The document discusses the concept of "Validation 4.0" in the context of Pharma 4.0. It argues that Validation 4.0 involves transforming old approaches to compliance into a new mindset focused on internal assurance, self-assurance, and authoring validation policies without needing FDA guidance. Validation 4.0 is about developing professionals and ensuring the integrity of their data and experience. The keynote talk will elaborate on Validation 4.0 and providing SMART ways to validate professionals and corporations to make progress in Pharma 4.0 credible.

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VALIDATION 4.0 MAKES
PHARMA 4.0 CREDIBLE
The notion of Validation 4.0 in the title of this keynote relates to
the development and maturity of people and professionals,
which I will elaborate on in the context of the ValGenesis
experience of its users and service providers.
I wish to acknowledge and appreciate some of the ongoing
efforts at the International Society for Pharmaceutical
Engineering to dialogue, roadmap, and provide practical
guidance for Pharma 4.0™
Among other things, Pharma 4.0 is envisioned to encompass
the notions of a SMART [Pharmaceutical] Factory in the context
of the Industry 4.0 revolution accelerating outside the pharma
sector.
To succeed in this endeavor, we need to transform our old ways
of approaching compliance to a new mindset and, to do so,
break with tradition and lay a new foundation for validation,
“Validation 4.0,” which also is a core operational topic of
discussion and practical guidance within the ISPE community.
Validation 4.0 in this talk is about internal assurance, self-
assurance, and self-authoring policies, plans, and procedures,
ideally without the need [to wait] for FDA guidance.

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MY ATTENTION IS ON
PROFESSIONAL DEVELOPMENT AND
SYSTEM MATURITY.
I draw inspiration from the Hermetic principle "As Above, So
Below - As Within, So Without" to consider the chaotic and
complex characteristics of socio-technical systems in which
we live and work.
I observe, make sense of, and seek a deeper understanding
of ways to empower minds in chaos to manage materials,
machines, and money.
In my understanding, I will elaborate on Validation 4.0 and
share some insights on SMART ways to achieve internal and
external validation of “people" and "professionals" in their
various roles and responsibilities, ensuring the integrity of
their data and experience.
In this sense, the title of my talk reads, Validation 4.0 of
professionals and corporations makes progress in Pharma
4.0 credible! This talk builds on a blog post I wrote many
years ago, Education, Training, Experience & 21 CFR 211.25:
Theory, Practice and Epistemology.

4. • ValGenesis VLMS 4.0 (2018)
• ValGenesis VLMS 3.0 (2014)
• …. ValGenesis November 2005
VLMS 4.2 (2023)
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5. “Built for modern
validation.”
But we live in a
post-modern, post-
truth world in an
experience
economy!
Validation 4.0
makes Pharma 4.0
credible.
Sustain and Build a Quality Culture in Today's Realities. KENX’s Computer Software Validation & Software Assurance University, (December 2021)

6. PAY AT T E N T I O N TO U X A N D V X .
WHEN
EXPERIENCE
MATTERS MORE
Validation 4.0
(IQ, OQ, PQ & CPV for Valid Experience)
Note: The genesis of “validation” stems from our need to control, and it evolves under the influences of our
“desires” and opinions. In a rule-based society, it is also a legal (mandate. In modernity, evidence-based practices
are highly valued, and impartial inspections confirm adherence to them. As a system matures and consistently
exhibits confident internal validation, its offerings create the sense of security we require, and the necessity for
external audits decreases and may even become discretionary, depending on an adequate level of objective risk
management. ValGenesis can be a SMART solution in this socio-technical context
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MANY [NEW] ASSOCIATES, ONE QUALITY VOICE?
HOW WE OPTIMALLY LEVERAGE DIVERSITY TO IMPROVE UX AND SX

8. MY VIEWPOINTS
Academia (1986-1994)
US FDA (January 1995-October 2005)
Advisor ValGenesis (November 2005- present)
Global Head Biosimilar Development, Sandoz/Novartis
CSO & VP Next Generation Products, Philip Morris
International
CSO President Biotechnology, Wockhardt, Ltd.
Insight Advise and Solutions, LLC
President National Institute for Pharmaceutical Technology
& Education
Presently advisor at ValGenesis and others such as Applied
SmartFactory, and CONTINUUS Pharmaceuticals, ….
The Nation Needs a Comprehensive Pharmaceutical Engineering Education and Research System (September 2005) (ISPE.org)
4 Life Sciences Lessons from the PAT to QbD Journey (Valgenesis.com)
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Assuring “integrity of
experience.” A personal
VLMS perspective.

9. 4 Life Sciences Lessons from
the PAT to QbD Journey
(Valgenesis.com)
Hone Quality through Research
before and after “approval.”
Education and Training Alone Cannot Overcome
Displacement by AI, Experience Integrity Matters
Facilitating Adult Human Development Empowers
Our SMART Future
Continual Professional Development is Essential

10. Seek a holistic view from different viewpoints:
Practice transitioning from intricate details to the bigger picture and vice versa. Get good (=
valid) at doing so effortlessly and with seamless precision.

