Process Analytical Technology

• 1. OutlineI. Process Analytical Technology A.Definition and Goals B. Framework 1. Process Understanding 2. ToolsII. Traditional Methods VS PATIII. Application of PAT in Mixing

2. PAT: Definitiona system for designing, analyzing, andcontrolling manufacturing throughtimely measurements of critical qualityand performance attributes of raw andin-process materials and processes(US Food and Drug Administration, 2009) 3. PAT: Goals understand and control themanufacturing process design and develop processes thatcan consistently ensure a predefinedquality at the end of themanufacturing process(US Food and Drug Administration, 2009) 4. PAT: Framework Process Understanding all critical sources of variability areidentified and explained variability is managed by the process product quality attributes can beaccurately and reliably predicted overthe design space established for materialsused, process parameters, manufacturing,environmental, and other conditions.(US Food and Drug Administration, 2009) 5. PAT: Framework PAT Tools Multivariate data acquisition and analysistools Modern process analyzers Process and endpoint monitoring andcontrol tools Continuous improvement and knowledgemanagement tools(US Food and Drug Administration, 2009) 6. PAT: Framework PAT Tools Modern process analyzers At-line(US Food and Drug Administration, 2009) 7. PAT: Framework PAT Tools Modern process analyzers At-line On-line(US Food and Drug Administration, 2009) 8. PAT: Framework PAT Tools Modern process analyzers At-line On-line In-line(US Food and Drug Administration, 2009) 9. TRADITIONAL VS PAT 10. Traditional 11. PAT 12. PAT IN MIXING 13. Process Analyzers Probes in manufacturing equipment UV/Vis Monitors reactions Monitors the concentration of one or morecomponents in a liquid mix Monitors pH changes(Ciurczak, 2004) 14. Process Analyzers Probes in manufacturing equipment Infrared(Naicker and Kilian, 2006) 15. Process Analyzers Probes in manufacturing equipment Light-Induced fluorescence Originally used laser instead of light High light flux induce fluorescence in materialsnot normally considered in fluorescenceanalysis Applicable in determination of blenduniformity(Ciurczak, 2004) 16. Process Analyzers Probes in manufacturing equipment Other probes used HPLC Chemical Imaging Raman Spectroscopy(Ciurczak, 2004) 17. PAT: Mixing Applications Mixing of Solids Determination of particle size and shape Determination of endpoint of mixing Mixing in Liquids Turbidity Sensor Color Sensor 18. PAT: Mixing Determination of particle sizeParticle Shape and Particle Size Analyzer WS Tyler 19. PAT: Mixing Determination of particle sizeParticle Shape and Particle Size Analyzer WS Tyler 20. PAT: Mixing Determination of endpoint of mixing 21. PAT: Liquids Turbidity Sensor Turbidimetry(Endress+Hauser, Inc., 2007) 22. PAT: Liquids Color Sensor Reads the wavelength Avoids batch differences(Endress+Hauser, Inc., 2007) 23. Conclusion PAT decreases production time assures product quality during the process promotes automation thereby reducesrisks for errors provides real time continuous processmonitoring 24. ReferencesCIURCZAK, EW. 2008. A spectroscopy guide to PAT. [online]. [Accessed 29 August 2012]. Available from World WideWeb: EL-HAGRASY AS, Drennen JK. 2006. A Process Analytical Technology approach to near-infrared process control ofpharmaceutical powder blending. Part III: Quantitative near-infrared calibration for prediction of blend homogeneityand characterization of powder mixing kinetics. Journal of pharmaceutical sciences., pp.422-434.FOOD AND DRUG ADMINISTRATION. 2004. Guidance for industry PAT - a framework for innovative pharmaceticaldevelopment, manufacturing and quality assurance. USA: FDA.HUSSAIN, AS. 2005. The Desired State: PAT and the Road to Enlightenment. [online]. [Accessed 29 August 2012].Available from World Wide Web: NAICKER, KKilian, G, Mandela, N and Olivier, J. 2007. Introducing PAT, Using NIR Analysis, to a Pharmaceutical BlendingProcess. [online]. [Accessed 29 August 2012]. Available from World Wide Web:SHI Z, Cogdill RP, Short SM, Anderson CA. 2008. Process characterization of powder blending by near-infraredspectroscopy: blend end-points and beyond. Journal of pharmaceutical and biomedical analysis., pp.738-745.