Towards establishing uniform validation procedures in Sasol analytical laboratories Piet de Coning Vina Thakally-Govender Piet de Coning Vina Thakally-Govender

Towards establishing uniform validation procedures in Sasol analytical laboratories

Towards establishing uniform validation procedures in Sasol analytical laboratories

Piet de ConingVina Thakally-GovenderPiet de ConingVina Thakally-Govender

Copyright reserved – Sasol Technology R&D

Overview of Sasol processes


Sasol global involvement


“Cleaner” fuels

Clean fuels burn cleanly

Emissions benefits are immediately realisable

GTL Diesel Low sulphur refinery diesel

Particulate emissions

Acidifying emissions(SOx and NOx)

upstream

production

transport

use

upstream

production

use


Method format

Based on ISO 78-2

Divided into five sections

Site specific cover page

Document informationNumber, Date, Revision history, Distribution, etc.

Method summary – Not IP sensitiveCan be copied for reports

Procedure – May be IP sensitiveSome methods are proprietary, others licensed e.g. ASTM

Typical data

Excluded from the method

Validation dataIssued as a separate report

Site and instrument specific proceduresDocumented as Standard operating procedures or Work instructions


Why should methods be validated?

Officially:To prove that a method is fit for its purpose

Practically:To protect the analyst from unreasonable demands / expectationsTo increase confidence in the analytical ability of the analyst / laboratoryTo facilitate laboratory managementTo give the analyst increased confidence in his/her results

Why estimate the measurement Uncertainty ?

Officially:It is an ISO requirement: Result = value + uncertainty + units

Practically:It sums up most of the validation in a single figureUncertainty = Confidence


Why are methods not validated?

It is not necessaryHighly qualified scientists

We have Integrity

But – do we have documented evidence of this that will stand up in court?

It costs too muchNot so, if offset against product failure and loss of sales

We do not have the time“Strangely there is never enough time to do things properly, but yet we always seem to find the time to do things over”

The equipment is the best and maintained by qualified service engineers

“Never before has it been so easy, and with so little effort, to produce bad results”

AttitudeAnalytical chemistry is the poor relative of the chemistry disciplines

“It is not that people are ignorant, it is just that they know so much that isn't so”

CEO office

Seniormanagement

Finances

Staffcaffeteria

Foyer with pot plants

Streetlevel

entrance

Centralair

conditioningBuildingutilities

Analyticallaboratory

Executive car park

Executiveboardroom

Humanresources

Sales

Typist pool


How?

ValidationDo only what is required to establish fitness for purpose

Do only what can be ...

Incorporated in the method uncertainty

Be used in the routine application of the method

Do additional validation tests only when ...

Specifically requested by the customer

The analyst considers it necessary

UncertaintyEstablish the purpose

Determine uncertainty requirement (how detailed?) in terms of

Method purpose

Customer requirements

Analyst’s experience & evaluation

StatisticsUse standard statistical tests at 95% confidence


The requirement specification

Establish the purpose

From this follows a validation plan


What ?

AccuracyThe single most important parameterDepends on:

CalibrationTruenessPrecision

UncertaintyDetermined from:

CalibrationTruenessPrecision

Uncertainty is the numerical value of the accuracy!

Determined during method development:

Specificity / SelectivityRobustness / RuggednessRecovery - correction

Determined from method calibration

SensitivityRangeQuantitation limits

upperlower

Detection limit


Calibration

Grubb’s tests

The linearity, slope, intercept and regression uncertainties - from Excel ANOVA function

The formula for conc. calculation provided

Range = LQL – UQL= lowest – highest standard

Calibration curve with prediction limits

Prediction limits used for MDL calculation

Regression significance tested with t- and F-tests

Fit evaluated using P-value and residual plots

P-value on std.dev. used to determine if WLS should be used

Several weighting models providedCopyright reserved – Sasol Technology R&D

Accuracy

Accuracy as truenessThree ways of doing it

Trueness by comparison with a reference standard

Trueness using a recovery study

Trueness by comparison with an alternative method

Accuracy as precisionRepeatability

Same analyst, same instrument, short time-scale

Reproducibility

Different analysts, different instruments, extended time-scale

Intermediate precision

Between repeatability and reproducibility

Precision limit

Qualitative analysesFalse positives and false negatives

RtR 2


Uncertainty

Uncertainty is a lot more uncertain


Implementation

The validation manualValidation philosophy

Validation procedures

Tools – generic formats, spreadsheets and workbooks

Statistical and mathematical procedures

PresentationsManagement: High level overview – essentials

Supervisors: More detailed presentation

WorkshopsLaboratory personnel

Selected methods

Next stepsIncorporate suggestions and criticism (e.g. flowcharts)

Benchmark validation procedure

Continued improvement


Acknowledgements

The Validation workgroup:Anna Potgieter (Sasol Infrachem laboratories)

Johann Drews (Sasol Infrachem laboratories)

Madelyn Bekker (Sasol Waxes)

Martiens Henning (Sasol Secunda Shared Services)

Rene Engelbrecht (Sasol Infrachem laboratories)

Roos van der Heide (Sasol Solvents)

Vina Thakally-Govender (Sasol Technology R&D, Analytical Solutions)

Special acknowledgement:

Prof. Willem de Beer (Tswane University of Technology)

Angelique Botha (National Metrology Institiute of South Africa)

David Coleman (Applied Statistician, Alcoa Technical Center, PA, USA)

Lynn Vanatta (Air Liquide-Balazs™ Analytical Services, TX, USA)

piet.deconing @ sasol.comCopyright reserved – Sasol Technology R&D

Documents

Towards establishing uniform validation procedures in Sasol analytical laboratories Piet de Coning Vina Thakally-Govender Piet de Coning Vina Thakally-Govender