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Insights on Culture of Quality What have I Learned 22 September 2015

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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?

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Insights on Culture of Quality What have I Learned 22 September 2015

  1. 1. Insights on Culture of Quality What 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
  2. 2. 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 9/20/2015© Ajaz S. Hussain Insight Advice and Solutions LLC 2
  3. 3. Critical Importance of Data Integrity My Viewpoints on ‘Culture of Quality’ Training Program on ‘Culture of Quality’ Background 9/20/2015© Ajaz S. Hussain Insight Advice and Solutions LLC 3
  4. 4. 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. 9/20/2015© Ajaz S. Hussain Insight Advice and Solutions LLC 4
  5. 5. 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 9/20/2015© Ajaz S. Hussain Insight Advice and Solutions LLC 5
  6. 6. 9/20/2015© Ajaz S. Hussain Insight Advice and Solutions LLC 6 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
  7. 7. 9/20/2015© Ajaz S. Hussain Insight Advice and Solutions LLC 7 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
  8. 8. 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. 9/20/2015© Ajaz S. Hussain Insight Advice and Solutions LLC 8
  9. 9. 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” 9/20/2015© Ajaz S. Hussain Insight Advice and Solutions LLC 9 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….
  10. 10. 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 9/20/2015© Ajaz S. Hussain Insight Advice and Solutions LLC 10
  11. 11. 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 9/20/2015© Ajaz S. Hussain Insight Advice and Solutions LLC 11
  12. 12. Changing incorrect attitudes & mindset – “Quality is Good” &”US FDA targeting India” Regulator heterogeneity Overcoming blind spots & irrational decisions Challenges 9/20/2015© Ajaz S. Hussain Insight Advice and Solutions LLC 12
  13. 13. 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 9/20/2015© Ajaz S. Hussain Insight Advice and Solutions LLC 13
  14. 14. Good Culture of Quality When 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. 9/20/2015© Ajaz S. Hussain Insight Advice and Solutions LLC 14
  15. 15. A simple framework for CoQ Quality by Design 9/20/2015© Ajaz S. Hussain Insight Advice and Solutions LLC 15
  16. 16. 9/20/2015© Ajaz S. Hussain Insight Advice and Solutions LLC 16 One example of impact assessment: One month after completion of training (anonymous survey via Survey Monkey).
  17. 17. 9/20/2015© Ajaz S. Hussain Insight Advice and Solutions LLC 17 •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
  18. 18. Why a growing cluster of cGMP issues [in India]? What “norms” & behaviors need to change? How a company can strengthen culture of quality? Questions 9/20/2015© Ajaz S. Hussain Insight Advice and Solutions LLC 18
  19. 19. 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 9/20/2015© Ajaz S. Hussain Insight Advice and Solutions LLC 19
  20. 20. 9/20/2015© Ajaz S. Hussain Insight Advice and Solutions LLC 20 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”
  21. 21. 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 9/20/2015© Ajaz S. Hussain Insight Advice and Solutions LLC 21
  22. 22. 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 9/20/2015© Ajaz S. Hussain Insight Advice and Solutions LLC 22
  23. 23. 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 9/20/2015© Ajaz S. Hussain Insight Advice and Solutions LLC 23

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