2. Outline
I. Process Analytical Technology
A.Definition and Goals
B. Framework
1. Process Understanding
2. Tools
II. Traditional Methods VS PAT
III. Application of PAT in Mixing

3. PAT: Definition
a system for designing, analyzing, and
controlling manufacturing through
timely measurements of critical quality
and performance attributes of raw and
in-process materials and processes
(US Food and Drug Administration, 2009)

4. PAT: Goals
• understand and control the
manufacturing process
• design and develop processes that
can consistently ensure a predefined
quality at the end of the
manufacturing process
(US Food and Drug Administration, 2009)

5. PAT: Framework
• Process Understanding
– all critical sources of variability are
identified and explained
– variability is managed by the process
– product quality attributes can be
accurately and reliably predicted over
the design space established for materials
used, process parameters, manufacturing,
environmental, and other conditions.
(US Food and Drug Administration, 2009)

6. PAT: Framework
• PAT Tools
– Multivariate data acquisition and analysis
tools
– Modern process analyzers
– Process and endpoint monitoring and
control tools
– Continuous improvement and knowledge
management tools
(US Food and Drug Administration, 2009)

7. PAT: Framework
• PAT Tools
– Modern process analyzers
• At-line
(US Food and Drug Administration, 2009)

8. PAT: Framework
• PAT Tools
– Modern process analyzers
• At-line
• On-line
(US Food and Drug Administration, 2009)

9. PAT: Framework
• PAT Tools
– Modern process analyzers
• At-line
• On-line
• In-line
(US Food and Drug Administration, 2009)

10. TRADITIONAL VS PAT

11. Traditional

12. PAT

13. PAT IN MIXING

14. Process Analyzers
• Probes in manufacturing equipment
– UV/Vis
• Monitors reactions
• Monitors the concentration of one or more
components in a liquid mix
• Monitors pH changes
(Ciurczak, 2004)

15. Process Analyzers
• Probes in manufacturing equipment
– Infrared
(Naicker and Kilian, 2006)

16. Process Analyzers
• Probes in manufacturing equipment
– Light-Induced fluorescence
• Originally used laser instead of light
• High light flux induce fluorescence in materials
not normally considered in fluorescence
analysis
• Applicable in determination of blend
uniformity
(Ciurczak, 2004)

17. Process Analyzers
• Probes in manufacturing equipment
– Other probes used
• HPLC
• Chemical Imaging
• Raman Spectroscopy
(Ciurczak, 2004)

18. PAT: Mixing
• Applications
– Mixing of Solids
• Determination of particle size and shape
• Determination of endpoint of mixing
– Mixing in Liquids
• Turbidity Sensor
• Color Sensor

19. PAT: Mixing
• Determination of particle size
Particle Shape and Particle Size Analyzer WS Tyler

20. PAT: Mixing
• Determination of particle size
Particle Shape and Particle Size Analyzer WS Tyler

21. PAT: Mixing
• Determination of endpoint of mixing

22. PAT: Liquids
• Turbidity Sensor
– Turbidimetry
(Endress+Hauser, Inc., 2007)

23. PAT: Liquids
• Color Sensor
– Reads the wavelength
– Avoids batch differences
(Endress+Hauser, Inc., 2007)

24. Conclusion
• PAT
– decreases production time
– assures product quality during the process
– promotes automation thereby reduces
risks for errors
– provides real time continuous process
monitoring

25. References
CIURCZAK, EW. 2008. A spectroscopy guide to PAT. [online]. [Accessed 29 August 2012]. Available from World Wide
Web: <http://www.pharmamanufacturing.com/articles/2008/103.html?page=full>
EL-HAGRASY AS, Drennen JK. 2006. A Process Analytical Technology approach to near-infrared process control of
pharmaceutical powder blending. Part III: Quantitative near-infrared calibration for prediction of blend homogeneity
and 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 pharmacetical
development, 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: <http://www.pharmamanufacturing.com/articles/2005/278.html?page=full>
NAICKER, KKilian, G, Mandela, N and Olivier, J. 2007. Introducing PAT, Using NIR Analysis, to a Pharmaceutical Blending
Process. [online]. [Accessed 29 August 2012]. Available from World Wide Web:
<http://www.pharmamanufacturing.com/articles/2007/081.html?page=full>
SHI Z, Cogdill RP, Short SM, Anderson CA. 2008. Process characterization of powder blending by near-infrared
spectroscopy: blend end-points and beyond. Journal of pharmaceutical and biomedical analysis., pp.738-745.