Model-assisted process characterization and validation for a continuous two-column protein A capture process | JoVE Visualize

Area of Science:

Biopharmaceutical Process Development
Chromatographic Separation Science
Process Analytical Technology (PAT)

Background:

Continuous manufacturing is increasingly adopted in biopharmaceutical production.
Process characterization is crucial for ensuring product quality and regulatory compliance.
Traditional methods for continuous chromatography (CaptureSMB) can be experimentally intensive.

Purpose of the Study:

To introduce and compare three process characterization approaches for continuous twin-column capture chromatography (CaptureSMB).
To evaluate the effectiveness of standard, model-assisted, and hybrid approaches in exploring the design space and enhancing process understanding.
To align process validation strategies with regulatory guidelines, such as those from the FDA.

Main Methods:

Development and application of three distinct process characterization approaches: standard, model-assisted, and hybrid.
Utilizing risk-based strategies, including process description, risk analysis, design-of-experiments (DoE), and statistical analysis.
Employing chromatographic process modeling and computer simulations to supplement or replace experimental runs in the model-assisted and hybrid approaches.

Main Results:

The standard approach using experimental DoE proved extensive and identified infeasible operating conditions due to inappropriate design space boundaries.
The model-assisted approach, incorporating process modeling and simulations, significantly enhanced process understanding and identified feasible design space boundaries automatically.
The hybrid approach combined elements of the standard method with simulations, offering a balance between experimental and computational strategies.

Conclusions:

The model-assisted approach offers a more efficient and insightful alternative to traditional experimental DoE for continuous chromatography process characterization.
Process modeling and simulation are valuable tools for reducing experimental burden and improving process understanding in continuous manufacturing.
The presented approaches incorporate key elements of FDA process validation guidelines, facilitating robust characterization of continuous chromatographic processes.