Transcript FDA Auditing of Computerized Systems

Executive Management and Quality
Systems Awareness
Gordon B. Richman
Vice President, EduQuest, Inc.
EduQuest
Education: Quality Engineering, Science & Technology
Presentation Topics
• Quality Systems – How Your World is Changing
• Basic Quality System Purposes and Principles
• Management Responsibility in the U.S. Environment
• Business Impact – Costs, Benefits, and Challenges
• Critical Awareness and Recommendations for Success
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The Changing World of GMP
• New quality systems based framework for GMP
– Not entirely new to FDA (experience with devices)
– Completely new to drug and biologics manufacturers
• FDA’s drug (CDER) and biologics (CBER) centers are
speaking a whole new language to these industries
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FDA’s New GMP Initiative
• The next step in FDA’s and the industries’ evolution
Product
Process
Systems
- 1970s
1980s - 1990s
21st Century *
Quality
Control
Quality
Assurance
Quality
System
* 1997 (Medical Devices)
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FDA’s New GMP Initiative
• Major fundamental shift in FDA’s approach
– Focus on quality-by-design and the controlled
reduction of process and product variability
– An enormous change for the pharmaceutical
and biologics industries
– Eventually will deliver tremendous benefits
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What Will Change?
• Process design, process controls, and resource allocations
– Based on “risk assessment” and “risk management”
• Long-standing concepts of “hazard control”
• FDA has mentioned FMEA and HACCP principles
• Not well-understood or routinely applied in the
drug and biologics industries
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Important FDA Recognition
• “At the end of the CGMP Initiative the pharmaceutical
community has arrived at a cross-road; one path goes
toward the desired state and the other maintains the
current state. The path towards the desired state is
unfamiliar to many while the current state provides the
comfort of predictability. The Agency hopes the
pharmaceutical community will choose to move
towards the desired state.”
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Key Components of FDA’s Model
• Management Responsibilities *
• Resources *
• Quality-by-Design and Product Development *
• Risk Management and Risk Assessment *
• CAPA (Corrective and Preventive Action) *
• Change Control
• The Quality Unit
• Six-System Inspection Model *
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Note – What Isn’t New
• FDA is pushing for quality system approaches that
have been used for a long time in other industries
– For example, the electronics, defense, oil and
gas, and telecommunications industries
– How the drug and biologics industries compare
• Acceptable quality/defect levels and PAT
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Impact on the Industry
• Will generate a lot of change and growing pains
• Huge increase in the need for early and very detailed
understanding of the process and product formulation
• GMP requirements will have much more impact on
pharmaceutical development – reaching back into
R&D more than our previous experience
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Impact on the Industry
• This shift is going to take a substantial effort
– Ongoing dedication of more resources on the
“front end” of process design and development
– Years to realize the benefits on the “back end”
• Probably much more time, effort, people, and money
than the process validation movement in the 1980s
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Basic Quality System Concepts
“Quality has to be caused, not controlled.”
From “Philip Crosby's Reflections on Quality”
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Purposes of a Quality System
• To provide a defined operational framework
– Including appropriate and clearly documented
processes and procedures
• To assure that quality is designed and built in
• To provide documented, objective evidence of what
was done during design/development and manufacture
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“Quality” and “Compliance”
• Quality and compliance are not the same
– Quality done right will result in compliance
– Compliance, on the other hand, will not necessarily
create or ensure the quality of processes or products
• Your organization must have both to succeed
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“Quality” and “Compliance”
• The quality of a product is governed by the quality
of the processes used in its manufacture
– If you have poor processes and procedures,
complying with your quality system will just
ensure that you consistently have poor quality
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Underlying Principles
• The quality system must be defined, documented,
implemented, and consistently followed to be
effective and compliant
• Constant self-critical and self-correcting loop
– Process and product knowledge, measurement,
control, and continuous improvement
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Underlying Principles
• A compliant quality system starts and ends with
management (or it simply doesn’t exist)
– Management will be held legally responsible
for the effectiveness or non-effectiveness of
the quality system
– Every quality system failure can and will be
tied back to management
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Underlying Principles
• Companies must implement “global” corrective and
preventive actions
– Similar changes should be made across all FDAregulated sites and operations
• Consistent with a systems-based approach
• Inconsistent with common industry practices
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GMP and the U.S. Regulatory Scheme
• Management responsibility is a very serious matter
• The U.S. law – Federal Food, Drug, and Cosmetic Act
– “Strict liability” criminal law
• The law establishes “prohibited acts”
– Including key provisions that relate directly to GMP
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Prohibited Acts and GMP
• Under the Food, Drug, and Cosmetic Act, it is illegal to -
– Manufacture, ship, deliver for shipment, or receive
after shipment an “adulterated or misbranded” food,
drug, device, or cosmetic
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“Adulterated” Drugs and Devices
• A drug or device not produced in compliance with GMP
– So failure to comply with any of the GMP
requirements makes the product adulterated and
illegal by definition under U.S. law
– Even if there is no evidence of an integrity problem
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FDA’s GMP Requirements
• The GMP regulations establish mandatory, minimum
requirements
– Compliance is not an option or a matter of choice
– Complying with GMP is the lowest acceptable
quality standard
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Management Responsibility
• The cornerstone of quality systems and FDA’s approach
– Management cannot delegate its responsibility or just
designate someone else to be on the hook
– The old ways of corporate management (“that’s
Quality’s job”) are not going to work anymore
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Management Responsibility
• Remember – this is a strict liability law
– Ignorance has never been a valid excuse
• Going forward, ignorance and/or a lack of direct
involvement will absolutely guarantee failure
– No matter how good your Quality organization is
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FDA Recognizes Costs and Benefits
• “[I]mplementing an effective quality system in a
manufacturing organization will require significant
costs in time and resources. However, the longterm benefits of implementing a quality system
will outweigh the costs.”
