3. Competency Standards_11

8/3/2019 3. Competency Standards_11

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Competency standards

ISO 17025

OECD Good Laboratory Practice

2011

RMIT University Slide 2


Specific standards ensure the competency of organisations with respect

to generating correct, accurate, quality scientific data & information

They share general principles but each has specific content and differing

emphases relating to the particular area of application

Competency standards generally incorporate the relevant elements of

quality management from ISO 9001 and it is not necessary to become

certified to ISO 9001 in addition to certification to a competency standard



Governments legislate that certain test data pertaining to health & safety

must be compliant with specified standards, eg, for food & water,

pathology, safety of chemicals & environment testing

Many products in human & animal health, agriculture and the food

industry must meet defined legal standards (as defined in relevant Acts

& associated Regulations) to be approved for marketing by the relevant

national regulatory authority

Data to support the quality, efficacy andsafety of a product (data

package) must be presented to regulators when requesting approval

Safety data must meet legal standards

All organisations must be aware of all legal requirements for generation

of quality data


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RMIT University Slide 4RMIT University Slide 4

Product approval

The regulatory standards and codes of practice adopted by national

regulatory authorities are generally compatible with international

standards & codes

Regulatory authorities (eg under Memoranda of Understanding) agree

to accept data which has met the requirements of corresponding

authorities in other countries

ie, test once generally accept everywhere

Products still have to be approved in each country by the relevant

national authority

Many companies who outsource critical activities requiring certified

data must demand the relevant certification of their sub-contractors to

ensure quality data


Biotechnology R & D

Certification of research laboratories doing early s tage applied research

for product development is not necessarily a requirement for acceptance

of data which may later be presented for product registration

Most research organisations are not certified to any standard nor is it

necessary that they be certified

However, knowledge of applicable regulatory requirements should guide

R & D so that the organisation performing product research

- produces relevant, regulatory-ready data which will likely be

acceptable to a regulatory authority

- which is generated with rigour in study design & execution, withadequate QC and fully documented

Failure to meet minimum quality requirements means work will have to be

done again at an acceptable level of competency

This lowers the value of the work for subsequent investors


The standards relevant to the biotechnology industry include

ISO/IEC 17025:2005 General requirements for the competence of

testing and calibration laboratories

ISO 15189 :2007 Medical laboratories. Particular requirements for

quality & competence

This applies to pathology testing, eg haematology, microbiology and

will not be discussed further

OECD Principles of Good Laboratory Practice (GLP)

OECD Principles of Good Manufacturing Practice (GMP)

ICH Code of Good Clinical Practice (GCP)


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(AS) ISO/IEC 17025:2005

General requirements for the competence of testing and

calibration laboratories

[Directions for accessing this standard are on the DLS]

This standard describes a quality management system for technical &

scientific operations and covers technical competence requirements

not covered by ISO 9001

Certification to ISO 17025 is mandatory (legislated) in Australia for

laboratories undertaking food & water testing, analytical testing and

environmental testing

Laboratories in Australia must be NATA accredited for the type of

testing performed eg chemical, food, water, biological


ISO 17025

Customers, regulatory authorities and certification bodies use it to

confirm the competence of many types of testing laboratories

It describes minimum good laboratory practice

While designed primarily for testing laboratories it is applicable to alltesting & experimental studies undertaken by research laboratories

particularly undertaking R&D

Relevant elements of the standard may be implemented without

seeking official certification of the organisation

This provides evidence of rigour in the generation of data which maylater be submitted in support of product approval

The regulator will likely accept the accuracy, correctness & quality of

the data


Value of ISO 17025 Certification

Laboratory certification to ISO 17025 means

client is confident that results are of accepted international standard

the data is the most competent achievable with current technology

quality scientific work will be maintained into the future

transparent procedures & open to inspection

acceptance of data between regulatory authorities & companies

The standard is implemented and documented in a formal way in every

laboratory so that the quality system can be understood by everyone

and can be readily audited by anyone

Everyone uses the same elements, dealing with the same issues &

numbered in the same way - selecting those pertinent to the operations

of the particular laboratory


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Management requirements (Sect 4)

