PAT

Real-Time, Data-Driven, and Predictive Modeling: Accelerating Digital Transformation in Drug Substance Commercial Manufacturing

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Biopharmaceutical drug-substance (DS) manufacturing consists of several unit operations. Upstream production includes multiple steps in growing bacterial or mammalian cells in culture. Upstream activities are followed by a series of downstream processing units including chromatography and filtration steps for removing impurities and purifying a therapeutic molecule (1). All these operations are inherently complex because of the natural variability associated with growing living cells and the intricacy of purification techniques used for collecting biological products. The US Food and Drug Administration…

February 9, 2023

Statistical Method for Establishing Control Limits for Nonnormal Data Distribution: Focus on Continued Process Verification Monitoring

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According to the US Food and Drug Administration’s (FDA’s) process validation guidance, critical quality attributes (CQAs) and critical process parameters (CPPs) are used to assess the statistical stability of a bioprocess and its ability to meet acceptable criteria as a part of a continued process verification (CPV) program using control charts (1). For those control charts, control limits are used to assess the statistical stability of process parameters and attributes. When data are normally distributed, control limits are established straightforwardly…

October 20, 2022

Raman Spectrometric PAT Models: Successful Transfer from Minibioreactors to Larger-Scale, Stirred-Tank Bioreactors

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Spectroscopic sensors are powerful tools for bioprocess monitoring within the process analytical technology (PAT) initiative of the US Food and Drug Administration (FDA). The PAT framework includes process understanding based on scientific background with the aim of monitoring and controlling critical process parameters (CPPs) that influence critical quality attributes (CQAs) of final biological products. The driving force for PAT implementation is a need to realize consistent product quality, process intensification, and real-time manufacturing control (1, 2). Using real-time spectroscopic measurements…

September 28, 2022

Hardware, Software, and Wetware: 20 Years of Advancements in Biopharmaceutical Production, Part 1

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The past couple of decades have witnessed significant advances in upstream bioprocess technologies and approaches. Since its establishment, BPI has been a facilitator of discussion in both print and professional conferences, as well as in webcasts and news online. To mark the 20th anniversary of the publication, we surveyed articles published over the past two decades and found hundreds that highlight significant advances in both emerging and established themes in biopharmaceutical production: • “hardware†and assets (e.g., analytical instrumentation, bioreactors,…

August 22, 2022

Smart, Real-Time Quality Insights Boost Life Sciences Manufacturing

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The COVID-19 pandemic has shone a light on restrictive business processes, information silos, and poor supply-chain visibility in many sectors. In biopharmaceutical manufacturing, for example, difficulties associated with product-quality management have been exposed and starkly felt. However, public healthcare measures over the past 18 months have put physical distance between team members, thereby hampering the usual form-filling, manual sign-offs and spreadsheet-based recordkeeping associated with monitoring traditional manufacturing processes. In some cases, a lack of formal face-to-face discussions in the workplace…

March 16, 2022

eBook: Sensors — Process Analytics for Modern Biopharmaceutical Workflows

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To achieve quality by design in biopharmaceutical production, manufacturers need tools that can ensure the stability of critical process parameters (CPPs) and other performance indicators related to product critical quality attributes (CQAs). Over the past couple of decades, sophisticated process analytical technologies (PATs) have emerged to address such needs. Offerings are now abounding for single-purpose sensors that measure temperature, pressure, pH, glucose, protein concentration, or dissolved oxygen. New in-line formats are enabling such instruments to provide data in real time,…

February 28, 2022

Automated Process Control Based on In Situ Measured Glucose Concentration

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A process analytical technology (PAT) strategy involves defining critical process parameters (CPPs) of a biomanufacturing process that influence critical quality attributes (CQAs) and controlling those CPPs within defined limits. Doing that enables consistent product quality and helps companies reduce waste and costs. Glucose is an important CPP in bioprocessing and cell therapy. Glucose often is fed as a bolus addition based on daily off-line measurements, but that can lead to high glucose fluctuations and to excessive glucose feeding, which can…

December 14, 2021

Seamless Integration of Glucose Control: Using Raman Spectroscopy in CHO Cell Culture

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The process analytical technology (PAT) and quality by design (QbD) guidelines promoted by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) support the idea that quality cannot be “tested into†a biologic product but must instead be part of its process design. Seamless integration of analytical data with bioprocess monitoring and control is crucial to understanding a process and overcoming manufacturing challenges that arise in the course of development. Monitoring of product quality attributes (PQAs)…

December 8, 2021

Simplifying the Bioprocessing 4.0 Journey

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Bioprocessing 4.0, the biopharmaceutical version of Industry 4.0, is on course to become a reality in the next decade (1). This is because its “cyber-physical systems†that comprise cloud computing, connected systems, and digital process control offer many benefits. They include better process monitoring and management of a biologic’s critical quality attributes (CQAs) and the chance to control intensified processes for faster, less-expensive production of protein-based biologics and vaccines. Automation also can reduce the number of skilled operators needed while…

September 30, 2021

PendoTECH Sensors and Industry 4.0: Integrating a PendoTECH Single-Use Sensor System with a Digital Highway

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Biopharmaceutical manufacturing is evolving with the progression of Industry 4.0. Industry 4.0 refers to the ongoing “fourth industrial revolution,†which is transforming modern manufacturing and production practices through the use of “smart†technology. This is appealing especially to the biopharmaceutical industry, where production can be a long, meticulous, complex process, and optimizing manufacturing procedures is critical for success. As a leading supplier of single-use technology for the biopharmaceutical industry, PendoTECH recently has explored how its products can be integrated easily…

August 27, 2021