How to Build Effective Pharmaceutical Quality Managment System & Self-development LIU Lecture 8 January 2018

How to build & maintain an
effective pharmaceutical quality
management system?
Ajaz S. Hussain Ph.D.
Adjunct Professor the Long Island University,
The Arnold and Marie Schwartz College of
Pharmacy
1/7/2018 ©Copyright 2017-2018 Ajaz S. Hussain, Ph.D. 1

[After graduation] Some adults
continue to develop but at
different rates, many do not!
©Copyright 2017-2018 Ajaz S. Hussain, Ph.D. 21/7/2018

After graduation how will you
continue your development?
What information
will affirm your
progress?

The know-how for
building an
effective quality
management
systems can be the
know-how to
continue your
development!
LIU education and training will open a door to enter a different
system; corporation, FDA, ….
How and what we experience, day to day, can be a critical component
of our continuous development
We often do not know how to utilize experience as part of the
development plan
We let it happen (ad hoc) and just count years on the job as
experience – this is inefficient and costs us many opportunities
21st century is the Experience Economy, then 911 changed the world -
making what we experience a more dominant factor
Healthcare, new drug pricing and drug development is changing and
confidence in generic is a growing concern
A systems approach was a major emphasis of the Pharmaceutical
Quality for the 21st Century Initiative; the sector is still struggling
The know-how for building an effective quality management systems
can be the know-how to continue your development!

How to share this know-how?
• Build on the goals of your LIU education and training
• Describe and illustrate how the Experience Economy has
already changed, and will continue to change, the
healthcare and new drug pricing and development and
impacting generic drugs
• Start with the ICH Q10 model of Pharmaceutical Quality
System and consider system within a system (individual
human being is a system) framework to identify common
effectiveness measures to illustrate steps to improve a
system and develop individuals (Amgen case example)
• Utilize relevant development and behavioural theories to
outline a easy to use/remember framework that students
can use as a starting point in writing their self-
development plan

Build on the goals of LIU
education and training
• Doctor of Philosophy in Pharmaceutics
• Goal 1: Design, conduct and defend original research in one’s field of expertise.
• Goal 2: Apply analytical and critical thinking in reviewing scientific literature and evaluating research
findings
• M.S. in Pharmaceutics with specialization in Industrial Pharmacy
• Goal 1: Demonstrate acquisition of knowledge of fundamental concepts in pharmaceutics/industrial
pharmacy
• Goal 2: Integrate advanced knowledge and concepts in pharmaceutical sciences.
• Goal 3: Effectively communicate scientific information both orally and in writing to inform and
educate professional and scientific peers.
• Goal 4: Develop group dynamic and teamwork abilities.
• M.S. in Drug Regulatory Affairs
• Goal 1: Demonstrate an understanding of the role of a medical products regulatory affairs specialist
and the dynamic nature of the regulatory field.
• Goal 2: Identify and utilize the laws and regulations that apply to the development, testing, and
production of new medical products, including medical devices, In-Vitro Diagnostics (IVDs,
pharmaceuticals, biotechnology-derived therapeutics, and biologics.
• Goal 3: Identify a specific regulatory issue for either a drug or device and be able to justify an
appropriate position or strategy through presentation and written skills that permits students to
acquire analytic and reasoning skills along with effective communication skills.
• Goal 4: Demonstrate the ability to develop personal and professional skills in the field of regulatory
affairs.

Building on the
“LIU opportunity”
you have been
utilizing to acquire
knowledge and
develop your skills.
• Demonstrate acquisition of knowledge of
fundamental concepts. Apply analytical and
critical thinking. Demonstrate the ability to
develop personal and professional skills.
Develop group dynamic and teamwork abilities.
Demonstrate an understanding of the dynamic
nature of the regulatory field. Educate
professional and scientific peers.
• Systems thinking is a different perspective on
reality. A perspective that sharpens our
awareness of wholes and how the parts within
those wholes interrelate.
• What and how we experience determines our
self-development. We must objectively
benchmark our Experience and leverage it; let
us discuss how to.

The Experience
Economy
Changing the healthcare
and new drug pricing
and development and
impacting generic
drugs.

Welcome to the Experience Economy!

Transforming Healthcare
Organizations for the 21st Century
• The Toyota Production System - a human-
centered (versus tool-based) business
performance improvement process
• Fundamental in the evolution of the
workplace is everyone’s ability to recognize
normal from abnormal, and have the ability to
do something about it.
• This “stop and look” approach minimizes
errors and inefficiencies while quickly
addressing and resolving issues as they arise.
©Copyright 2017-2018 Ajaz S. Hussain, Ph.D.
Mike Olive and Mike Brown. Toyota Production System: Transforming Healthcare
Organizations for the 21st Century. PSQH. November/December 2009.

Pharmaceuticals in the Experience
Economy: illustrative examples of
changing business models and the
rising need for Assurance

We are experiencing pain and inequality in ways that are unprecedented!

