Culture of-quality

CGMP ConferenceBaltimore, MD 4-5 June 2012

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Culture Of Quality

Mary Oates, Vice President, Global Quality Operations, Pfizer

• 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 l th l h i t th t

Commitment to Quality

place across the supply chain to ensure that every product meets appropriate quality standards

• Are systems and controls enough?

Example Supply Chain Complexity

• ~ 35,000 SKU’s• ~ 500 Sourcing Points• ~ 175 Logistics Centers• ~ 200 Transport providers

Scope


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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 canCriminal 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 maintenanceInadequate cleaning and maintenance• Inadequate complaint investigations• Inadequate training of employees


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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 qualitynecessary 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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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 b i t d i• Quality can be inspected in– 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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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

lit d f th f f thquality and for the performance of the 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 strongKnow about issues and trends via a strong notification to management process

• Ensure that patient safety drives decisions


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Effective Quality System: Example

• Robust deviation investigations– Identify root cause– Identify full scope of issue– Implement corrective actions to preventImplement 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 mitigatedunderstood 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 controlscontrols

– 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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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 qualityensure 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

l b llglobally


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Fundamental Value Proposition

Supply Reliability

Cost/ Value Delivery

Critical to balance all threeWe make difficult and tough choices...

...however, compromise to Quality/Compliance is NOT an option

Quality/ Compliance

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 facilitynew 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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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 assessmentsIn 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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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 andcommitted to the steps needed to create and sustain it

• Should be routinely assessed through the lifetime of a partnership


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Contractor Quality Risk Dashboard

Focus on QUALITY & COMPLIANCE aspects,

undiluted by business risks

DYNAMIC tool for assessing Contractor risk

COMMUNICATION tool

Provides VISUAL indication of the risk profile of our

Contractor base and change over time

Contractors evaluated every 2 months against 10 risk elementsRisk History

cGMP Inspection Profile

Communication with Quality oversight group

Quality of Investigation Process

Triggers ACTION on possible risk that occur (raises the

flag)

COMMUNICATION tool sharing information across

functions

Real‐time assessment of risk and initiation and follow up of mitigation

actions

Quality of Complaints

Significant Deviations

Change Management

Market Action/Stop Distribution

Quality System Oversight

Quality Culture

Quality Culture Internally

• If the assessment indicates the quality culture is not robust– Management must be committed to the actions necessary to sustain itnecessary 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 d i ti d i l t f ff ti ldeviations and implement a process for effectively raising them

– Management must establish a monitoring mechanism and track and publish metrics


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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 forwardM t t th t d i ti– Management must ensure that deviation 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 timeattribute 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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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 lotsPrevious 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 l h k– Can only react to what you know– 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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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 improvedlacking, improved• Management bears responsibility for taking the actions

necessary for creating and sustaining a quality culture

Business

Culture of-quality