This document summarizes a presentation on quality culture given at the 2012 CGMP Conference in Baltimore. The presentation discusses the importance of quality culture in protecting patient safety and product quality across complex pharmaceutical supply chains. It defines quality culture as an environment where everyone understands and embraces their responsibility for quality. Strong quality culture is identified as the most important indicator of an organization's ability to consistently deliver high quality products and services.

1. CGMP Conference
Baltimore, MD 4-5 June 2012
Culture Of Quality
Mary Oates, Vice President,
Global Quality Operations, Pfizer
Commitment to Quality
• Product quality and patient safety are of utmost
importance to all ethical participants in the
pharmaceutical supply chain
• Comprehensive systems and controls must be in
place across the supply chain to ensure that every
l th l h i t th t
product meets appropriate quality standards
• Are systems and controls enough?
Example Supply Chain Complexity
Scope
• ~ 35,000 SKU’s
• ~ 500 Sourcing Points
• ~ 175 Logistics Centers
• ~ 200 Transport providers
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2. CGMP Conference
Baltimore, MD 4-5 June 2012
Complex Environment Presents
Risk
• Potential for adulteration, including counterfeits
• Potential for non‐GMP conditions
– Could occur at any point in the supply chain
– More common type of risk
In the News: Intentional
Adulteration
• Heparin, melamine, capsules, etc
• Must be detected and removed from the supply
chain
• Criminal activity is difficult to prevent if money can
Criminal activity is difficult to prevent if money can
be made
• Quality culture is an irrelevant concept to a criminal
Warning Letters: GMP Findings
• Inadequate control of microbiological
contamination, e.g., poor aseptic practices
• Inadequate investigation of batch failures
• Inadequate cleaning and maintenance
Inadequate cleaning and maintenance
• Inadequate complaint investigations
• Inadequate training of employees
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3. CGMP Conference
Baltimore, MD 4-5 June 2012
Potential Explanations for a Pattern of Non‐
Compliance
• Intentional disregard of GMPs
– Should be eliminated from the supply chain
• Inconsistent understanding of requirements
necessary to protect product quality
necessary to protect product quality
– Many new participants in supply chain
– Could be educated, if willing
• Have understanding but have lost focus on the
fundamentals that protect product quality
– Quality Culture
What is Quality Culture?
• An environment in which each and every person
understands and embraces their responsibility for
protecting product quality and patient safety
• A firm can have all the SOPs, systems and controls
required but, without quality culture, product quality
and business continuity are not assured
• Cannot be externally imposed
Benefits of Quality Culture
• Protects patient safety
• Drives behaviors and ensures decision‐making is
based on what is best for product quality and patient
safety
–Employees will do the right thing at all times
–Ensures continuous improvement
• Protects the firm’s reputation and business
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4. CGMP Conference
Baltimore, MD 4-5 June 2012
Not Just About Outsourcing
• Manufacturing, testing and distributing
pharmaceuticals requires the MAH to involve
many other firms
– Purchased items: raw materials, packaging
components, artwork and labeling, drug
substance/API, etc.
– Purchased services: contractors performing any
number of activities, transportation providers,
distributors, etc.
• A strong quality culture must be in place at
every firm, including the MAH
Unfounded Beliefs
• Quality can be tested in
– If it passes the specifications, it must be
good
• Q lit
Quality can be inspected in
b i t di
– Traditional audits, internal or by a regulator,
can demonstrate that product quality will
consistently be acceptable
• Strong controls can mitigate all risks
The Reality
• Testing, inspection and other controls are
not enough
• A strong quality culture must be in place
• A firm’s quality culture is the single most
important indicator of their ability to
routinely provide a quality service or
product
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5. CGMP Conference
Baltimore, MD 4-5 June 2012
Compliance versus Quality Culture
• Compliance requires strong standards
that adhere to regulations, robust
systems, good training, management
oversight, etc.
• Compliance is foundational and enables
quality performance
• Quality culture is about decision‐making
and behaviors at all levels of the
organization every day
Management Responsibility
• Q10 states
– “Leadership is essential to establish and
maintain a company‐wide commitment to
quality and for the performance of the
lit d f th f f th
quality system.”
