Transcript Folie 1 - SAPRAA

ABCD
Initiate
Quality Risk Management
Quality Risk Management Process
Risk Assessment
Risk Identification
Risk Evaluation
Unacceptable
Risk Control
Risk Reduction
Risk Acceptance
Output / Results of the
Quality Risk Management Process
Risk Review
Review Events
QRM - SAPRAA 20 March 2009 PTS
Risk Management Tools
Risk Communication
Risk Analysis
20th March 2009 - SAPRAA
Helena van Schalkwyk
Quality Assurance Manager
Boehringer Ingelheim, South Africa
Dr. R. Beerbohm
Agenda
 Risk Management - The Essentials
 Background of QRM
 Structured Risk Management Process: ICH Q9
 Practical Implementation of QRM in your
company
 Summary and conclusions
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Agenda
 Risk Management - The Essentials
 Background of QRM
 Structured Risk Management Process: ICH Q9
 Practical Implementation of QRM in your
company
 Summary and conclusions
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Risk Management – The Essentials
• Keep Risk Management SIMPLE
- Beware of the following pitfalls ……
 Recruiting “Risk Management Experts”
 Writing a 30 page “Risk Management Policy/SOP””
 Seeing Risk Management as something NEW
 The appointment of Risk Management
CONSULTANTS
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Risk Management – The Essentials
(cont)
• We are already managing risks ……
Because we live in a world full of risks!
“Zero Risk” does not exist anywhere!
• Risk Management involves:
 Identifying risks (what can go wrong/ what are the hazards)
 Analysing risks (estimate risks associated with identified hazards)
 Evaluating risks (are these risk really that bad?)
 Controlling and reducing these risks
(mitigate severity, reduce probability of harm, increase likelihood of detection)
 Accepting residual risk (accept level of risk)
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Risk Management – The Essentials
(cont)
• ICH Q9 Definitions
 “Harm” – damage to health, including the
damage that can occur from loss of product,
quality or availability
“Hazard” – potential source of harm
 “ Risk” – combination of probability of occurrence of
harm
and severity of harm
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Risk Management – The Essentials
(cont)
• What is risk?
 You only have risk where a hazard exists
 Risk is the combination of probability of harm
and severity of that harm
 Some risks we can’t do anything about
 Other risks can be managed
 DRIVING to work is a risky business
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Risk Management – The Essentials
(cont)
• What is your perception of risk?
 High, medium or low
based on
 Probability of occurrence
 Severity of potential harm
Will you be satisfied with this
level
of risk or not?
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Risk Management – The Essentials
(cont)
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Risk Management – The Essentials
(cont)
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Risk Management – The Essentials
(cont)
Are you prepared to take your chances and accept the
risk?
or
 Accept that the risk is unacceptable and in need of
management and control?
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Risk Management – The Essentials
(cont)
• Acceptable risk?
 Your answer will depend on
your
 Attitude to risk
 Your objective and
subjective assessment
of
information available to
you
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Risk Management – The Essentials
(cont)
• The risks associated with DRIVING in South Africa:
 Approximately 14,627 people are killed each year on
South African roads
(Road Traffic Management Corporation - Road Traffic Report March 2008 dated 17 April 2008)
 That’s 40 people every day
 Roads will become even more congested
 Cars are becoming both faster and safer
Is the risk acceptable to you or not?
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Risk Management – The Essentials
(cont)
• Risk IDENTIFICATION
What can go wrong?
 You may be involved in a fatal road accident – (killing
yourself or someone else)
 You may be seriously injured and unable to work for a
period of time
 You may be sent to prison if found guilty of dangerous
driving
 Incur costs for repairs to damaged vehicles and the
inconvenience factor
 You driver’s license may be suspended due to
(multiple)
speeding offences
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Risk Management – The Essentials
(cont)
• Risk IDENTIFICATION (cont)
What can go wrong?
 The inconvenience of relying on public transport
(currently very limited availability in SA!)
 You may lose your job if you have lost your driver’s
license
 Social hardships as a result of no income
 Higher insurance premiums after the accident claim
 High fuel costs resulting from uneconomical driving
style
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Risk Management – The Essentials
(cont)
• DRIVING: Risk ANALYSIS
 What is the probability of occurrence?
 What are the potential consequences (severity)?
 Is this level of risk acceptable … or not?
 How can I control (manage) the risks?
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Risk Management – The Essentials
(cont)
• DRIVING: Risk ANALYSIS (cont)
Potential Risks
Severity
Probability
occurrence)
You may be involved in a fatal road
someone else)
High
?
