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 LLCNational 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


http://images.alfresco.advanstar.com/alfresco_images/pharma/2014/08/22/fcb413f5-f60b-4316-a400-c5e2f02cb9e8/article-178644.pdf

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 ActFDASIA ……………….

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


http://www.slideshare.net/a2zpharmsci/voice-of-the-patient-41299036

http://www.slideshare.net/a2zpharmsci/voice-of-the-patient-41299036

“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)


http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AdvisoryCommitteeforPharmaceuticalScienceandClinicalPharmacology/UCM263468.pdf

http://www.courthousenews.com/2015/03/11/disgraced-drugmakers-lawsuit-infuriates-judge.htm

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 controlQuality by

DesignQuality 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

43.4At many Pharma companies [in India] the staff would feel afraid to question asupervisor’s order even when they know forsure that the supervisor’s order is not in theinterest 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=263Skipped = 0

How would you respond to this statement?

I think management should urgently work towards making error/mistakereporting Normal, Easy and Rewarding.

5.86.6

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=259Skipped =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

EnvironmentLeadership Emphasis

Message Credibility Peer InvolvementEmployee

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.


http://www.fda.gov/Drugs/NewsEvents/ucm428298.htm

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…


Leadership & Management

QbD and CoQ IDMA Mumbai 24 March 2015 slideshare