ISO 9001 and 21 CFR 210 211ISO 9001 and 21 CFR 210 211““Working Together for QualityWorking Together for Quality””

Theresa McCarthy Theresa McCarthy 18 January 201118 January 2011

Agenda

What Requirements in ISO 9001:2008What Requirements in ISO 9001:2008can be used to enhance your existing can be used to enhance your existing cGMP cGMP quality system?quality system?

If you are ISO 9001:2008 registered what If you are ISO 9001:2008 registered what additional requirements are needed to additional requirements are needed to management comply with 21 CFR 210?management comply with 21 CFR 210?

Agenda

Background Information on StandardsBackground Information on Standards

ISO 9001:2008ISO 9001:2008

Voluntary StandardVoluntary Standard

FDA Quality SystemsFDA Quality Systems

LawLaw

Guidance Documents AvailableGuidance Documents Available

Discuss Additional RequirementsDiscuss Additional Requirements

Companies Here Today??

Medical DeviceMedical Device

21 CFR 82021 CFR 820

ISO 13485:ISO 13485:

Biotech/PharmaBiotech/Pharma

21 CFR 210, 21121 CFR 210, 211

ICH Q7ICH Q7

Other????Other????

Quality Management Systems

ISO 9001 first published 1987ISO 9001 first published 1987

ThenThen……..1994 ..1994

ISO 9001: 2000 ISO 9001: 2000 Technical RevisionTechnical Revision

15 November 2008 is an Amendment15 November 2008 is an Amendment--

Clarify points in the text Clarify points in the text

Enhance compatibility with ISO 14001:2004Enhance compatibility with ISO 14001:2004

700,000 worldwide certified700,000 worldwide certified

50,000 North America certified50,000 North America certified

ISO Quality Management System

QualityQuality ManualManualQuality Quality

ProceduresProcedures

Work InstructionsWork Instructions

Records Records

Management Review

Corrective andPreventive Action

Internal Audit

ISO 9001 Quality Management System

Customers Customers

Requirements

Satisfaction

Management Responsibility

Product Realization

Measurement, analysis and improvement

Productinput output

Resource Management

ISO 9001:2008

No legal requirement to comply with cGMPNo legal requirement to comply with cGMP

Voluntary StandardVoluntary Standard

RegisteredRegistered

Minimize Customer AuditsMinimize Customer Audits

UnlessUnless…………Device Companies Device Companies –– EuropeEurope

Technical FileTechnical File

CE Marking???CE Marking???

ISO 9001

4.04.0 Quality SystemQuality System

5.05.0 Management ResponsibilityManagement Responsibility

6.06.0 ResourcesResources

7.07.0 Product RealizationProduct Realization

8.08.0 Measurement, Analysis and Measurement, Analysis and ImprovementImprovement

NoteNote:: Configuration ManagementConfiguration ManagementAS9100, ISO13485, ISO14000, IPEC AS9100, ISO13485, ISO14000, IPEC ––GMP GuideGMP Guide

ISO Eyesoh=EqualISO Eyesoh=Equal

FDA Drug Mfg Inspection Systems

LaboratoryControl

SystemsProductionSystem

Packaging & Labeling

System Material System

QualitySystem

Facilities &Equipment

SystemMANAGEMENT

cGood Manufacturing Practices

Legally Required to comply with cGMPLegally Required to comply with cGMP

Regulations Enforceable by LawRegulations Enforceable by Law

Enforced by the FDAEnforced by the FDA

Register with FDA annuallyRegister with FDA annually

FDA

When publishing the Guidance for Industry "Quality When publishing the Guidance for Industry "Quality System Approach to Pharmaceutical cGMP" on 29 System Approach to Pharmaceutical cGMP" on 29 September 2004, the FDA took requirements from the ISO September 2004, the FDA took requirements from the ISO 9001 document on "Quality Management Systems" into 9001 document on "Quality Management Systems" into account in the field of pharmaceutical manufacture account in the field of pharmaceutical manufacture

Guide on Quality Systems ModelGuide on Quality Systems Model

Management ResponsibilitiesManagement Responsibilities

ResourcesResources

Manufacturing OperationsManufacturing Operations

Evaluation ActivitiesEvaluation Activities

ICH Q 10

International Council on HarmonizationInternational Council on Harmonization

““Pharmaceutical Quality SystemsPharmaceutical Quality Systems””

Guidance Model for Implementing Effective Quality Guidance Model for Implementing Effective Quality Management SystemManagement System

