Self-authorship bridging the Academia to Industry (A2I) Gap. The challenge in our systems asking why signifies ignorance. Perhaps until a correction is needed. But after corrective and preventive actions (CAPA) often nothing changes. Errors reoccur and we acquire an “immunity to change.”

1. Dissolution is a process: The A2I USP

2. An FDA
“Complete
Response
Letter”
Ajaz|Insights
• Few of several FDA comments
• We acknowledge the newly proposed dissolution method [USP II
paddle with XXXXX] in your XX, XX 2019 submission. However,
the newly proposed dissolution method does not show adequate
discriminating ability with regards to the different levels of API
crystalline content. Therefore, we recommend you develop an
appropriate dissolution method with adequate discriminating
ability for your proposed drug product.
• In consistency with the ICH Q6A guidance, we recommend the
use of dissolution testing to monitor for the amount/type of
polymorphic forms at release and on stability. For this purpose,
provide information/data showing that your proposed
dissolution testing methodology and proposed acceptance
criterion are able to reject batches with inadequate
amount/type of morphic form. Submit dissolution profiles as a
function of crystalline content (e.g., X%, Y%, Z%)
• In addition, the setting of the acceptable amount of crystalline
form allowed by the dissolution acceptance criterion should be
supported by clinical information (i.e., bioavailability, exposure-
response, etc.).
1/10/2021 2

3. A reason for FDA
Warning Letter:
“High risk for
failure” to meet
“tolerance
limits.”
1/10/2021 Ajaz | Insights 3

4. 1/10/2021 Ajaz | Insights 4
Industry Policy and NIPTE: My Departing Message https://youtu.be/guVo1wQD7f0

5. Care is Research: Experiential Learning in a
community of knowledge (NIPTE)
• The first question we pose here is the same question
one of us (AH) had posed at the US FDA in 2003 in the
context of concern to national security. How do we
develop and validate a dissolution test method – not
just the HPLC methods for sample analysis?
• In our mind, we record a benchmark of “favorable”
interlaboratory reproducibility standard of “10 of 14
comparisons were similar. ” We continue to the next
theme, “Discrimination: From Generalized to
Specified.”
• Let us “see beyond literal” was the call of a
contribution of NIPTE colleagues based on an analytic
investigation of the drug formulation-based recalls in
the USA.

6. Pharmaceutical Quality, Team Science, and Education Themes: Observations and
Commentary on a Remarkable AAPS PharmSciTech Theme Issue (to be submitted):
Dissolution is a Process

7. The A2I USP is self-
authorship. The challenge
in our systems asking why
signifies ignorance.
Perhaps until a correction
is needed. But after CAPA
often nothing changes.
Errors reoccur and we
acquire an “immunity to
change.”
http://econintersect.com/pages/opinion/opinion.php?post=201612051928

8. QTPP → → → → Recall
Traditional Education & Training: Subjects → Learning → Objectives

9. Experiential
learning is to:
Recall→→→
QTPP
1/10/2021 9
Ajaz | Insights

11. 1/10/2021 Ajaz | Insights 11

12. Ajaz | Insights 1/10/2021 12

13. What I can do. Not, what can I do?
1/10/2021 Ajaz | Insights 13

14. Realize the A2I USP: Dissolve barriers to continuous development.
1/10/2021 Ajaz | Insights 14
Dissolution is a process and so is Development
Process understood can be validated
Process in a state of control is “suitable and capable”
Suitable and capable of improving continually ?
Realize
2021 to 2030
Sustainable development
UN: Agenda 21 & 2030
Digitalization
Industry 4.0
Lockdowns
WEF: “Great Reset”
System Maturity
Social Credit System

15. Subjects → Learning
→ Objectives
Ajaz | Insights 1/10/2021 15

16. QbD- PV – CPV -
Continual
Improvement
Annual Product
Review
As “without”, so
“within”!
How you can use QbD- PV – CPV - Continual Improvement processes to self-empower, and self-author
your career growth and continuous professional development?

