QbD and CoQ IDMA Mumbai 24 March 2015 slideshare

IDMA – UL SUMMIT 24 March 2015, Mumbai
"Evolving Quality Culture in Indian Pharmaceutical Industry“
Strengthening Our Culture of Quality
Ajaz S. Hussain, Ph.D.
Insight Advice & Solutions LLC
National Institute for Pharmaceutical
Technology & Education
3/24/2015 © Ajaz S. Hussain | Insight Advice & Solutions LLC 1

February 25, 2005, Mumbai
The ISPE India- US FDA PAT
forum….
Sharing the stage with…
Dr. M. Venkateswarlu, Deputy
DCGI, and Dr. S. P. Adeshara,
Commissioner, FDCA Gujarat, ..

Organizational Culture, Good or Bad?
What can we learn from cases of
“Organizations Gone Wild”?* Normative
support for misconduct can occur in three
main ways:
Endorse it with varying degrees of explicitness
(e.g., ADM)
“Techniques of neutralization”; or a basis for
rationalization (e.g., SB)
Place a high value on achieving extraordinary
performance (e.g., Enron)
1
2
3
*HENRICH R. GREVE, DONALD PALMER, and JO-ELLEN POZNER. Organizations Gone Wild: The Causes, Processes, and Consequences of
Organizational Misconduct. The Academy of Management Annals Vol. 4, No. 1, (2010), 53–107
Also see: A Demon of Our Own Design
QMS

“And like the
heroes of the
French Revolution,
we look to a future
that will bring us
everything or
nothing, depending
on the public
trust”
 The Nation Needs a Comprehensive
Pharmaceutical Engineering Education and
Research System
 “A recent re-examination by the US Food and Drug
Administration of the current pharmaceutical quality
decision-making system raised fundamental
questions about its efficiency and its continuing
effectiveness to address the increasing
complexity of pharmaceutical systems.”
 “….low success rate for identifying the root
cause of deviations and out-of-specification
observations as well as the predominant focus
on end-product testing—often based on an
inadequate statistical consideration of inherent
variability and static process conditions— which,
some argue, evolved to facilitate regulatory document
expectations for “process validation.”
VIEWPOINT 2005
Pharmaceutical Technology SEPTEMBER 2005

 Indian Pharma & US Market Share
 2001 – 2014 CAGR 35% ; 15%
Volume Share
 “Pharmacy to the World“
 Relatively uniform US FDA cGMP
inspection findings for about a
decade; recently a cluster of
‘breaches in data integrity‘
 Is all of this rational? Is India being
tageted for its success?
 Today increasingly common
understanding and commitment
to work collaboratively
 Culture of Quality
 In the USA: 21st Centrury Initiative
 Shortages, several deaths/ injuries
from contaminated imported and
domestc products, generic product
recalls,.......
 Erroding confidence, new laws, FDA
funding to “test“ quality of generic
products, OPQ/CDEREvolving Context:
Culture of Quality
is a ‘hot’ topic

To remain true to ‘first do no harm’ we, the
legitimate pharmaceutical community, have
inherited, and accepted, a culture of quality
that demands that our intention, our
awareness and our skills deliver ‘quality by
design’ with continued vigilance to detect,
correct and to prevent errors that have caused,
or have the potential to cause, harm to the
patients we serve. We also recognize the
limitations of our pharmacovigilance.
We must more clearly recognize that CAPA is
not ‘continual improvement’ and that we
must strengthen our culture of quality to
deliver continual improvement in our ability
to assure quality, reduce costs and enhance
confidence in what we do. Ajaz S. Hussain, Ph.D., Mumbai, 24 March 2015
VIEWPOINT 2015

 1937
 1962
 1989
 2007
 2012
FD&C Act Kefauver-Harris
1984 Drug Price Competition
and Patent Term Restoration Act
FDASIA ……………….
A partial, historical, ‘snap-shot’ of the US FD&C Act
Proactive risk
classification &
mitigation
needed

