Author Archives: Konstantinos Spetsieris

Continued Process Verification: A Multivariate, Data-Driven Modeling Application for Monitoring Raw Materials Used in Biopharmaceutical Manufacturing

Biologics manufacturing entails multiple complex unit operations across three key process areas: cell culture, purification, and sterile fill–finish (Figure 1). Numerous raw materials are used to formulate reagents that are vital to those processes. For example, bioreactors require cell-culture media, and buffer solutions are used during both drug-substance filtration and drug-product final formulation. Changes in raw-material properties can introduce variation in the performance of intermediate processes and in product quality attributes. Therefore, raw-material properties must be monitored to help ensure…

Development of a Stand-Alone Monitoring Application for Purification Processes in Biomanufacturing

The ability to monitor unit operations in biomanufacturing is essential because it enables early fault detection and effective root-cause analysis. Below, we present a case study on the development of a stand-alone, data-driven, process-monitoring application for a biomanufacturing purification process. We review the application’s functionality and highlight its utility using a few examples from commercial manufacturing of a therapeutic protein. Lessons learned from the development of that application also are presented. The progress and performance of a purification process have…

Establishing a Digital Platform for Data Science Applications in Biopharmaceutical Manufacturing

Biopharmaceutical manufacturing consists of multiple processes with complex unit operations. Those include mammalian cell culture in upstream operations and downstream chromatography steps for removing impurities from production streams and purifying the therapeutic biological molecule (1). Biomanufacturers need enhanced understanding to ensure the process control and manufacture of safe and efficacious drug products. Process understanding also enables opportunities for improving manufacturing efficiency. Both process understanding and optimization can be facilitated by leveraging large volumes of biotechnology data — typically generated during…

Pathogen Safety Digital Platform for Biopharmaceuticals: The Journey from Ground to Cloud

Digital transformation is at the heart of many biopharmaceutical companies’ strategies for ongoing success. However, the definition of digital transformation and what it consists of differ within the bioprocess industry (and might even vary within a single company), specifically as it applies to the overall value chain from R&D to clinical trials, manufacturing, supply chain, and eventually commercial operations. To provide a perspective on what digital transformation could look like in bioprocessing, we present a case study about an exploratory…

Multivariate Data-Driven Modeling for Continued Process Verification

Continued process verification (CPV) is an integral part of process validation for the manufacture of human and animal drugs and biological products (1). It is designed to meet three primary goals: maintain a validated state of products, their processes, and related systems; enable continuous process improvements; and meet regulatory requirements for life-cycle validation. A CPV program for a biologic product entails regular collection of data related to critical process parameters (CPPs) and critical quality attributes (CQAs) and the preprocessing, analysis,…

Advanced Data-Driven Modeling for Biopharmaceutical Purification Processes

Purification is an essential process in biopharmaceutical manufacturing that separates a therapeutic protein in its active form from impurities. A typical purification process consists of several chromatography unit operations, and each unit operation comprises multiple phases. During the operation of each step, continuous (time-series data per parameter for each batch) and batch data (one data point per parameter for each batch) are generated by in-line sensors installed in chromatography skids on the production floor and with at-line/off-line in-process samples, respectively.…