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ASTM E2500 A New Approach to Validation Peter K. Watler, Ph.D., Principal Consultant and CTO, Hyde Engineering + Consulting, Inc.

ASTM E 2500 - Watler

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Page 1: ASTM E 2500 - Watler

ASTM E2500A New Approach to Validation

Peter K. Watler, Ph.D., Principal Consultant and CTO,

Hyde Engineering + Consulting, Inc.

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Where you can find it

Only 5 pageshttp://www.astm.org/Standards/E2500.htm$36.00

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ASTM E 2500 – 07, What is it?

“A risk-based and science-based approach to the specification, design, and verification of manufacturing systems and equipment that have the potential to affect product quality and patient safety.”

“The overall objective is to provide manufacturing capability to support defined and controlled processes that can consistently produce product meeting defined quality requirements.”

Approved June 1, 2007A voluntary consensus standardIt has legal relevance

Stresses expert analysis of critical element that affect product quality“quality”, (not Quality Assurance or Quality Unit) appears 44 times“expert” appears 21 times“critical” appears 20 times

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The National Technology Transfer Act of 1995

Public Law 104-113“The Congress finds the following:

(1) Bringing technology and industrial innovation to themarketplaceis central to the economic, environmental, and social well-being of the people of the United States. (2) The Federal Government can help United States businessto speed the development of new products and processes”

Provision (12(d)) - Utilization of Consensus Technical Standards by Federal Agencies;

all Federal agencies and departments shall use technical standards that are developed or adopted by voluntary consensus standards bodies, using such technical standards as a means to carry out policy objectives or activities deemed by the agencies and departments.

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What the Law Looks Like

http://www.nist.gov/director/ocla/Public_Laws/PL104-113.pdf

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What ASTM E 2500 Applies To

Pharmaceutical and biopharmaceutical manufacturing systems:

Facility equipmentProcess equipmentSupporting utilitiesProcess monitoring systemsProcess control systemsAutomation

Systems that have the potential to affect product qualitypatient safety

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ASTM E 2500-07 Highlights

The ASTM standard focuses onSpecificationDesignVerificationLifecycle

Alternative to ISPE Baseline Guide Vol 5 Commissioning & Qualification

complexity, cost, time

Replaces Design Qualification with a Design Review by Subject Matter Experts

Risk Assessments by Subject Matter Experts (SMEs)Eliminate Impact Assessment

Replaces sequential Commissioning and Qualification with “Verification”“Fit for intended use” - Not bound by the formal IQ, OQ PQ phases

Lifecycle ChangeContinuous process improvements and real-time monitoring (PAT)

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Why is it needed now?

“It is estimated that validation can add up to 25% of the total installation cost for new facilities.”

− M Guyader, LBP

E 2500 – puts focus on Critical areas that affect

Product Quality Patient Safety

I know Nothing!

Let’s Validate Everything!

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What’s Driving us to Consider new Validation Approaches

“Pharmaceutical manufacturing operations are inefficient and costly.”

“Pharmaceutical manufacturing will need to employ innovation, cutting edge scientific & engineering knowledge.”

"if we change the way both manufacturers and regulators operate, the industry could save an average of 15 per cent of manufacturing costs".

•Source: “PAT Team & Manufacturing Science Working Group Report”, 2004“Pharmaceutical Industry Wastes

$50 Billion a Year Due to Inefficient

Manufacturing”

Pharmaceutical Manufacturing Research Project , Georgetown University, October 2006

“If FDA could change the way it regulated…

the industry could save10 to 50% of the cost of goods sold.”

Pharmaceutical Manufacturing Research Project Benchmarking Study, Georgetown University, October 2006

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They Have!

FDA 2004: Pharmaceutical cGMPs for the 21st Century – A Risk Based Approach

“Encourage implementation of risk-based approaches”

FDA 2004: PAT — A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance

“encourage the voluntary development and implementation” of “Process Analytical Technology”

FDA 2006: A Regulatory Paradigm to Encourage Innovation. Keith Webber, CDER/OPS, FDA

FDA 2006: Guidance for Industry – Q9 Quality Risk Management

FDA 2007: Pharmaceutical Quality for the 21st Century A Risk-Based Approach Progress Report

FDA 2009: Guidance for Industry Q8(R1) Pharmaceutical Development

“science- and risk-based submissions” QbD

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3

Focus on Criticality, Ongoing Verification

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Why Now?

