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Objective
Slide 2
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Slide 3
Time consuming
Involves many people of differing opinion and background
Rigor of applying quantitative values to often intuitive situations can be tedious
Integration of QRM within the Quality System instead of being an additional activity
Ongoing maintenance as a living process
Risk Management plans, protocols, assessments and Risk Control Strategies
require significant resources to execute appropriately
2208, Genenteh
Slide 4
Multi-use refers to the types of products that can be produced within the
same Drug Substance manufacturing facility
Multiple commercial products
Clinical and commercial products
Products derived from different host cells
Multiple
commercial
products
Multiple clinical
and commercial
products
Multiple clinical
and commercial
products and
multiple host
cells
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Slide 5
QRM
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Slide 6
QRM
Operated multihost/multiproduct
clinical/commercial
facility
Risk Assessment
July 2009 CMC Strategy Forum
2208, Genenteh
Slide 7
QRM
2208, Genenteh
Slide 8
QRM
Asked by regulators to
include additional
granularity and detail in
risk assessment
Asked to perform multihost risk assessment by
regulators
Operated multihost/multiproduct
clinical/commercial
facility
Risk Assessment
July 2009 CMC Strategy Forum
2208, Genenteh
Growing network of
facilities with multi-use
considerations
Asked by regulators to
include additional
granularity and detail in
risk assessment
Asked by regulators to
perform risk assessment
for multi-host facility
Operated multihost/multiproduct
clinical/commercial
facility
Slide 9
QRM
Extension of concepts to
regulatory submission
strategies that can be
executed across multiple
products, facilities, and
types of multi-use
operations
2208, Genenteh
Slide 10
QRM
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Slide 11
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Slide 12
ICH Q9 QRM
Initiate
Quality Risk Management Process
Risk Assessment
Hazard Identification
Risk Communication
Risk Analysis
Risk Evaluation
Risk Control
Risk Reduction
Risk Acceptance
u
n
a
c
c
e
p
t
a
b
l
e
2208, Genenteh
Risk Identification
Slide 13
Failure Mode and Effect Analysis (FMEA) chosen as risk assessment tool.
Develop a process map grouping together similar unit operations, where possible
Assess risks that apply to more than one unit operation only once as a general risk
For each step of the process map identify relevant risk categories
Classify risks as either a cross-contamination or non-routine event
If the risk is a cross-contamination risk, determine the touch point
Identify all potential failure modes for the unit operation, risk category, and touch
point (as applicable)
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Risk Analysis
Slide 17
ICH Q9 requires the assessment of risk to patient safety, based on subject matter
expertise this may not be possible
The impact to product quality serves as a more conservative surrogate for patient safety
The severity scores for a contamination event remain the same regardless of where in
the process the event occurs.
The severity reflects the effect of the failure mode. Therefore, if the effect is unchanged, the
severity score must remain consistent regardless of process location.
2208, Genenteh
Scoring Criteria
Slide 18
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Slide 19
Multiple
commercial
products
Clinical and
Commercial
Products
Clinical and
Commercial
products;
Multiple hosts
10
10
10
10
10
Failure Effect
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Slide 20
2208, Genenteh
Slide 21
Multiple commercial
products
Clinical and
Commercial
Products
Clinical and
Commercial
products; Multiple
hosts
10
10
10
10
10
Failure Effect
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Slide 24
The resultant scores for severity, occurrence, and detection are multiplied to
obtain an overall score and represents the Risk Priority Number (RPN)
SEV x OCC x DET = RPN
The RPN score determines risk acceptability and directs discussion around
potential risk mitigation for unacceptable risks
Risk zones determine the extent of risk mitigation activities required
2208, Genenteh
Slide 25
2208, Genenteh
Risk Control
Slide 26
Risk control is the process through which decisions are reached and protective
measures are implemented for reducing risks to, or maintaining risks within
acceptable levels
The totality of the circumstances shall be taken into account when considering control
measures.
Risk acceptance is decided by the appropriate system/process owner or management team
Risk reduction
Processes for mitigation or avoidance of risk when it exceeds a specified level
May include mitigation of severity and probability of harm or improve the
detectability of hazards
New risks may be introduced by risk reduction measures and risk assessment may
need to be revisited
Risk acceptance
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Slide 27
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Slide 28
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Slide 29
Site
Inspection
Risk
Assessment
Expanded Comparability
Protocol
July 2009 CMC Strategy Forum
2208, Genenteh
Conclusions
Slide 30
2208, Genenteh
Acknowledgements
Emma Ramnarine
Krista Terry
Jennifer Sexton
Andrea Goddard
Mark Skoog
Eric Fallon
JP Gabriel
Christa Hartmann
Kathleen Bigelow-Houck
Euan Cunningham
Consuela Stewart
Wassim Nashabeh
Hoang Phan
Robert Caren
Jerry Cacia
Slide 31
Ron Williams
Vijay Palsania
Jenna Carlson
Lara Collier
Mary Beth Grace
2208, Genenteh