• Leadership creates and is responsible for
sustaining quality culture
Management’s Role
• Create and sustain an effective quality system
• Ensure sufficient resources are available to maintain
quality
• Know about issues and trends via a strong
Know about issues and trends via a strong
notification to management process
• Ensure that patient safety drives decisions
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6. CGMP Conference
Baltimore, MD 4-5 June 2012
Effective Quality System: Example
• Robust deviation investigations
– Identify root cause
– Identify full scope of issue
– Implement corrective actions to prevent
Implement corrective actions to prevent
recurrence
• Serves as an indicator of the focus and
behaviors of the organization
– Number of deviations, ability to prevent
recurrence, number overdue
Sufficient Resources
• Cost pressures may result in reduced
training, maintenance, people
• The risk of such reductions must be
understood and mitigated
understood and mitigated
– Risk assessment tools can be utilized
– The assessment may indicate the risk is too
great
Sufficient Resources (continued)
• Early indicators should be in place to determine
if reductions are adversely impacting quality
– Appearance of the facility
– Overdue deviation investigations, CAPAs and change
controls
– A backlog of complaint investigations
– Overdue testing, e.g. late stability testing
• If signals indicate decreased ability to maintain
quality, corrective actions should be
implemented immediately
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7. CGMP Conference
Baltimore, MD 4-5 June 2012
Notification to Management
• Local and global processes must ensure that
issues and trends are escalated and addressed
with patient safety driving the decision‐making
• Management must role‐model the appropriate
decision‐making behavior
• Employees must be trained in tools that enable
them to make the right quality decisions
How We Deploy Quality Across Pfizer
• Holistic, multi‐faceted
approach to product
quality and cGMP
compliance
• Requires vigilance to
ensure high quality
ensure high quality
product
• Rests on a strong
foundation of quality
culture
Pressures on Quality Culture
• Need to supply product to market
• Cost, including resource availability
• Complexity of operations, both locally and
globally
l b ll
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8. CGMP Conference
Baltimore, MD 4-5 June 2012
Fundamental Value Proposition
Supply Cost/
Reliability Value Delivery
Quality/
Compliance
Critical to balance all three
We make difficult and tough choices...
...however, compromise to Quality/Compliance is NOT an option
Example of Quality Culture
• First commercial use of a new manufacturing facility for
a biological compound
• Significant process enhancements were made to a
product at the same time that it was introduced to the
new facility
new facility
• In the first product lot, 70 deviations occurred
• The production manager shut down manufacturing to
identify and correct root causes
• The first lot after resumption of manufacturing had 20
deviations and the current average number per lot is 5
Can Quality Culture Be Measured?
• Quantitative tools can be developed to
evaluate quality culture
• Data should be derived primarily from
interviews of leadership, supervisors and
operators/technicians within the firm,
combined with review of supporting
documentation
• Such a tool can be used both internally
and externally
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9. CGMP Conference
Baltimore, MD 4-5 June 2012
Example Parameters
• Management’s attitude towards compliance and their
engagement and proactive commitment to systemic
problem resolution
• Identification, trending and communication to
employees of quality metrics
• Freedom of employees to bring issues forward
Freedom of employees to bring issues forward
• Understanding by employees of tasks being executed
and how these protect product quality
• Number of deviations from procedures or expected
results
– Are there too many or too FEW?
Assessment of Potential Partners
• Due Diligence
– Quality culture of potential partners should be
specifically evaluated
• In addition to other due diligence assessments
In addition to other due diligence assessments
• Purpose is to determine if the potential partner’s
culture supports sustainable supply of high quality
products or services
Diagnosing Quality Culture
• Each element evaluated should be assessed
based on criticality and an overall conclusion
should be drawn
• Two potential outcomes
Two potential outcomes
– A few system improvements are necessary but
overall quality culture is robust
– Quality culture is lacking
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10. CGMP Conference
Baltimore, MD 4-5 June 2012
Partner Assessment
• Output of quality culture evaluation is
part of an overall risk assessment of
potential partners
• Given all the information collected, a
decision must be made as to the
acceptability of the partner
• Could quality culture alone determine
the outcome?
