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Does any one question your laboratory results?

Lai-King Ng, Ph.D.Director, Bacteriology and Enteric Diseases Progra

Public Health Agency of Canada, Winnipeg, Manitoba, Canada

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Confidence in resultsDiagnosis of diseaseSupporting legal actionsInterventions: treatment, management of casesPolicies and interventions

SurveillanceContinuous collection of data, therefore, the laboratory results should be comparable over a long period of timeComparable results are required between techniciansbetween laboratories in region, country and other parts of the world

Importance of quality management in a laboratory?

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Consequences of Laboratory ErrorsClinical laboratories:

• Delayed in patient recovery• Treatment failure• Increased transmission of infections• Lack of confidence of patients to health care

system• False alarms: Scare and economic loss• Legal actions from patients and community

• Increased morbidity and mortality

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Consequences of Laboratory Errors

Food and veterinary laboratories• Unsafe food released to consumer• Increased cost to producers and processors: e.g

unnecessary recalls• Increased in disease burden• Reduced consumer confidence: market share and trade• Safe food could be discarded• Legal action liabilities

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Role of Laboratory Manager

• Set policies for the laboratory• Implement quality management system• Designate a quality manager if the Laboratory

manager is too busy• Develop and implement quality management

manual• To ensure compliance to quality management

system

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ISO Accreditation

• ISO 15189:2003• Medical laboratories –

particular requirements for quality and competence.

• ISO 17025:1999• General requirements for

the competence of testing and calibration laboratories.

• incorporates ISO 9001:2000

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Schedule

• Hire NML quality manager (Jan’04)• ISO 15189 training for NML staff (Feb’04)• Establish NML quality team (Feb’04)• Gap analysis of lab programs (Mar’04)• Define scope (Apr’04)• Internal auditor training (Mar’04)• Internal audit (Jun 1-2 ’04)• SCC pre-assessment (Sept’04)• SCC audit (Fall 2004)• Subsequent audits to expand scope

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ISO 17025Management Requirements (Section 4)

• 4.1 Organization and management• legally identifiable• client based• QA system

• 4.2 Quality management system• documented procedures• internal and external quality control• quality policy statement (scope)

• specify the tests to be accredited• quality manual• equipment calibration and preventive

maintenance

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ISO 17025 Management Requirements

• Modification of the existing capabilities of Labware LIMS to accommodate a document control system.

• Includes electronic approval of SOPs

• Automatic version control• Archive of past versions

• 4.3: Document Control: Labware LIMS

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ISO 17025 Management Requirements

• 4.6: Purchasing Services and Supplies

• - NML-wide database including all contact information for suppliers and any comments/complaints included.

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ISO 17025 Management Requirements (Section 4)

• 4.8 Resolution of complaints• records of complaints, investigations and corrective actions taken• obtain positive and negative feedback from clients on services

• 4.9 Identification and control of non-conformities• test non-conformances are documented, investigated, resolved and

monitored• 4.10 Corrective actions

• all problems to be investigated, documented and changes to procedures if necessary

• 4.11 and 4.12 Preventive action and continual improvement

• 4.14 Annual internal audits• 4.15 Annual quality management meeting with Director

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ISO 17025 Technical requirements (Section 5)

• 5.3 Laboratory equipment• Calibration, service and preventive

maintenance records• 5.4 Validation of Test Methods

Pre-examination procedures• requisition forms, sample collection,

sample receiving• Each in-scope test includes summary

outlining validation data and supporting literature

• 5.5 Examination procedures• requirement for appropriate, documented

test methods with proper validation• performance specs and procedure to be

reviewed annually• SOPs for each significant piece of

equipment• Preventive Maintenance schedules• Continuous monitoring of environment by

Facilities staff

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ISO 17025 Technical requirements (Section 5)

• 5.6 Assuring quality of examination procedures• Calibration Technician performs in-

house verification/calibration on:• Pipettes• Thermometers• Balances• Centrifuges• Ultra pure water

• 5.8 Reporting of results• Turn around times• All in-scope test includes stated

turn-around time • Includes particular requirements of

ISO 17025• Contains name and signature of

authorization

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Goals of the Quality System

• To achieve accreditation to ISO/IEC 17025: 1999 –General Requirements for the Competence of Testing and Calibration Laboratories

• Strengthen our testing quality thereby increasing the confidence of our clients

• Provide clear policies and procedures for NML staff

• Possess formal and international recognition of our Quality System

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ISO/IEC 17025:1999

• International Organization for Standardization (ISO) published ISO 17025 for quality in labs. Covers all requirements of ISO 9000 plus all technical and scientific requirements

• Canadian Accrediting Body is the Standards Council of Canada: Operate under ISO/IEC Guide 58

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NML Quality Management SystemOverview

• As of 2004, NML has implemented a quality system designed to meet the ISO 17025 standard.