17. “In over our head!” is a feeling, leverage it
to empower your adult development. How do
you (and others) know your education, training and experience
makes you suitable and capable for specified responsibility?
• What is your Quality Target Professional Profile?
• Choose to utilize the A2I opportunity to self-author
your development report and write a quality
overall summary (i.e., after the A2I experience).
• Be aware of “out of specifications” or OOS results
and be diligent in investigating why
• Detect, corrective and preventive OOS and
continue to monitor to be assured in your
suitability and capability
• Empower your continuous development. Suitable
and capable of increasing responsibility, career
growth and professional development
17

18. 1/10/2021 Ajaz | Insights 18

19. A2I USP
19
• Knowing you can actively expand your
“Order of Consciousness” (Subjective
Recall → Introspection → Objective
QTPP)
• Opportunities to expand awareness and
practice sensemaking
• You decide your Comfort Zone knowing
that development only occurs when you
step outside your Comfort Zone
• As above, so below; As within, so
without (as in real-world); Affair (at the
heart) of science

20. Care is Research
and Dissolution is
a Process
Ajaz S. Hussain, Ph.D.
1/10/2021 Ajaz | Insights 20

21. Experience a
senior
management
review
meeting
1/10/2021 Ajaz | Insights 21

22. R&D Project Review
Meeting: Progress vs. Plan
Ajaz | Insights
• Why review progress vs. plan
• How is progress measured,
and plan approved
• How should be invited to
participate
• What are the outcomes of a
review meeting
1/10/2021 22

23. Gates and
Go/No-go
Decisions

24. What can I do?
Comply with SOPs
to experience (you
are not a robot)

25. Don’t be Hurmat!

26. Formulation, Regulatory, Operations
and Quality Unit are intricately linked
via “design & validation”
Ajaz | Insights
• USP Prednisone Tablet RS acceptance
range (for Lot R001B0) for apparatus I
is 49-73% (stage 2). For other lots, this
range can be larger.
• This range exceeds the normal 10%
variation that FDA considers
acceptable - for example as in
setting specifications (+/-10% for
MR products) in an F2 test of
dissolution similarity (e.g., as in
SUPAC).
• Do you expect different lots of USP
Prednisone Tablet RS meet the
FDA's F2 criteria for dissolution
similarity? If you answer NO, is it
relevant? If so, how would you
reconcile in practice an apparent
dichotomy between PVT &
regulatory applications (e.g., OOS
investigations, CPV – risk of failure,
F2 similarity, specifications of MR
products)?
1/10/2021 26

27. Expand your consciousness to solve problems

28. Do not just be
informed. Reiterate
to clarify to know
your responsibility

29. Experience begins
before action;
visualize to imagine
the process to
identify measures
you will taken in
advance to prevent
errors

30. Experience is to
know why and how
each SOP relates to
other parts of a
system.

31. Be aware, do
homework to know
why, before asking
“what if” and “how to”
questions
Ajaz | Insights 1/10/2021 31

32. “Subjective” QTPP
1/10/2021 Ajaz | Insights 32
What is science? Theory, prediction, confirmation with valid measurement
system with known error rate and peer review.

33. Critical or
not?

34. Critical or
not?

35. Critical or
not?

36. “Subjective”
impact
assessment

37. “Subjective”
justification

38. Long story in short
• Approved by FDA
• Tech. Transfer & Process
validated
• BAD-I, Warning Letter, Import
Alert
• Tech. Transfer to a CMO in USA
• Process could not be validated
• An “FDA Approved” product that
can not be manufactured
1/10/2021 Ajaz | Insights 38

39. The process of science ... is
ultimately self-corrective, and
wiser, in a way, than the
scientists who pursue it, in the
end it is apt to lead us to the
truth, if only we have 'eyes to
see.'
Ajaz | Insights
39
1/10/2021

40. Risk Assessments
prelude to Development
• Beyond IP considerations, prior knowledge and
trends in therapeutic, regulatory and market
“assurance”
• Suitability and capability of raw materials and
suppliers
• Suitability and capability for available or
recommended measurement systems
• Release testing strategy considering facilities
suitability and capabilities for in process
controls, detecting, correcting and preventing
OOS, tech-transfer equivalence assessment,
scale-up and change management and
continued process varication
1/10/2021 Ajaz | Insights 40
US FDA’s One Quality Voice