You may be seriously injured and unable to
time
High
?
You may be sent to prison if found guilty of
High
?
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Risk Management – The Essentials
(cont)
• DRIVING: Risk ANALYSIS (cont)
Potential Risks
Severity
Probability
occurrence)
Costs for repairs to damaged vehicles and
Low
?
You driver’s license may be suspended due
offences
High to
Medium
?
The inconvenience of relying on public
limited availability in SA!)
Medium
?
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Risk Management – The Essentials
(cont)
• DRIVING: Risk ANALYSIS (cont)
Potential Risks
You may lose your job if you have lost
Social hardships as a result of no income
Higher insurance premiums after the
High fuel costs resulting from
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Severity
Probability
occurrence)
High
?
High to
Medium
Medium
?
Low
?
?
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Risk Management – The Essentials
(cont)
• DRIVING: Risk CONTROL
What actions can you take to
 Reduce severity?
 Reduce probability of occurrence?
 Increase ability to detection?
You could
 Drive slower
 Increase following distance between you and the car in front of
you
 Buy a car with better safety specifications
 Sell your high performance car for a slower/more economical
one
 Drive at a safer and slower speed
 Leave earlier to reach your destination in time
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Risk Management – The Essentials
(cont)
• DRIVING: Risk CONTROL (cont)
You could
 Purchase a “Radar Detector”
Please Note: Do NOT use RM to justify what you know is inherently
wrong!
(Like purchasing a “Radar Detector” system!)
 Attend an advanced driving skills course
 Talk to those who have witnessed accidents close by
 Travel at alternative times (non-peak hours) of the
day
 Ensure that your car is always in a roadworthy
condition
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Risk Management – The Essentials
(cont)
• DRIVING: Risk REVIEW
Circumstances or situations could change which may
then
influence
your original decision
 You may be able to afford a safer car
 You may decide to move to a job closer to home that would
result in less
stressful and dangerous travel
 You may witness a serious accident that would influence your
driving
behaviour/style
 New laws may be implemented to lower maximum speed limits,
and much tougher enforcement of the traffic laws
 You may have children which will motivate you to drive more
careful
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Risk Management – The Essentials
(cont)
• FINALLY….. remember the following:
 Never use Risk Management to justify what you
know is INHERENTLY wrong
 Invest in an advance driving skills course instead
of purchasing a “Radar Detector”
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Agenda
 Risk Management – The Essentials
 Background of QRM
 Structured Risk Management Process: ICH Q9
 Practical Implementation of QRM in your company
 Summary and conclusions
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Background of QRM
• FDA’s CONCERNS – 2001:
Pharmaceutical Manufacturing
 Innovation/continuous improvement difficult due to
delays in
approval at HA’s
 Many product formulations and processes derived
empirically
 Too little knowledge on mechanisms impacting
product quality
 Very low efficiency and high cost – the opposite of
what is necessary in a competitive global market
 Industry hesitant/afraid to use new technologies
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Background of QRM (cont)
• FDA’s CONCERNS – 2001 (cont):
FDA unable to deliver on their statutory
inspection obligations (low budget and high
demand)
• FDA’s CONCLUSION:
 Current approach likely to be
inadequate to meet future needs
 Need to place emphasis on science
and risk-based approaches
• FDA’s INITIATIVES since 2002:
 Process Analytical Technology (PAT)
– not just testing, but a philosophy of
Process Understanding
 Control in-process rather than endproduct testing
 Minimises risks of poor quality
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Background of QRM (cont)
• FDA’s INITIATIVES since 2002 (cont):
 Quality by Design (QbD) approach – which parameters are
critical to product quality?
