Thursday, September 22, 2022, Pearl Continental Hotel, Karachi

1. Maturing Drug Quality to Deliver Promise
Obaid Ali, R.Ph, Ph.D.
22 September 2022

2. Evidence is the Key
Pharmaceuticals are
better than placebo in
laboratory & clinical
trials

3. Post-marketing Changes
Marketing Authorization
Based on
Quality of Development

4. Challenges .. Challenges ..
Same Therapeutic Outcome
Assurances in Real World
depend upon
Quality of Development &
Effectiveness of QMS

5. Education, Training & Experience
Practical contact with
things in the real world
How do you know
what you know

6. Towards Systemic Transformation
We need to free
ourselves from
average thinking

7. Development
Errors of Omission have to be
eliminated by Quality by
Design
Error of Commission have to be
eliminated in Operation by self
authorship of SOPs

8. 2007 - 2012
7193

9. 2013 - 2019
Class I - 1139
Class II - 8034
Class III - 1070
Unclassified - 40
10284

10. NDAs 526
ANDAs
1186
Pharmacy 1580

11. cGMP Issues 905

12. cGMP Issues 905
Microbial Contamination 741

13. cGMP Issues 905
Microbial Contamination 741
Stability 606

14. Degradation 339

15. Degradation 339
Particulates 302

16. Degradation 339
Particulates 302
Data Integrity 266

17. Dissolution 198

18. Dissolution 198
Super potent 116

19. Dissolution 198
Super potent 116
Potency Failure 106

20. Tablet Injection Solution
1697 1061
1501

21. Capsule Creams Suspension
746 115
214

22. Ointment Syrup
51 45

23. CAPA are not
Continual Improvement
You can only improve a process
when you are in a state of
control
You can’t improve when it is in
need of Corrective &
Preventive Actions

24. Commercialization
Keep eye on lifecycle

25. 75 years of Independence
No new molecules,
Dependent on import for
Knowledge, Technology,
Equipment,
Materials, Excipients, Etc. etc.
Poorly sensitized to real time
observations & real world
evidences

26. Perfect Success & Perfect Failure
• Uncertainty, Shortages,
• Quality Concerns,
Import Alerts
• Export Restrictions,
Knowledge Crisis,
• Cross-pollination of
Myths

27. On one table
Subject matter experts,
determination, science, real
world evidence, real world
experience, real world data,
measurement, knowledge
& wisdom

28. Shortening of Drug Production Cycle
Data Science & Artificial Intelligence
Future
Patient

29. What is
Critical
Continual
learning
Risk
Based

30. Misconcep
tions
Wrong
assumptions
Misconcepti
ons
Prior
knowledge

31. Analytical method and the state of
control is key to determine process
control
Traditional practices are no longer
science based & to convert to science
based is
Maturity

32. Inherent limitations and block
From uni-variate thinking
to Multivariate Quality
Risk Management
Simply compendial
tests does not tell that
batch is ok

33. Chaos is a system that is
unpredictable beyond average ….
inability to understand extreme
sensitivity
Uncertainty &
Expectation Management

34. GMP ... Q10 … Maturity
What habits and
practices need to be
changed?

35. Are they falling
down again and do
we need to get them
back up
Is this a firm that is
much more mature,
has higher level of
quality and they
slipped
Just need to help
them a little bit
Need meeting or
something more
aggressive

36. Are the findings the
tip of the ice berg or
just an isolated case?
Is this a bigger thing
that affects other
drugs or other lots?
Is it an episodic
event?

37. Sustainable Compliance
Quality Metrics &
Quality Management
Maturity is the concept
of sustainable
compliance

38. Sustainable Compliance
Continue to encourage
companies to think about
not only meeting the
minimal expectations but
how to achieve a level of
sustainable compliance

39. Sustainable Compliance
Companies should have
mature system &
continually operate above
the bar instead of dipping
below & coming back

40. Digital Transformation

41. Identification

42. Identification
Critical
Quality
Attributes

43. Identification
Critical
Quality
Attributes
Critical
Processing
Parameters

44. How digitalization works?

45. Flexible Production Entering New Domains
Integrated Quality

46. Flexible Production Entering New Domains
Integrated Quality
A site’s ability to accommodate change
in production demand

47. Balanced and integrated quality system
Flexible Production Entering New Domains
Integrated Quality

48. Having the ability to quickly absorb
knowledge to implement new practices
Flexible Production Entering New Domains
Integrated Quality

49. Capability to provide
patients real time
information about
their condition and
collect patient data
for care analytics to
improve the
treatment
Beyond the Pill

50. Demand for better
data on the
medication efficacy
and patient quality of
life

51. Diverse and fast
changing global
regulations
demanding
infrastructure change
for compliance

52. Competent
resources, complex
supply chain,
emerging
information paradox
are operational
challenges

53. Science speaks

54. Differences in impurities are
acceptable, but
Generics should demonstrate
that this would not increase a
product’s risk
Synthetic
Peptide Drug
Products

55. For any new impurity
Greater than 0.5%
is not acceptable, it must be
less than 0.5%
Synthetic
Peptide Drug
Products

56. Impurities at 0.10%- 0.5%
identified, characterized and
justified for not affecting the safety
and efficacy, including comparative
immunogenicity risk tests
Synthetic
Peptide Drug
Products

57. Medroxyprogesterone acetate – 1
injection for 3 months
Aripiprazole - 1 injection for 2
months
How do we understand safety?
Suspension for
Injections
Nano size,
insoluble, extended
release

58. Excess volume should be carefully justified

59. Infection Allergic
Non Allergic
Nasal Product
Weight - of - Evidence Approach to establish BE
Rhinitis

60. RLD has two approved strengths:
500 mg and 750 mg
1. Approval for 1000 mg as generic
2. Approval for Biowaiver
Suitability
Petition

61. 1st is granted but 2nd is not
Although composition
proportionality in dissolution
supports
But
• Drug product not shown to be highly
soluble and permeable
• In-vivo evidence of dose
proportionality from innovator was
not performed
Suitability
Petition

62. • Different route of administration
• Different dosage form
• Different strength
• One API is substituted with other
API in a combination product
Suitability
Petition
Differences
considered

63. Thanks