12. A legacy of lingering errors of omission
Critical Path Initiative Challenges: FDA ACPS Meeting 19 October 2004

13. SMART MINDS
SMART machines, materials, and
money aligning with critical
[Pharma] 4.0 directional vectors
The FD&C Act (1938), CGMP Regulations, and
“Predicate rule” (Part 11)
Scientific training and experience to assess
evidence of “substantial effectiveness” fairly
and responsibly (Kefauver Harris Amendment,
1962)
21 CFR § 211.25 Personnel qualifications –
“education, training [and] experience”
Legacy, responsibility to adhere to and improve
In Over Our Heads — Robert Kegan | Harvard University
BioPhorum Resource - Digital plant maturity model

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HOW TO BREAK THE PHARMACEUTICAL 2-3 SIGMA BARRIER (LIKE
AMGEN) (PHARMACEUTICALONLINE.COM) 2017

15. “One Quality Voice” amidst variable qualia, systems
maturity, and quality culture.
FDA’s White Paper (2015): One Quality Voice and CDER’s Quality Management Maturity (QMM) Program (August 2023 update)

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DON’T FORGET THE LEGACY OF “FDA
APPROVED,” VALIDATED PROCESS!
• “Doing more is recognizing that our systems
are socio-technical systems. [System] maturity
is our maturity, to be suitable and capable of
moving from “don’t use and don’t tell” and “if I
don’t look, there is no problem” and “fail and
fix” to be able to “predict and prevent” harm.”
Pharmaceutical Quality, Team Science, and Education
Themes: Observations and Commentary on a Remarkable
AAPS PharmSciTech Theme Issue | SpringerLink (4 March
2021)
• “A grain of wise subjectivity tells us more
about the real world than any amount of
objectivity.” ― Judea Pearl, The Book of Why:
The New Science of Cause and Effect (2018)
“Root cause unknown” can point
to legacy “common causes”
To critically risk assess “common cause
variations,” make “common sense.”
Physicochemical failure modes for Narrow Therapeutic Index (NTI) drugs (europeanpharmaceuticalreview.com)

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HOW TO MAKE COMMONSENSE GOOD?
• Expand and share awareness to make sense in
a way that bridges the differences in
understanding
• Do so with the integrity of experience!
• Note that understanding is shared more
efficiently within a technical discipline (a
downside of ‘group think” poses a risk of
shared biases) than across disciplines; shared
sensemaking to mind the gaps fairly and
responsibly generates Team Science.
• In Team Science, we ask questions that induce
critical thinking without criticism, scientific
questions, not scientism
Validate sensemaking process? VLMS for good sensemaking
Adapted from Dennis K. Leedom. Final Report, Sensemaking Symposium, October 2001. Command and Control Research
Program, Office of the Assistant Secretary of Defense, for Command, Control, Communications, and Intelligence.

18. PHARMACEUTICAL “NEW PRIOR KNOWLEDGE”:
TWENTY-FIRST CENTURY ASSURANCE OF
THERAPEUTIC EQUIVALENCE | AAPS PHARMSCITECH (SPRINGER.COM)
• [A] No ANDA has been submitted for 10% of all FDA-
approved NDAs (100%) despite expired patents and
exclusivities.
• [B] Quoting an FDA-issued Federal Register notice—
“The drugs described in more than half of all FDA-
approved ANDAs are never marketed, marketed
only after a substantial delay after approval, or
marketed only intermittently. Such failures to
market contribute to drug shortages and hinder
consumer access to approved products.”
• [C] Percentage of approved and commercialized
ANDA’s
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VALGENESIS: A SMART SOLUTION
CRITICAL WITHOUT CRITICISM, SCIENTIFIC, NOT SCIENTISM
• I am eager to learn about the ValGenesis user
experience at Valconnect 2023 and learn what the
ValGenesis UX Research Team is up to now
• Dexcom’s experience migrating from a paper-based
system
• The story of using the Project Module in ValGenesis
VLMS to manage all validation deliverables for
projects and changes at Cardinal Health.
• Other experiences
• Satisfying individual needs and aspirations for
continual improvement, development, and
maturity
• Satisfying continual improvement,
development, and maturity of the VLMS
platform
• Satisfying aspirations of ValGenesis
development and maturity to remain a de facto
VLMS standard in life science
Satisfying UX Satisfying VX

20. VALGENESIS SMART
• Machines: Self-monitoring, analyzing and reporting
technologies
• Minds: Self-monitoring, analyzing, researching, and
testing [to detect and correct errors of omission]
• Integrating SMART machines and minds is crucial to
managing material variability and for the credibility
of efforts and outcomes while navigating in reality
with a Pharma 4.0 roadmap
• Attention to the integrity of UX and SX necessary
for Validation 4.0
• Validation 4.0 personally is self-assuring valid
sensemaking via self-authoring, making internal
validation normal, easy, and rewarding
• Externally, VLMS 4.0 opened the door to ValGenesis
SMART; now VLMS 4.2 helps place critical thinking
upfront and move towards an improved scientific
basis for risk management
SMART dimensions Validation 4.0 ([n the context of] Pharma 4.0
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