 Statistically designed experiments
 ICH Q8
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Background of QRM (cont)
• FDA’s INITIATIVES since 2002 (cont):
• PARADIGM SHIFT:
 Traditional Paradigm
Starting
Materials
Processing
Parameters
Product
Variable
Fixed
Variable
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Background of QRM (cont)
• PARADIGM SHIFT (cont):
 QbD paradigm:
Starting
Materials
Processing
Parameters
Product
Variable
Variable
Fixed
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Background of QRM (cont)
• ICH
 EU and Japan joined USA to define a new paradigm
at an ICH
workshop in Brussels in July 2003
 This workshop agreed a 5 year vision:
 Create a single, harmonised global
quality standard and interpretation based on
good
science and risk management principles
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Background of QRM (cont)
• ICH (cont)
 Achieve 5 year vision by incremental steps
Pharmaceutical Development (Q8)
Old:
New:
Data transfer / variable output
Knowledge transfer / consistent output
Quality Risk Management (Q9)
Old:
New:
Unstructured approach
Structured process
Quality Systems (Q10)
Old:
New:
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Large variability on Q-systems
Consistency on Q-systems
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Background of QRM (cont)
• ICH (cont)
Flexible Regulatory Approach
 Regulators evaluate risk, based on:
 Product and Process Design (Q8)
 Measures to evaluate and manage risks (Q9)
 Q-system implementation (Q10)
 Regulators determine risk and modify level of oversight
accordingly for:
 Submissions
 Post-approval review
 GMP Inspections
 Result
 Removal of barriers to continuous improvement
 Efficient use of resources by industry and regulator
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Background of QRM (cont)
• Design Space
Design space is the multi-dimensional combination and interaction of input variables (e.g. material
attributes) and process parameters that have been demonstrated to provide assurance of quality
Knowledge
Space
Design Space
Batch process/control
parameters
The batch process/control parameters are NOT registered and, hence, moving them within the Design
Space
is NOT a change
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Background of QRM (cont)
• ICH Q10 – Pharmaceutical
Quality
System
 Objective of Q10 - to
establish a new guideline
describing model for an
effective QMS for the
Pharmaceutical Industry,
referred to as the
Pharmaceutical QMS
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Background of QRM (cont)
• Q10 and Management Responsibility
 Management commitment, management review and
communication are important
 Senior Management
 Establish a PQS appropriate for the organisation and compliant
with regulations
 Ensure that PQS responsibilities and authorities are defined and
communicated
 Has ultimate responsibility to foster a company-wide commitment to
quality and for the successful functioning of the PQS
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Background of QRM (cont)
• ICH Q11 – API Development
 Q11 will aim to define the development process for API’s similar to those
contained in Q8 for medicinal products
(Detail for the 3.2.S.2 Section of the CTD)
• The New Regulatory Paradigm –
Conclusion
 It makes sense
 FDA is driving it forward
 If we can make it to work, it will benefit patients,
industry and regulators
 We should focus on what adds value for patients
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Background of QRM (cont)
• QRM – Summary
 Realise that
 current situation is not sustainable


By Industry
By Regulators
 current situation is not in the best interest for
patients
QRM is a win: win: win situation for:



Industry
Regulators
and Patients
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Agenda
 Risk Management – The Essentials
 Background of QRM
 Structured Risk Management Process: ICH Q9
 Practical Implementation of QRM in your
company
 Summary and conclusions
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Structured Risk Management Process:
ICH Q9
•
Q9 – Table of Contents
1. Introduction
2. Scope
3. Principles of QRM
4. General QRM Process
5. RM Methodology
6. Integration of QRM process into industry and regulatory
operations
7. Glossary
8. References
Annex I – RM Methods and Tools
Annex II – Potential Appliances of QRM
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Structured Risk Management Process: ICH Q9
(cont)
•
Q9 – Principles of QRM
Two primary principles:
1. The evaluation of the quality risk should be based
on scientific knowledge and always links back to
the
protection of the patient.
2. The level of effort, formality and documentation of
the QRM process should be corresponding with
the
level of risk.