Experience and The Gold Standard
Clinical Trial System is
“Broken” and there need to
be new ways to collect and
utilize patient data
Dr. Janet Woodcock
(September 2017)
1
Interactions between the
brain and spinal cord
mediate value effects in
nocebo hyperalgesia.
Science, 358(6359), 105-
108 (2017).
2
Pharmacodynamics of
Placebo: Expectation
effects of price as a proxy
for efficacy.
Neurology. 10: 766-767
(2015)
3
The double-blind,
randomized, placebo-
controlled trial: Gold
Standard or Golden Calf?
Journal of Clinical
Epidemiology, 54(6): 541-
549 (2001)
4
Why Is the Placebo Effect Exploding in The U.S. But Nowhere Else?
Forbes. 7 October 2015

Experiencing Automatic Substitution
Annals of internal medicine. 161(2), pp.96-103 2014
Burden of Changes in Pill Appearance for
Patients Receiving Generic Cardiovascular
Medications After Myocardial Infarction.
The Washington Post. 14 July 2014.
If Color or Shape of Generic Pills Changes,
Patients May Stop Taking Them.
Final Guidance. June 2015
Guidance for Industry. Size, Shape, and Other
Physical Attributes of Generic Tablets and
Capsules. Pharmaceutical Quality/CMC.
Generics for Me, but a
Brand for You! #@*
Research in Social and
Administrative Pharmacy, 8(6),
pp.574-578 (2012)

Assurance is a CQA! Need to account for placebo/nocebo effects in practice.
©Copyright 2017-2018 Ajaz S. Hussain, Ph.D. 151/7/2018

Levothyrox Experience in France
Aug. 24 2017
Levothyrox: The controversy over one of
France's most commonly prescribed drug
explained (The Local)
Sep. 11 2017
No fraud, no conspiracy, no error: France
and Merck say reformulated Euthyrox is
safe (in-Pharma Technologist.com)
Sep. 16 2017
France to bring back old thyroid drug after
complaints (RFI)
Oct. 4 2017
Police raid Merck pharmaceutical plant
amid mysterious drug crisis. Is something
wrong with hormone therapy or are
patients over-reacting? (arsTECHNICA)

Experience New & Improved Formulation!
Assuring the Quality of
the Most Prescribed
Drug
New formulation
launched in France,
March 2017
Within a few weeks,
the social media
started buzzing.
The backlash
intensified; the media
storm posed political
problem for the
French government!
Just wondering if anyone else is taking the new Levo formula from XYZ. I've been on it about 2 or 3
weeks and so far gained three kilos. 😩😩!
“France brings back a phased-out drug after patients rebel against its
replacement” - Science Magazine. 27 September 2017
Germany, New Zealand,….

Value-based pricing
Novartis signs on to value-based
pricing for Entresto® (May 2016)
CAR-T, Kymriah® - $475,000 Cancer
Drug Comes With A Money-Back
Guarantee (August 2017)
71% of pharma executives believe such arrangements could be rewarding for
companies that bring innovative products to market (PwC, 2017)

Economy Industrial Service Experience
Function Make Deliver Stage
Offering Tangible Intangible Memorable
Attribute Standardized Customized Personal
Supply Inventory On-demand Revealed over time
Seller Manufacturer Provider Stager
Buyer User Client Guest or Member
Need/Demand Features Benefits Sensations
New Drugs Clinical Trials → Personalized & Patient-centric
Real-world medical errors, adherence, and
experience: pharmacodynamics of drugs,
placebos & noceboes. “Pay for performance.”
Generics “Therapeutic Equivalence” →
Automatic substitution. Same INN,
no brand name, “bioequivalent.”
Real-world adherence and outcomes.
I love my generics; they work and save me a ton!
Who makes the medicine I take?
Generics for me, brand for you?
Biosimilars
“Totality of Evidence of
Similarity” →
Unique INN, Brand-name; criteria
for interchangeability?
Currently evolving - a hybrid of the new and
generic experience?
Summary of key trends in the Pharmaceutical Experience Economy

The ICH Q10 model of
Pharmaceutical Quality System
System within a system
4 A’s: Availability,
Assurance, Assurance
and Affordability
1/7/2018©Copyright 2017-2018 Ajaz S. Hussain, Ph.D. 20

System for
managing
quality [and
money]
• ICH Q10: Pharmaceutical Quality System; augments Good
Manufacturing Practices – What does this mean? A folder of
policies and procedures does not make is a quality system!
• This tripartite harmonized ICH Guideline was finalized under
Step 4 in June 2008.
• It applies to pharmaceutical drug substances and drug
products, including biotechnology and biological products,
throughout the product lifecycle.
• The elements of Q10 should be applied in a manner that is
appropriate and proportionate to each of the product lifecycle
stages, recognizing the differences among, and the different
goals of each stage.
• Download from:
http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products
/Guidelines/Quality/Q10/Step4/Q10_Guideline.pdf
• Also see: Integration of Q8, Q9, & Q10 ….. [Draft Q 12]
• http://www.ich.org/products/guidelines/quality/training-
programme-for-q8q9q10/presentations.html

Quality of Money?
• Counting and accounting of money – "objective”?
• Quality of Money - is it objective or subjective?
• Quality of “Fiat Money” – is the comforting sensations
of “belief and trust”, distributed among a population, in
the stability and capability of the political order issuing
the currency
• Expenditure in R&D is an investment; In manufacturing
it is a cost.
Quality of Pharmaceuticals?
• Pharmaceutical management system – must strike the
“right” balance between profit and patients.
• To ensure effectiveness of a PQMS, among other things, we
must factor in the knowledge that human beings are
motivated by cognitive biases of which they are largely
unaware.

