This presentation provides an overview of pharmaceutical manufacturing and regulation. It discusses key performance metrics for the industry in 2017, the importance of safety, efficacy and quality, and outlines the process validation lifecycle. Challenges like inspections, recalls and drug shortages are also addressed. The presentation emphasizes learning, applying science-based approaches, and maintaining a culture of quality.

1. Khalid Yousaf Saheb
We shall not look upon
one in our community
like him. He will be
deeply remembered
May Allah bless him
with eternal peace &
success

2. Pharmaceutical Manufacturing
Dashboard 2017 Review
Obaid Ali, R. Ph., Ph. D.
Alumni CDER, US-FDA & HPFB, Health Canada
Member ISPE & PDA
14 Jan 2018

3. D
I
S
C
L
A
I
M
E
R
Personal Point
of View
No
Obligation
on DRAP
Knowledge &
Experience
Current
Judgment
This presentation discusses science, nothing
more and nothing less

4. Learn, Un-learn & Re-learn
So reading and writing are no longer bench mark of literacy
Alvin Toffler

5. H. Gobind Khorana
Nobel-Winning Scientist (1968)
Graduation Multan (1943)
Ph. D. Lahore (1948)
Deciphered
The genetic code
9 Jan 1922 to 2011

6. Revenue
$ 177.52 billion
in 2016
Increased
17.8% in 2017
Lets think who are players and
where we are

7. Safety Efficacy
& Quality
Lets understand

8. Pre
registration
applications
Sound
science
Risk
based
Robust Consistent

9. ProcessValidation
Process control
Understanding of Variability
Use of statistical method

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

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

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

13. Product Lifecycle
Development
Technology
Transfer
Commercial
Manufacturing
Product
discontinuation

14. 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

15. Inspections
Consistent Purity
Integrity Dignity

16. Post
marketing
Recall Safety
Trend Complain

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

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

21. Scenarios
Engage with us and decide ….

22. All API drums were deemed compliant even though not
all drums have actually been sampled
Critical Major Minor

23. It took more than 6 months for action to be taken after a
critical deviation was discovered
Critical Major Minor

24. The complaint management was not always performed
by QA
Critical Major Minor

25. There were diversions b/w manufacturing yield and
amount of used material
Critical Major Minor

26. There were no maximum reject rate for batch release
Critical Major Minor

27. There was a high environmental risk in the production
Critical Major Minor

28. Developmental Batch Sizes

29. Size of lab scale batch
What is meant by Lab (3rd small) scale?

30. Oral dosage forms
NLT 25% of the
pilot scale batch
Powders/solutions/
suspensions
NLT 25% of the
pilot scale batch Transdermal patches
NLT 60% of the
pilot scale batch

31. Parenteral
NLT 25% of the pilot scale batch
(50 Lit if unit is > 2ml)
(30 Lit if unit is up to 2ml)
Cream/ Ointment/Gel
Not less than 40% of Pilot
(At least 100 kg or 10% of
proposed commercial batch,
whichever is larger)

32. I perform each test on batch
Do we still need to do process validation?

33. If an equipment used in manufacturing
for 8 hours
Can data from first two hours is sufficient
to assure the process?

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

35. 46
New drug
approvals in USA
(2017)
11 BLAs
34 NDAs
01 gene
therapy

39. Priority Fast Track
Accelerated Breakthrough
Review

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

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

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

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

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

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

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

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

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

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

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

51. 2017
USP and Chinese
Pharmacopeia extend
partnership

52. 2017
Rare disease is a
priority
Orphan drugs
promotion

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

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

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

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

57. Benefits of Question based Review
Align
industry and
regulators
on critical
aspects
Promotes
dialogue
b/w industry
& reviewer
Opneness &
Smart when
discussing
deficiencies
or issues
Better
ability to
predict
quality &
performance

58. Biopharmaceutical Evaluation Affairs
From Fiction to Reality

59. Performance
should be the
same way

60. No Worse
Performance
should be the
same way

61. No Worse
No Better
Performance
should be the
same way

62. Please make it clear
They are not
clinical studies
Nothing to do
with Safety &
Efficacy of
molecule
Evaluating the
Similarity of
Trends
&
Kinetics

65. Novartis/ MIT