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Towards establishing uniform validation procedures in Sasol analytical laboratories Piet de Coning Vina Thakally-Govender Copyright reserved – Sasol Technology R&D Overview of Sasol processes Copyright reserved – Sasol Technology R&D Sasol global involvement Copyright reserved – Sasol Technology R&D “Cleaner” fuels Clean fuels burn cleanly Emissions benefits are immediately realisable Particulate emissions use transport production upstream Acidifying emissions (SOx and NOx) use GTL Diesel Low sulphur refinery diesel Copyright reserved – Sasol Technology R&D production upstream Method format Based on ISO 78-2 Divided into five sections Site specific cover page Document information Number, Date, Revision history, Distribution, etc. Method summary – Not IP sensitive Can be copied for reports Procedure – May be IP sensitive Some methods are proprietary, others licensed e.g. ASTM Typical data Excluded from the method Validation data Issued as a separate report Site and instrument specific procedures Documented as Standard operating procedures or Work instructions Copyright reserved – Sasol Technology R&D Why should methods be validated? Officially: To prove that a method is fit for its purpose Practically: To protect the analyst from unreasonable demands / expectations To increase confidence in the analytical ability of the analyst / laboratory To facilitate laboratory management To 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 figure Uncertainty = Confidence Copyright reserved – Sasol Technology R&D Why are methods not validated? It is not necessary Highly qualified scientists We have Integrity But – do we have documented evidence of this that will stand up in court? It costs too much CEO office Executive boardroom Senior management Human resources Not so, if offset against product failure and loss of sales We do not have the time Finances “Strangely there is never enough time to do things properly, but yet we always seem to find the time to do things over” Street The equipment is the best and maintained by qualified service engineers level entrance “Never before has it been so easy, and with so little effort, to produce bad results” Attitude Sales Staff caffeteria Typist pool Foyer with pot plants Executive car park Central air conditioning Building utilities Analytical 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” Copyright reserved – Sasol Technology R&D Analytical laboratory How? Validation Do 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 Uncertainty Establish the purpose Determine uncertainty requirement (how detailed?) in terms of Method purpose Customer requirements Analyst’s experience & evaluation Statistics Use standard statistical tests at 95% confidence Copyright reserved – Sasol Technology R&D The requirement specification Establish the purpose From this follows a validation plan Copyright reserved – Sasol Technology R&D What ? Determined during method development: Specificity / Selectivity Robustness / Ruggedness Recovery - correction Determined from method calibration Sensitivity Range Quantitation limits upper lower Detection limit Accuracy The single most important parameter Depends on: Calibration Trueness Precision Uncertainty Determined from: Calibration Trueness Precision Uncertainty is the numerical value of the accuracy! Copyright reserved – Sasol Technology R&D 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 provided Copyright reserved – Sasol Technology R&D Accuracy Accuracy as trueness Three 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 precision Repeatability Same analyst, same instrument, short time-scale Reproducibility Different analysts, different instruments, extended time-scale Intermediate precision Between repeatability and reproducibility Precision limit R t 2 R Qualitative analyses False positives and false negatives Copyright reserved – Sasol Technology R&D Uncertainty Uncertainty is a lot more uncertain Copyright reserved – Sasol Technology R&D Implementation The validation manual Validation philosophy Validation procedures Tools – generic formats, spreadsheets and workbooks Statistical and mathematical procedures Presentations Management: High level overview – essentials Supervisors: More detailed presentation Workshops Laboratory personnel Selected methods Next steps Incorporate suggestions and criticism (e.g. flowcharts) Benchmark validation procedure Continued improvement Copyright reserved – Sasol Technology R&D 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.com Copyright reserved – Sasol Technology R&D