Post on 07-Feb-2017
1
Process Risk Assessment Model
Robert C. Menson, PhD
Robert C. Menson, PhD 2
What Risks Must Be Managed?
Business
Product liability
Regulatory
Risk to safety of patients, 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 provided by 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 of critical quality parameter and performance attributes of raw and in-process materials and processes, 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
anag
emen
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 ResultsFunction Failure Effect(s) Cause(s) Controls P Action(s) and Target Actions R
Mode of Failure of Failure N Complete Date Taken S O D PN
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 FieldDefinedCausing
Repeat 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 Destinati
onNo Valve closed
Line blockedPump broken
Tank empty Valve closedHopper full
More Pump fast Larger tankInaccurate gage
Other than
LiquidWrong powder
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HACCPHazard 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 ProcessMap Process
1. Risk Assessment
2. ECP Analysis
3. ECP Review 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 very difficult 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<5
Yes
Yes
No Det<5
Assign ECP to Process
No
Assign ECP toDetection
(Either at thatpoint or
downstream)
Yes
ReduceProbability or
IncreaseDetection
No
Assign ECP toReduced
Parameter
No
Yes
Begin
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Sev>5
END
Prob>5
Det<5
Yes
Yes
No Det<5
Assign ECP to Process
No
Assign ECP toDetection
(Either at thatpoint or
downstream)
Yes
ReduceProbability or
IncreaseDetection
No
Assign ECP toReduced
Parameter
No
Yes
Begin
Risk Assessment Decision Tree
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Risk Assessment Decision Tree
Sev>5
END
Prob>5
Det<5
Yes
Yes
No Det<5
Assign ECP to Process
No
Assign ECP toDetection
(Either at thatpoint or
downstream)
Yes
ReduceProbability or
IncreaseDetection
No
Assign ECP toReduced
Parameter
No
Yes
Begin
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Risk Assessment Decision Tree
Sev>5
END
Prob>5
Det<5
Yes
Yes
No Det<5
Assign ECP to Process
No
Assign ECP toDetection
(Either at thatpoint or
downstream)
Yes
ReduceProbability or
IncreaseDetection
No
Assign ECP toReduced
Parameter
No
Yes
Begin
Step 1: Identify Risks Using Process Map
• Convene 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
ECPWhere
3Pull released raw materials Stability
Subpotency: delayed medical treatment
LIMS not referencing new #, ManMan only references old # causing incorrect CofA
Visual check of CofA with LIMS
and ManMan(produc
tion) 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 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
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
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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 HazardPotential
Cause Existing controls Detection Method Sev Prob Det
ECP Y/N
ECPWhere
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 YESUSP Test Procedure
Risk Assessment Document
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 Failure
P-F7010Specific Batch
Record
count <25/250mL / no objectionables
QB-I5008USP micro
limits
milliflex sensor IIvitek DLSA1030
hood 409164incubator 68955-1pH meter 45057
QCP-017 (equip)report 49 micro
cal HVA-0101-SPcal SPT-0595-QCcalibration Daily
sampling QG-I5034Training
Procedure 020912 / records
Quality Control (J. D.)
ECP Plan Document
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Step 3: Compile Risk Review Matrix
• Break each ECP into review tasks based on SOP’s, 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 Failure
P-F7010Specific Batch
Record
count <25/250mL / no objectionables
QB-I5008USP micro
limits
milliflex sensor IIvitek DLSA1030
hood 409164incubator 68955-1pH meter 45057
QCP-017 (equip)report 49 micro
cal HVA-0101-SPcal SPT-0595-QCcalibration Daily
sampling QG-I5034Training
Procedure 020912 / records
Quality Control (J. D.)
ECP Plan Document
Item #
(1)
ECP #(s)(2)
SOP #(s)
Remediation Task
(3)
Prerequisites Required or Prerequisite
to (4)
Responsibility
(5)
Completion Date (6)
Reference Document
(7)
Link to:(8)
Comments(9)
14.1. 4.2,
4.3QB-I5008
Review/Generate TMV for QB-I5008
QCP-017
24.1. 4.2,
4.3QB-I5008
Milliflex sensor II qualification
QCP-017
34.1. 4.2,
4.3QB-I5008
Vitek DLSA qualification SN1030
Report 49 micro
Risk Review Matrix
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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)
Remediation Task
(3)
Prerequisites Required or Prerequisite
to (4)
Responsibility
(5)
Completion Date (6)
Reference Document
(7)
Link to:(8)
Comments(9)
14.1. 4.2,
4.3QB-I5008
Review/Generate TMV for QB-I5008
QCP-017
24.1. 4.2,
4.3QB-I5008
Milliflex sensor II qualification
QCP-017
34.1. 4.2,
4.3QB-I5008
Vitek DLSA qualification SN1030
Report 49 micro
Risk Review Matrix
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