Risk Assessment Document

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


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


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


Elements of the Risk Management Process

Risk Analysis

Risk Evaluation

Risk Control

Post-Production Information

Asse

ssm

ent

M

anag

emen

t


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


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


HAZOP ModelDesign Statement

Activity Material Destination

Transfer Powder Hopper


HAZOPTransfer Material Destinati

onNo Valve closed

Line blockedPump broken

Tank empty Valve closedHopper full

More Pump fast Larger tankInaccurate gage

Other than

LiquidWrong powder


HACCPHazard Analysis and Critical Control Point Risk Management System

Biological Hazards Chemical Hazards Physical Hazards

Requires Prerequisite Quality System Program Traditionally GMPs


Risk Assessment ProcessMap Process

1. Risk Assessment

2. ECP Analysis

3. ECP Review 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 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.


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


Sev>5

END

Prob>5

Det<5

Yes

Yes

No Det<5


No



downstream)

Yes


IncreaseDetection

No


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




Improper sampling technique Training, SOP

USP / EP water test, 10 10 3 YES

USP Test Procedure

Risk Assessment Document


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




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


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


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


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


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


Risk Assessment Document

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