In “improving quality” we can lose trust! Professional development for continual evolution and a revolution. “Revolution” embedded in Evolution: In the “real world” mind trumps matter! Legacy can be hard-wired in minds. Assurance is critical to public health! We must listen to “Canary Tweeting in our Mind”!

1. Leadership for PAT and Industry 4.0
Ajaz S. Hussain, Ph.D.
National Institute for
Pharmaceutical Technology
& Education, Inc
3/4/2019 (C) Ajaz S. Hussain, Ph.D. IFPAC 2019 Maryland USA 1

2. Professional development for
evolution and a revolution
• Background: Lessons in the FDA’s PAT &
CGMP’s for 21st Century Initiatives
• Challenge: Equivalence in Inequality
• Question: Operational, tactical and
strategic considerations?
• Answer: Assurance is as important as
control; to give assurance to others one
must be self-assured.
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3. Experiential
Learning
• USA
• India
• Switzerland
• Europe
• Japan
• Canada
• Mexico & South America
• South Korea
• Middle-east
• Africa
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4. Lessons in the PAT
Initiative
• Perceived “risk” and “fear”
are MAJOR hurdles; we
underestimate its impact
• FDA’s PATRIOT Team
building & certification
• FDA CRADA with Pfizer and
Novartis
• Aventis “Real time release”
approval in 2004
• PAT: Tit for Tat experience
that followed Sau (Larry) Lee March 2017
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5. PAT Implementation: Aventis 2004
RPS/FDA Meeting, London – 14 December, 2004
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6. “Revolution” embedded in Evolution:
In the “real world” mind trumps matter!
CPAC Satellite Meeting Rome, March 25, 2010ISPE Hamburg, 19th of April 2013
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7. The Alternative Plan (larger sample size)
provides a better assurance of quality
than USP: But!
• What is the probability of rejecting a good batch?
(Producer risk)
• What is the probability of releasing a bad batch?
(Consumer risk)
• The USP OC curve shows 90% probability of passing a
batch with 2% product outside 85-115% of Label Claim
• The Alternative Plan OC curve shows 0% probability of
passing a batch with 2% outside 85-115% of Label
Claim
• Legacy challenges and fear of OOSGraham D. Cook. CPAC Satellite Meeting Rome,
March 25, 2010
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8. Legacy can
be hard-
wired in
minds
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9. 21 CFR 211.192: 17 years ago…
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10. 3/4/2019 (C) Ajaz S. Hussain, Ph.D. IFPAC 2019 Maryland USA 10

11. Equivalence in Inequality
3/4/2019 (C) Ajaz S. Hussain, Ph.D. IFPAC 2019 Maryland USA 11

12. Assurance critical to public health!
3/4/2019 (C) Ajaz S. Hussain, Ph.D. IFPAC 2019 Maryland USA 12

13. We must listen to “Canary Tweeting in our Mind”!
3/4/2019 (C) Ajaz S. Hussain, Ph.D. IFPAC 2019 Maryland USA 13

14. In “improving
quality” we
can lose trust!
• Joint position statement of European Thyroid Association and Thyroid
Federation International. European Thyroid Journal. 2018;7(5):1-5.
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15. Value information about a drug (such as the price tag)
can strongly affect its therapeutic effect
Science. Vol. 358, Issue 6359, pp. 105-108. 06 Oct 2017
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16. Summary so far: A canary
tweeting in my mind
• Lessons in PAT: Legacy challenges and perceived
“risk” and “fear” are MAJOR hurdles; we
underestimate its impact
• Assurance critical to public health! The on-going
levothyroxine multinational saga reminds us that in
“improving quality” we can lose trust!
• We are on a journey, as FDA reminds us, to achieve a
“One Quality Voice” within the sector
• We must recognize the “real world” challenges of
“Equivalence in Inequivalence” as an “Ontological
Conflict”
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17. Question: Operational, tactical and strategic considerations?
Workshop on Process Analytical Technologies for Biologicals 15th March 2007, Room 3A, EMA
Fisher, Shewhart, Deming…. What else?
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18. Fisher, Shewhart, Deming…. What else?
For additional information visit:
https://www.slideshare.net/a2zpharmsci
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19. To err is human, professional development via
design & systems thinking
Why metamorphosis to meaningful experience necessary!
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20. Where ontological conflicts exists attention to representational
practices and epistemology, however important, are insufficient.
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25. NIPTE Creating Experiential Learning Opportunities for
Continuing Education with Professional Development
• Personalized continual development while
utilizing principles and know-how in ICH Q8 -
11 and FDA’s Process Validation 2011
• Identifying legacy blind-spots, problem-
solving and optimal science-technology-
behavior integration across product life cycle
to reduce regulatory uncertainty
• Self-authorship a path to self-assurance; e.g.,
improving quality of Development Reports
and QOS (to prevent CRL) and effective
investigations and CAPA to build an effective
pQMS (to prevent Warning Letters)
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26. NIPTE’s NPK: Ability to
measure demands
responsibility to explain
• To publish in AAPS PharmSci Tech.
• Open Access, please download
The paradoxical combination of “new”
and “prior knowledge” is intended to
distinguish NPK from traditional and
proprietary pharmaceutical “prior
knowledge.” Critically, it is also intended
to draw attention to the paradoxical
state of collective inattention to the
root cause of challenges to the
availability of affordable medicines with
a high assurance of quality.
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27. Summary
• Lessons in PAT: Legacy challenges
and perceived “risk” and “fear”
are MAJOR hurdles; consequence
of underestimating its impact is
significant
• Assurance is critical to public
health! The levothyroxine
multinational saga is a canary
reminding us that in “improving
quality” we can lose trust!
• We are on a journey, as FDA
reminds us, to achieve a “One
Quality Voice” within the sector
• We must recognize the
“information asymmetry in real
world an “Ontological Conflict” to
be prepared to address the
challenge of “Equivalence in
Inequivalence”
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28. Summary (contd.)
• QbD, effective investigations to
system wide CAPA, continual
improvement and Industry 4.0
demands higher Orders of
Consciousness
• We must build a cadre of leaders
who can deliver “Equivalence in
Inequality”
• Personalized-PD is self-authorship
in the interest of patients at every
level; individual, corporate and
sector level (e.g., consensus stds.)
• Self-authorship in the interest of
patients can be the “butterfly
effect” we need to evolve with
care the revolution called Industry
4.0 or SmartFactory
• NIPTE stands ready to support the
sector achieve “One Quality
Voice” and reduce “understanding
asymmetry” in the real world!
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29. Vision 2020:
I can see
more clearly
now!
We cannot and must not ignore the “root cause”, it is us!
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30. For additional
information on
NIPTE programs
• Please e-mail me at Ajaz@nipte.org
or Vadim J. Gurvich at
vadimg@nipte.org
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