C. Markert-Hahn, K. Schiffl, M. Strohmeier, Nonclinical Statistics Conference,

Transcription

1 Roche Pharma Producton Penzberg Practcal Applcatons of Statstcal Process Control C. Markert-Hahn, K. Schffl, M. Strohmeer, Roche Dagnostcs GmbH, Penzberg Operatonal Excellence Statstcs Nonclncal Statstcs Conference, Development Process Development QbD Manufacturng Tranngs SPC DoE, Valdaton Analyss of Process Data, 2 Why do we use SPC? SPC System Goal: Detect devatons from a standard process n tme Reduce loss of batches Communcaton wth management Actvely nvolve project team How? Establsh approprate control charts for process parameters. In Control In Control (reduced varaton) Not n Control (exceptonal varaton) Crtcal Qualty Attrbutes, # 15 Key Performance Indcators, # 30 Process Parameters (ncludng trend data) #

2 SPC System Control Chart Example: Indvdual Movng Range Chart Example: Tter[g]* Indvdual Measurements and Movng Ranges. Easy nterpretaton, routnely montored. Interpretable after Statstcs Tranng, Montored from Process Experts, e.g. Multvarate Control Charts MR x x 1 MR m 1 CL x 1 2 M R 3 d d 32 M R UCL M R 3 d 22 =Mean of the range for a sample of 2 from N(,1) d 22 *smulated data m MR 22 5 SPC for s SPC for s Man Work: Establsh approprate control charts and defne standard process- Calculate control lmts based on hstorcal data. Control charts are accessble e.g. va web reports generates daly control charts based on actual data SPC Server Alarm Emals are automatcally sent n case of dentfed rule volatons Process Expert 7 8 2

3 SPC System Prncpal Component Analyss Easy nterpretaton, routnely montored, e.g., IR Chart Interpretable after Statstcs Tranng, Montored from Process Experts, e.g. Multvarate Control Charts Samples n Parameters p X: mean centered or auto-scaled X = T Scores P t Loadngs + E Resduals Loadngs: Parameter Weghts, p s the egenvector of Cov(X) correspondng to the egenvalue λ X X Cov ( X ) Scores: New Coordnates, t n 1 = Xp 9 Multvarate Statstcal Process Control Hotellng T 2 Control Chart Graphcal Interpretaton: Sample wth large Q Loadngs p 1 Sample wth large T 2 Loadngs p 2 Measure of varaton n each sample wthn the PCA model. 11 T 2 =t λ t T,where t s the -th row of T and λ s the dagonal matrx contanng all egenvalues of X correspondng to the k prncpal components. 12 3

4 Lack of Ft, Q Control Chart Multvarate SPC for further Process Parameters Multvarate Control Charts: Montor the stablty of a multvarate process consderng many parameters at the same tme Causes of a multvarate alarm: Indvdual varables beng outsde ther allowable range Fouled relatonshp between two or more varables Multvarate Control Charts are analyzed by experts, no alarm emals are sent. Measure of dstance between a sample and ts projecton nto the k prncpal components. Q =e e T,where e s the -th row of E Process behnd SPC Process Qualty problem Root Cause Analyss Qualty optmzaton/ stablzaton Adjust SPC System Establsh SPC system Alarm Multvarate Data Analyss Analyze avalable process data Small Scale Experments (DoE) Adjust Process, Elmnate Problem Adjust SPC System Innovaton für de Gesundhet 4

5 Outlook IR-Chart Constants Defne hstorcal data sets for multvarate control charts for further process steps and products. Apply non-standard control charts Consderaton of Covarates n Control Charts Consderaton of repeated measures n d 2n 2 1, , , , , , ,849 Hartung, (2009) n d 3n 2 0, , , , , , ,820 Handl (1999) 18 Western Electrc Rules!!! Wetere Nelson Rules!!!!!! 5