Industry and Regulatory Agencies are striving to be more efficient, reduce costs and improve quality and safety

Decades of pharma & bio manufacturing experience

More knowledge of systems

Solid understanding of operations

Less ‘anything can happen’ philosophy

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Implementing ASTM E 2500

Some will wrongly interpret this as simply shifting validation responsibilities:

“This new approach will significantly shift the current qualificationresponsibilities and activities associated with facility qualification, equipment qualification, and utility qualification to the company’s corporate engineering group”

Some will wrongly interpret this as simply changing the terminology:

“Out goes the Design Qualification (DQ) with a Design Review (DR).Also for those that do them, Impact Assessments are out. Commissioning and Qualification are replaced by “Verification”, the qualification phases (IQ, OQ, PQ) are obsolete.”

ASTM E 2500 is a new Concept, requiring new ApproachesIt’s more than simply re-naming documentsIt’s more than a ‘re-org’ of shifting responsibilities from one group

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Implementing ASTM E 2500

To implement the concepts of E 2500

Approach has to changeExpertise (of the people involved) has to changeTools have to change

Otherwise there will be no real change

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Is ASTM E 2500 About This?

OLD

NEW?

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GAMP Validation “V” Model

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ASTM E 2500 Is:

A standard approach for validating equipment, facilities, processes

Streamlined processRisk based – reduce costsQbD – develop then employ best practicesMore consistent qualificationSupports current regulatory guidance (FDA, ICH)− Knowledge (expert) based− Risk based

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ASTM E 2500 Process Map

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Planning & Documentation

Identify Subject Matter

Experts

UserRequirementsSpecification

Risk Assessment

FunctionalSpecificationsand Design

Verification Plan

FactoryAcceptance

Tests

SiteAcceptance

Tests

Installation/OperationalQualification

Tests

PerformanceQualification

Tests

Verification Summary Report

GMP Operation andChange Management

VendorDocumentation

ETOP

E2500 System Lifecycle and Validation Approach

TraceabilityMatrix

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The New Standard is About Fundamental Change!

RiskBased ApproachScience Based ApproachQuality by Design (QbD)Process AnalyticalTechnologies (PAT)Design SpaceCritical ParametersCritical Quality Attributes (CQA)

Knowledge & UnderstandingSubject Matter Experts (SMEs)Good Engineering Practice, (GEP)Lifecycle conceptsChange implementationContinuous process improvementVendor documentation

To more efficiently and better, design and implement manufacturing systems…

ASTM E 2500 embraces, leverages and brings together the cutting edge concepts of:

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E 2500 Key Concepts for Design &Implementation of Manufacturing Systems

Methodologies

1. Requirements2. Specification & Design3. Verification

Toolbox

1. Design Review2. Subject Matter Experts3. Risk Management

Process4. Change Management

Plan

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Benefits of Implementing E 2500

LEANer manufacturing systemsRemove waste

Elevate our industry to more knowledge, better understanding of our manufacturing systems

Data, PAT, Design Space

Focus on what’s important (Critical)More is not better

Better technical understanding (Subject Matter Experts)

Less waste & repetition Use vendor doc’s

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Implementing ASTM E 2500

1. Planning and Documentation:VMPVerification Team and ResponsibilitiesDocument Matrix (planning, design & verification)Eligible vendor documentation

Document Matrix prepared by: Date: 20-Oct-09

HYDE Task

Title Doc. # Status Doc. # Status Doc. # Status Doc. # Status FAT SAT IOQ PQ Enhanced Comm

IOQ PQ Summary Reports

002FMECA RISK ASSESSMENT SOP

TEC-005 APPROVED 19MAY09

002COMMISSIONING PLAN COM-001 APPROVED

24JUL09

002VERIFICATION PLAN PROTOCOL TEMPLATE

APPROVED 04AUG09

003

HVAC SYSTEM- AIR HANDLERS

URS-50058-66

APPROVED 29SEP09

RSK-50058-66

DRAFT

004AUTOCLAVE (2 DOOR) URS-50043 APPROVED

13MAY09RSK-50043 APPROVED

25JUN09

005BAS- BUILDING AUTOMATION SYSTEM

URS-50054 APPROVED 08AUG09

RSK-50054 DRAFT

006

CHILLER SYSTEM URS-50050 APPROVED 02JUL09

007CLEAN DRY AIR SYSTEM URS-50049 APPROVED

25JUN09RSK-50049 APPROVED

18SEP09

008

COOLING TOWER SYSTEM

URS-50056 APPROVED 09JUL09

009ELECTRICAL/ LIGHTING SYSTEM

010

EMERGENCY GENERATORS

URS-50053 APPROVED 03AUG09

RSK-50053 APPROVED 03AUG09

Phase 2 Design & DevelopmentPhase 1 Planning and Definition Validation

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Implementing ASTM E 2500

2. Identify Subject Matter Experts:(§6.7) SMEs have primary responsibility for specification, design and verification of the manufacturing systems “individuals with specific expertise and responsibility in a particular area or field (for example, quality unit, engineering, automation, development, operations.”