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NML Quality Management SystemTimeline

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NML Quality Management SystemScope

• Virology• Rubella IgG Avidity• Measles Plaque Assay• INNO-LIA J Hepatitis-C Ab III• Human Papilloma Virus (HPV) Genotyping by PCR Amplification

and Sequencing of a Type-Specific E1 region

• Bacteriology• Radiometric Susceptibility Testing of Mycobacterium

tuberculosis to Primary Drugs • Identification and Speciation of Salmonella• Identification and Speciation of e. coli• Identification and Speciation of e. coli

• Support Services• Veterinary Technical Services• Media Preparation/Decon Wash-up

Tests accredited by the SCC in 2005 to CAN-P-4D (ISO/IEC 17025:1999):This system includes:

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NML Quality Management SystemScope

• Additional tests currently being accredited to CAN-P-4E (ISO/IEC 17025:2005):• COBAS TaqMan™ Hepatitis-B Virus (HBV) Test• SDS Polyacrylamide Gel Electrophoresis and Immunoblotting

Assay of Human CSF for 14-3-3 Protein• Influenza Hemagglutination Inhibition Test• Measles RT-PCR• Varicella-Zoster Virus (VSV) Strain Differentiation• Identification and Speciation of Shigella• Identification and Speciation of Listeria• Identification and Speciation of Aeromonas• Identification and Speciation of Vibrio

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NML Quality Management SystemScope

• Additional tests currently being accredited to CAN-P-4E (ISO/IEC 17025:2005) – cont’d:• Gram Negative Identification• Real Time PCR Procedure for Identification of Bacillus anthracis• SERODIA-TP-PA Test for the Detection of Antibodies to

Treponema pallidum• PULSE Scientific Rapid Plasma Reagin (RPR) Screening Test for

Syphillus• Pulsed Field Gel Electrophoresis of Campylobacter jejuni/coli• Pulsed Field Gel Electrophoresis of Listeria monocytogenes• Pulsed Field Gel Electrophoresis of Vibrio spp.• General PFGE of Escherichia coli, Salmonella spp., Shigella spp.

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NML Quality Management SystemScope

• Additional tests currently being accredited to CAN-P-4E (ISO/IEC 17025:2005) – cont’d:• Microbroth Dilution (MIC) Method for Susceptibility

Testing of Rapidly Growing Mycobacteria• Microbroth Dilution (MIC) Method for Susceptibility

Testing of MAI and Slowly Growing Mycobacteria

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NML Quality Management SystemScope

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NML Quality Management SystemClient Communications

• CPHLN RCASC external review of programs (3 year cycle) -continual improvement

• NML appreciates input on their activities/performance from their clients

• Clients may provide feedback and raise concerns the following ways:• Contacting specific laboratory Section Heads via email or

telephone• Contacting the NML Quality Management Office:

April Powell, Quality OfficerPh: 204-789-2048Fax: 204-784-5953April_Powell@phac-aspc.gc.ca

• Bi-annual CPHLN meetings• NML website feedback form:

http://www.nml-lnm.ca/english/contact.htm

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NML Quality Management SystemClient Communications

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NML Quality Management SystemGuide to Services

• NML has developed an online Guide to Services• Allows clients to see:

• Services provided by NML, searchable by lab or organism• Specifics regarding specimen submission criteria, TATs,

principles of tests (printable PDF format)• Requisitions (printable PDF format)

• Accessible at:• http://www.nml-lnm.ca/english/guide/default.asp

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NML Quality Management SystemGuide to Services

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NML Quality Management SystemGuide to Services

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NML Reference Services

Prion Diseases

Bacteriology & Enteric Diseases

Viral Diseases

Zoonotic Diseases & Special Pathogens

Surveillance

Diagnostics

Research

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Scope (2006)

• Tests accredited by the SCC in 2005 to CAN-P-4D (ISO/IEC 17025:1999):• INNO-LIA Hepatitis-C Virus (HCV) Score Test• Rubella IgG Avidity• Human Papilloma Virus (HPV) Genotyping by PCR Amplification

and Direct Sequencing• Identification and Speciation of Escherichia coli• Phagetyping of Enteric Pathogens• Identification and Speciation of Salmonella• Radiometric Susceptibility Testing of Mycobacterium

tuberculosis to Primary Drugs

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Expansion of Scope (2007)

• Additional tests currently being accredited to CAN-P-4E (ISO/IEC 17025:2005):• COBAS TaqMan™ Hepatitis-B Virus (HBV) Test• SDS Polyacrylamide Gel Electrophoresis and Immunoblotting

Assay of Human CSF for 14-3-3 Protein• Influenza Hemagglutination Inhibition Test• Measles RT-PCR• Varicella-Zoster Virus (VSV) Strain Differentiation• Identification and Speciation of Shigella• Identification and Speciation of Listeria• Identification and Speciation of Aeromonas• Identification and Speciation of Vibrio

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• Additional tests currently being accredited to CAN-P-4E (ISO/IEC 17025:2005) – cont’d:• Gram Negative Identification• Real Time PCR Procedure for Identification of Bacillus anthracis• SERODIA-TP-PA Test for the Detection of Antibodies to

Treponema pallidum• PULSE Scientific Rapid Plasma Reagin (RPR) Screening Test for

Syphillus• Pulsed Field Gel Electrophoresis of Campylobacter jejuni/coli• Pulsed Field Gel Electrophoresis of Listeria monocytogenes• Pulsed Field Gel Electrophoresis of Vibrio spp.• General PFGE of Escherichia coli, Salmonella spp., Shigella spp.

