Culture of Quality, Data Integrity, Quality by Design: Connecting the Dots

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These slides were used for a invited presentation @ Patheon Seminar – Bridgewater, NJ, 31 July 2014. Some modification have been made to connect the dots for the audience who will review this slide-deck on the internet. The presentation provides a very brief snap-shot of a day long training program conducted recently at a company in India. In preparing the day long training session I had asked the following questions: (1) How to effectively communicate to an audience of a group of young and bright Indian professionals in any company in India and their supervisors/management about the importance of cGMPs and QbD? (2) How do I understand their challenges, perspectives and biases? and (3) How do I connect with them to share the joy of Quality by Design? The response received has been overwhelming from the audiences in India and yesterday at the Patheon Seminar in Bridgewater, NJ. I hope you will also the see some of the important dots and the connections. How this content connects to regulatory requirements is not covered in this slide deck – it connects via ‘A, B, C, D’ to 21 CFR, Quality Systems Approach to cGMP, ICH 7, 8, 9, 10, and 11. .....

Transcript of Culture of Quality, Data Integrity, Quality by Design: Connecting the Dots

  • PharmaceuticalCultureofQuality, AssuranceofDataIntegrity&Qualityby Design:ConnectingtheDots Ajaz@ajazhussain.com 8/1/2014 Ajaz S. Hussain | INSIGHT, ADVICE & SOLUTIONS LLC 1 A modified version of a presentation @ Patheon Bridgewater, NJ Seminar Thursday, July 31, 2014 Quality by Design - Experience, Trends and Outlook
  • Prologue These slides were used for a invited presentation @ Patheon Seminar Bridgewater, NJ, 31 July 2014. Some modification have been made to connect the dots for the audience who will review this slide-deck on the internet. This presentation provides a very brief snap-shot of a day long training program conducted recently at a company in India. In preparing the day long training session I had asked the following questions How to effectively communicate to an audience of a group of young and bright Indian professionals in any company in India and their supervisors/management about the importance of cGMPs and QbD? How do I understand their challenges, perspectives and biases? How do I connect with them to share the joy of Quality by Design? The response received has been overwhelming from the audiences in India and yesterday at the Patheon Seminar in Bridgewater, NJ I hope you will also the see some of the important dots and the connections How this content connects to regulatory requirements is not covered in this slide deck it connects via A, B, C, D to 21 CFR, Quality SystemsApproach to cGMP, ICH 7, 8, 9, 10, and 11. 8/1/2014 Ajaz S. Hussain | INSIGHT, ADVICE & SOLUTIONS LLC 2
  • TheGoldSheet March 2014 Cox:Confronting Illusions ofQuality in IndianGenerics Manufacturing Thakur: Data Integrity requires stronger local enforcement Cahilly: Focus on India masks the real data integrity problems Hussain: Empowering workers is the key to data integrity Takahashi: Look out for these data integrity Issues 8/1/2014 Ajaz S. Hussain | INSIGHT, ADVICE & SOLUTIONS LLC 3 Understanding the behaviors it is a human issue & this is not about India. http://www.pharmamedtechbi.com/publications/the-gold-sheet/48/3/confronting-illusions-of-quality-in-indian-generics-manufacturing
  • Empowering workers is the key to data integrity -thisismy personaljourneytoseeifIcan help. How to effectively communicate to an audience of a group of young and bright Indian professionals in any company in India about cGMPs and QbD? How do I understand their challenges, perspectives and biases? How do I connect with them to share the joy of Quality by Design? 8/1/2014 Ajaz S. Hussain | INSIGHT, ADVICE & SOLUTIONS LLC 4
  • Quality by Design Deming -The journey requires leadership with Profound Knowledge as a guide. 8/1/2014 Ajaz S. Hussain | INSIGHT, ADVICE & SOLUTIONS LLC 5 The challenge at hand is that of human reliability it is a global issue We must do certain things consciously; and cultivate some good habits - subconsciously. Irrationality, Biases,Thinking Fast, and Slow connections to econometrics suggested. Where do corporate managers, schooled in rational assumptions .go from here? When organizations acknowledge and anticipate irrational behavior, they can learn to offset it and avoid damaging results. Is there a culture of error management where theres a genuine effort to learn from mistakes, or is it one of error aversion, where errors are avoided at all cost?
  • Quality by Design What is it? Doing things consciously stuck in my mind FDAs ACPS Meeting October 2005 Topic - Achieving and demonstrating Quality by Design with respect to drug release/dissolution performance for conventional or immediate release solid oral dosage forms A PhRMA Perspective presented by C. Sinko and R. Reed. Features of Quality by Design: Doing things consciously 8/1/2014 Ajaz S. Hussain | INSIGHT, ADVICE & SOLUTIONS LLC 6
