process risk assessment model
TRANSCRIPT
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Process Risk AssessmentModel
Robert C. Menson, PhD
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What Risks Must Be Managed?
Business
Product liability
Regulatory
Risk to safety ofpatients, users, handlers
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Intended Use/Intended Purpose
Use of a Product, Process or Service
in accordance with the specifications,instructions and information providedby the manufacturer
ANSI/AAMI/ISO 14971:2000, definition 2.5
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PAT(Process Analytical Technologies) Systems for the analysis and control of
manufacturing processes based on timely
measurement during procession ofcriticalquality parameterand performance attributesof raw and in-process materials andprocesses, to assure acceptable end-product
quality at the completion of the process.
FDA Subcommittee on PAT Proposed Definition
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Elements of the Risk
Management Process
Risk Analysis
Risk Evaluation
Risk Control
Post-Production Information
Asse
ssm
ent
M
anagemen
t
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Risk Assessment Tools Risk Matrix
PHA= Preliminary Hazard Analysis
FTA=Fault Tree Analysis
FME(C)A=Failure Mode Effects(Criticality) Analysis
HAZOP=Hazard Operability Analysis HACCP=Hazard Analysis and Critical
Control Point
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POTENTIAL FAILURE MODE AND EFFECTS ANALYSIS
X-Ray ZM Device FMEA Number
Subsystem Page of
Component ____________________ Responsibility Prepared By
Process FMEA Date (Orig.) (rev.)
Core Team:
_______________________________________________________________________________________________
Device/ Potential Potential S Potential O Current D R Recommended Responsibility Action Results
Function Failure Effect(s) Cause(s) Controls P Action(s) and Target Actions RMode of Failure of Failure N omplete Date Taken S O D P
N
Field DefiningLightVisible TreatmentField Indication
1) LightFailure
Treatmentsetup timeincreases
2 Burn OutBulb
4 4 32 -Better lightsource-Redundantsource-Quick changelight bulb
2
1
1
3
1
1
4
2
4
24
2
4
2)AlignmentFailure
Wrong FieldDefinedCausingRepeat x-rays and
additionalsetup time
3 a) lightsourcemoved
1 4 12
3 b) Mirrormoved
5 4 60
FMEA Model
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HAZOP ModelDesign Statement
Activity Material Destination
Transfer Powder Hopper
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HAZOPTransfer Material Destination
No Valve closed
Line blockedPump broken
Tank empty Valve closed
Hopper full
More Pump fast Larger tank
Inaccurategage
Otherthan
Liquid
Wrong powder
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HACCP
Hazard Analysis and Critical Control Point
Risk Management System
Biological Hazards
Chemical Hazards
Physical Hazards
Requires
Prerequisite Quality System Program
Traditionally GMPs
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Risk Assessment Process
Map Process
1. RiskAssessment
2. ECP
Analysis
3. ECPReview Matrix
4. ECP
Action Plan
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Create SOD Tables Severity (S)
Link to end product functional failure
Medical Department involvement Occurrence (O)
Use historical data
Similar processes products
Detection (D) Method validation studies
Historical data
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Evaluation Rules Concept of ECP:
A process that is in control ( i.e. does not
produce significant defects) but is verydifficult to verify by testing.
The corollary is a process with a "high"level of defects that can be detected
before shipment to the end user. If (S) >5 and (D) or (P) >5 then an
ECP is assigned.
