wettability
• Particle size
• Surface area
• Morphology
• Polymorphs
Composition &
Characteristics ….
• Excipient
• Hardness
• Manufacturing
process
• Manufacturing
conditions
Dissolution
Method….
• Method
Apparatus
• Medium
• Sampling
• Test conditions
• Sample Analysis

49. Meaningful in vitro
dissolution testing may be
used if suitability is justified
through petition

50. Large heterogeneity
in observing, recording,
and interpreting
The same is in cGMP related
observations because of blindness

51. Formal education, training, experience is required to bring it …
Which subject you include & which you exclude?
What do you know,
how do you know
What you understand &
how you understand

52. Thanks