The End of Rational Economics
HBR July-August 2009
• We’re painfully blinking awake to the falsity of standard
economic theory—that human beings are capable of always
making rational decisions and that markets and institutions, in
the aggregate, are healthily self-regulating.
• We are finally beginning to understand that irrationality is the
real invisible hand that drives human decision making. It’s been a
painful lesson, but the silver lining may be that companies now
see how important it is to safeguard against bad assumptions.
Armed with the knowledge that human beings are motivated by
cognitive biases of which they are largely unaware (a true
invisible hand if there ever was one), businesses can start to
better defend against foolishness and waste.

FDA classifies as therapeutically equivalent those
products that meet the following general
criteria:
• They are approved as safe and effective;
• They are pharmaceutical equivalents in that they contain identical
amounts of the same active drug ingredient in the same dosage form
and route of administration, and meet compendial or other
applicable standards of strength, quality, purity, and identity;
• They are bioequivalent in that they do not present a known or
potential bioequivalence problem, and they meet an acceptable in
vitro standard, or if they do present such a known or potential
problem, they are shown to meet an appropriate bioequivalence
standard;
• They are adequately labeled, and
• They are manufactured in compliance with Current Good
Manufacturing Practice regulations.

Cognitive Biases & Therapeutic Equivalence

Prescription for trouble - How flaw in FDA safety net
may pose a risk to the public with generic drugs.
The San Francisco Chronical - 22 December 2002.
• Bioequivalence assessment with apple
juice - “bioINequivalence,” not
submitted to FDA; instead, submitted
study done with chocolate milk which
“passed”! ANDA approved in 1998.
• The company spokesperson - “FDA
required only one study showing
equivalence”. Disclosure of the failed
(apple juice) study in spring of 2000;
forced the recall.
• On October 29, 2003, FDA proposed to
amend its regulations to require generic
(ANDA) applicant to submit data from all
bioequivalence studies. The final rule
went into effect July 15, 2009.

Stages of adult development – the Orders of Consciousness (Kegan)

Awareness of Experience: noun -practical contact with and observation
of facts or events and verb - feel an emotion (with epistemology)
To raise the Order of Consciousness: Self-authored mind to Self-transforming mind!

Recognize how adults and corporations mature (or not)

PQS effectiveness
depends on a
critical mass of
4th and 5th Order
Consciousness!
Effective

Culture of Pharmaceutical Quality – QMS – Individual Practitioners: System within Systems

Building on the goals of your
LIU education and training
• We learned how the Experience Economy has already
changed, and will continue to change, the healthcare and
new drug pricing and development model and how it is
impacting generic drugs
• Using the ICH Q10 model we adopted a system within a
system framework to identify common effectiveness
measures – Assurance, Availability, Adherence and
Affordability to understand how these relate improvement
of a system and development of individuals (Amgen case
example)
• Outlined an easy to use/remember framework that we can
use as a starting point in writing their a self- development
plan

Believing Vs Knowing
• We often take action based on our belief
• We draw conclusions based on our assumptions
• We make assumptions based on what it means to
us
• We are makers of meaning (per our cultural and
personal beliefs)
• We are prone to select data based on what we
believe
• We observe, record data (and “feel” - experience)

Build on the “LIU
opportunity” and
objectively
benchmark
Experience and
leverage it
• Demonstrate acquisition of knowledge of
fundamental concepts. Apply analytical and
critical thinking. Demonstrate the ability to
develop personal and professional skills.
Develop group dynamic and teamwork abilities.
Demonstrate an understanding of the dynamic
nature of the regulatory field. Educate
professional and scientific peers.
• Systems thinking is a different perspective on
reality. A perspective that sharpens our
awareness of wholes and how the parts within
those wholes interrelate.
• What and how we experience determines our
self-development. We must objectively
benchmark our Experience and leverage it!

Polarization in America
Pictures from: https://www.salon.com/2016/06/06/study_liberals_and_conservatives_have_different_brain_structures_partner/
Eliminating the “middle ground”!

Experience Economy, 911, political
polarization – changing brain structures?
• Our inability to find middle ground on practically anything
• Political views reside on a continuum that is mediated in
part by universal human emotions such as fear
• Size of right amygdala increased. Amygdala processes
emotional information—specifically fear-based
information!
• https://www.scientificamerican.com/article/calling-truce-
political-wars/
• https://www.salon.com/2016/06/06/study_liberals_and_c
onservatives_have_different_brain_structures_partner/

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