I wonder, seriously - Does working in some of the current GXP regulated environments impede adult human development? Anticipating a glimpse of a framework for a 21st Century Pedagogy - One Quality Voice , continually developing professionals and improving PQS – in the interest of patients and the next generation of professionals.

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Ajaz S. Hussain, Ph.D., President
The National Institute for Pharmaceutical Technology & Education, Inc.

2. My interest and viewpoints
• My interest
• Make high pharmaceutical quality (i.e., assurance) affordable
and globally available
• My viewpoints
• Pharmacy & Pharmaceutical Science
• Academic (Ohio Northern University & University of Cincinnati)
• US FDA – SUPACs, IVIVC, BCS, PAT and Pharmaceutical Quality for the 21st
Century 1.0
• Sandoz/Novartis – Biosimilars and Complex Generics
• Philip Morris International – Plant based vaccines, iQOS® -
Modified Risk Tobacco Product
• Wockhardt – Biosimilars and Complex Generics
• Insight, Advice & Solutions LLC
• NIPTE Our knowledge pyramid topples easily!
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Also note – Advisor (pro bono) to the USP on PCM

3. I wonder,
seriously
• Does working in some of the current
GXP regulated environments impede
adult human development?
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4. I seek to understandstages of adult
development in the context of PQS; individual &
corporate
• What dangers he/she “knows” to be present that causes
him/her anxiety?
• CEO: Loosing access to market, delay in accessing
markets, …..
• FDA leaders: The next “Heparin Tragedy”,…….
• Head of R&D: Delay in clinical trial, missing the “filing
date”,…..
• QC Analyst: The next Out of Specification (OOS)
observation, the next Inspection
• FDA Investigator: High rate of invalidated OOS ,
Cheating by Design,….
• How change leaves him/her feeling defenseless or “In over
his/her head”?
• How it all relates to his/her know-how-what-why and
to his/her stage of development – Looking Good,
Being Good, Doing Good…..
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Life-cycle of a pharmaceutical professional
Looking Good
Being Good
Doing Good
Procrustes

5. BAD-I
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6. Contribute to efforts seeking to fill epistemological gaps in our knowledge and create a
professional design space within which our practices prevent Procrustes within us to
surface and all have opportunity to achieve a higher order of consciousness.
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Design Space
Procrustes
Epistemology
Then and now?

7. Quality?
An elephant in
the dark! Not Six
Blind[folded]
Men and the
Elephant
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If each of us held a candle there, and if we went in together, we could see it - Rumi.

8. 21 CFR 211.25: Not on a solid
theoretical foundation! Nor can it
be expected to have a rich practice
experience.
• The only source of knowledge is experience.
• Rational behavior requires theory. Reactive
behavior requires only reflex action.
• We're blind to our blindness. We have very
little idea of how little we know. We're not
designed to know how little we know.
• What we mean by maturity in people's
thinking is not a matter of how smart they are,
but it is a matter of the order of consciousness
in which they exercise their smartness or their
lack of it.
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Einstein, Deming, Kahneman, Kegan

9. Leading
Indicators:
Cause the
Desired
Effect
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Double-blind, placebo controlled clinical trials – the “Gold Standard”
Quality predominantly confounded in clinical trial information!
Why not require a double-blind, placebo controlled QC testing system?
Oh, that is silly! Is it?

10. NIPTE 2017 Conference
In partnership with the USP
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NIPTE Pharmaceutical Education Mission
Center of Excellence - Pharmaceutical Education &
Certification Roadmap Integration

11. USP Pharmaceutical Education Programs for
Compendial Standards
USP Quality Standards
for Biologics
Excipients Up-to-Date
– the Importance of
Stakeholder
Engagement with USP
Pharmaceutical
Education at US
Pharmacopeia

12. Pharmaceutical Education Needs and Ways to
Improve the Impact of NIPTE’s contributions
Pharmaceutical
Certification Rationale and
Structure: Purdue
University Model
Evolving Industry Trends:
Science-Based Education
Distance Masters and PhD
Program at The University
of Kansas
Training of FDA Reviewers:
Lessons Learned and
Future Perspective
Industry Training in QbD:
Lessons Learned and
Future Perspective
Perspective: Generic
Industry
Perspective: Brand Industry
Pedagogy: Knowledge
Framework, Relating
Science and Engineering to
Development, Assessment
of Competences
[Best] Practices in
Pharmaceutical Education
NIPTE Certification in
Pharmaceutical Science
Pharmaceutical Education:
Priorities, [Best]Practices,
Sustainability
Certification: Explicit and
Implicit Value
Methods of Delivery;
“Flipped” Course

