Moving from Quality Control to Quality Assurance (Proactive Compliance!)

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Moving from Quality Control to Quality Assurance (Proactive Compliance!) Guy Wingate, VP & Compliance Officer Global Manufacturing & Supply, GlaxoSmithKline

Disclaimer The views and opinions expressed in the following PowerPoint slides are those of the individual presenter and should not be attributed to GlaxoSmithKline These PowerPoint slides are the intellectual property of the individual presenter and are protected under the copyright laws of the United States of America and other countries. All rights reserved. The ISPE logo is a registered trademark. All other trademarks are the property of their respective owners. 2 Slide 2

Our Collective Challenge Oxford English Dictionary: Proactive - creating or controlling a situation rather than just responding to it after it has happened Compliance in accordance with rules or standards In other words as it applies to many of us... Assuring sustained higher performance (often during a period of significant change) with no nasty surprises Slide 3

Contents Current Controls Framework Step Change Performance Challenge Key Elements of Holistic Control Framework Ghosts in the Machine Management Accountability Summary Slide 4

Everything we do is to ensure they can do more, feel better, live longer

Simplified Supply Chain Drug Substance Product Quality QC Checks Predictable Performance Robust Manufacture Finished Products Secure Supply Assured Stability QC Checks Slide 6

Mature Control Framework? Examples of Established Industry Controls Quality Management System aligned to cgmp/ich Independent & Experienced Quality Organisation Tiered Quality Governance for Escalation and Review Validation & Incident Review Processes Science-Based Risk Assessments Regular Training & Communication Supplier Quality Audits Examples Applied to Automation GAMP5 Guidance Independent & Experienced Validation Professionals Tiered Quality Governance for Escalation and Review Validation & Incident Review Processes Science-Based Risk Assessments Regular Training & Communication Supplier Quality Audits Highly dependable integrated systems? Slide 7

Step Change Challenge Semi- Conductor Pharma Red Zone Highlights the need for reliable KPIs and performance data Slide 8

Key Elements of Holistic Control Framework Systems & Processes Governance & Management Mindset & Behaviours Supporting Elements QbD Technology Procedures Organisation Facility/Systems Investment Risk Management Nurture & Refresh Company values to be in evidence as part of decision making processes SpeakUp culture to raise concerns in the right and respectful way Incentives support improved sustained performance Slide 9

S Chart: Content mity 4 3 2 1 0-1 -2-3 QbD Technology (Example) Normal Probability Plot Mfg.. Batch -4 85 90 95 100 105 110 115 Capability Plot 0.99 0.95 0.85 0.70 0.50 0.30 0.15 0.05 0.01 Mfg.. Discrete Units Within Overall Spec. Limits 150 125 100 75 50 25 Within SD: 3.330; Cp: 1.502; Cpk: 1.495 Overall SD: 3.519; Pp: 1.421; Ppk: 1.415 LSL: 85.00; Nom.: 100.0; USL: 115.0 Population of Many Quality assessed by sampling post manufacture 80 85 90 95 100 105 110 115 120 85% Capability Histogram LSL -3.*S Nominal +3.*S USL Tablet N= 520 PpK =1.4 0 80 82 84 86 88 90 92 94 96 98 100 102 104 106 108 110 112 114 116 118 115% Population of One Quality assessed on-line for every tablet Process Capability Report Drop Volume: Mean of 150 Drops (Specification Limits +/- 3% of Overall Mean) Process Data LSL -3.s +3.s USL LSL 350 Target Frequency 300 250 200 150 0 Droplet N= 606 PpK =16 Slide 10 PPK 100 Lower 95% CL PPL 85% 115% 50 PPU USL Sample Mean Samples Sample N Total N StDev(Within) StDev(Actual) PP Actual Capab Level Capability 6.94E6 6.96E6 6.98E6 7E6 Observed Performance PPM < LSL 0 7.02E6 7.04E6 7.06E6 7.08E6 7.1E6 7.12E6 7.14E6 7.16E6 Exp. Within Performance PPM < LSL 0 7.18E6 7.2E6 7.22E6 7.24E6 7.26E6 7.28E6 7.3E6 7.32E6 Exp. Actual Performance PPM < LSL 0 PPM > USL 0 PPM > USL 0 PPM > USL 0 PPM Total 0 PPM Total 0 PPM Total 0 7.34E6 7.36E6 Potential Cap CPK CPL CPU CP CPM