CFR21 §211.34 “Consultants advising on the manufacture, processing, packing, or holding of drug products shall have sufficient education, training, and experience, or any combination thereof, to advise on the subject for which they are retained.”

Who are they?

Where do you find them?

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SME Qualifications

Experience>10 y experienceDesigned & implemented systems or practices

Process/System ExpertiseKnowledge of GMP, compliance, design elements, risk factorsApplies engineering equations, principles to the design, sizing & scaling of systems.In-depth knowledge of the subject

Methodology Expertise Proficient in standard methodologies for design and implementation, such as ICH Quality Guidelines (Q8, Q9, Q10), FDA Guidance, CFRs, ASME Standards (BPE, E 2500), ISPE Guides (GAMP, Baseline)Completed formal training courses

Recognized Competence Recognized by peers and professional associations, published, teaches topicProfessional credentials, license

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Implementing ASTM E 2500

3. Requirements Specification:Identify specific requirementsBasis for specification, design,and verification of the system (§7.2)

SMEs product and process knowledge and understandingbased on scientific data (QbD, Design Space).

This knowledge is the basis of scientific understanding for the system FDA 2009: Guidance for Industry Q8(R1) Pharmaceutical Development What is critical

SME

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Implementing ASTM E 2500

4. Risk Management ProcessFDA 2006: Guidance for Industry – [ICH] Q9 Quality Risk Management

Perform risk assessments at appropriate stages to evaluate the risks to product quality and patient safety

Performed by an appropriate SME

Identify controls and verification techniques to manage risk to an acceptable level

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Implementing ASTM E 2500

5. Specification and Design :Leverage qualified equipment vendor expertise (SME)to identify & document elements which affect critical quality attributes

Communicate the factors that impact product quality to the system (e.g. equipment) designer.

Strive to mitigate product quality & patient safety risks through the design

Functional Specifications provide acceptance criteria for functional tests specified in the Verification Plan.

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Potential Design Requirements

TemperatureShearFlow rateMembrane Area

Requirements Definition:

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Implementing ASTM E 2500

6. Verification Plan (§5.1, §7.4)Verify the critical aspects of the manufacturing system

DesignProperly installedOperating correctlyMeets performance requirements“Fit for intended use”

Identifies all required testing & documentationExtent of verification and documentation should be based on risk to product quality and patient safetyCriticality, risk factors identified in the URS, FMECA Risk Analysis, and detailed designTesting occurs from “FAT” to “PQ”

Acceptance criteria:Developed and approved by subject matter expertsCritical aspects approved by the quality unit

A ‘Traceability Matrix’ summarizes required testing and when it occurs

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Verification Plan Traceability Matrix

Identifies required test functionsIdentifies when testing will be executed

FAT, SAT, IQ, OQ, PQ

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Implementing ASTM E 2500

7. Verification Plan Execution:Subject matter experts perform or oversee activities, and document results (§7.4.3.1)

“Vendor verification documentation may be used” (§7.4.3.2)

Leverage FAT/SAT testing “rather than repeating vendor activities and replicating vendor documentation” (§6.8.2)

Testing occurs across FAT, SAT, IQ, OQ, PQThe more critical testing or additional testing may occur during IQ/OQ to mitigate risk

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The Role of System Vendors

“The key to a competitive parts supply system is the way theassembler works with its suppliers” – Womack, The Story of Lean Production

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Implementing ASTM E 2500

8. Verification Summary ReportApproved FAT, SAT, ETOP, IOQ and PQ Reports collectively providedocumented verification that the manufacturing system is fit forintended use (E 2500 §7.5.1)

Summary Report provides an overview of test results and non-conformances with acceptance criteria (§7.5.2)

Completed verification documentation reviewed by qualified and independent subject matter expert(s) (§7.4.4.1)

SME reviews overview of results and any nonconformance with critical acceptance criteria

Systems with critical aspects should be approved by the quality unit.