  • Doing something Consciously or Subconsciously The End of Rational Economics - [Allen Greenspan] made a mistake in presuming that the self-interest of organizations, specifically banks and others, was such that they were best capable of protecting their own shareholders. Dan Ariely Harvard Business Review July 2009 8/1/2014 Ajaz S. Hussain | INSIGHT, ADVICE & SOLUTIONS LLC 7 Scientific methodology Engineering Design Plan-Do-Check-Act Consciously Habits (work to get rid of bad ones) Habits (work to cultivate good one) Keystone habits (Safety @ Alcoa; A.L.C.O.A. of data integrity) Subconsciously The Power of Habit: Why We Do What We Do in Life and Business. Charles Duhigg
  • Intention to care duty of care 8/1/2014 Ajaz S. Hussain | INSIGHT, ADVICE & SOLUTIONS LLC 8
  • KahnemanandTversky,the firstresearcherstoidentify andrigorouslystudy cognitivebiases,provedthat asimpleversionofexpected utilitytheorydidnot accuratelydescribehuman behavior.Theirresponsewas todevelopprospecttheory,a modelofhowpeoplereally makedecisions. 8/1/2014 Ajaz S. Hussain | INSIGHT, ADVICE & SOLUTIONS LLC 9 Daniel Kahneman, Nobel Prize 2002 KAHNEMAN, Daniel, and AmosTVERSKY, 1979. Prospect Theory: An Analysis of Decision under Risk. Econometrica, 47 (2), 263292
  • Chemometric, Pharmacometrics & Econometrics AjazS.Hussain.SWISS PHARMA34(2012)Nr.6. 8/1/2014 Ajaz S. Hussain | INSIGHT, ADVICE & SOLUTIONS LLC 10 Chemometrics Econometrics Review & Approval Commercial operations, profitability & availability
  • Two products Medicineand Evidence. Better than Placebo Evidence of benefit and risk is collected carefully in well controlled clinical trials to eliminate many sources of variability and biases To be on the market the evidence must convincingly conclude that the benefit outweighs the risks, often compared to a placebo There is no evidence without adequate assurance of data integrity Our assurance of data integrity distinguishes our products from adulterated and counterfeit products 8/1/2014 Ajaz S. Hussain | INSIGHT, ADVICE & SOLUTIONS LLC 11
  • FDACDER Challenges & Changes FDAsSternWarningOnDataIntegrity (ThePinkSheets,21July2014) If the agencys trust is lost it will be difficult to earn it back; posing challenges far beyond an initial manufacturing setback. Complete honesty after a slip up will go a long way Although India and China have been the current focus, FDA is seeing data integrity breaches everywhere to some degree. Thenew(proposed)Officeof PharmaceuticalQuality,CDER,FDA One QualityVoice;Value Statements Put patients first by balancing risk and availability Have one quality voice by integrating review and inspection across product lifecycle Other points; see: FDA/CDERsOffice of PharmaceuticalQualityhttp://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/UCM404568.pdf 8/1/2014 Ajaz S. Hussain | INSIGHT, ADVICE & SOLUTIONS LLC 12
  • Life cycle of regulatory communications Review (CMC,) Design of specifications and controls; prior knowledge and statistical confidence Clinical relevance, failure-mode and risk-based New, Biosimilar, and Generic; differences in review approaches Question base Review improvements on going Tightening specifications after development not aligned with QbD cGMPCompliance & Inspection Life-cycle approach to process validation Continued process verification and statistical confidence cGMP remediation in response to 483 orWL Life-cycle approach to error management Quality Metrics & Culture of Quality 8/1/2014 Ajaz S. Hussain | INSIGHT, ADVICE & SOLUTIONS LLC 13
  • What does it take to come out of the cGMP crisis? 8/1/2014 Ajaz S. Hussain | INSIGHT, ADVICE & SOLUTIONS LLC 14 Persuasive demonstration of: (1) Ability to face facts (2) Legal & regulatory requirements, 3) Systems approach to quality, 4) Changing behavior & culture What is often missed or is unconvincing is how you will strengthen culture of quality. Let one who wants to move and convince others, first be convinced and moved themselves. Thomas Carlyle Signals that question the competence, motivation, and/or integrity of company personnel Do not defend the plainly indefensible; it adds further serious credibility costs
  • Effective format for communication 8/1/2014 Ajaz S. Hussain | INSIGHT, ADVICE & SOLUTIONS LLC 15 Evidence/ Data Claim(s) Warrants Evidence/Data Claims
  • Let one who wants to move and convince others, first be convinced and moved themselves. ThomasCarlyle How do we communicate Culture of Quality Within the organization? In response to 483s andWL? In drug applications? Today the phrase Culture of Quality is a hot topic of discussion Why is it so? What is it? How do we strength it? 8/1/2014 Ajaz S. Hussain | INSIGHT, ADVICE & SOLUTIONS LLC 16
  • Data integrity deviant behaviors AliciaM.Mozzachio,RPh,MPH ,July15, 2014,FDLI,Washington,DC Not recording activities contemporaneously Backdating Fabricating data Copying existing data as new data Re-running samples Discarding data 8/1/2014 A