Mahatma Gandhi Vidyamandir's

Pharmacy College, Panchavati ,Nashik,422003

Seminar on

Process Analytical Technology

(PAT )

Presented By Under the Guidance of

Chetan Pralhad Warude Dr. Kunal Bhambar
Roll No. 48 Head of Department of Pharmaceutical
Quality Assurance

1
Vision :
To be center of professional excellence by contributing honestly to pharmacist molding
process.
Mission :
• Impart high quality education to graduates.
• Contribute to all sphere of professional activities.
• Uphold human value and ethics.
• Nature them into globally competent professional

2
 Content

Sr. No. Topics Slide No.

1. Introduction 4
2. Objectives 5
3. Generalized Flow of PAT 6
4. Types of PAT Implementation 7
5. Current Approaches in PAT System 10
6. Advantages of PAT 13
7. Application of PAT 14
8. Disadvantages 15
9. FDA initiative tools 16-18
 Multivariate Tool for Design, Data Acquisition, and Analysis
 Process Analyzer
 Process Control Tool
 Continuous Improvement and Knowledge Management Tools
10. References 19
3
 INTRODUCTION

Process Analytical Technology

PAT has been defined as "a system for designing, analyzing, and controlling manufacturing through timely
measurements (i.e., during processing) of critical quality and performance attributes of raw and in-process
materials and processes, to ensure final product quality"

According to the United States Food and Drug Administration (FDA), Process Analytical Technology (PAT) is
defined as a mechanism for designing, analyzing, and controlling pharmaceutical manufacturing processes
through the measurement of Critical Process Parameters (CPP) that affect Critical Quality Attributes (CQA).

General Principle

Quality cannot be tested into a final product; it should be built-in or by design.

4
Objectives of PAT
1. PAT enhances process understanding by identifying critical parameters
early.
2. It reduces waste and improves yield by preventing scrap and reprocessing.
3. Real-time release of batches is facilitated by implementing PAT in a three-
step process.
4. Design space exploration begins early to optimize unit operations.
5. Critical quality attributes & process parameters are identified in this
phase.
6. Understanding process intricacies is essential for effective PAT
implementation.
7. General FDA guidelines are needed to standardize PAT practices and
5
ensure regulatory compliance.
Generalized flow of PAT System:-

1. Selection of Process

2. Selection suitable PAT System

3. Identification of CPP

4. Design Process

At line Test On line Test In line Test

6
Types of PAT Implementations

Initial Phase Process Optimization

Scale-up Phase Comparing Data

Temporary Process:-
Gaining process information & understanding the process

Permanent Process:-
Actual Process Monitoring and Control

7
There are 4 key elements play an important role in PAT Implementation
1. Building Science
2. Process monitoring and control
3. Validation of PAT System
4. Regulatory Strategy

1. Building Science:

 Understanding chemical and physical properties of raw materials and intermediates.

 Characterizing reaction kinetics and thermodynamics.
 Identifying critical quality attributes (CQAs) and critical process parameters (CPPs).

2. Process Monitoring and Control:

 Implementing real-time analytical techniques such as spectroscopy and chromatography.

 Integrating sensors for continuous monitoring of temperature, pressure, pH, etc.
 Employing advanced data analytics for predictive modeling and control algorithms.

8
3. Validation of PAT System:

 Conducting method validation studies for analytical techniques.

 Assessing the robustness and reliability of real-time monitoring systems.
 Performing process validation to demonstrate the effectiveness of control strategies in maintaining
product quality.

4. Regulatory Strategy:

 Documenting the implementation and performance of the PAT system in a comprehensive validation
report.
 Engaging with regulatory agencies to discuss and gain approval for using PAT in manufacturing
processes.
 Demonstrating compliance with regulatory requirements through thorough documentation and
adherence to industry guidelines.

9
 Current Approaches in the PAT System

1. Spectroscopy:
Application: Employed for real-time analysis of pharmaceutical ingredients and formulations.
Techniques:
NIR spectroscopy for content uniformity testing,
IR spectroscopy for identification of raw materials,
Raman spectroscopy for in-line monitoring of crystallization processes.

