ICH Q9 and Q10 EUGMP the ICH and a "how to"

11/02/2011
EUGMP the ICH and a "how to"
guide on integrating ICH Q9 and Q10
within your current QMS
Mark Dignum
Contract QP Limited
ICH Q9 and Q10
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What is the ICH?
What are Q9 and Q10?
What do they mean to us?
What do we have to do?
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The ICH?
• International Conference on Harmonisation
• EU, USA and Japan
• Four areas - Quality, Safety, Efficacy,
Multidisciplinary.
ICH - Quality
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Q1 Stability
Q2 Analytical Validation
Q3 Impurities
Q4 Pharmacopoeias
Q5 Quality of Biotechnology Products
Q6 Specification
Q7 GMP for Active Pharmaceutical Ingredients
Q8 Pharmaceutical Development
Q9 Quality Risk Management
Q10 Pharmaceutical Quality System
Q11 Development and manufacture of drug substance
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EU GMP and ICH?
• Some ICH Guidelines are already more than a little familiar
• For Example
– ICH Q1 defines the stability conditions and requirements that
we are familiar with.
– ICH Q2 analytical method validation has been the accepted
standard for some considerable time.
– ICH Q7 has been transposed into EU GMP Part II
• Adoption of ICH guidelines is well chartered in the EU.
– ICH Q9 is Annex 20 of EU GMP
– ICH Q10 incorporated into Part I / GMP Part III ?
ICH Q9
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Where is it?
What should we do with it?
Examples of implementation.
Key points
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ICH Q9 Quality Risk Management
• Annex 20 – Direct transcript of ICH Q9
• Amendment to Chapter 1 of EU GMP
Quality Risk Management
1.5 Quality risk management is a systematic process for the assessment, control,
communication and review of risks to the quality of the medicinal product. It can
be applied both proactively and retrospectively.
1.6 The quality risk management system should ensure that:
the evaluation of the risk to quality is based on scientific knowledge,
experience with the process and ultimately links to the protection of the
patient
the level of effort, formality and documentation of the quality risk
management process is commensurate with the level of risk
Examples of the processes and applications of quality risk management can be
found inter alia in Annex 20.
ICH Q9 Quality Risk Management
• Looks fantastic ... What
is it?
• What do I need to do?
• What can this do for
me?
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ICH Q9 Quality Risk Management
• “The quality risk management system should
ensure that…”
• Implication here is that a system is required –
an SOP would be a good start
– What about a smarter approach
– A Quality Risk Management Policy
– Integrating risk management into our existing
forms and processes.
ICH Q9 Quality Risk Management
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ICH Q9 Quality Risk Management
• We already do this ... More or less.
• It could be as simple as calling some of the
things that we already do risk assessments.
– May seem a little petty though it does affect the
culture or mind set of the organisation.
ICH Q9
EU GMP Chapter 1
1.6 The quality risk management system should
ensure that:
• the evaluation of the risk to quality is based on
scientific knowledge, experience with the process
and ultimately links to the protection of the
patient
• the level of effort, formality and documentation
of the quality risk management process is
commensurate with the level of risk
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ICH Q9 - FMEA
• FMEA a worked example:
Component
Severity
Risk of
Occurrence
Risk of NonDetection
Score
Reconcilliation
Required
Carton Labels
PILS
TE Seal
Syringe Labels
Packing Tube Labels
Filled Syringe
Packing tubes
Plugs
Cartons
Shipping Box
ICH Q9 - FMEA
• Rules and Caveats
– Note 0 is not acceptable.
– Printed components and components scoring
higher than 125 should be reconciled.
• Why 125?
– 5x5x5=125 Could this be smarter? See later.
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ICH Q9 - FMEA
Component
Carton Labels
PILS
TE Seal
Syringe Labels
Packing Tube Labels
Filled Syringe
Packing tubes
Plugs
Cartons
Shipping Box
Severity
9
9
6
9
9
9
9
9
9
5
Risk of
Occurence
5
3
4
3
2
1
1
1
1
1
Risk of NonDetection Score
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360
8
216
4
96
2
54
2
36
1
9
1
9
1
9
1
9
1
5
Reconcilliation
Required
X
X
X
X
X
ICH Q9 - FMEA
Acceptability Score – Another Approach.
Conclude to schedule an audit when,
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Compliance/Severity: Safety & Efficacy = medium (3) or more
Compliance/Severity: Availability = major (4) or more
Complexity: Probability = indirect use for patient (2) or more
History: Detectability = 3 years ago (4) or more
This would result in 3 x 4 x 2 x 4 = 96
Basically Have a rationale that you can support – Scientific Knowledge
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ICH Q9 Risk Management Techniques
• Their are lots of techniques.
