Process analytical technology (PAT) for biopharmaceuticals

Abstract

Process analytical technology (PAT), the regulatory initiative for building in quality to pharmaceutical manufacturing, has a great potential for improving biopharmaceutical production.The recommended analytical tools for building in quality, multivariate data analysis, mechanistic modeling, novel models for interpretation of systems biology data and new sensor technologies for cellular states, are instrumental in exploiting this potential. Industrial biopharmaceutical production has gradually become dependent on large-scale processes using sensitive mammalian cell cultures. This further emphasizes the need for improved PAT solutions. We summarize recent progress in this area based on an expert workshop held at the 8 th European Symposium on Biochemical Engineering Sciences (Bologna, 2010), and highlight new opportunities for exploiting PAT when applied in biopharmaceutical production. We conclude with recommendations for advancing PAT applications in the biopharmaceutical industry.

Hybrid semi-parametric modeling in process systems engineering: Past, present and future

“…Recently, the value added by hybrid semi-parametric modeling to the PAT initiative was outlined by Gernaey and Gani (2010) and Glassey et al (2011). Interestingly, the requirements on the "PAT tools" reads as the list of hybrid semiparametric model properties.…”

New Insights into Cell Encapsulation and the Role of Proteins During Flow Cytometry

“…The Process Analytical Technology (PAT) initiative, launched by the Food and Drug Administration (FDA) encourages extensive process understanding to achieve the desired quality of pharmaceutical and bioactive protein products rather than a 'quality-by-testing' approach. Thus, elucidating and monitoring variations within protein production, purification and encapsulation systems is fundamental for quality control, protein detection and localisation (Glassey et al, 2011). One key issue for PAT is the use of on-line process analysers; in this context, 'on-line' is used in the sense of 'fully automatic' or 'without any manual interaction'.…”

Preliminary Modeling of an Industrial Recombinant Human Erythropoietin Purification Process by Artificial Neural Networks

“…Industrial biopharmaceutical production has gradually become dependent on large-scale processes using sensitive mammalian cell cultures (Glassey et al, 2011). The biopharmaceutical market has witnessed the arrival of many new complex therapeutic proteins produced in mammalian cell lines (Teixeira et al, 2009).…”

“…Their ability to reduce dimensionality by removing the redundancy and noise leads to the identification of salient features in the data. These features can subsequently be used in bioprocess monitoring, fault detection and process optimization, as has been described extensively in the literature over the years (Teixeira et al, 2009;Glassey et al, 2011). The inner workings of the majority of batch pharmaceutical processes are not well understood for a fundamental or knowledge-driven model to be developed.…”