abcd qrm - sapraa 20 march 2009 pts dr. r. beerbohm quality risk management 20 th march 2009 -...

QRM - SAPRAA 20 March 2009 PTSDr. R. Beerbohm

ABCD

Quality Risk Management

20th March 2009 - SAPRAAHelena van SchalkwykQuality Assurance ManagerBoehringer Ingelheim, South Africa

QRM - SAPRAA 20 March 2009 2

Agenda

Risk Management - The Essentials

Background of QRM

Structured Risk Management Process: ICH Q9

Practical Implementation of QRM in your company

Summary and conclusions


Agenda

Risk Management - The Essentials

Background of QRM





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


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)



• 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



• 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



• 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?



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?



• Acceptable risk?

Your answer will depend on your

Attitude to risk

Your objective and subjective

assessment of information available to you



• 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?



• 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



• 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



• 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?



• DRIVING: Risk ANALYSIS (cont)

Potential Risks Severity Probability (of

occurrence)

You may be involved in a fatal road accident – (killing yourself or someone else)

High ?

You may be seriously injured and unable to work for a period of time

High ?

You may be sent to prison if found guilty of dangerous driving

High ?





occurrence)

Costs for repairs to damaged vehicles and the inconvenience factor

Low ?

You driver’s license may be suspended due to (multiple) speeding offences

High to Medium

?

The inconvenience of relying on public transport (currently very limited availability in SA!)

Medium ?





occurrence) You may lose your job if you have lost your driver’s license

High ?

Social hardships as a result of no income

High to Medium

?

Higher insurance premiums after the accident claim

Medium ?

High fuel costs resulting from uneconomical driving style

Low ?



• 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



• 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



• 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



• 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”


Agenda


Background of QRM





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


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 end-product testing

Minimises risks of poor quality



• FDA’s INITIATIVES since 2002 (cont): Quality by Design (QbD) approach – which parameters

are critical to product quality? Statistically designed experiments ICH Q8



• FDA’s INITIATIVES since 2002 (cont):

• PARADIGM SHIFT: Traditional Paradigm

Starting Materials

Variable

Processing Parameters

Fixed

Product

Variable



• PARADIGM SHIFT (cont): QbD paradigm:

Starting Materials

Variable

Processing Parameters

Variable

Product

Fixed



• 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



• ICH (cont)

Achieve 5 year vision by incremental steps

Pharmaceutical Development (Q8)Old: Data transfer / variable outputNew: Knowledge transfer / consistent output

Quality Risk Management (Q9)Old: Unstructured approachNew: Structured process

Quality Systems (Q10)Old: Large variability on Q-systemsNew: Consistency on Q-systems



• 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



• 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



• 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



• 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



• 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



• 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


Agenda


Background of QRM






• 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


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.



• 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



• 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


Example of process mapping

ABCD



Deciding on the Risk Management Approach:



Formal tools of Risk Assessment according to ICH Q9, Annex I:



• 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


Agenda


Background to QRM






• 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


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



• 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)



• Planning for SUCCESSFUL Implementation (cont)

Important Rules to remember: RULE 1Ensure that you have expert knowledge of your

PRODUCTS, PROCESSES, PROCEDURES at operational level,

on each site and in each department

RULE 2Ensure your organisation is aware of ICH Q9 and the

opportunity it affords

Provide education and training and start with SENIOR MANAGEMENT



• Important Rules (cont): RULE 3Encourage 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



• 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



RULE 6Be open to new ways of thinkingExpect 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


Agenda


Background of QRM






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!***************************************************

********


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)

abcd qrm - sapraa 20 march 2009 pts dr. r. beerbohm quality risk management 20 th march 2009 -...

Documents

agenda risk management

risk management experts

risk management simple

risk acceptable

residual risk

perception of risk

levelof risk

page risk management