Many generic pharma companies seeking regulatory approval uncritically follow “past” practices and prior knowledge. Few, if any, correct errors and innovate to improve past expertise and techniques. The idea of SMART "QbD in ANDApplications" (not “submission”) builds on this observation.

1. SMART Quality by
Design (QbD) in
ANDAs.:
Enhancing Assurance of
Generic Drug Quality
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2. The idea of SMART QbD in
ANDApplications (not “submission”)
builds on this observation. I begin by
recalling an experience of a citizen
petition against ANDAs.
• October 2011 and onwards
– Doing what can and needs to be done vs. waiting for FDA
to tell us what to do [attitude]
– Draft Guidance on Enoxaparin Sodium
– Scientific considerations in the review and approval of
generic enoxaparin in the United States (2013) | Nature
Biotechnology
• July 23, 2010
– Citizen-Petion-Response.pdf (fda.gov)
– Sandoz ANDA, dated August 26, 2005, approved.
Collaborating since 2003, Sandoz and Momenta provided
the FDA with substantial data demonstrating the Sandoz
generic's equivalence to Lovenox and addressed potential
immunogenicity issues.
• February 19, 2003
– A citizen petition was submitted on behalf of Aventis
Pharmaceuticals, Inc.
– It requests that the FDA withhold approval of any ANDA
until enoxaparin has been fully characterized or the
manufacturing process used to create the generic drug
product is determined to be equivalent to Aventis's
manufacturing process
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Observation: Companies seeking ANDA
approval uncritically follow “past”
practices and prior knowledge. Few, if
any, correct errors and innovate to
improve past expertise and techniques.
Top of ANDA approvals list, low on IP index - Express Pharma

3. This is my Citizen Petition
for SMART QbD.
• I believe that ANDAs are a crucial
steppingstone for India Pharma to maintain
its leadership and innovation in claiming to
be the "pharmacy to the world.“
• Pharmaceutical science underpins
regulations but is pinned down in
“approvals,” so it struggles to self-correct,
and errors erode patient and public trust.
• Any sector claiming to be the "pharmacy to
the world" is rightly or wrongly blamed for
this erosion.
• SMART QbD is taking responsibility and
finding a way to intuitively strengthen
institutions to enhance assurance of generic
drug quality “on top of ANDAs with an [high]
IP index.” My definition of IP extends to
intellectual prowerse.
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Subscribe on LinkedIn.

4. SMART MANAGEMENT & MINDS
Self-monitoring, analyzing, and reporting technology
Self-monitor assumptions, research, and test to verify
Self-monitor attitude and resetting to transformative
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Correct past errors, prevent
mistakes, improve, and
innovate at every level of the
hierarchy that makes up the
“corporate” system, from
front lines to board rooms.

5. What assumptions
and attitudes require
transformation?
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6. What are you assuming?
Science is a self-correcting
process!
Pharmaceutical science underpins
regulations but is pinned down in
“approvals,” so it struggles to self-
correct, and errors erode patient
and public trust.
"Ignorance is brought about by
assumption." ~ T. D. Jakes
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System performance: ANDA approvals?

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Physicochemical failure modes for Narrow Therapeutic
Index (NTI) drugs (europeanpharmaceuticalreview.com)

9. Who takes the blame?
One who submits.
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It is SMART to go beyond submission
and apply the scientific method!

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But who insisted on the particular dissolution test and acceptance criteria?

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A paradox in two reports from 12/08/2023 caught my attention.
The Untold: Generics vs. Branded Generics—here’s how India’s
Drug Price ‘Control’ kills the Patient, by C H Unnikrishnan, 29
May 2023 (cnbctv18.com)
Recurring mistakes point to the immaturity of “the system.” All are part of the system.

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What type of system are we operating in? Chaotic, extreme sensitivity to “initial conditions.”

15. Let us reflect back
Assumptions and attitudes?
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This Photo by Unknown Author is licensed under CC BY

16. If incorrect assumptions lie at the root of every failure,
what are the “big assumptions”?
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“Vision 2020” Pharmaceutical Quality for the 21st Century
Generic Drug Scandal To Prevent the Next Scandal “Ranbaxy and BAD-I My journey to 2020 and currently

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2015

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Video: 360 Degree View of Quality by Design, USP International Conference 2017

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2010

21. About my Journey to 2020
• Since the end of the 20th century, we moved into
an “experience economy,” but we didn’t
adequately adjust our practices to remain
reasonable in this changing economy.
• A journey to experience and derive insights while
paying attention (ALCOA) to the “integrity of my
experiences.” I documented on LinkedIn (>110
insightful posts in articles and editions of a
newsletter), SlideShare (> 100 slide decks), trade
magazines, and scholarly journals.
• I recommend a similar journey to 2030 to you!
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Welcome to the Experience
Economy, 1998 (hbr.org)

22. SMART MANAGEMENT & MINDS
Self-monitoring, analyzing, and reporting technology
Self-monitor assumptions, research, and test to verify
Self-monitor attitude and resetting to transformative
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Correct past errors, prevent
mistakes, improve, and
innovate at every level of the
hierarchy that makes the
system front-lines to board
rooms.

23. Assumptions are our long-learned,
automatic responses, and attitude is our
habitual ways of responding to
assumptions we hold
What assumption do we need to research and
test? How we specify QTTP ensures it is not a 2-
3 sigma trap!
What habits do we need to reset to bring about
transformation? A product and performance
life-cycle approach to take a continuous
development stance!
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Self-monitor
Assumption Attitude
Research Reset
Test Transform

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25. A transformative attitude is the
courage to question, research, and
test accepted assumptions and
take action to correct, prevent, and
improve.
For instance, we can begin the
transformation in how we conduct
the Annual Product Review and
Performance Reviews.
"Incorrect assumptions lie at the root of
every failure. Have the courage to test
your assumptions." ~ Brian Tracy
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26. Let India’s journey towards
becoming one of the world's largest
economies be unhindered by
submissions in the Pharma sector.
SMART QbD in ANDApplications (not
“submissions”) can be and should be the self-
assurance underpinning the assurance of quality
any “pharmacy to the world” delivers.
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28. We know quality is not
a quantity that can be
tested in a laboratory.
So, starting in 2024, why don’t we begin
anew by calling our QC labs Quantity
Control Laboratories?
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