Patients' trust in medicine and information
Trusting our ability as a reliable information provider
involves a reliance on us having the right attitude
towards the possible consequences of our epistemic
work. Torsten Wilholt. Epistemic Trust in Science. Br J Philos
Sci (2013) 64 (2): 233-253

“Generics is all about file first and figure out later” State
of QbD Implementation Report to FDA June 2010, Ted Fuhr,
Mckinsey& Company
“It would also mean the FDA had no power to deny tentative
approval to an application that clearly could never win final approval -
an applicant could state in its ANDA that it planned to
manufacture a generic drug in an outhouse behind the
applicant's house using a child's chemistry set.“
U.S. District Judge Beryl Howell (March 11, 2015)

Staff Supervisors Sr. Mgmt.
R&D
Operations
Quality Unit Others
CEO
Company X: Normative support for Culture of Quality?
Baddi
Mumbai

Do these questions continue to linger in
Company X?
What is pharmaceutical quality?
Compendial testing sufficient?
Process validation – representative of commercial manufacturing?
Any deviation from cGMP means the product is ‘adulterated’?

Practice, Control, Process: Maturity
Initial
• Unpredictable
Managed
• Characterized,
but reactive
Defined
• Characterized;
proactive
Measured &
Controlled
• In control
Optimizing
• Focus on
improvement
Capability Maturity Model Integration; Carnegie Mellon University
A validated process?

Maturity Level & Assurance of Quality
Managed Characterized,
but reactive
High risk of
‘Cheating by
Design’
“Trial
Injections”
“Testing in to
Compliance”
Defined Characterized;
proactive
Lower level of
assurance
Stopping &
Correcting
Batch
Rejection
Measured &
Controlled
In control
Quality by
Design
Quality
Assured
Improvement
Opportunities

Risk of unintended or intended normative
support for ‘testing into compliance’?
attitude
toward
performing
the
behavior
Process
validation is
done so
quality is
good;
test prone to
error
“Batch failure
means I made
a mistake”
subjective
norm
Documents
not critical;
Compendial
testing
sufficient
Local
regulators
collect & test
samples – no
issue there!
“Testing into compliance”

Patterns suggestive of ‘intentional holes’
“….records not
completed
contemporaneously”
“…observed analyst
back-date logbooks”
“…trial injections…..”
“…results failing
specifications are
retested until acceptable
results are obtained….”
“…over-writing
electronic raw data…..”
“…OOS not investigates
per XYZ SOP”
“…appropriate controls
not established….”
Each additional
observation adds
reasons to confirm
that this is very
likely a system with
intentional ‘holes’
in its defenses.

Organization (Policies
& Sr. Mgmt.)
Technology
(Constraints & Controls)
Individual
(Training & Certification)
Team & Supervisor
(Soft Defenses)
Defenses
(Quality Management System)
Error
Latent अप्रकट conditions Goal conflicts & mixed messages
Design flaws
Production pressures
Fear of error
“WE CANNOT CHANGE THE HUMAN CONDITION. BUT…WE CAN
CHANGE THE CONDITIONS UNDER WHICH HUMANS WORK”
JAMES REASON

How would you
respond to this
statement? 15.21
9.9
14.1
17.5
43.4
At many Pharma companies
[in India] the staff would feel
afraid to question a
supervisor’s order even when
they know for
sure that the supervisor’s
order is not in the
interest of patients.
3/24/2015 Ajaz S. Hussain | Insight Advice & Solutions LLC 18
I disagree with this
statement
I completely agree with
this statement
N=263
Skipped = 0

How would you respond to
this statement?
I think management should
urgently work towards
making error/mistake
reporting Normal, Easy and
Rewarding.
5.8
6.6
17.4
32.8
31.54
3/24/2015 Ajaz S. Hussain | Insight Advice & Solutions LLC 19
It is already easy – so
this is not urgent.
It is very difficult currently so this is
very urgent topic
N=259
Skipped =4

Rationalization &
Attitude
Pressure &
Incentive
Opportunity –
‘holes in the QMS”
“The key to good
decision‐making is not
knowledge, it is
understanding. We are
swimming in the former.
We are desperately
lacking in the latter” ‐
Malcolm Gladwell

Going beyond rules pays..