SME confirms manufacturing system is fit for intended us (§7.5.3)

Approved by SME and Quality Assurance (§7.5.4).

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Implementing ASTM E 2500

9. GMP Operation Acceptance, Release & Change Management:

After Verification Summary Report approval,

Quality Assurance issues authorization to release the system for GMP operational use (§7.5.5).

As part of the system life-cycle, equipment, and procedures are periodically reviewed.

Modifications are controlled via Change Management throughout the system lifecycle (E 2500 §8.4.3). Changes are approved by system subject matter experts.Changes to critical aspects or to aspects that affect system requirements relative to product quality and patient safety are additionally approved by Quality Assurance (§8.4.2, §8.4.3)

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The Role of QA in ASTM E 2500

7.4.1.3 Acceptance criteria of critical aspects (that is, critical to product quality and patient safety) should be approved by the quality unit.

7.4.2.3 The verification plan should be developed and approved by subject matter experts. Verification plans for systems containing critical aspects should be approved by the quality unit.7.5.4 Such documentation should be prepared and approved by subject matter experts. Such documentation for systems with critical aspects should be approved by the quality unit.

8.4.2 Before acceptance, change management should be applied. This process should be managed by, and changes approved by, subject matter experts. Changes affecting critical aspects of manufacturing systems should be communicated to the quality unit.

8.4.3 After acceptance, prior to manufacturing for commercial use, operational change management should be applied. Under operational change management, all changes related to specific requirements relative to product quality and patient safety require prior approval by the quality unit, unless predefined arrangements are establishedcovering

Mitigate Risk with Additional Oversight

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What Else is Needed?

Risk Management ProcessICH Q9Perform risk assessments at appropriate stages to evaluate the risks to product quality and patient safety

Performed by an appropriate SME

Identify controls and verification techniques to manage risk to an acceptable level

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“Although there are some examples of the use of quality risk management in the pharmaceutical industry today, they are limited and do not represent the full contributions that risk management has to offer.“

Risk Based Quality SystemsRisk Based ValidationRisk Based Process MonitoringRisk Based Documentation

ICH Published 09 Nov 2005FDA Published Federal Register, June 2, 2006

Risk Management Program

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ICH Q9 Describes Several Risk Assessment Tools

Basic Risk Management Facilitation Methods (Flowcharts, Check Sheets Etc.)Failure Mode Effects Analysis (FMEA)Failure Mode, Effects and Criticality Analysis (FMECA)Fault Tree Analysis (FTA)Hazard Analysis And Critical Control Points (HACCP)Hazard Operability Analysis (HAZOP)Preliminary Hazard Analysis (PHA)Risk Ranking and FilteringSupporting Statistical Tools

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Risk Management - FMEA Method

Severity addresses the impact on a process in the event a parameter is out of range.

Occurrence assesses the likelihood a parameter will be out of range.

Detection addresses the ability of detecting a defect if a parameter is out of range.

Risk Priority NumberRPN = Severity x Occurrence x Detection

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FMEA Risk Assessment - Identifying Criticality

Assemble multidisciplinary teamManufacturing, Process Development, Manufacturing Sciences, Engineering and Quality Assurance

Prepare “FMEA Data Sheet”All operating inputs and proposed operating rangesWhat are the potential failure modes (process, equipment, operators)Typical sources of failure in systemsWhat are causes of these failures

Scoring based uponKnowledge, known equipment capability, maintenancePrevious experience and expertise

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Risk Assessment SOP

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FMEA WorksheetSeverity x Occurrence x Detection = RPN

Process

Unit Operation

Leader

Participants

Operational Parameter Current Range Failure Mode Cause(s) Potential Effect(s) Severity Occurrence Detection RPN

PreparationVerify TFF-08207 is within cleaning

expiration date 30 days Out of date Operator error / Process delay Expired equipment used in process

Install dip tubes Incorrect dip tube orientation Operator error / Incorrect alignment of alignment pin

Foaming / Over concentration / Yield loss

Perform pre-use visual inspection Clean Not cleaned Faulty cleaning cycle Dirty equipment used in process

Set-up TFF for processing per MO173 System set-up incorrectly Operator error / Incorrect SOP revision Production delay / Product loss

System hose connections Incorrect system hose connections Operator error Inadequate flushing of system /

