1. The Pharmaceutical Industry and ICH Q9
Peter H Gough
Partner, David Begg Associates 1

2. 21st Century GMP Initiative
“Seeks to integrate quality systems and risk management approaches into the existing programmes and encourages adoption of modern and innovative manufacturing technology.”
“Use existing and emerging science and analysis to ensure that limited resources are best targeted to address important quality issues, especially those associated with predictable or identifiable health risks.”
Lester M. Crawford, FDA Deputy Commissioner, August 2002 2

3. FDA’s “Desired State”
Regulatory policies tailored to recognise the level of scientific knowledge supporting applications, process validation and process capability
Risk-based scrutiny related to:
Level of scientific understanding
Capability of process control strategies to prevent or mitigate risk of producing a poor quality product 3

4. International Conference on Harmonisation (ICH)
EU and Japan joined USA to define a new paradigm at an ICH GMP Workshop in Brussels, July 2003 4

5. ICH – Structure and Members
Q uality
S afety
E fficacy
M ultidisciplinary
Expert Working
Groups (EWGs) 5

6. ICH GMP Workshop ICH GMP Workshop in Brussels, 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 6

7. Incremental Steps to Achieve the Vision
The GMP Workshop agreed that the Vision would be achieved by ‘incremental steps’:
Q8 EWG, on Pharmaceutical Development, established in September 2003
Q9 EWG, on Quality Risk Management, established in November 2003
Q10 EWG, on Pharmaceutical Quality System, established in November 2005 7

8. Achieve by Incremental Steps
Pharmaceutical Development (Q8) Old: Data transfer / variable output
New: Knowledge transfer / Consistent output
Changed Paradigm
Quality Risk Management (Q9)
Old: Unstructured approach
New: Opportunity to use a structured process
Quality Systems (Q10) Old: Large variability on Q-systems
New: Consistency on Q-systems Q8
Q10 Q9 8

9. Risk Management We all do risk management every day
Driving to work
Extreme sports
Everything in life has some degree of risk
Can NEVER have zero risk
We all manage risk but we have different risk thresholds 9

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13. If you do not manage risk; it will manage you.
Risk and Management
If you do not manage risk; it will manage you. 13

14. What is Risk Management?
PROACTIVELY:
Identifying risks (what can go wrong?)
Analysing risks
Evaluating risks
Controlling and reducing these risks
Accepting residual risk 14

15. Pharmaceutical Industry and Risk Management
Pharmaceuticals have lagged behind related industries in adopting formal risk management, e.g.
Medical devices, ISO 14971
Food, HACCP
We are using risk management but historically
Implementation was patchy
It was often not fully integrated with rest of the Quality System
Was performed retrospectively 15

16. Quality Risk Management
Pharmaceutical Quality Risk Management is about:
Knowing your processes (manufacturing and business)
Identifying what’s truly important
Focusing your money, time, energy and people on the things that are really important, i.e. things which have potential to impact patients 16

17. Advantages of Risk Management
Systematic, scientific and data-driven process
Reduces subjectivity
Ranks risk - allows prioritisation
Improves decision making
Identifies what gives most benefit to the patient
Documented - improves communication 17

18. Risk Management Must do risk management properly
Poor risk management will not impress regulators
They will think we do not know what’s really important
If everything is critical, nothing is critical
Ultimately, it is about credibility
Have to begin with the question “What is the impact on the patient?” 18

19. Why Did We Need ICH Q9 ? Needed ICH Q9 to:
Explain what quality risk management is and how it can be applied to pharmaceuticals
Provide a common language and an agreed process for the pharmaceutical industry and regulators 19

20. Why Did We Need ICH Q9?
To ensure both industry and regulators have common understanding of Quality Risk Management (QRM)
To facilitate moving to the ‘Desired State’
To facilitate communication and transparency
To move from ‘fire fighting’ to management of risk 20

21. 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 harm and severity of that harm
These are the definitions used in the ICH Q9 Guideline on Quality Risk Management. 21

22. What Does ICH Q9 Deliver? ICH Q9 provides: The key principles of QRM
A common language and process
Potential methodologies for QRM
Potential applications where QRM can add value 22

23. ICH Q9 – Principles of Quality Risk Management
Two primary principles:
1. The evaluation of the quality risk should be based on scientific knowledge and ultimately link back to the protection of the patient
2. The level of effort, formality and documentation of the quality risk management process should be commensurate with the level of risk 23

24. ICH Q9 Quality Risk Management Process
Initiate
Quality Risk Management Process
Risk Assessment
Risk Communication
Risk Identification
Risk Analysis
unacceptable
Risk Management Tools
Risk Evaluation
Risk Control
Risk Reduction
Risk Acceptance
Output / Results of the
Risk Management Process
Risk Review
Review Events 24 24

25. ICH Q9 – Annex 2 Potential Applications for Quality Risk Management
To provide a comprehensive evaluation of suppliers and contract manufacturers (e.g., auditing, supplier quality agreements)
To provide information for ensuring the availability of pharmaceuticals (e.g., ranking risks to the supply chain) 25

26. Supply Chain Risks Recent events have exposed several areas of risk:
Heparin contamination is USA and elsewhere
Melamine contamination of milk in China
Further cases of diethylene glycol contamination of glycerol
Counterfeit products entering the legitimate supply chain in the EU 26

27. Supply Chain Risks These supply chain risks are real
Probably rank amongst the highest hazards currently faced
The must be managed proactively
ICH Q9 and this PQG Guide provide an excellent approach 27

28. PQG Supply Chain Risk Management
When we wrote Q9 we hoped it would encourage greater understanding of risk & risk management in the pharmaceutical industry
This PQG Guide is exactly the type of detailed thinking that we hoped to see 28

29. Watch Out ! To add value QRM must be done properly
You must have the right experts on your team
You must consider all reasonable hazards
You must use the right weightings for hazards
Ultimately it must be about the patient 29

30. Watch Out ! FMEA Risk Priority Numbers
The absolute number is unimportant
RPN allows risks to be ranked
Allows action to be prioritised
Provides justifiable basis for decision making… including doing nothing! 30

31. Conclusion We are already doing Quality Risk Management
Using a structured, systematic process adds value in many more complex situations
Supply Chains are complex!
The PQG Guide provides a good framework
Use it pro-actively 31

32. Thank you
DBA
David Begg Associates 32