Management system (4.2)

Quality Manual covering

Standard of service specified

Quality of all testing services

Commitment to good professional practice

Technical processes

Responsibilities of technical management


Document control (4.3)

Document control is particularly important for testing & R&D

organisations (and for all laboratories where data needs to be accepted

by other organisations)

Research institutes doing industry contract research and biotech

companies generally sell know-how, show-how, information, data

All of which must be carefully documented for

investors, buyers or licensees

regulatory authorities for approval to market a product

service users (eg contract research performed for other organisations)

All data must be traceable throughout all phases of testing and for all

inputs to the final report


Document control (4.3)

Control of all documents in the specified QMS

Eg manuals, SOPs, data collection, analysis, reports, equipment

service & calibrations, laboratory workbooks

Documentary identification (& traceability) of all test items (eg cell

lines, vectors, micro-organisms, reagents)

Distribution of documents to relevant persons & sections

Record of all amendments (dated)

Full records (hard copy & electronic)

Archived records (according to legal requirements)


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Document control

Benefits of document & data management

verification of compliance with standards protects integrity & confidentiality of valuable data

proof of right to Intellectual Property (IP)

proof of contract fulfillment

protection against allegations of research fraud

protection against allegations of commercial fraud

protection against litigation in any area


Subcontracting of testing (4.5)

Many activities in multidisciplinary R&D are outsourced to

contract research organisations (CRO)

contract manufacturing organisations (CMO)

other organisations (eg universities, PROs)

Use of competent subcontractors

Sub-contractors must comply with any applicable standards or

certifications applicable to the contracting organisation

Responsibility for quality rests with the organisation doing the sub-

contracting

Companies which outsource critical activities require certified sub-

contractors to ensure the quality of data and must ensure they are so

qualified


Purchasing (4.6)

Control ofcritical supplies, ie, directly affecting quality of test result

Organisation is responsible for the quality of supplies/service care in

selection of suppliers - important to maintain good relationships

Commercial suppliers provide customised services & often participate

in R&D (eg reagent & equipment design)

Biotechnology organisations are very dependent on the quality of all

critical materials used in R&D and product manufacture

Full specification all critical purchased products (eg purity, full

characterisation of enzymes, radio-labeled compounds, cell lines)

Control of critical suppliers (selection, evaluation, performance)

Reception, inspection, storage (SOPs)Verification as fit-for-use before release for use


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Control of nonconforming testing (4.9)

How to know when something has gone wrong and the quality of the

product is compromised

Definition of the quality control system(s)

Definition of what constitutes nonconforming results or errors

& how they will be detected, eg, test QC, audits, staff reports,

supervisor review, client complaints

Evaluation of the significance of the nonconformance to product

quality


Corrective Action (4.11)

Analysis of the cause of the problem & decision on, and

implementation of a corrective action

Action should be appropriate to the magnitude and risk of occurrenceof the problem

Monitoring of actions for effectiveness

Preventive Action (4.12)

Identification & rectification of potential sources of nonconformances

Identification of areas needing improvement

Risk analysis for critical activities

Risk management plan (RARM is required by most regulators)

Proficiency testing results (for testing laboratories)


Control of records (4.13)

Quality & technical records (hard copy or electronic)

Eg, original observations, derived data, analyses, test reports,

laboratory notebooks

Must be identifiable to task & operator & test item

Retention times (by law) - some records relating to personal health

must be kept indefinitely

Security & confidentiality provisions

Protection against loss or deterioration

Required to meet due diligence investigations by organisations

(companies, auditors, government agencies)


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Personnel (5.2)

Staff competence (scientific & technical) is particularly important

Selection procedures for critical staff

Job descriptions that match the activities and the level of

competence of incumbents

Induction processes

Supervision & training in duties

Education & training to improve skills


Methods & validation (5.4)

Standard Operating Procedures (SOP)