People Helping Hands Training Capability Human Error Mandated and optional training Clear work practices Allowance for personal judgement Competency test Q&A opportunity Technical know-how Leadership and effective teams Personal Style (consistency and motivation) Link to development plan and succession planning Data robustness? Real root cause identified Understand impact of local culture, mindset and behaviour Solution shared as part of company production system Slide 11

Facilities/Systems Investment Equipment maintenance budgets Calibration schedule adherence Refurbish/refresh to keep up with current expectations New equipment, facility and IT investment and validation Plan for healthy levels of depreciation Risk Management Eliminate risks at root cause rather than symptom Avoid silo thinking, see bigger picture Reduce risks in timely manner to acceptable level Verify mitigation is effective and locked-down Recognise CA & PA management as separate process Slide 12

Ghost in the Machine Culture QUALITY Ideally, we want to keep all 3 elements in harmony COST...but when we need to prioritise, its only possible to have TWO. SUPPLY If Cost & Supply are allowed to dominate then Quality can be viewed as something that can be fixed later Slide 13

Embracing a Culture of Quality Aspiration Quality for All Transformational Change Right First Time Sustainable Improvement Preventive Solutions Execution Enterprise Thinking Visibility of True Situation Tackle Root Cause Meaningful KPIs Science/Risk Based Decisions Foundation No compromise to fundamentals SpeakUp Culture (Disclosure) Visible commitment to do the right thing Slide 14

Ghost in the Machine - Hidden Factory Effective ROOT Cause Analysis Mandated Standard Work Deviation Process cgmp CAPA Process Verification Incident Reviews Change Control Foundation cgmp Processes 1. Deviation Management 2. Root Cause Analysis 3. Corrective & Preventative Action 4. Escalation & Incident Review 5. Quality Governance 6. Risk Management 7. Change Control 8. Total Disclosure 9. Auditing 10. cgmp Training Slide 15

Being Brilliant at the Basics Deviation Management ensuring transparency and prioritised management Root Cause Analysis getting to the real root cause quickly and efficiently CAPA corrective action and preventative action Management engagement alongside team, understanding the issues and ensuring resolution Effective governance driving improvement Slide 16

Inspection Ready Ghost in the Machine Inspection Readiness As Is To Be Preparations for Specific Inspection Preparations for Specific Inspection Inherent Audit Readiness Inherent Audit Readiness Slide 17

Assurance Pyramid Independent oversight of the control environment including ethical decision-making, behaviours and risk management. 4 External Audits and Reviews 3 Internal Auditing 2 Management Owned Monitoring 1 Self Assessment Slide 18

Management Accountability FDA looking closer at the root causes of cgmp failures May reflect management inattention Deliberate decisions to defer investment in modern production facilities Corporate disregard for the Quality Dept. DOJ also looking at role of senior managers in cgmp failures Do we have the right people? (capability and attitude employees, contractors, suppliers) Do people have the right incentives to see, report and fix problems? Are people satisfied and engaged? Do policies and procedures acknowledge how real people work and what they are capable of? Do managers have personal visibility into what people are actually doing? Is there a supportive organisational culture that recognises the patient at the end of the supply chain? [1] Janet Woodcock (Head of CDER FDA), FDA/ISPE Conference held 4th June 2012 [2] Maame Ewusi-Mensah Frimpong, (Deputy Assistant Attorney General for DOJ's Consumer Protection Branch), Pharmaceutical Compliance Congress held 29th January 2013 Slide 19

Summary Proactive Compliance Tone from the Top holistic approach to compliance; never compromise the fundamentals Remember quality is perishable so avoid nasty surprises... maintain a sustainable control framework with everyone playing their role in ensuring Quality Trusting and open environment needed to report issues with obligation to resolve them Slide 20

Everything we do is to ensure they can do more, feel better, live longer

Questions?