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Significant Benefits in the Long Run
• Better science, efficiency, predictability, and control
– Real business benefits (in cost, time, and efforts)
– Less waste, rejection of materials, and re-work
– Improved process control and yields
– Problem avoidance through knowledge
– Greater ability to identify and correct root causes
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Significant Benefits in the Long Run
• Improved ability to understand and implement
changes with less FDA oversight and pre-approval
• Faster and more predictable FDA review, analysis,
and approval of new products and CMC changes
• Fewer pre-approval and shorter GMP inspections
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Big Challenges Ahead
• The basis for achieving all of the benefits will require
a substantial change in the industry’s business model
– Process understanding and development to a degree
that are far beyond the current way of working
– Shifting from a process focus to a systems focus
• Seeing all problems as quality system failures
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Big Challenges Ahead
• Major challenge to overcome the current business
model and speed-to-market pressures
– Investing much more time and scientific effort
up front to be quicker on the “back end” of the
product life cycle – process transfer from R&D
to manufacturing, submission to FDA, and
throughout the commercial life of the product
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Recommendations for Success
• The drug and biologics GMP regulations have not changed
– Quality system approach is only reflected in guidance
• FDA may revise the GMP regulations eventually
– Don’t wait for that to happen before moving forward
– The quality system train has already left the station
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Philip Crosby's Reflections on Quality
“It is erroneous to think that quality is intangible,
and therefore unmeasurable. It is precisely
measurable by the oldest and most respected of
means – cold, hard cash.”
“The price of nonconformance in manufacturing
is more than your pretax profit.”
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Critical Awareness and Acceptance
• New approach will require a significant culture change
– Going far beyond new policies, procedures, manuals,
standards, and training
– Truly affecting day-to-day operations and behavior
– A culture of resistance to change will not succeed
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Critical Awareness and Acceptance
• Need to understand the seriousness and potential
consequences to the company and to individuals
– Throughout the entire company
– Every person in the organization needs to know
the rules of the game
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Critical Awareness and Acceptance
• Changing the common mindset about quality issues
– Cannot just be resolved by the Quality organization
– Should be viewed as corporate governance problems
– Will need the full and active involvement of the
entire organization to be successful
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Critical Awareness and Acceptance
• Management will need to demonstrate that the company
really “gets it” and is serious about its commitments
– Needs to be done through actions and not just words
– Cannot demonstrate it to FDA without clearly and
consistently demonstrating it internally
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Common Traps and Failures
• The management “reality gap”– failure to recognize
significant gaps between senior management
perception of compliance issues and the reality of
the operations on the ground
– Often coincides with a corporate culture that does
not support or encourage the reporting of negative
information up through the chain of command
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Common Traps and Failures
• The “no observation – no problem” rationale
– Management is not willing to correct a problem
until and unless FDA cites it in a 483 observation
– Sends a clear message that defects and poor quality
are acceptable as long as FDA doesn’t detect them
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Common Traps and Failures
• A company’s view of “risk” should never include
what is commonly called “regulatory risk”
– The risk of detection of a problem by FDA
– The potential consequences of being “caught”
• FDA expects risk analyses to be documented, so
those documents are in-scope during inspections
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Recommendations for Success
• Focus first on sound logic and good scientific practices
– This is what the regulators are usually looking for
• Companies fail because they continue to apply poor
practices that cannot be justified or defended
• “Do it right, and compliance will follow”
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Questions?
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