Process Risk Assessment Model

Robert C. Menson, PhD

What Risks Must Be Managed?

Risk to safety of patients, users, handlers

Business

Regulatory

Product liability
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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

Robert C. Menson, PhD

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

Robert C. Menson, PhD

Elements of the Risk Management Process

Assessm ent

Risk Analysis

Risk Evaluation
Risk Control

Post-Production Information
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Robert C. Menson, PhD

Management

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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Robert C. Menson, PhD

FMEA Model
POTENTIAL FAILURE MODE AND EFFECTS ANALYSIS
X-Ray ZM Device Subsystem Component ____________________ Process FMEA Number Page of Prepared By FMEA Date (Orig.) Responsibility (rev.) Core Team: _______________________________________________________________________________________________

Device/ Function

Potential Failure Mode

Potential Effect(s) of Failure

Potential Cause(s) of Failure

Current Controls

R P N

Recommended Responsibility Action Results Action(s) and Target Actions R Complete Date Taken S O D P N

Field Defining Light

Visible Treatment Field Indication

1) Light Failure

Treatment setup time increases

Burn Out Bulb

4 32 -Better light source -Redundant source -Quick change light bulb 4 12

2 3 4 24 1 1 2 1 1 4 2 4

2) Alignment Failure

3 Wrong Field Defined Causing Repeat xrays and additional setup time 3

a) light source moved

b) Mirror moved

4 60

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HAZOP Model
Design Statement
Activity Transfer Material Powder Destination Hopper

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HAZOP
Transfer
No Valve closed Line blocked Pump broken Pump fast

Material
Tank empty

Destination
Valve closed Hopper full

More

Larger tank Inaccurate gage Liquid Wrong powder

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Other than
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HACCP

Hazard Analysis and Critical Control Point Risk Management System

Biological Hazards Chemical Hazards Physical Hazards Prerequisite Quality System Program Traditionally GMPs

Requires

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Risk Assessment Process

Map 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

Method validation studies Historical data

Detection (D)

Robert C. Menson, PhD

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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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Robert C. Menson, PhD

Risk Assessment Decision Tree

Begin Sev>5 Yes Prob>5 No Det<5 No Yes

Yes Reduce Probability or Increase Detection No

No

Det<5

Yes Assign ECP to Reduced Parameter Assign ECP to Detection (Either at that point or downstream) Assign ECP to Process

END

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Risk Assessment Decision Tree

Begin Sev>5 Yes Prob>5 No Det<5 No Yes

Yes Reduce Probability or Increase Detection No

No

Det<5

Yes Assign ECP to Reduced Parameter Assign ECP to Detection (Either at that point or downstream) Assign ECP to Process

END

Robert C. Menson, PhD

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Risk Assessment Decision Tree

Begin Sev>5 Yes Prob>5 No Det<5 No Yes

Yes Reduce Probability or Increase Detection No

No

Det<5

Yes Assign ECP to Reduced Parameter Assign ECP to Detection (Either at that point or downstream) Assign ECP to Process

END

Robert C. Menson, PhD

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Risk Assessment Decision Tree

Begin Sev>5 Yes Prob>5 No Det<5 No Yes

Yes Reduce Probability or Increase Detection No

No

Det<5

Yes Assign ECP to Reduced Parameter Assign ECP to Detection (Either at that point or downstream) Assign ECP to Process

END

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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
Risk Assessment Document
Step Process Failure Mode Hazard
Subpotency: delayed medical treatment

Potential Cause
LIMS not referencing new #, ManMan only references old # causing incorrect CofA

Existing controls

Detection Method

ECP ECP Sev Prob Det Y/N Where

Issue: 23, 24, 26 4 4 3 NO

Pull released raw materials

Stability

Visual check of CofA with LIMS and ManMan(produc tion) WFI System Validation, SOP (equipment, preventive maintenance, manual cleaning, manufacturing, training, USP / EP water environmental, procedures) test,

4.1

Collect Water @ 126 drop / WFI System (Processing High Count/ obj tank #1,2,3) organism Collect Water @ 126 drop / WFI System (Processing tank #1,2,3) Collect Water @ 126 drop / WFI System (Processing tank #1,2,3)

