Process Risk Assessment Model as a reference model

Process Risk Assessment Model

1. 1
Process Risk Assessment
Model
Robert C. Menson, PhD

2. Robert C. Menson, PhD 2
What Risks Must Be
Managed?
Business
Product liability
Regulatory
Risk to safety of
patients, users, handlers

3. Robert C. Menson, PhD 3
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

4. Robert C. Menson, PhD 4
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

5. Robert C. Menson, PhD 5
Elements of the Risk
Management Process

Risk Analysis

Risk Evaluation

Risk Control

Post-Production Information
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6. Robert C. Menson, PhD 6
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

7. Robert C. Menson, PhD 7
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 PotentialSPotentialOCurrentDRRecommended ResponsibilityAction Results
Function Failure Effect(s) Cause(s) Controls P Action(s) and TargetActions R
Mode of Failure of Failure N Complete DateTakenSODP
N
Field Defining
Light
Visible Treatment
Field Indication
1) Light
Failure
Treatment
setup time
increases
2Burn Out
Bulb
4 432-Better light
source
-Redundant
source
-Quick change
light bulb
2
1
1
3
1
1
4
2
4
24
2
4
2)
Alignment
Failure
Wrong Field
Defined
Causing
Repeat x-
rays and
additional
setup time
3a) light
source
moved
1 412
3b) Mirror
moved
5 460
FMEA Model

8. Robert C. Menson, PhD 8
HAZOP Model
Design Statement
Activity Material Destination
Transfer Powder Hopper

9. Robert C. Menson, PhD 9
HAZOP
TransferMaterial Destinatio
n
No Valve closed
Line blocked
Pump
broken
Tank empty Valve closed
Hopper full
More Pump fast Larger tank
Inaccurate
gage
Other
than
Liquid
Wrong powder

10. Robert C. Menson, PhD 10
HACCP
Hazard Analysis and Critical Control
Point

Risk Management System

Biological Hazards

Chemical Hazards

Physical Hazards

Requires

Prerequisite Quality System Program

Traditionally GMPs

11. Robert C. Menson, PhD 11
Risk Assessment Process
Map Process
1. Risk
Assessment
2. ECP
Analysis
3. ECP
Review Matrix
4. ECP
Action Plan

12. Robert C. Menson, PhD 12
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

13. Robert C. Menson, PhD 13
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.

14. Robert C. Menson, PhD 14
Risk Assessment Decision
Tree
Sev>5
END
Prob>5
Det<5
Yes
Yes
No Det<5
Assign ECP to
Process
No
Assign ECP to
Detection
(Either at that
point or
downstream)
Yes
Reduce
Probability or
Increase
Detection
No
Assign ECP to
Reduced
Parameter
No
Yes
Begin

15. Robert C. Menson, PhD 15
Sev>5
END
Prob>5
Det<5
Yes
Yes
No Det<5
Assign ECP to
Process
No
Assign ECP to
Detection
(Either at that
point or
downstream)
Yes
Reduce
Probability or
Increase
Detection
No
Assign ECP to
Reduced
Parameter
No
Yes
Begin
Risk Assessment Decision
Tree

16. Robert C. Menson, PhD 16
Risk Assessment Decision
Tree
Sev>5
END
Prob>5
Det<5
Yes
Yes
No Det<5
Assign ECP to
Process
No
Assign ECP to
Detection
(Either at that
point or
downstream)
Yes
Reduce
Probability or
Increase
Detection
No
Assign ECP to
Reduced
Parameter
No
Yes
Begin

17. Robert C. Menson, PhD 17
Risk Assessment Decision
Tree
Sev>5
END
Prob>5
Det<5
Yes
Yes
No Det<5
Assign ECP to
Process
No
Assign ECP to
Detection
(Either at that
point or
downstream)
Yes
Reduce
Probability or
Increase
Detection
No
Assign ECP to
Reduced
Parameter
No
Yes
Begin

18. 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 SevProbDet
ECP
Y/N
ECP
Where
3
Pull released
raw materialsStability
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 3YES
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 4YESCIP / 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 3YES
USP Test
Procedure
Risk Assessment Document
Robert C. Menson, PhD 18

19. 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 ModeHazard
Potential
Cause Existing controls
Detection
Method SevProbDet
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 3YES
USP 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-F7010
Specific Batch
Record
count
<25/250mL / no
objectionables
QB-I5008
USP micro
limits
milliflex sensor II
vitek DLSA1030
hood 409164
incubator 68955-1
pH meter 45057
QCP-017 (equip)
report 49 micro
cal HVA-0101-SP
cal SPT-0595-QC
calibration Daily
sampling
QG-I5034
Training
Procedure
020912 /
records
Quality
Control
(J. D.)
ECP Plan Document
Robert C. Menson, PhD 19

20. 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-F7010
Specific Batch
Record
count
<25/250mL / no
objectionables
QB-I5008
USP micro
limits
milliflex sensor II
vitek DLSA1030
hood 409164
incubator 68955-1
pH meter 45057
QCP-017 (equip)
report 49 micro
cal HVA-0101-SP
cal SPT-0595-QC
calibration Daily
sampling
QG-I5034
Training
Procedure
020912 /
records
Quality
Control
(J. D.)
ECP Plan Document
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)
1
4.1. 4.2,
4.3
QB-
I5008
Review/Gener
ate TMV for
QB-I5008
QCP-017
2
4.1. 4.2,
4.3
QB-
I5008
Milliflex
sensor II
qualification
QCP-017
3
4.1. 4.2,
4.3
QB-
I5008
Vitek DLSA
qualification
SN1030
Report 49
micro
Risk Review Matrix
Robert C. Menson, PhD 20

21. 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)
1
4.1. 4.2,
4.3
QB-
I5008
Review/Gener
ate TMV for
QB-I5008
QCP-017
2
4.1. 4.2,
4.3
QB-
I5008
Milliflex
sensor II
qualification
QCP-017
3
4.1. 4.2,
4.3
QB-
I5008
Vitek DLSA
qualification
SN1030
Report 49
micro
Risk Review Matrix
Robert C. Menson, PhD 21