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

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The Pharmaceutical Industry and ICH Q9

Peter H GoughPartner, David Begg Associates

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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, 21 August 2002

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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

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International Conference on Harmonisation (ICH)

EU and Japan joined USA to define a new paradigm at an ICH GMP Workshop in Brussels, July 2003

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ICH – Structure and Members

Q Q ualityS S afetyE E fficacyM M ultidisciplinary

Expert WorkingGroups (EWGs)

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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

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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

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Achieve by Incremental Steps

ChangedParadigm

Q8

Q9

Q10

Pharmaceutical Development (Q8)

Old: Data transfer / variable outputNew: Knowledge transfer /

Consistent output

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

Quality Risk Management (Q9)

Old: Unstructured approachNew: Opportunity to use a structured

process

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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

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Risk and Management

If you do not manage risk;

it will manage you.

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What is Risk Management?

PROACTIVELY: Identifying risks (what can go wrong?)

Analysing risks

Evaluating risks

Controlling and reducing these risks

Accepting residual risk

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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

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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

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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

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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?”

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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

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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

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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

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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

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ICH Q9 – Principles of Quality Risk ManagementTwo 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

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ICH Q9 Quality Risk Management Process

Risk Review

Risk Assessment

Risk Evaluationunacceptable

Risk Control

Risk Analysis

Risk Reduction

Risk Identification

Review Events

Risk Acceptance

InitiateQuality Risk Management Process

Output / Results of theRisk Management Process

R

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un

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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)

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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

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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

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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

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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

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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!

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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

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Thank you

David Begg Associates

www.DBA-global.com