Hypothetical Example
• Due diligence identified the acceptability of all
relevant systems, controls and processes
• A visit to follow up on a few outstanding
questions identified concerns about quality
culture
• Purely on this basis, the business agreement
was not pursued
• Evaluated firm’s partners later recalled product
due to quality concerns
Quality Culture at Partners
• Cannot be externally imposed nor can it be
changed in the near‐term
• Can be enhanced over time if management is
committed to the steps needed to create and
committed to the steps needed to create and
sustain it
• Should be routinely assessed through the
lifetime of a partnership
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11. CGMP Conference
Baltimore, MD 4-5 June 2012
Contractor Quality Risk Dashboard
DYNAMIC tool for assessing
Contractor risk
Contractors evaluated every 2 months
against 10 risk elements
Provides VISUAL indication of
Focus on QUALITY & Risk History
the risk profile of our
COMPLIANCE aspects, cGMP Inspection Profile Contractor base and change
undiluted by business risks over time
Communication with Quality oversight
group
Quality of Investigation Process
COMMUNICATION tool tool Quality of Complaints
sharing information across Triggers ACTION on possible
functions Significant Deviations
risk that occur (raises the
Change Management flag)
Market Action/Stop Distribution
Quality System Oversight
Quality Culture
Real‐time assessment of risk and
initiation and follow up of mitigation
actions
Quality Culture Internally
• If the assessment indicates the quality culture
is not robust
– Management must be committed to the actions
necessary to sustain it
necessary to sustain it
• If they are not, they must be replaced
– Then the facility can begin addressing the
individual issues found in the assessment
Example Actions
• If there are too few deviation investigations
– Management must proclaim the value of deviation
investigations
– Management must help employees recognize
deviations and implement a process for effectively
d i ti di l t f ff ti l
raising them
– Management must establish a monitoring
mechanism and track and publish metrics
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12. CGMP Conference
Baltimore, MD 4-5 June 2012
Example Actions (continued)
• If there are too few deviation investigations
– Management must celebrate an increase in
deviations and hold accountable those who do not
bring them forward
–MManagement must ensure that deviation
t t th t d i ti
investigations are performed quickly and thoroughly
– Management must ensure that holistic corrective
actions are implemented to prevent recurrence
Hypothetical Example to
Illustrate the Importance of
p
Quality Culture
Hypothetical Example
• A potential partner was evaluated via due
diligence
– Identified the need to improve quality systems
before product supply was initiated
– Quality culture was not considered a quantifiable
attribute at the time
attribute at the time
• System changes were implemented over the
course of one year
• Additional testing, person in plant and review
of all deviations, changes, etc put into place
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13. CGMP Conference
Baltimore, MD 4-5 June 2012
Hypothetical Example (continued)
• Post‐manufacturing inspection of containers from one
product lot found a high number of a specific defect
• The supply chain partner removed the containers with
the defect and released the lot without investigation
• Previous information on this type of defect in other lots
Previous information on this type of defect in other lots
(inspection data, complaint reports, etc.) was not
reviewed
• The defect did exist in earlier released lots and, when
discovered, resulted in a Class 1 recall of all lots on the
market
Why Did This Happen?
• Failure of deviation investigation system at the partner but
more importantly
• Failure of quality culture
• Risk mitigation activities by the MAH did not prevent the issue
–C Can only react to what you know
l h k
– Every firm must have a quality culture that ensures that
the right decisions will be made by employees at all levels
of the organization at all times
Criticality of Quality Culture
• Without a strong quality culture, risks to product
quality cannot be fully mitigated
– Testing, person in plant, review of deviations, regular
audits, regulatory inspections are not enough
– Quality culture cannot be externally imposed and is not
introduced only through changes to GMP systems
– Quality culture cannot be changed in the near‐term
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14. CGMP Conference
Baltimore, MD 4-5 June 2012
Conclusion
• Standards and systems alone are not enough
• Without a strong quality culture, risks to product quality and
patient safety cannot be fully mitigated
• Quality culture can and must be measured and, if found
lacking, improved
lacking improved
• Management bears responsibility for taking the actions
necessary for creating and sustaining a quality culture
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