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Risk Assessment Decision Tree
Sev>5
END
Prob>5
Det
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Sev>5
END
Prob>5
Det
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Risk Assessment Decision Tree
Sev>5
END
Prob>5
Det
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Risk Assessment Decision Tree
Sev>5
END
Prob>5
Det
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Step 1: Identify Risks Using Process MapConvene participants from all relevant areas (Production, QA, QC, Packaging)
Identify and rate failure modes for each process step by severity, probability,
and detection Assign Essential Control Points (ECP) based on ratings
Step Process Failure Mode Hazard Potential Cause Existing controls
Detection
Method Sev Prob Det
ECP
Y/N
ECP
Where
3Pull releasedraw materials Stability
Subpotency:
delayed medicaltreatment
LIMS not referencing new
#, ManMan only
references old # causingincorrect CofA
Visual check of
CofA with LIMS
and
ManMan(production) 4 4 3 NO
Issue: 23,
24, 26
4.1
Collect Water
@ 126 drop /
WFI System
(Processing
tank #1,2,3)High Count/ obj
organism
Infection requiring
medical
intervent ion WFI System failure
WFI System Validation,
SOP (equipment,
preventive maintenance,
manual cleaning,
manufacturing, training,
environmental, procedures)
USP / EP water
test, 10 8 3 YES
USP Test
Procedure
4.2
Collect Water
@ 126 drop /WFI System
(Processing
tank #1,2,3)High Count/ obj
organism
Infection requiring
medical
intervention
Container (tanks)
contamination
Manual cleaning validation,
equipment qualification None 10 10 4 YES CIP / SIP
4.3
Collect Water
@ 126 drop /
WFI System
(Processing
tank #1,2,3)High Count/ obj
organism
Infection requiring
medical
intervention
Improper sampling
technique Training, SOP
USP / EP water
test, 10 10 3 YES
USP Test
Procedure
Risk Assessment Document
Robert C. Menson, PhD 18
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Step 2: Identify key elements of ECPs Migrate ECPs from Risk Assessment to ECP Plan
Assign process drivers/ owners for each ECP in the Plan
Collect relevant Information (SOP#s, Equipment used, Training documents)
Step Process Failure Mode Hazard
Potential
Cause Existing controls
Detection
Method Sev Prob Det
ECP
Y/N
ECP
Where
4.1
Collect Water @
126 drop / WFI
System
(Processing tank
#1,2,3)
High Count/ obj
organism
Infection
requiring
medical
intervention
WFI System
failure
WFI System Validation,
SOP (equipment,
preventive maintenance,
manual cleaning,
manufacturing, training,
environmental,
procedures)
USP / EP
water test,10 8 3 YES
USP Test
Procedure
Risk Assessment Document
ECP#
(1)
Process
(2)
FailureMode
(3)
Potential
Cause
Procedure/Step
(4)
QualityAttribute
(5)
HowDetermined
(6)
Equipment
(7)
ReferenceDocuments
(8)
RelatedIssues
(9)
ECPOwner
(10)
4.1
Collect Water
@ 126 drop /
WFI System
(Processing
tank #1,2,3)
high
count/obj.
organism
WFI System
FailureP-F7010
Specific Batch
Record
count
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Step 3: Compile Risk Review MatrixBreak each ECP into review tasks based on SOPs, trainings, and other documents
Each item # created is a distinct action item
ECP
#
(1)
Process
(2)
Failure
Mode
(3)
Potential
Cause
Procedure
/Step
(4)
Quality
Attribute
(5)
How
Determined
(6)
Equipment
(7)
Reference
Documents
(8)
Related
Issues
(9)
ECP
Owner
(10)
4.1
Collect Water
@ 126 drop /
WFI System
(Processing
tank #1,2,3)
high
count/obj.
organism
WFI System
FailureP-F7010
Specific Batch
Record
count
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Step 4: Create Remedial Action Plan Prioritize each item # and assign responsibilities and completion dates
Track items to completion
Item
#
(1)
ECP
#(s)
(2)
SOP
#(s)
Remediati
on Task
(3)
Prerequisites
Required or
Prerequisite
to (4)
Respon
sibility
(5)
Completion
Date
(6)
Reference
Document
(7)
Link
to:
(8)
Comm
ents
(9)
14.1. 4.2,
4.3
QB-
I5008
Review/Generate TMV for
QB-I5008
QCP-017
24.1. 4.2,
4.3
QB-
I5008
Milliflex
sensor II
qualification
QCP-017
34.1. 4.2,
4.3
QB-
I5008
Vitek DLSA
qualification
SN1030
Report 49
micro
Risk Review Matrix
Robert C. Menson, PhD 21