The document discusses the application of near infrared (NIR) spectroscopy for real-time moisture measurement and intelligent control in the drying process at Pfizer. It highlights the development and validation of calibration models for different product groups, aiming to improve process efficiency and reduce costs. The Intellicentictm platform provides consulting services and advanced technologies to enhance pharmaceutical manufacturing processes and regulatory compliance.

1. Real Time Moisture Measurement
Using NIR for Intelligent Control and
Real Time Optimization of a Multi
Step Drying Process
Metrohm webinar, November 6, 2013
Ke Hong, Ph.D.
Advanced Manufacturing Technology
Technology & Business Solutions
Global Technology Service

2. Presentation Outline
 Near Infrared Spectroscopy Applications in Pfizer Global
Supply
 An example of NIR Applications
 Real Time Moisture Measurement Using NIR
 IntellicenticTM
Platform Technologies
 NIR Method Development and Validation Best Practices

3. Background
 Pfizer has a long history of using Near Infrared Spectroscopy (NIR)
in Manufacturing
 Applying NIR to fermentation processes in the 80s
 Many lab and at-line applications have been developed in the 90’s
 As technologies advanced, more on-line/in-line applications have been
developed in 00’s
 One of the main PAT tools for understanding processes,
minimizing variation, monitoring and controlling critical process to
achieve product and process robustness, reducing cycle time, and
improving process performance

4. Examples of NIR Applications
 Lab/At-line:
• Blends (identity and uniformity)
• Raw materials (identity and quality)
• Packaging materials (identity)
• Tablet (identity, potency, moisture, content uniformity)
 Online/inline:
• Dryer monitoring (API and drug product)
• Blending monitoring (uniformity)
• Tablet analysis (potency, moisture, content uniformity)
• Reaction monitoring

5. REAL TIME MOISTURE
MEASUREMENT USING NEAR
INFRARED SPECTROSCOPY
INTELLIGENT CONTROL AND REAL TIME
OPTIMIZATION OF A MULTI STEP DRYING
PROCESS

6. Business Driver
 To ensure acceptable Process Capability,
in many processes over-processing is
utilized – e.g. over-drying powders
 This commonly results in increased
costs & cycle time
 Advanced Process Control aims to
control the process with minimal
variation close to the economical target
by manipulating the process inputs

7. Background
Powder Drying Process
Objective is to develop an intelligent control and optimization
system to improve drying rate and moisture content

8. A PAT Based Advanced Process Control System
A measurement system with following capabilities is
needed:
Accurately measure the powder moisture in real-time as
the real time measurement of the moisture not only
reduces the need for sampling and risk of contamination,
but measures the moisture immediately after the dryer to
allow accurate control (versus manual sampling at a later
location)
Has the capabilities of advanced two way communication
with the PLC, APC, and SCADA, advanced self diagnostic,
and being remotely controlled and monitored, tested from
the SCADA system in the control room

9. Instrumentation
 Different NIR Spectrometers were evaluated
 FOSS Process XDS with stainless steel spoon probe
was chosen

10. Calibration Model Development
• Plant produces over 20 products
• Can be categorized into 4 groups
• Pilot samples were prepared for calibration model
building ranging from 1.3 – 4.4%
• Commercial samples were added to the
calibration data set to improve robustness
• Four models were built to accommodate the 4
product groups

11. Model Performance
Group 1 SEC = 0.08%, R2 = 0.95 Group 2 SEC = 0.10%, R2 = 0.96
Group 3 SEC = 0.11%, R2 = 0.95 Group 4 SEC = 0.05%, R2 = 0.99

12. Model Evaluation
Group 1, SEP = 0.06 Group 2, SEP = 0.10
Group 3, SEP = 0.12

13. Model Performance
In-Process NIR Measurement vs Final Product Reference Value -
Showing Over Two Months of Data with Multiple Products
Monitored

14. System Integration Architecture
Process PLC
APC System
SCADANIR PCNIR
Analyser

15. NIR Data Acquisition Diagram
Product Name
Batch Number,
Date, Time
Method/Model
selection
Spectral Data
NIR Analyzer
NIR PC
NIR PC
APC System
Self Diagnostics
/Prediction

16. SCADA NIR Screen

17. Model Transfer
• Same application was replicated in another dryer
• Calibration models transferred directly
• Initial model performance was reasonably well
• Due to new product being manufactured, models
were updated to improve accuracy

18. Intellicentic™ Platform Technology
 Intellicentic™ refers to a broad mix of consulting services and advanced
platform technologies developed in concert with key pharmaceutical
manufacturing suppliers, service providers and Pfizer Inc’s experience and
broad manufacturing knowledge
 These platforms are based on technologies developed for Pfizer’s internal
use. Open access to these mature and proven technologies will promote
technology uptake in the industry and provide significant benefit to other
Pharma companies without the need to replicate such an undertaking, and
accelerate regulatory awareness and acceptance that will in turn benefit
Pfizer and eventually the patients
 Drying example is one of the Intellicentic™ Platform technologies -
ProSolids
 Metrohm is a partner for this platform technology

19. NIR Method Development and
Validation Best Practices

20. Categorization
 NIR Applications
 Offline, at-line, on-line, or in-line
 NIR Methods
 Identification, Qualitative, or Quantitative
 Intended Use of NIR Application
 Technology Development and Evaluation
 Monitoring and Control with no associated risk to quality and
regulatory compliance
 Monitoring and Control with associated risk to quality and regulatory
compliance

21. NIR Method Development
Multistep and Iterative Process
• Application Proof of Concept
• Sample Materials for Development
• Sample Preparation
• Spectral Acquisition
• Reference value determination
• Spectral Manipulation and Outlier detection
• Selection of Calibration and Validation Sets
• Model Development

22. NIR Method Validation
 Risk Assessment and Validation Planning
 The extent of validation of PAT based analytical methods should be
commensurate with the risk to quality and regulatory compliance and
aligned to the NIR application purpose
 The traditional parameters used to validate analytical
methods can largely be applied to PAT/NIR analytical methods.
 ICH Guidelines should be followed
 NIR method maintenance should be considered

23. Thank you