13. A wish; that we change the we think about -
Best, Good and Emerging Practices
Regulation of pharmaceutical quality is based on the assumption
that the processes contained within it are complicated (i.e.,
predictable, for a set defined starting conditions) so that Good
Practices such as defined Operational Routines (SOPs) and Project
Management are sufficient to reliably deliver the desired output.
Occasional errors (nothing is perfect) are quickly detected,
understood, corrected and prevented.
• Best; for simple systems that do not require any sophisticated attention
to education, training and experience
• Good; for complicated systems that require sophisticated attention to
education, training and experience
• Emerging; for complex systems that are not reliably predictable due to
multiple interactions and non-linearities
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14. Key points
• One Quality Voice @ FDA, USP, Industry and Academia
Priorities
• To the patients.
• Performance based standards that promote development of
pharmaceutical professionals and the Pharmaceutical Quality SystemValue
• Educational offering : Fundamentals and Specialized
• Stand-alone system for Assessment (Certification)Delivery
1

15. On an
average day
in the USA
91 people die from an opioid-related overdose (CDC
National Vital Statistics System)
Across the country, people like Riha are going in to fill
prescriptions only to discover that the cost has
doubled, tripled and in some cases soared by 1,000
percent or more (AARP)
In recent years, shortages of all sorts of drugs —
anesthetics, painkillers, antibiotics, cancer treatments
— have become the new normal in American
medicine. The American Society of Health-System
Pharmacists currently lists inadequate supplies of
more than 150 drugs and therapeutics, for reasons
ranging from manufacturing problems to federal
safety crackdowns to drug-makers abandoning low-
profit products. (NY Times)
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1

16. The engine of Affordability in the USA:
Current State (July-August 2017)
1
With U.S.
Generic Drug
Market in Chaos,
Indian Upstarts
Rise
2
Generic price
increased …..
reduced
manufacturer
counts
3
Market .. small
revenue .. supply
… duopoly or
monopoly in
recent years
4
FDA to boost
generic approval
to help
consumers lower
their .. costs
5
Maintain FDA’s
gold standard
for rigorous,
science-based
regulation
Assurance
a concern
Affordability
decreased
Availability +
Affordability
at Risk
One Quality Voice?
Prevailing “blind-spots”?
Increased complexity
increased uncertainty

17. Today, this is
not funny!
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18. Performance
Standards
Regulatory
Compendial
Corporate
Professional
Human Development
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19. Pharmaceutical Quality for the
21st Century 2.0.
• The future of pharmaceutical
quality is six sigma – 3.4 dpm!
• Path to get there- economic
drivers, performance-
based regulation, Quality by
Design, advanced manufacturing
technologies, continuous
improvement and operational
excellence.
• Six-sigma is rarely seen in the
pharmaceutical sector
External Failure: Class I Recalls
Lawrence X. Yu and Michael Kopcha
International Journal of Pharmaceutics 2017
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Note: All recalls > 7000 in just the 2007-2012 period

20. Adulteration
Within our system
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21. How the “Pill Ghost” and the
Procrustean Legacy maintains
our immunity to change?
• Under a shadow; the Generic Drug
Scandal - decisions of Judge Wolin –
left a lasting imprint on the “C” in
CGMP
• In the US; CMC reviewers pushed
back on considering Pharmaceutical
Development Report – “Black Art”!
• Then, what is critical? or Risk?
remained uncertain; everything is
critical and risky – paralysis!
• Increasing material and performance
complexity, increased concern on
controls and generalizability of
SUPAC – defaults (10X, 3-batches,….)
• Regulatory decisions without state-
of-art “pharmaceutical technology”
knowledge became untenable
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22. The legendary quote –still a good summary of the
current state of affairs; good news is that few
exceptions have emerged – such as Amgen!
•“We are a six sigma sector
with 2-3 sigma processes!”
• This was then and as it is now –
The Little Secret (WSJ 3
September 2003)
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Note: The author has no association with Amgen.

23. Amgen’s journey to six sigma – 3.4 dpm: The Background
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Martin VanTrieste, R.Ph CAPA within the Pharmaceutical Quality System, ICH Q10 Conference; October 4-6, 2011 – Arlington, Virginia

24. If I don’t look there is no problem!
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Martin VanTrieste, R. Ph. Improving the Quality of Investigations. PIA Meeting – June 21, 2012

25. From – “If I do not look there is no problem”
to “We are here to serve patients”
The critical question leaders at Amgen
posed - Why are Investigations
Important? Their answer - Stuff
Happens! They decided to leave
behind a mindset – If I do not look
there is no problem - and began their
journey with a reaffirmation “We are
here to serve patients.”
By 2010 – error rates reduced 90%, scrap
reduced 54%, disposition cycle time reduced
54%, and 65% of the manufacturing process
and product parameters were at six sigma.
By end of 2014, 82% of parameters are
performing at six sigma, 14% at 3-6 sigma
and 4% had CAPA open to improving
performance; cost savings cumulated (over
$ 300 million).

