Moving from Quality Control to Quality
Assurance (Proactive Compliance!)
Guy Wingate,
VP & Compliance Officer
Global Manufacturing & Supply, GlaxoSmithKline
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Slide 2
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
Predictable Performance
Product Quality
‘QC’ Checks
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
SemiConductor
Pharma
Red Zone
Highlights the need for reliable KPIs and performance data
Slide 8
Key Elements of Holistic Control Framework
Governance &
Management
Systems &
Processes
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
d S Chart: Content
rmity
4
3
Mfg….. Batch
2
1
Mfg….. Discrete Units
0.99
0.95
0.85
0.70
0.50
0.30
0.15
0.05
0.01
0
-1
-2
-3
-4
85
90
95
100
105
110
115
Capability Plot
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
Within
Overall
Spec.
Limits
80
“Population of Many”
Quality assessed by
90
95
100
105
110
115
sampling Capability
post Histogram
manufacture
85
LSL
-3.*S
Nominal
+3.*S
“Population of One”
Quality assessed on-line
for every tablet
120
Process Capabi l i ty Report Drop Vol ume: Mean of 150 Drops
(Speci fi cati on Li mi ts +/- 3% of Overal l Mean)
LSL
350
USL
150
-3.s
Process Data
+3.s
USL
LSL
Targ et
USL
125
100
75
85%
50
Tablet
N= 520
PpK =1.4
300
Droplet
N= 606
PpK =16
250
115%
25
0
80 82 84 86 88 90 92 94 96 98 100 102 104 106 108 110 112 114 116 118
200
150
Frequency
0
QbD Technology (Example)
Normal Probability Plot
85%
Sample Mean
Samples
Sample N
Total N
StDev(Within)
StDev(Actual)
Actual Capab
PPK
100
Slide 10
50
115%
Lower 95% CL
PPL
PPU
PP
0
Level
Capability
Exp. Actual Performance
7.36E6
7.34E6
7.32E6
7.28E6
7.3E6
7.26E6
0
7.24E6
PPM < LSL
7.22E6
7.18E6
Exp. Within Performance
7.2E6
7.16E6
7.14E6
7.12E6
7.08E6
7.1E6
0
7.06E6
PPM < LSL
7.04E6
7.02E6
6.98E6
7E6
6.96E6
6.94E6
Observed Performance
Potential Cap
CPK
CPL
PPM < LSL
0
PPM > USL
0
PPM > USL
0
PPM > USL
0
CP
PPM Total
0
PPM Total
0
PPM Total
0
CPM
CPU
People – Helping Hands
Training
Mandated and
optional training
Clear work practices
Allowance for
personal judgement
Competency test
Q&A opportunity
Capability
Human Error
Technical know-how
Data robustness?
Leadership and
effective teams
Real root cause
identified
Personal Style
(consistency and
motivation)
Understand impact of
local culture, mindset
and behaviour
Link to development
plan and succession
planning
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
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
Execution
–
–
–
–
–
–
–
–
–
–
Quality for All
Transformational Change
Right First Time
Sustainable Improvement
Preventive Solutions
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
Foundation cGMP Processes
Incident Reviews
Deviation
Process
Effective ROOT
Cause Analysis
CAPA
Process
Mandated
Standard Work
Verification
cGMP
Change
Control
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
Ghost in the Machine – Inspection Readiness
“To Be”
“As Is”
Preparations for
Specific Inspection
Inspection Ready
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?