PROCESS ANALYTICAL TECHNOLOGY IN PHARMACEUTICAL

PROCESS ANALYTICAL TECHNOLOGY

1. PROCESS ANALYTICAL TECHNOLOGY SHIVANI H RANA 012300600026002012 PHARMACEUTICAL MANUFACTURING TECHNOLOGY GUIDE : DR. RAKESH YADAV

2. CONTENT 1 WHAT IS PAT ? GOAL HOW PAT WORKS MERITS DEMERITS PAT REGULATORY GUIDANCE PAT FRAMEWORK [TOOLS] PAT IMPLEMENTATION

3. WHAT IS PAT ? 2 PAT is a framework for designing, analyzing & controlling pharmaceutical manufacturing processes through the measurement of process parameters (cpp) which affect critical quality attributes (CQA).

4. 3 It’s about the processing of critical quality & performance attributes of raw & in-process materials & processes. PAT is the : Understanding of the process Identification of critical control point (CCP) Application of knowledge-base to control the process.

5. 4 Identify the defects in process manufacturing. Reduce process variation. Enhance process safety. Produce product quality information in high time. Building quality into product. Enhance understanding & control of manufacturing process.

6. HOW PAT WORKS 5 SELECTION OF PROCESS SELECTION OF SUITABLE PAT SYSTEM IDENTIFICATION OF CRITICAL CONTROL POINTS DESIGNING OF PROCESS ON-LINE TESTING/IN-LINE TESTING

7. MERITS 6 Reduction in production time. Prevent reprocessing & rejection. Increase automation. Improve operation safety. Reduce human error in continuous process. Controlling variability. Continuous improvement. Improving energy & material usage.

8. DEMERITS 7 Requires efforts during design. Specialized expert person required. Maintenance cost is high. Costly.

9. PAT REGULATORY GUIDANCE 8 Regulatory agencies like US-FDA , ICH, who has been active in the areas of PAT in the development of standards for use of PAT in pharmaceutical industry internationally in their standards committee E55. US-FDA was published PAT final guidance in SEP 2004.

10. PAT FRAMEWORK 9 A. Process Understanding B. PAT Tools

11. A. PROCESS UNDERSTANDING 10 All critical sources of variability are identified. Variability is managed by the process. Product quality attributes can be accurately & reliably predicted over the design space established.

12. 11

13. PAT TOOLS 12 1] Multivariate tools for Design, data acquisition & analysis. 2] Process analyzer 3] Process control tools 4] Continuous improvement & knowledge management tools

14. 13 1] MULTIVARIATE TOOLS FOR DESIGN, DATA ACQUISITION & ANALYSIS From the physical, chemical or biological perspective, pharmacetuical products and process are complex multi-factorial systems which is complex to monitor.

15. 14 For this, the purpose can be achieved through the use of multivariate mathemathical approaches, such as statistical design of experiments, response surface methodologies, process simulation & pattern recognition tools, in conjunction with knowledge management system.

16. 2] PROCESS ANALYZER 15 Some process analyzers provide nondestructive measurements that contain information related to biological, physical & chemical attributes of the materials being processed. These measurements can be :

17. 16 A] at-line : Measurement where the sample is removed, isolates form & analyzed in close proximity to the process stream. B] on-line : Measurement where the sample is diverted from the manufacturing process & may be returned to the process stream. C] in-line : Measurement where the sample is not removed from the process stream & can be invasive or noninvasive.

18. 3] PROCESS CONTrOL TOOLS 17 It is important to emphasize that a strong link between product design & process development is essential to ensure effective control of all critical quality attributes. Strategies should accommodate the attributes of input materials, the ability & reliability of process analyzer to measure critical attributes & the achievement of process end points to ensure consistent quality of the output materials & the final product.

19. 18 Identify & measure critical process attributes Design process measurement system Design process controls Development of mathematical relationships Desing & optimisation of drug formulations & manufacturing process within PAT Framework can include the following step :

20. 4] CONTINUOUS IMPROVEMENT & KNOWLEDGE MANAGEMENT 19 Continuous learning through data collection & analysis over the life cycle of a product is important. information technology infrastructure makes the development & maintenance of this knowledge base practical.

21. 20 Approaches & information technology systems that support knowledge acquisition from databases are valuable for the manufacturers & can also facilitate scientific communication with the FDA.

22. PAT IMPLEMENTATION 21 The challenge to date with PAT for pharmaceutical manufacturers is knowing how to start. The following criteria serves as a basic framework, Picking a simple process. (ex. water for injection [WFI] or Building monitoring system [BMS]. All details & nuances are well understood & explained for that process. Determine what information is easily collected & accessible

23. 22 through current instrumentation. 4. Understanding the appropriate intervals for collecting that data. 5. Evaluating the tools available for reading & synchronizing the data.

24. MEASUREMENT ACROSS THE PROCESS 23

25. 24

26. 25

27. THANK YOU