Laboratory & operating procedures of a repetitive nature

sampling, handling, transport, storage of test items

equipment instructions eg use of pH meter, preparation of reagents

Test methods (latest edition)

International or national methods preferred

Methods published by technical organisations

Validated laboratory-developed methods

Estimation of uncertainty of measurement eg limits of detection

Control of data calculations and data transfers

Most research assays are not validated may be unsuitable for

support of product registration


Equipment (5.5)

Specified equipment & software (critical to quality of test result)

Equipment specifications and commissioning (where relevant)

Maintenance & calibration (reference standards as applicable)

Proper use (operation & instructions, trained operators)

Protection

Equipment in R&D is often very new or developmental

Often unvalidated, very complex & custom designed to be project-

specific eg microarrays, chromatography systems, high throughput

assay sets

Suppliers play role in development & validation


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Handling of test items (5.8)

Procedures for

transportation to & receipt in laboratory

assessing suitability for testing or use in experiments

identification & handling

protection through testing procedures

storage, archiving, disposal

Test item must be continuously traceable to all documentation, test &

experimental results & to the final report


Quality control (5.9)

QC to monitor accuracy of tests

Measurement trends

Statistical analysis of results

Reference standards (as available)

Replicate or repeated tests

Test method internal controls

Run new reagents, kits etc against old

Proficiency testing with masked samples

OECD Principles of Good

Laboratory Practice (GLP)

2011


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Principles of Good Laboratory Practice (OECD)

Quality system fornon-clinical health & environmental safety studies

of chemicals

All non-clinical safety studies of chemicals (in vitro and in animals)

must be undertaken in compliance with GLP Principles

Do not confuse this with ISO 17025 certification

The name GLP suggests a broad application to any laboratory work but

is has a very narrow application

Do not use the term GLP for general competence in testing

laboratories

It applies only to the generation of high quality reliable test data (in vitro

and in vivo) related to the safety of industrial chemicals

OECD GLP

Cooperative action among OECD countries to protect man, animals and

environment from hazardous chemicals\

Principles to ensure accurate, reliable, test results relating to the safety

of chemicals

Designed to ensure the Mutual Acceptance of Data (MAD) forchemical

hazard assessment by all countries agreeing to accept this standard

Only tests and assays showing the safety level for humans, animals,

the environment are required to be conducted under GLP certification


OECD GLP

GLP is important for

Public

Protection from exposure to hazardous chemicals

Regulators

Assures quality of studies and data packages ensuring the safety of

chemical products (eg drugs, vaccines)

Company & investors

International acceptance of safety data

Reduces rework & duplication of safety studies

Ensures a risk management plan is in place in organisations certifiedto GLP


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GLP Principles

Generic not specific to test type or discipline area

GLP is concerned with organisationalprocess and the conditions

under which data is generated

Guarantees studies were conducted at an appropriate standard and

generate accurate safety data

Does not guarantee scientific or technical validity of studies

Regulators decide on scientific & technical validity of study design and

interpretation of results

Regulatory authorities may adopt the generic GLP principles or use

them to develop a specific standard for a given product

Eg US FDA CFR Pt 58 GLP for non-clinical laboratory studies (which

applies to therapeutic prescription medicines)


Requirement for GLP studies

GLP has very broad applications across many types of testing that

applies to determining the safety of a natural or synthetic chemical

GLP compliant data is required for chemical products such as

Human pharmaceuticals (drugs and vaccines)

Veterinary drugs & products

Industrial chemicals

Agricultural chemicals eg pesticides, herbicides, growth promoters

Food & feed additives eg vitamins, hormones, bulking agents,

colours, flavour compounds


GLP studies


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GLP studies

In vitro, in vivo and field studies undertaken in

contained laboratory, greenhouse, animal house

open facilities such as hospital, clinic, field station, farm or wild sites

Physico-chemical (characterisation, analytical & biochemistry)

Biological assays

Safety pharmacology & toxicology studies in animals

Ecotoxicological studies (environmental effects)

