In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and TeachingWenclawiak, B.: Fit for Purpose – A Customers View © Springer-Verlag Berlin Heidelberg 2003

Fit for Purpose -A Customers View

Bernd Wenclawiak

In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and TeachingWenclawiak, B.: Fit for Purpose – A Customers View © Springer-Verlag Berlin Heidelberg 2003

In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and TeachingWenclawiak, B.: Fit for Purpose – A Customers View © Springer-Verlag Berlin Heidelberg 2003

Analytical measurements should be made to satisfy an agreed requirement

In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and TeachingWenclawiak, B.: Fit for Purpose – A Customers View © Springer-Verlag Berlin Heidelberg 2003

Analytical measurements should be Analytical measurements should be made using methods and equipment made using methods and equipment

which have been tested to ensure which have been tested to ensure they are they are

fit for purposefit for purpose

In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and TeachingWenclawiak, B.: Fit for Purpose – A Customers View © Springer-Verlag Berlin Heidelberg 2003

Staff making analytical measurements Staff making analytical measurements should be both:should be both:qualified and competent to undertake the task and to undertake the task and demonstrate that they can perform demonstrate that they can perform the analysis properlythe analysis properly

In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and TeachingWenclawiak, B.: Fit for Purpose – A Customers View © Springer-Verlag Berlin Heidelberg 2003

There should be a regular independent There should be a regular independent assessment of the technical assessment of the technical performance of a laboratoryperformance of a laboratory

In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and TeachingWenclawiak, B.: Fit for Purpose – A Customers View © Springer-Verlag Berlin Heidelberg 2003

Analytical measurements Analytical measurements made in one location made in one location should be consistent should be consistent

with those made elsewherewith those made elsewhere

In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and TeachingWenclawiak, B.: Fit for Purpose – A Customers View © Springer-Verlag Berlin Heidelberg 2003

Organizations making analytical Organizations making analytical measurements should have well measurements should have well

defined quality control and defined quality control and quality assurance proceduresquality assurance procedures

In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and TeachingWenclawiak, B.: Fit for Purpose – A Customers View © Springer-Verlag Berlin Heidelberg 2003

Method validation is an important Method validation is an important requirement in the practice of requirement in the practice of

chemical analysischemical analysis

In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and TeachingWenclawiak, B.: Fit for Purpose – A Customers View © Springer-Verlag Berlin Heidelberg 2003

What is Validation?

Confirmation by examination and provision of objective evidence that the particular requirements for a specified intended use are fulfilled

ISO 8402 (1994)

In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and TeachingWenclawiak, B.: Fit for Purpose – A Customers View © Springer-Verlag Berlin Heidelberg 2003

What is Method Validation? - 1 The process of establishing the performance

characteristics and limitations of a method and the identification of the influences which may change these characteristics and to what extent.

Which analytes can it determine in which matrices in the presence of which interferences?

Within these conditions what levels of precision and accuracy can be achieved?

In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and TeachingWenclawiak, B.: Fit for Purpose – A Customers View © Springer-Verlag Berlin Heidelberg 2003

What is Method Validation? - 2

The process of verifying that a method is fit for purpose, i.e. for use for solving a particular analytical problem

This means the method must be suitable

Method validation is not solely the process of evaluating the performance parameters

In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and TeachingWenclawiak, B.: Fit for Purpose – A Customers View © Springer-Verlag Berlin Heidelberg 2003

The Method Validation Process Implies:

the use of equipment within its specifications

that the operator is fit for purpose

In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and TeachingWenclawiak, B.: Fit for Purpose – A Customers View © Springer-Verlag Berlin Heidelberg 2003

Why is Method Validation Necessary?

Importance of analytical measurement

The professional duty of the analytical chemist

In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and TeachingWenclawiak, B.: Fit for Purpose – A Customers View © Springer-Verlag Berlin Heidelberg 2003

When should Methods be When should Methods be Validated ?Validated ?

Comparing methods

Replacement of instruments

Change of operator

Other significant changes

In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and TeachingWenclawiak, B.: Fit for Purpose – A Customers View © Springer-Verlag Berlin Heidelberg 2003

How should Methods be Validated?

Who carries out method validation? Deciding what degree of validation is

required The analytical requirement

In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and TeachingWenclawiak, B.: Fit for Purpose – A Customers View © Springer-Verlag Berlin Heidelberg 2003

Choosing, Developing and Evaluating Methods

Problem requiring chemical analysis:

Set analytical requirement

Identify existing method or develop

new method

Further development

feasible?

Evaluatemethod – fit for

purpose as used inthe laboratory

Relaxanalytical

requirement?

Developmethod

Analytical work proceeds

Analytical requirement re-stated in terms of

what has been accomplished

Unable to do work – subcontract?

End

Yes

Yes Yes

No No

No Method validation consists of this evaluation stage, together with any performance parameters that may be evaluated under method development

„Fit for purpose...“ . Regardless of what existing performance data may be available for the method, fitness for purpose will be

In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and TeachingWenclawiak, B.: Fit for Purpose – A Customers View © Springer-Verlag Berlin Heidelberg 2003

How should Methods be Validated?

Who carries out method validation?