2. Chromatography:
Usage: Integral for analyzing drug purity, stability, and impurity profiles.
Techniques:
HPLC for quantification of active pharmaceutical ingredients (APIs),
GC for volatile impurity analysis, and
LC-MS for identification of unknown compounds.
LIMITATIONS of Both Spectroscopy & Chromatography

1. Cost of equipment 2. Training of personnel and skill

3. Dependency on skilled personnel 4. Time consuming
5. Maintenance 6. Expertise 10
3. Multivariate Analysis:

Implementation: Enables real-time monitoring and control of critical process parameters.

Methods:
PCA and PLS regression were utilized for data interpretation and process optimization.
LIMITATIONS:
1. Data Integrity 2. Computer-based expertise
3. Complexity in system

4. Real-time Monitoring:

Significance: Crucial for ensuring batch-to-batch consistency and compliance with regulatory requirements.
Parameters:
Monitoring of temperature, pressure, pH, and API concentration during various manufacturing stages.
LIMITATIONS
1. Sensor reliability 2. Data Integrity
3. Deviations during a continuous process

11
5. Advanced Sensor Technologies:
Integration: Incorporation of advanced sensors for precise monitoring of manufacturing processes.
Examples:
Fiber optic probes for in-situ measurements,
Mass spectrometers for gas analysis, and
Electrochemical sensors for monitoring reaction kinetics.
LIMITATIONS
1. Cost of advanced techniques 2. Maintenance of that system
3. Performance reliability 4. Data interpretation
6. Modeling and Simulation:
Development: Creation of mechanistic models to simulate pharmaceutical processes.
Purpose: Predictive modeling for process optimization, scale-up, and risk assessment.

7. Automation and Control Systems:

Role: Integration of PAT with automated control systems for adaptive process control.
Benefits:
Facilitates real-time decision-making,
Reduces batch-to-batch variability, and
Enhances overall manufacturing efficiency.
12
 LIMITATIONS of Modeling and simulation and Automation and Control system

1. Cost of advanced techniques 2. Maintenance of that system

3. Performance reliability 4. Data interpretation
5. Adoption 6. Validation
7. Mainataince etc.

Advantages of PAT System

1. Enhanced process understanding. 2. Real-time monitoring for immediate adjustments.

3. Improved product quality and consistency. 4. Reduced production cycle times.
5. Enhanced process control and optimization. 6. Lower production costs through waste reduction.
7. Facilitated regulatory compliance. 8. Minimized risk of batch failures.
9. Increased efficiency in resource utilization. 10. Enables continuous manufacturing processes.
11. Supports faster product development cycle 12. Enhances scalability for large-scale production.
13. Enables early detection of process deviations.
13
 Application of PAT
SR.NO. PROCESSE STEPS PAT tech. (At line, outline, inline )
1. Raw material dispensing NIR, Weighing System
2. Reaction monitoring Mid-IR, FTIR, Raman Spectroscopy, UV Spectroscopy

3. Crystallization Focused Beam Reflectance Measurement (FBRM),NIR

4. API drying NIR Spectroscopy, Moisture sensor

5. Wet Granulation NIR Spectroscopy, NIR chemical scanning
6. Fluidized bed drying NIR Spectroscopy, Moisture sensor
7. Blending NIR, Raman Spectroscopy
8. Lubrication NIR, Raman Spectroscopy
9. Coating Terahertz (THz),
10. Packaging Visual inspection system, barcode and RFID (Radio Frequency Identification)

11. Microscopy N IR, Raman Spectroscopy , Optical Microscopy

14
 Disadvantage of PAT
1. High setup costs: software, hardware, training.
2. Complex integration with existing systems.
3. Limited flexibility for business process changes.
4. Security risks with sensitive data and system vulnerabilities.
5. Disruptions due to technical issues.
6. Job displacement and employee resistance.
7. Reduced human oversight, and potential errors.
8. Customization and scalability challenges.
9. Implementation and maintenance stages are high.
10. Require specialized, expert person.
11. Costly.
15
 FDA INITIATIVE ON PAT

• The FDA's initiative on Process Analytical Technology (PAT) aims to modernize pharmaceutical
manufacturing processes by encouraging advanced analytical and monitoring techniques.

