insights on culture of quality what have i learned 22 september 2015

Insights on Culture of QualityWhat have I learned from Teaching a course on

Culture of Pharmaceutical Quality?

Ajaz S. Hussain, Ph.D. Insight Advice & Solutions LLC

9/20/2015© Ajaz S. Hussain Insight Advice and Solutions LLC 1

Outline

Background

• Breaches in data integrity

• My viewpoints

• About the training program

Challenges

•Breaches – being detected currently are not necessarily new;

•GMP remediation's slow and/or ineffective (repeat violations)

•Assumptions and blind-spots; irrational decisions and behaviors of Management and Staff

Questions

•Why criticality of CGMPs not widely appreciated as expected by the customer (US FDA)?

•What “norms” provide reasons to rationalize cGMP deviations?

•How a company can re-build lost credibility? Better option improve credibility?

Insights

On the three questions posed


Critical Importance of Data Integrity

My Viewpoints on ‘Culture of Quality’

Training Program on ‘Culture of Quality’

Background9/20/2015© Ajaz S. Hussain Insight Advice and Solutions LLC 3

Data Integrity: One of the most important and

relevant topics currently discussed

“Testing into compliance, data manipulation, data deletion/ record

destruction, misreporting, disregarding failing and/or questionable

results, all leading to possible breaches in the integrity of critical

data, has become one of the most important and relevant topics

currently discussed by industry and regulators from around the

world.”

Carmelo Rosa. Data Integrity, Essential Part of a Quality System. DIA Multicenter International Data Integrity Workshop. 13-14, Nov. 2014. Bangalore, India.


My Viewpoints

Education, Training & Experience

B. Pharm. (Mumbai)., Ph.D. (Cincinnati)

Teaching Pharmacy @ Ohio Northern University & University of Cincinnati

US FDA

Sandoz (Biosimilars)

Philip Morris International (Plant based vaccines & Harm reduction)

Wockhardt (Biosimilars & Complex Generics)

Since 2013 - Insight Advice & Solutions LLC (50%)

Since 2014 - National Institute of Pharmaceutical Technology & Education (50%)

Culture of Quality Training

Effective training [and resolution of issues] requires us

to make effort “Dil Se”; “without ‘finger-pointing”

A framework based on ‘Behavioral Economics’, as

opposed to ‘Ethics/Morality’, developed

Highlight consequences of biases, blind-spots and

irrational behaviors & showcase importance of

System!

Linked to current and emerging regulatory

expectations; but not focusing on specific regulatory

requirements

See authors LinkedIn and Slideshare sites for

additional information


https://www.linkedin.com/in/ajazshussain

http://www.slideshare.net/a2zpharmsci/edit_my_uploads


Decision under risk and uncertainty are

subject to a “framing effect” – and it is

powerful. How we ask a question –

“framing” -can influence how people

react to it. This can also affect our

memories of the event. We are subjected

to many other biases. We are

predictably irrational!

Professor Kahneman’s System 1 and System 2 of human cognition conceptualized


Behavioral Economics:Predictability Irrational Behaviors The psychological principles that govern the

perception of decision problems and the evaluation of probabilities and outcomes produce predictable shifts of preference when the same problem is framed in different ways.

Reversals of preference are demonstrated in choices regarding monetary outcomes, both hypothetical and real, and in questions pertaining to the loss of human lives.

… A man [or woman] could be judged irrational either because his [her] preferences are contradictory or because his desires and aversions do not reflect his/her pleasures and pains.

Amos Tversky and Daniel Kahneman. The framing of decisions and the psychology of choice. Science. 1981 Jan 30;211(4481):453-8

Daniel Kahneman and Amos Tversky. Prospect Theory: An Analysis of Decision under Risk. Econometrica, 47(2), pp. 263-291, March 1979

Losses have a bigger emotional impact than an equivalent amount of gain.

People often make decisions to avoid a loss (short-term) at the expense of gains (often long-term)

Company finances are allocated differently –R&D is a “Gain” or “Investment” where as Operations are “Costs” or “Losses” (in the extreme)

This imbalance creates many challenges in the day-to-day operations - which, among others, is what a Culture of Quality must address

http://www.ncbi.nlm.nih.gov/pubmed/7455683

Case example: Testing into Compliance

An analyst in a Quality Control (QC) laboratory, after the requisite training is doing dissolution test for a modified release dosage form. The results he obtains are ‘out of specification’ (OOS).

Per SOP, analyst has to file a deviation report so that an investigation can be initiated. He does so.

Later in the day the Head of operations calls the analyst and his supervisor.

