Process analytical technology (PAT) for biopharmaceutical products: Part II. Concepts and applications

2009/09/03 by E.K. Read, Rakhi B. Shah, R.B. Shah +6 · 200 citations
Biochemistry, Genetics and Molecular Biology · Decision Sciences · Engineering · Mathematics · #Biochemical engineering #Biology #Biopharmaceutical #Biotechnology #Chemometrics #Computer science #Downstream (manufacturing) #Engineering #Manufacturing engineering #Mathematics #Operations management #Optimal Experimental Design Methods #Pharmaceutical manufacturing #Process (computing) #Process analytical technology #Process engineering #Product (mathematics) #Protein purification and stability #Quality (philosophy) #Quality by Design #Systems engineering #Viral Infectious Diseases and Gene Expression in Insects #Work in process

paper · doi:10.1002/bit.22529

published in Biotechnology and Bioengineering 105(2), 285-295 (Wiley)

openalex publication_date 2009/09/03 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28

Abstract

Implementing real-time product quality control meets one or both of the key goals outlined in FDA's PAT guidance: "variability is managed by the process" and "product quality attributes can be accurately and reliably predicted over the design space established for materials used, process parameters, manufacturing, environmental, and other conditions." The first part of the paper presented an overview of PAT concepts and applications in the areas of upstream and downstream processing. In this second part, we present principles and case studies to illustrate implementation of PAT for drug product manufacturing, rapid microbiology, and chemometrics. We further present our thoughts on how PAT will be applied to biotech processes going forward. The role of PAT as an enabling component of the Quality by Design framework is highlighted. Integration of PAT with the principles stated in the ICH Q8, Q9, and Q10 guidance documents is also discussed.

Cited by

• Development of a 3D Printed Flow Cell for Application as an In-line Optical Particle Analysis Tool
• Applications of Artificial Intelligence, Deep Learning, and Machine Learning to Support the Analysis of Microscopic Images of Cells and Tissues
• Propagation of measurement accuracy to biomass soft-sensor estimation and control quality. [europepmc]
• Mesenchymal Stromal Cells: From Discovery to Manufacturing and Commercialization. [europepmc]
• Wanted: more monitoring and control during inclusion body processing. [europepmc]
• Mass spectrometry-based methods in characterization of the higher order structure of protein therapeutics. [europepmc]
• Application of quality by design in the current drug development. [europepmc]
• Generative data augmentation and automated optimization of convolutional neural networks for process monitoring. [europepmc]
• Basic regulatory science behind drug substance and drug product specifications of monoclonal antibodies and other protein therapeutics. [europepmc]
• Continuous Process Verification 4.0 application in upstream: adaptiveness implementation managed by AI in the hypoxic bioprocess of the Pichia pastoris cell factory. [europepmc]
• Applications of Artificial Intelligence, Deep Learning, and Machine Learning to Support the Analysis of Microscopic Images of Cells and Tissues. [europepmc]
• Aspects and Implementation of Pharmaceutical Quality by Design from Conceptual Frameworks to Industrial Applications. [europepmc]
• Continuous Manufacturing of Recombinant Drugs: Comprehensive Analysis of Cost Reduction Strategies, Regulatory Pathways, and Global Implementation. [europepmc]
• Liposome Particle Size Prediction by In-Line Process Analytical Technology (PAT)-Integrated Machine Learning. [europepmc]

Related

• Accelerating attribute‐focused process and product development through the development and deployment of autonomous process analytical technology platform system
• A Review on Quantitative Process Analytical Technology for Continuous Downstream Processing of Monoclonal Antibodies
• Applications of Machine Learning in Biopharmaceutical Process Development and Manufacturing: Current Trends, Challenges, and Opportunities
• A high-resolution multi-attribute method for product characterization, process characterization, and quality control of therapeutic proteins
• From Discovery to Production: Challenges and Novel Methodologies for Next Generation Biomanufacturing