• FDA's initiative on PAT provides a framework and guidance for pharmaceutical manufacturers to adopt
innovative approaches to product development, manufacturing, and quality assurance, ultimately leading to
safer and more effective medicines for patients.

• PAT TOOLS: There are many tools available that enable process understanding for scientific, risk-managed
pharmaceutical product development manufacture & quality assurance.

The PAT tools are categorized into the following type

1. Multivariate Tool for Design, Data Acquisition, and Analysis

2. Process Analyzer
3. Process Control Tool
4. Continuous Improvement and Knowledge Management Tools

16
1. Multivariate Tool for Design, Data Acquisition, and
Analysis:
These tools allow for the analysis of complex datasets to
identify correlations between process variables and
product quality attributes, aiding in the design of
experiments and optimization of processes.
Example: Multivariate Data Analysis (MVDA) software
packages like SIMCA, Umetrics MODDE, and CAMO
Unscrambler.
2. Process Analyzer:
These instruments provide real-time or at-line
measurements of critical process parameters and product
attributes, allowing for continuous monitoring and control
of the manufacturing process.
 At-line Measurement: The sample is removed
from the process stream and analyzed nearby.
Example PAT Tool Portable NIR
Spectrometer
 On-line measurement: The sample is diverted
from the process, analyzed, and returned.
Example PAT Tool: On-line Raman
Spectroscopy System
 In-line Measurement: The sample is not
removed from the process stream.
Example PAT Tool: In-line Near-Infrared
(NIR) Analyze
Examples: Near-Infrared (NIR) Spectroscopy systems,
Raman Spectroscopy systems, or Mass Spectrometry
systems.
17
3. Process Control Tool:

These tools enable automated control of manufacturing processes based on real-time data from process analyzers and
other sensors, ensuring that critical parameters remain within predefined limits.
Examples: Programmable Logic Controllers (PLCs), Distributed Control Systems (DCS), or Supervisory Control and
Data Acquisition (SCADA) systems.

4. Continuous Improvement and Knowledge Management Tools:

These tools facilitate data management, documentation, and analysis, supporting continuous improvement initiatives
and knowledge management efforts within the organization. They help capture and share process knowledge, facilitate
decision-making, and support regulatory compliance efforts.
Examples: Electronic Laboratory Notebooks (ELNs), Manufacturing Execution Systems (MES), or Quality
Management Systems (QMS).

Each of these PAT tools plays a critical role in implementing the principles of PAT in pharmaceutical manufacturing,
enabling real-time monitoring, control, and optimization of processes to ensure product quality and consistency.

18
 References

1. Process Analytical Technology (PAT) in Pharmaceutical Development [Internet]. Available from:

http://www.americanpharmaceuticalreview.com/Featured-Articles/115453-Process-Analytical-Technology-
PAT-in-Pharmaceutical-Development/

2. Process Analytical Technology [Internet]. Available from: http://www.gmpua.com/World/Manu/07/j.htm

3. Process Analytical Technology (PAT) - Initiative [Internet]. Available from:

https://www.fda.gov/aboutfda/centersoffices/officeofmedicalproductsandtobacco/cder/ucm088828.htm4.

4. Guidance for Industry PAT - A Framework for Innovative Pharmaceutical Development, Manufacturing,
and Quality Assurance [Internet]. 2004 Sep. Available from:
https://www.fda.gov/downloads/drugs/guidances/ucm070305.pdf5.

5. Process Analytical Technology and Validation [Internet]. Available from:

https://www.researchgate.net/publication/6706941_Process_analytical_technology_in_the_pharmaceutical
_industry_A_toolkit_for_continuous_improvement
19
Thank You !!!

20