Infection requiring medical intervention WFI System failure

10

USP Test YES Procedure

4.2

High Count/ obj organism

Infection requiring medical Container (tanks) intervention contamination

Manual cleaning validation, equipment qualification

None

10

10

YES CIP / SIP

4.3

High Count/ obj organism

Infection requiring medical Improper sampling intervention technique

Training, SOP

USP / EP water test,

10

10

USP Test YES Procedure

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Step 2: Identify key elements of ECPs

Migrate ECPs from Risk Assessment to ECP Plan Collect relevant Information (SOP#s, Equipment used, Training documents) Assign process drivers/ owners for each ECP in the Plan
Risk Assessment Document
Step Process Failure Mode Hazard Potential Cause Existing controls Detection Method Sev ECP Prob Det Y/N ECP Where
WFI System Validation, Collect Water @ SOP (equipment, Infection 126 drop / WFI preventive maintenance, High Count/ obj requiring WFI System 4.1 System manual cleaning, organism medical failure (Processing tank manufacturing, training, intervention #1,2,3) environmental, procedures)

USP / EP water test,

10

YES

USP Test Procedure

ECP Plan Document

ECP # (1) Process (2)
Collect Water @ 126 drop / WFI System (Processing tank #1,2,3)

Failure Mode (3)

Potential Cause

Procedure /Step (4)

Quality Attribute (5)

How Determined (6)

QB-I5008 USP micro limits

Equipment (7)

Reference Documents (8)

Related Issues (9)

ECP Owner (10)

Quality Control (J. D.)

4.1

high count WFI System count/obj. P-F7010 <25/250mL / no Failure organism Specific Batch objectionables Record

sampling milliflex sensor II QCP-017 (equip) QG-I5034 vitek DLSA1030 report 49 micro Training hood 409164 cal HVA-0101-SP Procedure incubator 68955-1 cal SPT-0595-QC 020912 / pH meter 45057 calibration Daily records

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Step 3: Compile Risk Review Matrix

Break each ECP into review tasks based on SOPs, trainings, and other documents Each item # created is a distinct action item
ECP # (1) Process (2)
Collect Water @ 126 drop / WFI System (Processing tank #1,2,3)

Failure Mode (3)

ECP Plan Document

Potential Cause Procedure /Step (4) Quality Attribute (5)

How Determined (6)

QB-I5008 USP micro limits

Equipment (7)

Reference Documents (8)

Related Issues (9)

ECP Owner (10)

Quality Control (J. D.)

4.1

high count WFI System count/obj. P-F7010 <25/250mL / no Failure organism Specific Batch objectionables Record

sampling milliflex sensor II QCP-017 (equip) QG-I5034 vitek DLSA1030 report 49 micro Training hood 409164 cal HVA-0101-SP Procedure incubator 68955-1 cal SPT-0595-QC 020912 / pH meter 45057 calibration Daily records

Risk Review Matrix

Item # (1)
1

ECP Remediati SOP #(s) on Task #(s) (2) (3)

Review/Gener 4.1. 4.2, QBate TMV for 4.3 I5008 QB-I5008 Milliflex 4.1. 4.2, QBsensor II 4.3 I5008 qualification Vitek DLSA 4.1. 4.2, QBqualification 4.3 I5008 SN1030

Prerequisites Respon Completion Reference Required or sibility Date Document Prerequisite (5) (6) (7) to (4)
QCP-017

Link to: (8)

Comm ents (9)

QCP-017 Report 49 micro

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Step 4: Create Remedial Action Plan

Prioritize each item # and assign responsibilities and completion dates Track items to completion
Risk Review Matrix
Item # (1)
1

ECP Remediati SOP #(s) on Task #(s) (2) (3)

Review/Gener 4.1. 4.2, QBate TMV for 4.3 I5008 QB-I5008 Milliflex 4.1. 4.2, QBsensor II 4.3 I5008 qualification Vitek DLSA 4.1. 4.2, QBqualification 4.3 I5008 SN1030

Prerequisites Respon Completion Reference Required or sibility Date Document Prerequisite (5) (6) (7) to (4)
QCP-017

Link to: (8)

Comm ents (9)

QCP-017 Report 49 micro

Robert C. Menson, PhD

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