41. Recall to “Objective”
QTPP (theory, predict, confirm with valid
measurements with known error rate, peer review)
• Assay
• USP: NLT 95% and NMT 105.0% of the labeled amount
of levothyroxine sodium. Establish internal target value
and alert limits to consistently demonstrate stability &
capability (CPV): E.g., Mean: 100% of label claim; Std.
Dev: less than 1.5 ( for a representative sample size of
30 @ 99% Confidence / 95% Probability using a 95 %;
ASTM E2709-12
• Polymorphic form
• Anhydrous and hydrate forms; hydrate stoichiometry
not explicit in the USP
• Dissolution
• NLT 80% (Q) of the labeled amount of C15H10I4NNaO4
is dissolved in 45 min [utilize ASTM standard to set
company specific limits to confidently conform, when
tested, for USP requirements]
• Water content (DS)
• NMT 11.0% (DS). Establish internal target value and
alert limits to consistently achieve and demonstrate
stability & capability (CPV)
1/10/2021 Ajaz | Insights 41

42. Suitability and capability for available or recommended measurement systems
1/10/2021 Ajaz | Insights 42

43. Facilities suitability
and capabilities
• Release testing strategy, considering facilities process
controls and systems for detecting, correcting and preventing
OOS, tech-transfer equivalence assessment, scale-up and
change management and continued process varication
1/10/2021 Ajaz | Insights 43

44. 1/10/2021 Ajaz | Insights 44
Can the Dew Point data of the U.S. Weather Bureau in
Puerto Rico suggest a causal factor of dissolution failures?
Suitability and capability of raw materials and suppliers

45. Collecting,
Selecting and
Connecting the
Dots: Putting the
Pieces Together
US FDA. A Regulatory Perspective on the Quality Overall
Summary: Putting the Pieces Together
HTTPS://WWW.FDA.GOV/MEDIA/110657/DOWNLOAD

46. Putting the
Quality Pieces
Together
Quality Overall Summary: Keep it
patient-focused, summarize the
overall control strategy to guide the
Regulator.
46

47. Ajaz | Insights 1/10/2021 47
Dissolution is a process and so is your Development. A process that is
understood can be validated. A process in a state of control is “suitable
and capable, "it is improving continually.

48. 1/10/2021 Ajaz | Insights 48

49. 1/10/2021 Ajaz | Insights 49
HTTPS://WWW2.SLIDESHARE.NET/A2ZPHARMSCI/FDA-TREND-NEW-VALIDATION-STRATEGIES

50. Ajaz|Insights
1/10/2021 50
HTTPS://WWW2.SLIDESHARE.NET/A2ZPHARMSCI/FROM-DEMING-TO-ORDERS-OF-CONSCIOUSNESS
360 DEGREE VIEW OF QUALITY BY DESIGN, USP INTERNATIONAL CONFERENCE HTTPS://YOUTU.BE/UDAJECUDXCC

51. 1/10/2021 Ajaz | Insights 51

52. A2I USP
52
• You know that you can actively expand your
“Order of Consciousness” (Subject Recall →
Introspection → Objective QTPP)
• You are aware of opportunities to expand
consciousness by practicing sensemaking
• You only can decide your Comfort Zone
knowing that development only occurs
when you step outside your Comfort Zone
• A2I is as above, so below; As within, so
without (as in real-world); it is an affair (at
the heart) of science

53. The A2I USP: Self-authorship
1/10/2021 Ajaz | Insights 53
Seeing our world through the eyes of a migratory
bird need not be a “spooky experience.” Grammar, Logic and Argumentation: 95%
Confidence is just a door opener; 2 σ to 6 σ

54. ARTHUR AMOS NOYES as the President of the American
Association for the Advancement of Science, in 1928
• "While science has through daily experience come to be universally recognized
as vitally important, yet it is often not realized that science does not 'just
grow'—that it arises from research, and that research is a sensitive plant which
will grow successfully only from carefully selected seeds—the best brains of the
nation; and which must be protected against the frost of dogmatic intolerance,
against the drought of administrative routine, against the flood of modern mass
education, against over-forcing through the impatient demands of practical
men, and against the blights of poverty and social neglect. Research will come to
its own in any community only when its members, in the words of Pasteur,
regard their research laboratories as their temples."
Ajaz | Insights 1/10/2021 54

55. 1/10/2021
THE RATE OF SOLUTION OF SOLID
SUBSTANCES IN THEIR OWN SOLUTIONS.
Arthur A. Noyes and Willis R. Whitney
J. Am. Chem. Soc. 1897, 19, 12, 930–934
December 1, 2020: 123rd anniversary
Ajaz | Insights 55