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Writer's pictureDr. Shivang Chaudhary

How to implement Process Analytical Technology (PAT) for Pharmaceutical Products Manufacturing ?

Process Analytical Technology (PAT) A System for-

• Designing,

• Analyzing &

• Controlling Manufacturing through Timely Measurements (i.e., during processing) of Critical Quality and Performance attributes of raw and in-process materials and processes with the goal of ensuring final product quality.

There are main 3 phases for implementation of PAT System:

Phase 1 : Designing Phase

After Risk Identification, High Risk Critical Factors, i.e. risks identified as CMAs & CPPs, are optimized with respect to CQAs through QbD at Lab Scale Developmental level with AT LINE / OFF LINE Analyzers for Prediction of Real Time Data & then Control Strategies for each CMAs & CPPs are proposed for Commercial Scale by:

1. Designing of Experiments (RSM)

2. Evaluation of Regression Model Statistics

3. Development of Design Space

4. Proposal of Control Space

Phase 2 : Analyzing Phase

In Analyzing Phase, Real Time Data are analyzed at Scale UP/Exhibit Manufacturing Scale by IN LINE/ ON LINE / AT LINE / OFF LINE analyzers & Real time data are compared with Raw scale OFF LINE / AT LINE data for Finalization of Control Strategies for Commercial Scale by:

1.In Line Analysis: Sample is not removed from process stream, can be invasive or non-invasive

2.On Line Analysis: Sample is diverted from process stream, may be returned to the process stream

3.At Line Analysis: Sample is removed , isolated from & analyzed in close proximity to the process

4.Off Line Analysis : Sample is removed , isolated from & analyzed in far apart lab afterwards

Phase 3 : Controlling Phase

According to the ranges specified in final control strategies derived through QbD,

Autonomous Controllers are utilized at Real Time Manufacturing Scale for Continuously attaining Acceptable ranges of CMAs &/or CPPs to achieve desired in-process &/or finished product CQAs

Through implementation of PAT system along with QbD; Gains in quality, safety and/or efficiency will vary depending on the process and the product, and are likely to come from:

· Reduce production cycle times by using on-, in-, and/or at-line measurements and establishing real time controls

· Facilitate Real time release (Parametric Release) ability to ensure the in-process and/or final product quality based on in-process measurements

· Increase Process Automation which can improve operator safety and reduce human errors

· Improve energy and material use and increasing capacity

· Reduce or Prevent Product rejections, scrap, and re-processing

· Facilitate continuous processing with use of dedicated series of small-scale equipment to eliminate certain scale-up issues & to improve efficiency and manage variability

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