Culture of
Quality
Normal
Rewarding
Easy
QMS
System
Knowledge
Variation
Behavior
Behavior -
GXPs
Fear
Removed
Mastery
Awareness
Environment
Leadership
Emphasis
Message Credibility Peer Involvement
Employee
Empowerment
Connect to
CoQ
Connect
to GXPs
A Framework and a Tool (for gap analysis)

Culture of Error गलती
Management प्रबंधन
What words would you use to
describe how you feel and
react to mistakes?
Your own, of a co-worker, of a
subordinate.
How does your supervisor
react?
Picture purchased from www.pixtastock.com

Culture of Error Management प्रबंधन
• Error strain
• Covering up
Fear of Errors
X
• Anticipation
• Risk taking
Awareness
Y
• Development QbD/RFT
• Error detection, Communication
• Analyzing errors, Correction
Mastery
orientation
Z

Two products; better than placebos
Culture of
Quality
Quality
by
Design
Good
[Manufacturing]
Practices
Quality
Management
System
Immediate Attention:
Management responsibilities – leadership emphasis and
message credibility to remove even a perception of
normative support for cGMP deviations; reduce fear
Effective training, coaching and mentoring: System,
design and statistical thinking; Culture of quality training
Setting the ‘right specification’
Effective root-cause investigations and CAPA; improve
logic and communication
Change current regulatory requirements for post-
approval supplements to facilitate effective CAPA

“Both industry and the FDA need a culture of
quality” (see link to FDA website)
• Industry and the FDA have the shared
obligation to reduce quality errors and
provide high quality medications to the
American public.
• To fulfill this responsibility, both industry
and the FDA need a culture of quality.
• A true quality culture is an environment in
which the entire organization not only
follows quality guidelines but also is
focused on continuous improvement.
• It is important to recognize that financial
incentives don’t always reduce errors.
• Employees must be passionate about
eliminating mistakes and making quality
their driving principle.

 Systems thinking: System is the product of interacting parts; improving the parts
taken separately will not improve the system
CEO &
Sr. Management
Culture
of Quality
Managers &
Leaders
Effective
QMS
GXP
Compliance
All
Employees
Quality is Easy

9. Into a blind darkness they enter who follow after the Ignorance, they as if into a greater darkness who devote
themselves to the Knowledge alone.
10. Other, verily, it is said, is that which comes by the Knowledge, other that which comes by the Ignorance; this
is the lore we have received from the wise who revealed That to our understanding.
11. He who knows That as both in one, the Knowledge and the Ignorance, by the Ignorance crosses beyond
death and by the Knowledge enjoys Immortality
Isha Upanishad: Knowledge and Ignorance, Verses 9 – 11
VIDYA AND AVIDYA
VOLUME 17 THE COMPLETE WORKS OF SRI AUROBINDO (2003)
The problem of reductionism: - it works for small, not for big steps - it misses the
whole - it misses the meaning - in the end, it undercuts itself.
Systems approach……
Note. I have take a different point
of view from that of Dharm P. S.
Bhawuk, Science of Culture and
Culture of Science: Worldview and
Choice of Conceptual Models &
Methodology. The Social Engineer.
Vol. 11, No. 2, July, 2008.
Practicing to improve
(awareness of) our
intentions is our
wisdom tradition, and
is reflected in our laws,
in US, India and
around the globe…

QbD and CoQ IDMA Mumbai 24 March 2015 slideshare

Empfohlen

Empfohlen

Weitere ähnliche Inhalte

Was ist angesagt?

Was ist angesagt? (20)

Ähnlich wie QbD and CoQ IDMA Mumbai 24 March 2015 slideshare

Ähnlich wie QbD and CoQ IDMA Mumbai 24 March 2015 slideshare (20)

Mehr von Ajaz Hussain

Mehr von Ajaz Hussain (20)

Kürzlich hochgeladen

Kürzlich hochgeladen (17)

QbD and CoQ IDMA Mumbai 24 March 2015 slideshare