Harmonization EffortHarmonization Effort

European UnionEuropean Union

JapanJapan

United StatesUnited States

Augment Rather than Replace Current RegulationsAugment Rather than Replace Current Regulations

Harmonize with the Regional GuidanceHarmonize with the Regional Guidance

ICH Q7ICH Q7

CGMP More Detailed Validation Requirements

EquipmentEquipment

Facilities Facilities

Methods Methods

CleaningCleaning

SoftwareSoftware

Electronic SystemsElectronic Systems

21 CFR Part 1121 CFR Part 11

ISO 9001 Process Based

Identify ProcessesIdentify Processes CoreCore SupportSupport

ProcessProcess

Input Input

OutputOutput

PhasesPhases

Gates/ReviewsGates/Reviews

CC22 QQ

M&MM&M

ISO 9001 Control of Documents

While reviewing Records in ISO 9001:2008 SystemWhile reviewing Records in ISO 9001:2008 System

cGMP Documentation PracticescGMP Documentation Practices

Are there complete mfg instructionsAre there complete mfg instructions

Raw MaterialRaw Material

EquipmentEquipment

Steps: Performed By: Steps: Performed By: Verified By:Verified By:

Documents that impact product quality reviewed Documents that impact product quality reviewed by and approved by Quality (independent)by and approved by Quality (independent)

Operating ParametersOperating Parameters•• (more than 6 SOPs required)(more than 6 SOPs required)

Adding ISO 9001 to a GMP System

Develop a Quality ManualDevelop a Quality Manual

Develop a Quality PolicyDevelop a Quality Policy

CommunicateCommunicate

How do you Contribute?How do you Contribute?

Continually Continually Improve Improve the Effectiveness of the the Effectiveness of the QMSQMS

ISO 13485ISO 13485-- Maintain Maintain

Customer Focus

ISO ISO –– How are customer requirements determined How are customer requirements determined and translated into the Quality System?and translated into the Quality System?

GMPGMP-- S I S P QS I S P Q

Safety Safety

IdentityIdentity

StrengthStrength

PurityPurity

QualityQuality

Planning

Top Management shall ensure that Quality Top Management shall ensure that Quality Objectives are establishedObjectives are established

Product Product

ProcessesProcesses

Responsibility and Authority

GMP GMP

Quality Unit??? Quality Unit??? –– Independent Reporting Independent Reporting Relationship Between Production and Relationship Between Production and Quality Unit. Quality Unit.

Management Responsibility

ISOISO Management RepresentativeManagement Representative

AppointedAppointed

Establish ProcessesEstablish Processes

ReportReport

Promote awareness of Customer RequirementsPromote awareness of Customer Requirements

Management Review

Review InputReview Input

AuditsAudits

Customer FeedbackCustomer Feedback

Process Performance and Product Process Performance and Product ConformityConformity

Status of Preventive and Corrective Status of Preventive and Corrective ActionAction

Follow UpFollow Up

Changes that could affect qmsChanges that could affect qms

Recommendation for ImprovingRecommendation for Improving

Note: 13485Note: 13485------Regulatory Regulatory RequirementsRequirements

Notes: Notes: Quality CouncilQuality Council–– Annual Product Annual Product

Review?? APRReview?? APR0

102030405060708090

1stQtr

2ndQtr

3rdQtr

4thQtr

EastWestNorth

cGMP Resources Needed in ISO 9001

Section 6.0 ISO Standard Resource ManagementSection 6.0 ISO Standard Resource Management

6.1 Provision of Resources6.1 Provision of Resources

6.2 Human Resources6.2 Human Resources

Competence, Awareness and TrainingCompetence, Awareness and Training•• GMP training should be sufficient frequency to GMP training should be sufficient frequency to

ensure employees remain familiar with GMP.ensure employees remain familiar with GMP.

Personal HygienePersonal Hygiene

6.3 Infrastructure6.3 Infrastructure

Buildings and FacilitiesBuildings and Facilities

Equipment Equipment -- CommissioningCommissioning•• Construction Construction –– Contact SurfacesContact Surfaces•• Maintenance Maintenance -- SOPSOP•• Computer Systems Computer Systems –– Access controls backupAccess controls backup•• Utilities Utilities –– risk of contaminationrisk of contamination•• Water Water ––treatment and monitoringtreatment and monitoring

cGMP Resources Needed in ISO 9001

6.4 6.4 Work Environment Work Environment –– shall determine shall determine and manage environment needed to achieve conformity to and manage environment needed to achieve conformity to product.product.