Product loss

Connect chilled water supply Incorrect connection / utilities failure Utilities failure / Operator error Temperature spike / Product

loss

Conncect AWFI Incorrect connection / utilities failure Utilities failure / Operator error Inadequate flushing of system /

Product loss

Conncect CDA Incorrect connection / utilities failure Utilities failure / Operator error System will not operate / valves

will not toggle

Drain the system per MO173 System not drained Operator error / Equipment failure System not flushed of storage solution

Verify Hydraulic Pressure Unit is in the run setting > 1150 psig Incorrect pressure on

membranesWrong setting selected / Faulty

Hydraulic Pressure UnitMembranes not sealed /

Product lossOpen and download file "Automated TFF

Method VER01" Wrong file downloaded Operator error Product Loss

Buffer Manifold Flush Flush valves for > 2 min

Valves not flushed for sufficient tim Incorrect flow rate / Valve failure System not flushed of storage

solution

System AWFI flush System not adequately flushed with AWFI

Incorrect system connections / Insufficient volume / Incorrect flow

path

System not flushed of storage solution / Product loss

Robert S, Bill E, Fred J, Mary S, Jill R

Failure Modes and Effects AnalysisHealgen

TFF

John Smith

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System or Process Name: Compiled by:

Reference Drawings

URS

Component Description & Function Potential Failure Mode Potential Failure Effects Potential Failure Causes Compensating Provisions

SEV

OCC

DET

RPN

Recommended Actions Resp. Actions Taken

SEV

OCC

DET

RPN

Revised Conditions

Team:

Original Date: Revision Date:

System/ProcessFailure Mode, Effects and Criticality Analysis

(FMECA)

System Owner: Primary SME:

Existing Conditions

FMEA WorksheetSeverity x Occurrence x Detection = RPN

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FMECA Worksheet

Component Description & Function Potential Failure Mode Potential Failure Effects Potential Failure Causes Compensating Provisions

SEV

OCC

DET

RPN

3 WFI Distribution System WFI distribution pipe Contamination

WFI water quality out of spec Dead leg, Non-turbulent flow, wrong surface finishing and/or incompatible material (MOC) for WFI piping

Check design, commissioning, validation, PM & EM program

8 5 5 200

Particle Test Program-Yearly by Intarcia?

Commissioning & Qualification Testing (RPN=200 Undesirable)1. Verify no dead leg L/D >2.02. Verify surface finish3. Verify MOC (elastomers, SS grade)4. Verify Reynolds number (circulation flowrate)5. Verify Design Review

RPN

DET

OCC

SEV

Actions Taken

Resp.

Recommended Actions

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Criticality Ranking

1 2 4 6 8 10Certain Very High Moderate Low Remote Uncertain

100 100 200 400 600 800 100080 80 160 320 480 640 80070 70 140 280 420 560 70060 60 120 240 360 480 60050 50 100 200 300 400 50042 42 84 168 252 336 42036 36 72 144 216 288 36030 30 60 120 180 240 30024 24 48 96 144 192 24016 16 32 64 96 128 16012 12 24 48 72 96 1209 9 18 36 54 72 906 6 12 24 36 48 601 1 2 4 6 8 10

Number of RPN's in Range

Intolerable 343-1000 37Undesirable 189-336 26Tolerable 72-180 23Negligible 1-70 34 Commission

ACTION

Moderate Risk

Detection Rank

Design modification required to mitigate riskQualification testing or design modification required to mitigate riskQualification testing may be required to mitigate risk

Risk Score

High Risk

Low Risk

RISK CRITICALITY

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Manufacturing FMEA

RPN’s can range from 1 to 1,000RPN ≥100 indication may be a high risk item

Manufacturing:Nine unit operations analyzedFMEA evaluated 445 operational inputsRPN’s ranged from 3 to 158

Only 6 operational inputs received RPN scores ≥100 Indicates robustness, procedural controls and equipment capabilities have minimized the risk of failureFewer parameters to validateMore Targeted ValidationBetter understanding, better quality, lower cost

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FMEA Results

Validate only CRITICAL & KEY ParametersFrom FMEAFrom SeverityFrom Knowledgebase

Unit Operation Parameter RPN

Production Fermentation Raw Material Addition 111

Production Fermentation Sampling for Culture Purity Analysis 102

SEC Elution Buffer (BT018) pH 158

SEC Elution Buffer (BT018) Conductivity 155

SEC Load Volume 144

SEC Remove Bioburden, LAL Samples 113

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FMECA Risk Analysis Report

“conducted in accordance with… good documentation

practices.