Here are some messages to consider on Leadership Emphasis and Message Credibility

Emphasis/Message Credibility L1: Head of Operations is

upset that the analyst did not do his job carefully. The

product is FDA approved and process validated. On

previous occasion after a lengthy investigation it turned

out to be an assay error. Complete the investigation

quickly and release the batch on time.

Emphasis/Message Credibility L2: The Head of Analytical

department learns about what happened. He calls the

supervisor (in the discussion above). He is concerned

that when the owner of the company will learn about

this it will not look-good (for him, and his Analytical

department). He tells the supervisor – add as many

resources as needed for the investigations and get it done quickly.


Humans tend to select [irrational] risky option more often in response to negatively framed problems; this effect is more pronounced when there are [easy] “reasons to rationalize”


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

Documentation not critical;

Compendial testing sufficient

Regulators collect & test samples – no

issue there

“Testing into compliance”

In general – low empowerment is

a significant challenge (low

perceived behavioral control);

plus reasons to rationalize….

Additional Information

CoQ Framework and Blind-spots - for more detail click on the following

Explaining the Behavioral Economics context of Culture of Quality

Product Quality & Patient Safety USP Workshop Mumbai 12 June 2015

Good Regulators of Pharmaceuticals (GRP) 22 October 2014

Dr Venkateswarlu Memorial Lecture 2015

Chemometrics Pharmacometrics Econometrics of QbD. Swiss Pharma-6 2012

Excipient Knowledge Management Mumbai 12 March 2015 Part 1 & 2

If the links above fail to connect to the information please use: http://www.slideshare.net/a2zpharmsci


http://www.slideshare.net/a2zpharmsci/explaining-the-behavioral-economic-context-of-culture-of-quality

http://www.slideshare.net/a2zpharmsci/product-quality-patient-safety-usp-workshop-mumbai-12-june-2015?related=1

http://www.slideshare.net/a2zpharmsci/good-regulators-of-pharmaceuticals-grp-22-october-2014?related=2

http://www.slideshare.net/a2zpharmsci/venkateswarlu-memorial-lecture-2015-final-24-may-2015

http://www.slideshare.net/a2zpharmsci/chemometrics-pharmacometrics-econometrics-of-qb-d-swiss-pharma6-2012?related=1

http://www.slideshare.net/a2zpharmsci/excipient-knowledge-management-mumbai-12-march-part-1-2

http://www.slideshare.net/a2zpharmsci

About the Culture of Quality Training

Conducted for?

3 companies; WL, Import Alert (US FDA)

1 Company; significant FDA 483

2 Companies; Proactive (before US FDA Inspection)

> 3000 management & staff at facilities in the states of Goa, Gujrat, Karnataka, Madhya Pradesh, Maharashtra, and Telangana and in the Union Territory of Dadra and Nagar Haveli.

Key issue: Preventing “Breaches” in data integrity

Learning Objectives

Provide an opportunity to improve understanding of Culture of Quality (CoQ) and how it relates to Quality Management System (QMS) and compliance with Good Practices (GXPs)

Focus on Why and not 21 CFR;

Specifically to appreciate the value of systems approach to quality, identify behaviors that strengthen it and behaviors that need to change

Specifically to appreciate the value of systems approach to quality, identify behaviors that strengthen it and behaviors that need to change


Changing incorrect attitudes & mindset – “Quality is Good” &”US FDA targeting India”

Regulator heterogeneity

Overcoming blind spots & irrational decisions

Challenges9/20/2015© Ajaz S. Hussain Insight Advice and Solutions LLC 12

Overcoming the challenges

Starting point – agreement & commitment of Top management build a Culture of Quality

Deliberate breaches in data integrity is cheating and fundamentally against the basic principles of professional conduct and of India’s founding principle – “Satyamev Jayate”

Nothing is perfect (so avoid “zero tolerance” slogans) –improve awareness and mastery and remove fear to identify, report and correct errors.

Walk the talk – not “Quality Policy on the Wall”

Emphasizing Why by sharing examples from authors experience on topics such as:

“We make two products – medicine and evidence”; both must be better than “placebo”; data integrity distinguishes between legitimate and criminal intent

Testing is not sufficient to assure quality; case examples of harm caused by violating cGMPs and why it is hard to detect harm; “lack of reports of harm is not evidence of no harm”

Quality must be by design; i.e., by intent and working consciously; ‘plan-do-check-act’

Systems approach to quality is a must; what is a System, what is systems thinking, how to make a Quality Management System effective


Good Culture of QualityWhen employees can say without hesitation:

We do our best to develop products that meet the needs of patients – we

develop our products consciously – this Quality by Design.

We recognize that nothing is perfect and there will be some errors in our design,

systems and procedures, or we may make mistakes in following set procedures.

It is normal, easy and rewarding to work within our quality management system,

without fear, to detect, correct and to learn from errors.