Air Handling Air Handling –– RecirculationRecirculation

Controlled Environment Controlled Environment -- MonitoringMonitoring

Cleaning and Sanitary Conditions Cleaning and Sanitary Conditions –– Schedules, WasteSchedules, Waste

Pest Control Pest Control –– Free of Infestation, Contractor RecordsFree of Infestation, Contractor Records

Lighting Lighting -- AdequateAdequate

Drainage Drainage -- AdequateAdequate

Washing and Toilet FacilitiesWashing and Toilet Facilities

7.0 Product Realization GMP Needs

Planning of Product RealizationPlanning of Product Realization

Customer Related ProcessesCustomer Related Processes

Customer CommunicationCustomer Communication

Design and Development Design and Development –– (defined point at which GMP (defined point at which GMP applies in Mfg)applies in Mfg)

PurchasingPurchasing

Supply Chain Approach ChangingSupply Chain Approach Changing

Quality AgreementsQuality Agreements

HeparinHeparin

BSE TSE BSE TSE

7.0 Product Realization GMP Needs

Customer PropertyCustomer Property

Chain of CustodyChain of Custody

Preservation of ProductPreservation of Product

HSPPD HSPPD ––

Temperature Mapping Warehouse Temperature Mapping Warehouse

Pallets Pallets •• ISO 9001??? ISO 9001???

7.6 Calibration

Out of ToleranceOut of Tolerance——OOTOOT

Actions taken if found to be beyondActions taken if found to be beyond

How is system documented?How is system documented?

Is there an SOP in ISO9001 or are Is there an SOP in ISO9001 or are Records required of the results?Records required of the results?

8.0 Measurement Analysis and Improvement

M & M ProcessesM & M Processes

Demonstrate conformity to Demonstrate conformity to productproduct

9001 and GMP9001 and GMP

Customer SatisfactionCustomer Satisfaction

““Customer Perception:Customer Perception:

Methods for Obtaining Feedback Methods for Obtaining Feedback

8.0 Measurement Analysis and Improvement

Analysis of DataAnalysis of Data

Demonstrate Suitability and Demonstrate Suitability and EffectivenessEffectiveness of of QMSQMS

Customer SatisfactionCustomer Satisfaction

Conformity to Product RequirementsConformity to Product Requirements

Characteristics and Trends of Processes and Characteristics and Trends of Processes and ProductsProducts

•• Opportunities for Preventive ActionOpportunities for Preventive Action

SuppliersSuppliers

8.2.2. Internal Audits

Does 21 CFR 210, 211 call for Internal Does 21 CFR 210, 211 call for Internal Audits?Audits?

Laboratory Controls M&M of Product

Procedures and RecordsProcedures and Records

Out of Specification Test ResultsOut of Specification Test Results

Retained SamplesRetained Samples

Certificates of AnalysisCertificates of Analysis

Impurities Impurities –– Residual SolventsResidual Solvents

Stability Stability

8.0 Measurement Analysis and Improvement

Continual ImprovementContinual Improvement

Corrective ActionCorrective Action

Prevent Prevent ReRecurrencecurrence

Preventive ActionPreventive Action

Prevent Prevent OccurrenceOccurrence

Working Together for Quality

YesYes…….Both Systems Need.Both Systems Need

ManpowerManpower

MethodsMethods

MeasurementsMeasurements

MaterialsMaterials

MachinesMachines•• Money?Money?

Summary

ISO9001ISO9001

Create Quality Control Unit with More Create Quality Control Unit with More Responsibility and Authority than a Responsibility and Authority than a Management Representative Management Representative

Create required systems and procedures Create required systems and procedures required by GMPrequired by GMP--Product SpecificProduct Specific

Trained and Aware of Legal Trained and Aware of Legal Responsibilities inherent in GMPResponsibilities inherent in GMP

Summary

GMP need to DevelopGMP need to Develop

Metrics and Procedures for Measuring Metrics and Procedures for Measuring the Effectiveness of QMSthe Effectiveness of QMS

Management Review ProgramManagement Review Program

Program for Capturing Customer Program for Capturing Customer Satisfaction DataSatisfaction Data

Thank You for Your Participation

Theresa.McCarthy@comcast.netTheresa.McCarthy@comcast.net

Note: Boscon Conference Note: Boscon Conference

Waltham WoodsWaltham Woods

April 11, 12April 11, 12•• Asqboston.orgAsqboston.org