This recommendation is consistent with ICH guidance

for industry, Q10 Pharmaceutical Quality System.9 241

Decisions and justification of the controls should be

sufficiently documented” – FDA Guidance Nov 18, 2008

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E 2500 Implementation Gaps

ASTM E 2500 lays out a ‘standard” roadmap for the overall approach

It is not a ‘how to’ guide,“Firms should develop appropriate mechanisms to communicate requirement inputs, including product quality considerations, tothose responsible for design”

Firms will need to developProcessesTools & templates suited to their operations

Not one size fits all – needs to address corporate risk, nature of business, expertise of staff, organization resources

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What Else is Needed?

Design Review ProcessPlanned and systematic reviews throughout the system lifecycle:− Specifications− Design− Design development− Continuous improvement changes

Ensure product and process requirements are satisfied by the design

Unacceptable risks are mitigated by design or other means

Design is performed by appropriate SMEs

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What Else is Needed?

Change Management ProcessDevelop a change management plan before releasing the systemChange is good, is expectedManaged by, changes approved by SMEsChanges affecting critical aspects communicated to the quality unit

Changes related to product quality and patient safety require prior approval by the quality unit, unless predefined plan

PAT – provides scientific data to support changes and manage risk

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ASTM E 2500 – The Role of Vendors

“The key to a competitive parts supply system is the way the assembler works with its suppliers”

(Womack et al., 1990)

Partner with a supplier (LEAN)vs

Bid them against each other (MASS)

“Preferred Suppliers”Few in number, single sourced?Share information – needs, specificationsSupplier becomes the solution provider

Encourages use good vendor documentation and testing to support qualification

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Implementation Gaps

GapsHow do you do a risk assessment eg. FMEA SOP?How often, at what points in the process?How do you qualify to be an SME?How many QA staff will be needed? What expertise will they need?Where will you find them?How do you manage changes during design & implementation?How do you manage change to enable improvements to be implemented?How do you efficiently address deviations from the Verification Plan?How do you determine the ‘Critical aspects of the manufacturing system’How to define & document the verification approach

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E 2500 Implementation Gaps

ASTM E 2500 lays out a ‘standard” roadmap for the overall approach

It is not a ‘how to’ guide,“Firms should develop appropriate mechanisms to communicate requirement inputs, including product quality considerations, tothose responsible for design”

Firms will need to developProcessesTools & templates suited to their operations

Not one size fits all – needs to address corporate risk, nature of business, expertise of staff, organization resources

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E 2500 Efficiency & Cost Savings

The extent of verification and the level of detail of documentation should be based on risk, including those associated with product quality and patient safety, and the complexity.

“Only companies that achieve a high level of process understanding will have the opportunity to justify a more flexible regulatory path.”

FDA 2004

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Yes, ASTM E 2500 is Being Implemented

Hyde Client, Commercial Device FacilityE2500 Based facility and systems commissioning and qualification

Amgen, Thousand Oaks Clinical Mfg50-70% reduction in IQ/OQ for chromatography skid − Phil Bowles, ISPE Tampa 2009

Bristol-Myers Squibb Biologics“Applying ASTM E2500 to a Greenfield Site”− E Bramhall, Director Validation, ISPE 2008 Annual Meeting

Perkin Elmer“Best Practices for Qualification of Laboratory EquipmentUtilizing ASTM E2500”

Major East Bay Pharmaceutical CompanyRisk based commissioning & qualification

Major Bay Area Biotech CompanyRisk based validation for new facility commissioning

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FDA Guidance

“Guidance for Industry Process Validation: General Principles and Practices” - FDA Nov 18 2008 Guidance

In keeping with the spirit of ASTM E 2500 Standard, the document uses the term “verify”rather than “validate” when referring to facility systems.

IQ, OQ, DQ, PQ are industry terms and standards, not FDA mandated.

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Summary

ASTM E 2500-07 provides a cutting edge framework for planning and execution of riskbasedapproach to designing and implementing reliable manufacturing systems

ASTM E 2500 has many parallels to existing approaches, but relies on more risk management and higher expertise

The challenge is to address the implementation gaps and develop the custom tools

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Contact Info

Peter K Watler, PhDPrincipal Consultant andChief Technology Officer

Hyde Engineering + Consulting, Inc.

[email protected]