• Fishbone, HACCP and FMEA are good
examples.
– Probably enough for many situations
• Lots of guidance and examples
– Annex to Q9
– ICH Q9 Briefing Pack
ICH Q9 – Key Points
• It is here!!!
• It can be used to your and your companies
advantage – integration.
• Level of effort is commensurate with the level
of risk
– Keep it simple when you can.
• Think of your company culture – think and
practice risk assessment as routine.
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ICH Q10 Pharmaceutical Quality
System
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What is it?
Quality Manual
CAPA
Knowledge Management
ICH Q10 Pharmaceutical Quality
System
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ICH Q10
• The objective is to describe a model for an
effective quality management system for the
pharmaceutical industry, referred to as the
pharmaceutical quality system, that:
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Ensures the realization of a quality drug
product
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Establishes and maintains a state of control
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Facilitates continual improvement over the
product lifecycle
ICH Q10
• Q10 will:
– Augment existing GMPs
– Provide a bridge between different regional
regulations
– Complement and facilitate implementation of
Q8 “Pharmaceutical Development” and Q9
“Quality Risk Management”
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ICH Q10 – Site Master File?
1.8 Quality Manual
• A Quality Manual or equivalent documentation approach
should be established and should contain the description of
the pharmaceutical quality system. The description should
include:
– (a) The quality policy (see Section 2);
– (b) The scope of the pharmaceutical quality system;
– (c) Identification of the pharmaceutical quality system
processes, as well as their sequences, linkages and
interdependencies. Process maps and flow charts can be useful
tools to facilitate depicting pharmaceutical quality system
processes in a visual manner;
– (d) Management responsibilities within the pharmaceutical
quality system (see Section 2).
ICH Q10
• CAPA System
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Q10 - CAPA
Pharma industry definition
Corrective Action – Fix the batch.
Preventative Action - Fix the system.
ISO ICH Definitions of CAPA
• Corrective Action – Action to eliminate the cause
of a detected non-conformity or other
undesirable situation.
• Preventive Action – Action to eliminate the cause
of a potential non-conformity or other
undesirable situation.
• ISO 9001 has an Additional Category
– Correction – Action to eliminate a detected non
conformity.
• In other words Fix the batch
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Q10 - CAPA
• Corrective action
– Amend SOP
– Review System/Process.
• Preventive action
– Proactively look for things that may go wrong in
the future.
– Self inspection / trending of incidents.
Enablers
• Knowledge Management
– Deviation systems generally log failure
– Near Miss?
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Incident Report
• Objective of this is to capture the noise and to
apply a filter to detect the signals within the
noise.
• Health and Safety are well ahead of us on this.
• Empower department managers to manage
quality in their departments.
• Resource is deployed were it is going to be
required.
INCIDENT REPORT - INTERNAL; Part A
Incident Number
Customer / Supplier:
Product (if applicable including strength):
Work Order:
For Clinical Trials Only:
Cubicle / machine
Component Batch
Number / Lot:
Job Batch Number:
Leg
No:
CTS No:
Protocol No:
DESCRIPTION OF INCIDENT (What, where, when, Qty affected, how discovered etc)
IMMEDIATE ACTIONS TAKEN (What, where, who)
Reported by:
Date:
FURTHER INFORMATION
Completed by (sign):
Date:
Incident Categorisation: (what was issue (not root cause)) Pre Production 1
Production
2
Post Production
3
e.g. Pre-production, Low risk, Materials = 1aB
Medium
b
High
c
Paperwork A
Materials
B
Low
Process
C
a
Handling
D
Equipment E
Personnel
F
Incident category:
Further assessment required – Incident Risk Assessment / Corrections Part B required
Department Manager:
Sign
Date
YES / NO
QA: Sign
(delete as applicable)
Date
A copy of the completed document to be attached to the Batch Documentation if applicable. The original document to be retained by the Quality Assurance Department
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Incident Report
• Don’t get worked up about root cause
– You will not have the resource
– Sometimes it isn’t worth the effort.
• Trend your incidents
– Act on the warning signs
– Deploy resources were the knowledge tells you it is
required.
• Empower the department manager to manage
quality in their department.
– Maintain a QA oversight.
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Knowledge Management
• Filter the information from the data.
• Act on the information.
ICH Q10
• Bring your site master file in from the cold.
– Integrate it into your QMS
• CAPA – Preventive Action
– Proactively looking for continual improvement
– Not just waiting for or acting on things that go wrong.
• Self inspection
• Incident Report
• Enablers
– Knowledge and Risk Management
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