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Structured Risk Management Process: ICH Q9
(cont)
• QRM is:
A systematic process for the assessment, control,
communication
and review of risks to the
quality of the drug (medicinal) product across the product
lifecycle
• QRM Process:
 Consists of three stages:
 Risk Assessment
 Risk Control
 Risk Review
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Structured Risk Management Process: ICH Q9
(cont)
Initiate
Quality Risk Management Process
Risk Assessment
Risk Identification
Risk Evaluation
Risk Control
Risk Reduction
Risk Acceptance
Output / Results of the
Quality Risk Management Process
Unacceptable
Risk Management Tools
Risk Communication
Risk Analysis
Risk Review
Review Events
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Structured Risk Management Process: ICH Q9
(cont)
• When a “situation/deviation” occurs
 Appoint a “situation/deviation” owner and start to
investigate
 Seniority dependent on initial severity assessment
 Decide what approach to Risk Assessment is
applicable
 Use a multi-disciplinary team approach
 People with the right knowledge and experience for the
situation/deviation
 Team Leader
 At least one person who understands Risk Management tools/methods
 FACILITATOR
 Determine deadline for completion
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Example of process mapping
ABCD
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Structured Risk Management Process: ICH Q9
(cont)
Deciding on the Risk Management
Approach:
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Structured Risk Management Process: ICH Q9
(cont)
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Structured Risk Management Process: ICH Q9
(cont)
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Structured Risk Management Process: ICH Q9
(cont)
Formal tools of Risk Assessment according to ICH Q9, Annex I:
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Structured Risk Management Process: ICH
Q9 (cont)
• Conclusion:
 Using a structured, systematic process for QRM
adds value in more complex situations
 ICH Q9 provides a good framework for this structured
approach
 Your company should develop its own implementation
approach
 Focus to be pro-active
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Agenda
 Risk Management – The Essentials
 Background to QRM
 Structured Risk Management Process: ICH Q9
 Practical Implementation of QRM in your
company
 Summary and conclusions
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Practical Implementation of QRM in your
company
• Implementation – Making it happen in your company
“If you want to make enemies, try and change something” - Woodrow
Wilson
To effectively plan the process to move to a more effective way of
using QRM you have to look at the following:
Context
Organisation
Culture
QRM
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Practical Implementation of QRM in your
company (cont)
• Planning for SUCCESSFUL Implementation
 Involve people early on in the process
 See the change from the perspective of others
 Create dissatisfaction with the current situation
(status quo)
“ let them know there must be a better way of doing
things”
• Your company MUST
 Accept an open “risk aware” culture
 Acknowledge that ZERO RISK doesn’t exist
 Accept that you have “been doing” RM from day one
 RM must be kept SIMPLE
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Practical Implementation of QRM in your
company (cont)
• Planning for SUCCESSFUL Implementation
(cont)
 There must be a clear objective – give DIRECTION
 Start small and go for early wins
 Communicate extensively
 Publicise your successes and give credit to people
 Make sure that your company
 Is aware of ICH Q9 and the business benefits
 Is aware that your competitors are already using RM as
well
 Does not re-invent the wheel … learn from others (HSE, etc)
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Practical Implementation of QRM in your
company (cont)
• Planning for SUCCESSFUL Implementation
(cont)
Important Rules to remember:
 RULE 1
Ensure that you have expert knowledge of your
PRODUCTS, PROCESSES, PROCEDURES at operational level,
on each site and in each department
 RULE 2
Ensure your organisation is aware of ICH Q9 and the opportunity it
affords
Provide education and training and start with SENIOR
MANAGEMENT
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Practical Implementation of QRM in your
company (cont)
• Important Rules (cont):
 RULE 3
Encourage an open, risk awareness culture
 Understand that risks always exist
 Understand current QRM approach
 Take ICH Q9 into account during your QRM process
 Identify opportunities for improvement
 Where will a more structured approach add
value?
 Complex issues, recurring deviations
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Practical Implementation of QRM in your
company (cont)
• Important Rules (cont):
 RULE 4
Keep RM SIMPLE
 Focus on the outcome, not the tools
 Learn from others (HSE, Medical Devices, Food Industry, etc.)
 RULE 5
Integrate QRM with existing QMS
 Remember ICH Q8, 9 and 10 work together
 Q9 needs to be applied across the whole product lifecycle
 Do NOT set up separate risk departments
 Coordinate implementation and allocate resources
 Prioritise projects
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Practical Implementation of QRM in your
company (cont)
 RULE 6
 Be open to new ways of thinking
 Expect resistance – this is normal. Work with resistance, NOT against it
 Remember that you can’t force anyone to do anything … unless they
really want to
 Proper PLANNING = successful IMPLEMENTATION
QRM is a better way of doing what you are already doing
WHEN it is necessary. – Peter Gough, DBA
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Agenda
 Risk Management – The Essentials
 Background of QRM
 Structured Risk Management Process: ICH Q9
 Practical Implementation of QRM in your
company
 Summary and conclusions
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Summary and conclusions

We must do RM properly
 Poor RM will not impress the regulators
 The regulators will think we do not know what’s
really
important

If we don’t know what’s insignificant,
how can we know what’s important?

If EVERYTHING is critical, NOTHING is
critical
Ultimately, it is all about CREDIBILITY!
***********************************************************
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Acknowledgements and References
• Contents of QRM Presentation prepared for the SAPRAA Meeting
of 20 March 2009 based on contents of presentation slides and
notes from “Practical Application of QRM” course presented by
David Begg & Associates and with the permission of David Begg &
Associates to use material from DBA in this presentation.
Please visit: www.david-begg-associates.com for more
information
about the company and services offered.
• ICH Q8, 9 and 10
• Annex 20 to the updated proposed South African GMP Guide
(4.01 SA Guide to GMP Sept08 v3.doc)
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