26. If I don’t look there
is no problem –
Problem-solving -
Prevention of errors
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Stages of Development
Individuals and Corporations

27. Stages of Pharmaceutical Professional Development
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28. Order
Mindset – Leadership -
Regulatory Context
Cognitive Intrapersonal Interpersonal
3rd
Socialized; Leader:
Ineffective; FDA
Approved – All Okay
Know and follow the
rules, seek support
Are we OK?
Mend
relationships
4th
Self-authored;
Leader: Effective; FDA
Approved – but we are
responsible for quality
Problem-solving,
systems orientation
Did I achieve my
goals?
Follow a process;
methodology
5th
Self-transforming;
Leader: Exceptional;
“Our quality standards”
better than the
minimal requirements.
Explore options,
prevention of problems;
system of systems
Did I achieve a
valued outcome?
Value and learn
from the conflict
Stages of adult human development – the Orders of Consciousness (Kegan)
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4th Order; Self-authored (in every job, line-worker to CEO)
and problem solving know-how – needed for effective PQS!

29. The Amgen’s Journey (Biotech)
• Analytical characterization of raw materials, manufacturing
processes, and products; not just in the development
phase but also, as needed, in the commercial setting
• Will of the management and their involvement to identify,
track and control variation via process capability
assessment
• Continually monitoring to ensuring robust analytical
methods, manufacturing processes, and products (e.g.,
using industry benchmark for analytical variability and
decreasing assay variability; relevant to Invalidated OOS
Rate discussion to follow)
• Training, Qualification, Certification and Mentoring
support to ensure flawless execution, and
• Focus on supply chain controls and confidence.
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Connect to the Pharmaceutical Quality for the 21st Century 2.0.
Economic drivers, Performance-based regulation –
We must simultaneously achieve
Availability, Availability & Assurance and
ensure similar or equivalent performance
improvement in the Biosimilar and Generic
sector.

30. How I wish we would
organize our multiple
cognitive processes?
Remember Einstein’s
challenge that we will
never solve the problems
tomorrow with the same
order of consciousness we
are using to create the
problems of today!
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31. Take a systems, life-cycle, approach
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32. PQS Enablers & Elements: Link GDP to GMP over 5P Life-cycle
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Root-cause of many
OOS issues are often
built in R&D and CMC
Review!
Cognitive biases
Knowledge illusion
Business model: File
first – figure it out
later!
FDA Approved,
Validated – often
reasons for
rationalization!

33. Recognize how adults and corporations mature (or not)
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Recognize that a critical mass of 4+ Order Consciousness (at FDA and in industry)
necessary for effective PQS & Performance-based regulation
Warning Letters, Import Alerts
File first figure out with CMC review staff
- Multiple Review Cycles
Management-based regulations
2nd
3rd
4th
Per CMC reviewer demands
Per CMC reviewer demands
Science based & Risk assessed

34. Synthesis Across
Three Dimensions &
align and link to solutions and tools in HR Systems
(e.g., operational excellence tools industry uses)
• Cognitive competencies involve thinking,
reasoning, and related skills
• Intrapersonal competencies involve self-
management and the ability to regulate
one’s behavior and emotions to reach goals
• Interpersonal competencies involve
expressing information to others as well as
interpreting others’ messages and
responding appropriately
• Professional development stages looking-Good,
being-Good, to doing-Good to Good; in the context
of GXP’s and how these relate to societal needs.
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In the Context of
Pharmaceutical Quality for the 21st Century
Supporting pharmaceutical professional’s success.
2
3
4 5

35. Building on the 2016 initiatives
with a 2020 Vision
• Build on experience and lessons
from NIPTE-Sun Pharma Module 1
• Expanding collaboration beyond
FDA: USP and Industry
• New Prior Knowledge for
Availability, Affordability and
Assurance
• Credibility and business acumen –
“Third Leg of the Stool”

36. Looking forward to discussion @ NIPTE 2017
Anticipating a glimpse of a framework for:
21st Century Pedagogy
One Quality Voice , continually developing
professionals and improving PQS – in the
interest of patients and the next generation of
professionals.
A global [PT] education &
certification system for
individuals and corporation
seeking to achieving and
demonstrate:
One Quality Voice in the
context of PQS via “self-
authorship” relevant to their
current responsibility (front-
lines to CEOs) and future
growth aspirations and
benchmark their continual
development and improved
understanding and
capabilities to solve
contemporary problems.
General module – One
Quality Voice in the context
of PQS & Other Modules
Fundamental and advanced
levels
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37. Acknowledgment
The synthesis of Amgen’s journey discussed in this presentation was shared with Martin VanTrieste
(Chief Quality Office, retired, at Amgen) to ensure that my independent outside-view accurately
represented this journey. Martin graciously reviewed and confirmed its accuracy (7 August 2017).
Thank you! Martin suggested that it would be useful to add - on human performance - that a lot of
the system incorporated learning from systems used by the United States Nuclear Navy.
Also, please see: https://www.linkedin.com/pulse/break-2-3-sigma-barrier-biopharma-case-
example-ajaz-s-hussain-ph-d-/
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