This document provides an overview of key topics related to data, knowledge, and wisdom in the context of drug regulation and pharmaceutical quality. It discusses trends seen in drug approvals and post-market safety events in the US from 2001-2010. It also covers challenges in understanding variability between individuals. Additional sections describe the integration of various data sources and knowledge management approaches at regulatory agencies. Priority review programs for innovative drugs are also summarized. The talk concludes with discussions of opportunities and challenges for generic drug approvals, including for complex products.

1. Data, Knowledge & Wisdom
Integration
24th Oct 2018, PC Hotel Karachi
Obaid Ali
Deputy Director, DRAP
Civil Service Officer, Government of Pakistan

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, Papers from
Pharmaceutical Technology & Review Scientific
Articles are used to construct presentation
Disclaimer
Reference

3. 222 - novel drugs approved
123 - post market safety events
071 - require actions
061 – boxed warnings added
003 – withdrawn / terminated
Study revealed
2001 … 2010

4. Evidence of different drug
behaviors in different human
beings emerged as a complex
challenge to understand the
reason
Hope & Fear together

5. Data
Pre-Clinical & Clinical Data
Drug Developmental Data
Drug Manufacturing Data
Post Marketing Data

6. Knowledge
From data reviews
From experiment & experience
From publication & literature
From sharing agreements

7. Pre Approval
Inspection
Compliance
Inspection
Post
Approval
Inspection
Pre Market
Review
Variations
Review
Post Market
Review

8. Pre Approval
Inspection
Compliance
Inspection
Post
Approval
Inspection
Pre Market
Review
Variations
Review
Post Market
Review
Integrations
Knowledge Sharing
Knowledge Management
Multidisciplinary teams

9. Safety Efficacy &
Quality
Lets have another
look

10. Pre
registration
applications
Sound
science
Risk
based
Robust Consistent

11. Use of statistical method
Process Validation
Process Control
Understanding of Variability

12. Design your process
Build
knowledge &
understanding
Development & Scale
up experience
….
Establish
strategy for
process control
1/3

13. Qualify your process
Expect
certainty on
commercial
manufacturing
Sufficient
statistical
confidence
2/3
Extensive sampling,
monitoring

14. Continued Process Verification
Assurance that
process is in
state of control
Impact of
variability &
Knowledge
Management
3/3
Regularly collect &
analyze product &
process data

15. Product Lifecycle
Development
Technology
Transfer
Commercial
Manufacturing
Product
discontinuation

16. Product Lifecycle (Process)
F
D
A
E
M
A
Design
Q8, Q11,
Inspections
Qualification
Facility, Utility, Equipment
Performance Qualification
Contd. Verification
GMP inspection, Q10,
Quality Review
Development
Q8, Q11,
Submission
Qualification
Traditional Cont. Verification
Assessment in Inspection
Contd. Verification
GMP inspection, Q10,
Quality Review

17. Inspections
Consistent Purity
Integrity Dignity

18. Post
marketing
Recall Safety
Trend Complain

19. Science the only answer
Integrity above all
Culture of Quality

20. Learn, Un-learn & Re-learn
Change is the process by which the future invades our lives
Alvin Toffler

21. Lets take a breath and have a glance
What is happening, Where is happening,
How it is happening

22. 46
New drug
approvals in USA
(2017)
11 BLAs
34 NDAs
01 gene
therapy

26. Priority Fast Track
Accelerated Breakthrough
Review

27. Priority Fast Track
Accelerated Breakthrough
Review
Significant improvement
in safety or effectiveness
of the treatment when
compared to prevailing
situation

28. Priority Fast Track
Accelerated Breakthrough
Review
Significant improvement
in safety or effectiveness
of the treatment when
compared to prevailing
situation

29. Priority Fast Track
Accelerated Breakthrough
Review
Clinically significant
endpoint observed on
irreversible morbidity or
mortality

30. Priority Fast Track
Accelerated Breakthrough
Review
Clinically significant
endpoint observed on
irreversible morbidity or
mortality

31. Priority Fast Track
Accelerated Breakthrough
Review
If no therapy exists

32. Priority Fast Track
Accelerated Breakthrough
Review
If no therapy exists

33. Priority Fast Track
Accelerated Breakthrough
Review
Use of surrogate endpoint
for survival of cancer
patients

34. Priority Fast Track
Accelerated Breakthrough
Review
Use of surrogate endpoint
for survival of cancer
patients

35. Transformative Medicinal Challenges
CAR-T therapy (gene therapy)
Genome editing
technology
Oligonucleotide
(antisense)
therapy
CMC & QRM as a
challenge

36. Use of current
technology in facilities
will no longer be an
option but an obligation
Dec 2017

37. Sep 2017
WHO launches
biosimilar program for
Rituximab and
Tarstuzumab … insulin
for prequalification

38. 2017
USP and Chinese
Pharmacopeia extend
partnership

39. 2017
Rare disease is a
priority
Orphan drugs
promotion

40. Storm and
Puerto Rico
Drug shortage and
strategic crisis on road
Sep 2017

41. Global targets Breakthrough in Alzheimer & hepatitis
Cancer focused, new methodologies/ biologic intervention
Medical devices, Introduction of insulin pump

42. Generic pilot project about to complete
Orphan drug policy change
Fast drug approvals in US including generics

43. Leveraging
from the
History to
walk in
Future Integrated
Approach
Inspections
QbR

44. Lets try to give simple & clear words to sounds around

45. Therapeutic Equivalence is target
CMC
Bio studies
Plant GMP
Label
Generic Drug & API Sameness

46. Sameness is requirement
Same API
Same dosage
Same route
Identical strength
Pharmaceutical Equivalence

47. Small molecule with defined
structure … peptides, natural &
synthetic polymers
Mixture of few small molecules in a
fixed ratio … heterogeneous mixture
of small molecules &
macromolecular complex
Simple & Complex

48. Source of starting material,
reaction scheme, structural
signature analysis,
physicochemical & biological
properties
E.g.: Enoxaprin
Considerations

49. Sameness is determined
if equivalence of all four is
established
Literature support &
justifications are considered in
characterization of sameness
Totality of Evidence

50. Every generic is not
simple … sometimes
complex
like peptides, complex mixture of
API, complex routes of delivery,
complex dosage, complex drug
device combination, complex
formulation
Simple & Complex

51. 69 billion USD sale from 1992 to 2017Advair
www.fiercepharma.com

52. Lack of generic drug trend in
complex generics & minimum
competition …
All the opportunity to challenge &
influence in regulatory decisions but
within science
Opportunity

53. Insufficient data or inadequate
acceptance criteria for
characterization (e.g.
physiochemical properties) …
Analysis of multiple batches of
RLD may be used to justify the
acceptance criteria …..
Common Deficiencies or
Challenges

54. Inadequate reference standard
or its characterization for assay
…
Justify or describe how
potency is determined …
Common Deficiencies or
Challenges

55. Inadequate acceptance criteria
or assessment of potential
impurities in characterization
with regard to purity
Focus on compendial
monograph … strengthen
process knowledge, analytical
techniquesCommon Deficiencies or
Challenges

56. Inadequate designation of
starting material specification
Use Q11 to justify
Common Deficiencies or
Challenges

58. Novartis/ MIT

59. Thank You