Ecological studies (environmental fate eg chemical biodegradation,

bioaccumulation & chemical residues in plant & animal tissues

The quality elements are substantially the same as those articulated in

ISO 17025, ie, the same quality issues are addressed

The naming and ordering of elements is different


Test facility management

Laboratory, plant house, field station, farm site, hospital

Quality management system in place

Qualified personnel

Study Director, other investigators, technical personnel

Appropriate facilities & equipment for care, housing & containment of

biological test systems

Separation & isolation of test systems

High level of confidentiality & security especially in non-contained

sites


Test facility management

QA activities

Data & documentation control

Test systems, test & reference materials

Handling & storage of samples, test items

Data analysis & storage of raw and analysed data

Storage & retention of records & materials

Inspections (facilities, processes, critical study phases)

Cleaning, decontamination & sterilisation (of all sites)


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GLP Field test sites

Experimental activities partly undertaken outside contained facilities in the

environment of use of the chemical limited containment or un-contained

eg agricultural in-door or outdoor siteswild sites, patient clinics

processing & manufacturing facilities

Includes laboratories where specimens or samples are analysed

Often use test sites at different geographical locations conducting similar

activities or components or phases of an overall study

Each site may have a different management system & on site investigator

Under direction of Study Director who may be geographically remote

Clear lines of authority & communication & assigned responsibilities

Ensure activities carried out according to study plan


Field test sites

Complex ecological system parameters - difficult to characterise &

document

Little or no control over environmental conditions

Security & oversight of facilities & operations is difficult

Potential for contamination to, from, environment is likely

On-site facilities & equipment, sample collection & transport difficult to

control & maintainNeed for analysis of pre-treatment & post treatment control samples

Documentation on site can be a problem

Need for clean-up of sites and continued monitoring after study closes

eg 5 year monitoring of a test site where GM plants were grown

Eg monitoring of participants in a clinical trial

Setting up a QS

The standards set out agreed general principles (as above)

The QS has to spell out in detail how these will be achieved in an

organisation to ensure critical operations meet the st ipulated quality

objectives

Applying general principles to an organisations often unique operationsrequires thought & planning, takes time and is expensive both to set up

and maintain

Regulatory consultants with experience in an organisations area of

operations (eg food testing lab) assist in interpreting how generalprinciples may be applied in a particular set of circumstances

Certification bodies also give advice in what they expect

Together a documented QS is set up which must be practicable, as

simple as possible, and consistently implemented


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National Association of Testing

Authorities (NATA)

Australia


NATA

Independent, not-for-profit organisation - member-owned

http://www.nata.asn.au/

NATA is not a statutory authority regulating activities defined under

an Act of Parliament

National provider of certification for laboratoriestesting to

ISO 17025-2005

GLP 2002ISO 15189-2007

http://www.nata.asn.au/go/accreditation/types-of-accreditation

Explore the website for services

NATA has Mutual Recognition Agreements with corresponding

certification bodies worldwide acceptance of data generated by

NATA certified organisations


Laboratory certification

NATA certifies testing authorities against a general standard but also

certifies specific tests (those required by law)

Eg a medical pathology lab would be certified for general competence

but also for the performance of specified tests, eg haematology,

biochemistry, microbiology

Laboratory specifies the scope of testing and itemises the specific

tests for which it seeks certification

This certification of the performance of specific tests differs from

general practice worldwide
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Organisations wishing to be certified apply for membership of NATA

Certification process is outlined on NATA website

Desk audit of the Quality Manual (better done early)

On-site audit of facilities and operations against the specifiedstandard eg for

Facility suitability, procedures & documentation

Staffing training supervision

Methods QC data analysis standards

Equipment

Test item custody

Recording & reporting results



Site audits by NATA personnel and recruited experts in the relevant

discipline area

Audit is expensive

Certification has to be maintained

Proficiency testing is required

Regular audits eg 2-3 yearly

Annual membership fee

Maintenance of the system is expensive wrt money, staff time and

resources

Generally only undertaken if required by law for specific test types

Documents

3. Competency Standards_11