Deciding what degree of validation is required

The analytical requirement

Method Development The different performance parameters

of a method and what they show

In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and TeachingWenclawiak, B.: Fit for Purpose – A Customers View © Springer-Verlag Berlin Heidelberg 2003

How should Methods be Validated?

The different performance parameters of a method and what they show Confirmation of identity and selectivity/specificity Limit of detection Limit of quantitation Working and linear ranges Accuracy Trueness

In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and TeachingWenclawiak, B.: Fit for Purpose – A Customers View © Springer-Verlag Berlin Heidelberg 2003

How should Methods be Validated? Interpreting bias measurements

Measured value(laboratory mean)

True value

Interlaboratorymean

Total bias

Laboratory bias Method bias

Note: Laboratory and method biases are shown here acting in the same direction.In reality this is not always the case

In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and TeachingWenclawiak, B.: Fit for Purpose – A Customers View © Springer-Verlag Berlin Heidelberg 2003

How should Methods be Validated? The different performance parameters of a

method and what they show Confirmation of identity and selectivity Limit of detection Limit of quantitation Working and linear ranges Accuracy Trueness Interpreting bias measurements

precision repeatability reproducibility sensitivity ruggedness or robustness recovery

In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and TeachingWenclawiak, B.: Fit for Purpose – A Customers View © Springer-Verlag Berlin Heidelberg 2003

How should Methods be Validated? The different performance parameters of a method and

what they show Confirmation of identity and selectivity Limit of detection Limit of quantitation Working and linear ranges Accuracy Trueness Interpreting bias measurements precision repeatability reproducibility sensitivity ruggedness-robustness recovery

In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and TeachingWenclawiak, B.: Fit for Purpose – A Customers View © Springer-Verlag Berlin Heidelberg 2003

The Tools of Validation Blanks reagent blanks sample blanks Samples/test materials fortified materials/solutions spiked materials incurred materials independently characterised materials (Measurement) Standards Reference Materials Certified reference materials Statistics Replication

In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and TeachingWenclawiak, B.: Fit for Purpose – A Customers View © Springer-Verlag Berlin Heidelberg 2003

Using Validated Methods

Two issues to consider: are existing validation data adequate is the analyst sufficiently competent

can he achieve the performance level claimed in the method?

In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and TeachingWenclawiak, B.: Fit for Purpose – A Customers View © Springer-Verlag Berlin Heidelberg 2003

Rules Recommended to Ensure Acceptable Performance

Analyst should be familiar with method before using it for the first time Work firstly under supervision get training think ahead of process, solutions etc required

Make an assessment how many samples can be handled at a time

Make sure everything needed is available before work starts

In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and TeachingWenclawiak, B.: Fit for Purpose – A Customers View © Springer-Verlag Berlin Heidelberg 2003

Using Validation Data to Design QC

Internal QC

External QC

In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and TeachingWenclawiak, B.: Fit for Purpose – A Customers View © Springer-Verlag Berlin Heidelberg 2003

Using Validation Data to Design QC

Internal QC includes: blanks chemical calibrants spiked samples blind samples replicate analysis QC samples control charts (recommended)

In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and TeachingWenclawiak, B.: Fit for Purpose – A Customers View © Springer-Verlag Berlin Heidelberg 2003

Using Validation Data to Design QC

External QC e.g. proficiency testing (external quality

assessment) participation in proficiency testing schemes

In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and TeachingWenclawiak, B.: Fit for Purpose – A Customers View © Springer-Verlag Berlin Heidelberg 2003

Documentation of Validated Methods 1

When the validation process is complete document the procedures of the method (also important for auditing and evaluation purposes)

With appropriate documentation reuse of method is more consistent uncertainty contribution is decreased

Test quality of documentation with a competent colleague

In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and TeachingWenclawiak, B.: Fit for Purpose – A Customers View © Springer-Verlag Berlin Heidelberg 2003

Documentation of Validated Methods 2 Standard guidance for documentation is

found in ISO 78 series “house style” is also adequate Documented methods form an important part

of a lab’s quality system document control

is documentation complete authorized for use which version which date author copyrights when last updated

In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and TeachingWenclawiak, B.: Fit for Purpose – A Customers View © Springer-Verlag Berlin Heidelberg 2003

Method Documentation Protocol

In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and TeachingWenclawiak, B.: Fit for Purpose – A Customers View © Springer-Verlag Berlin Heidelberg 2003

Implications of Validation Data for Calculating Results and Reporting

Translate data in results to solve customers problem

Consider: are observed differences significant?

precision data for repeatability and reproducibility Quality controls confirm method is in control

based on validation data producing meaningful results Estimation of measurement uncertainty enables

expression for level of confidence

In: Wenclawiak, Koch, Hadjicostas (eds.) Quality Assurance in Analytical Chemistry – Training and TeachingWenclawiak, B.: Fit for Purpose – A Customers View © Springer-Verlag Berlin Heidelberg 2003

Implications of Validation Data for Calculating Results and Reporting

The analyst needs access to validation data to support validity of results The customer may not need or understand

it Information about uncertainties might

not be understood by everybody (lawyers) When required: uncertainty should be

reported (confidence limits e.g. 95 %)