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BioContinuum Platform for Next Generation Bioprocessing
Merck Advances Bioprocessing 4.0
Through PAT-Focused Collaboration with Agilent Technologies

Process Analytical Technology (PAT)

Process Analytical Technology (PAT) is a regulatory framework initiated by the United States’ Food and Drug Administration (FDA) that encourages innovation in pharmaceutical development, manufacturing, and quality assurance. The goal of PAT is to build quality into biopharmaceutical production processes by monitoring and controlling the process in real time. Through the identification of critical process parameters (CPP) and critical quality attributes (CQA) and maintenance of CPPs and CQAs within a specified design space, PAT facilitates a dynamic manufacturing process that can compensate for variability in raw materials and equipment. Quality is therefore built into the process by Design (QbD), rather than being tested into the products.

In bioprocessing, PAT typically involves the use of chromatographic, spectroscopic and/or mass spectrometric sensors that are integrated into upstream and downstream unit operations in an inline, online, or at-line fashion to enable real-time monitoring and control of the process.

As a PAT tool for bioprocessing industries, inline Raman spectroscopy is used for process understanding, analyzing, controlling manufacturing, and monitoring of CQA & CPP in-process materials and processes, with the goal of ensuring final product quality and performance. Compared with other spectroscopic technologies such as Near-Infrared (NIR), Mid-Infrared (MIR) and UV-Vis, Raman spectroscopy is demonstrating clear advantages from a technical and theoretical aspect in upstream (USP) or downstream (DSP) processes. Indeed, Raman spectroscopy is an analytical technique providing a chemical fingerprint of the sample by molecule differentiation. These differences can be observed on spectral data acquired with the Raman analyzer. Then, after spectral treatments, qualitative & quantitative analyses can be performed for process monitoring.

Video: Meet the Experts

Video: Episode 1 - Process Analytical Technology (PAT)

Video: Episode 2 - Raman Spectroscopy

Video: Episode 3 - Chemometrics and Model Building

Video: Episode 4 - Applications and Use of Raman in Bioprocessing

Raman spectroscopy applied to upstream and downstream applications

Today, the bioprocessing industry is a key actor in enabling innovative pharmaceutical manufacturing. Indeed, nearly 85% of the biopharmaceutical market products were produced from bioprocesses in 2020 and a strong growth is expected in the coming years1.

Consequently, it can be easily understood that implementing a PAT strategy is becoming more and more crucial for the development, optimization and monitoring of biotechnology USPs and DSPs.

However, bioprocesses in general are based on several and complex processing steps to reach the desired product.

Thanks to the advantages of Raman:

  • Real-time and in-situ measurements
  • Non-destructive analytical technique
  • The capacity to collect the entire biological and chemical information in one spectrum
  • Highly selective technique: each molecule gives a well-defined spectral signature
  • Easy implementation of the technology in the process thanks to an inline probe

combined with a chemometric approach (spectral statistic analytical methods), the concentration of several key compounds in complex liquid media can be identified, quantified, and measured in real time in USP or DSP.

See the In-Line Real-Time Monitoring of CHO Cell Culture Process Parameters using Raman Spectroscopy application note as an example.

1. Forecast for Biomanufacturing Capacity, Bioprocess International, by Dawn M. Ecker and Patricia Seymour, 2020

ProCellics™ Raman Analyzer with Bio4C® PAT Raman Software

An Easy-to-Use GMP PAT Platform to Monitor Cell Cultures In-Line and in Real Time, from Process Development to Manufacturing

Today’s mammalian cell culture’s monitoring strategies lack real-time measurement and rely on daily manual sampling and feeding, which increases the risk of contamination and batch failures.

Specifically designed for the bioprocessing industry, ProCellics™ Raman Analyzer with Bio4C® PAT Raman Software enables you to perform in-line and real-time measurement of CPPs and CQAs, from process development to manufacturing. Our Raman PAT Platform helps improve processes, save time and provide flexibility to operators, reduce the risk of contamination and batch failures, and even implement a nutrient control loop strategy, a first step towards automation.

  • Process improvement: Monitor in real-time process parameters and quality attributes for greater process understanding and optimization, control and reproducibility increase during development phases.
  • Process automation: Reduce off-line sampling and manual feeding via an automated nutrient control loop strategy. Decrease the risk of contamination and minimize the risk of batch failures.
  • Easy-to-use: Specifically designed for the bioprocessing industry, easy to use hardware and software for both Raman experts and team members unfamiliar with Raman technology and multivariate analytics.
  • Easy-to-implement: Get comprehensive support and services from our experienced engineers and chemometric bioprocessing experts to ensure successful implementation and use, from process development to manufacturing.

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