In doing so we act consciously in the interest of patients – especially when no

one is looking, and continually improve our quality by design and aim for right first

time.


A simple framework for CoQ

Quality by Design



One example of impact assessment: One month after completion of

training (anonymous survey via Survey Monkey).


•Leadership emphasis

•Message credibility

•Peer involvement

•Employee empowerment

Re-shaping the Environment

•Quality is normal

•Quality is easy

•Quality is rewarding

Re-setting the Norms

•Commitment to the System

•Knowledge based

•Understanding & controlling variations

•Safe-guards + pride of workmanship

Ensuring effective QMS

•Fear removed

•Mastery

•Awareness

Promoting proactive behaviors

Score-card; Key Areas of

Improvement and

Recommendations

Illustrative Score Card: For a

company currently in cGMP

remediation.

Stars & color codes

Good progress, continue efforts

already initiated

Blind-spots, current efforts need

additional considerations

Blind-spot + new targeted

projects/efforts needed

Why a growing cluster of cGMP issues [in India]?

What “norms” & behaviors need to change?

How a company can strengthen culture of quality?

Questions9/20/2015© Ajaz S. Hussain Insight Advice and Solutions LLC 18

Why a growing cluster of cGMP issues?

Are the cGMP issues now being noted “new”?

Not likely – rigor and frequency of US FDA inspections changed; More “unannounced” inspections & an increased fear component (for operators)

Improved ability (of a few investigators) to conduct a through “IT” system review; Large “regulator heterogeneity” blatantly visible

Incorrect organizational assumptions – “FDA Approved”, “Process Validated”; push for

“speed” and uninformed “Lean” programs to improve efficiency

Systemic weakness in QMS – inadequate systems thinking – and a general disregard for

the intrinsic (as opposed to just satisfy FDA) value of documentation and assurance of

data integrity; Quality by Design - much misunderstood & “file first and figure it out later”

Local regulatory norms providing addional reasons to rationalize deviations from cGMPs

and attempt to justify interpretation of “adulteration” narrowly to analytics



Why a growing cluster of cGMP issues? Holes in the system

Holes not filled or

filled after FDA InspectionBreaches

Reasons to rationalize irrational behaviors

‘Framing” effects & irrational decisions

Opportunity & “not harming anybody”

Namesake QMS

(A folder of papers – often written by consultants)

Ineffective training &

inadequate supervision

Inability to say NO or to

explain what is required

Push for results!

Assumption:

‘Quality is

Good”;

“FDA approved,

validated, past

inspections

okay”

What “norms” & behaviors need to change?

Differing “quality” to Quality Unit; quality is everyone's responsibility

‘Regulator heterogeneity’ is often used as an excuse; Adherence to commitment is a Management responsibility

Defense of domestic vs. export quality; this is the time to commit to ‘One Quality Standard” –and a plan to achieve it in a reasonable time period

Policies and SOP’s written by consultants to satisfy FDA; Systems thinking is essential to strengthen QMS

“First to file” without systematic preparation to mitigate risks; now a automatic “red flag” for data integrity at FDA

Reliance on “defaults” – 10X, 3-batches,etc., without questioning their relevance; Life-cycle approach to process and analytical method validation a must

Check-box training; need to improve training across the board and ensure it is effective in providing ‘mastery’, improving ‘awareness’ and reducing “fear” and irrational behaviors

Quality policy “on the wall”; management must walk-the-talk


How a company can strengthen culture of quality?

It starts with the Top management! Walking the talk

Leadership emphasis (and metrics), message credibility, peer involvement (top management) and employee empowerment (reveres the need for all decisions to come to the top)

Aiming high – not just to satisfy the next inspection; effective QMS

Appreciation for the System, Theory of Knowledge (Plan-do-check-act), Knowledge of Variations (common/special cause). Incentivize rational behavior (System 2- working consciously) and pride of workmanship

Preventative controls

Effective training to improve awareness, ensure mastery, and reduce fear

Nothing is perfect – avoid slogans such as “Zero tolerance”

Make it normal, easy and rewarding to detect, report and correct errors


Summary

Background

• Breaches in data integrity

• My viewpoints

• About the training program

Challenges

•Breaches – being detected currently are not necessarily new;

•GMP remediation's slow and/or ineffective (repeat violations)

•Assumptions and blind-spots; irrational decisions and behaviors of Management and Staff

Questions

•Why criticality of CGMPs not widely appreciated as expected by the customer (US FDA)?

•What “norms” provide reasons to rationalize cGMP deviations?

•How a company can re-build lost credibility? Better option improve credibility?

Insights

On the three questions posed


insights on culture of quality what have i learned 22 september 2015

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