Expansion of Scope (2007)

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• Additional tests currently being accredited to CAN-P-4E (ISO/IEC 17025:2005) – cont’d:• Microbroth Dilution (MIC) Method for Susceptibility

Testing of Rapidly Growing Mycobacteria• Microbroth Dilution (MIC) Method for Susceptibility

Testing of MAI and Slowly Growing Mycobacteria

Expansion of Scope (2007)

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NML Website

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Feedback and Continual Improvement

• External review of programs (3 year cycle) - continual improvement

• Clients may provide feedback and raise concerns the following ways:

• Contacting specific laboratory Section Heads via email or telephone

• Contacting the NML Quality Management Office:• Bi-annual CPHLN meetings• NML website feedback form:• http://www.nml-lnm.ca/english/contact.htm

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Guide to Services

• NML has developed an online Guide to Services• Allows clients to see:

• Services provided by NML, searchable by lab or organism• Specifics regarding specimen submission criteria, TATs,

principles of tests (printable PDF format)• Requisitions (printable PDF format)

• Accessible at:• http://www.nml-lnm.ca/english/guide/default.asp

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Quality Lab Work

Ensuring Excellence is

Your Responsibility

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Overview

• Laboratory Safety

• Quality System

• Proficiency Testing and Training

• Method Validation

• Contamination Issues

• Maintenance and Calibration

• Pipette Techniques

• Reporting High Profile Test Results

• Privacy

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Laboratory Safety

• Biological and chemical hazards• Proper documented training• Conscientious staff• Consistent protocols• Protect

• Yourself• Others

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SOP’s

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NML Standard Operating Procedures SOP#Title:Date of Issue: DRAFT

1. Purpose2. References3. Responsibility4. Definitions5. Policy6. Safety Precautions7. Equipment and Materials8. Instructions

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Training & Proficiency Testing

• Initial Training:• Lab specific methods in SOP format• Training exercises documented and approved

• Proficiency:Internal

• Performed at least annually• Ensures technicians’ on-going competency

External• Assessed by an independent body• Ensures laboratories’ competency

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Method Validation

• Test is acceptable for its intended purpose• Evidence that it is “fit for use”

• Establish performance characteristics

• Without a method validation, the quality of diagnostic results could be brought into question

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Reagent Quality

• pH• Sterility• Expiration date• Lot numbers• Proper labelling• Avoid sharing of reagents, if possible

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Contamination Issues

• Tissue Culture• Media, supply, & equipment integrity• Mycoplasma contamination• Meticulous sterile techniques• BSC cleaned & maintained

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Contamination Issues

• PCR• Dedicated reagents & equipment• Specified workflow• Restricted access • (+)ve and (-)ve controls

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Maintenance and Calibration

• Services provided by the Quality OfficeCalibrations

• Thermometers• Pipettes

Verifications• Microfuges• Orbital Shakers• Balances• Thermal Cyclers• Water Conductivity

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Pipette Techniques

1. Pre-wet tip2. Ambient temperature3. Examine tip4. Standard mode5. Pause consistently6. Pull straight out7. Minimize handling8. Immersion depth9. Correct Tip10. Consistent pressure & speed

Techniques courtesy of Artel

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Laboratory Information Management System (LIMS)

• Commercial software (Labware)• LIMS Team

• IT• Programs

• Specimen tracking and reporting• Quality system support

• Document approval and control• Tracking corrective/preventative actions

• Cognos implementation for end-user searches of database• Future directions

• Electronic submission of requisitions• Bar-coding of samples• Electronic reports

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Reporting High Profile Test Results

• Sensitive or “high profile”• e.g. smallpox, SARS, bioterrorism

• Strict reporting procedures ensure:• Client/patient receives correct results• Accurate & precise info for external

parties

• Important public health consequences• High media interest

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Reporting High Profile Test Results

NML Procedure:

Potential High Profile Submission

Diagnostic Testing Section Head/Chief Reviews Results

Further Testing

Inform Division Director &Scientific

Director General

Result Authorized by Scientific Director

General

Section Head/Chief or Division Director send results

to client lab

Communication of results to external parties at

discretion of Scientific Director General

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Patient Confidentiality and Privacy

• Privacy Act: It’s the law!!• Must be maintained by NML employees• Privacy video outlines specifics

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Acknowledgements

• Quality Office• April Powell, Hannah Richards and Sharla Beddome

• Reference Services• Tamara Kruk

• Surveillance• Graham Tipples, Tracie EisBrenner

• LIMS• Garrett Sorensen

• Enterics Division• Helen Tabor