Process Risk Assessment Model

7/30/2019 Process Risk Assessment Model

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1

Process Risk AssessmentModel

Robert C. Menson, PhD


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Robert C. Menson, PhD 2

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



HAZOP ModelDesign Statement

Activity Material Destination

Transfer Powder Hopper



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



HACCP

Hazard Analysis and Critical Control Point

Risk Management System

Biological Hazards

Chemical Hazards

Physical Hazards

Requires

Prerequisite Quality System Program

Traditionally GMPs



Risk Assessment Process

Map Process

1. RiskAssessment

2. ECP

Analysis

3. ECPReview Matrix

4. ECP

Action Plan



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



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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Sev>5

END

Prob>5

Det


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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


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


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 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
