Biomedicines, among which vaccines and monoclonal antibodies are the most widespread, offer very promising prospects for addressing globally the current needs in healthcare. It is acknowledged in the Pharmaceutical industry that the complexity of upstream cell culture development and downstream bioprocess makes it a challenge to maintain a profitable industrial activity based on these products.
Responding to unsatisfied needs
- Better understanding of cell culture processes
- Improving quality control of the final product by implementing Quality by Design (QbD)
- Enhancing batch yield and prevent batch failure by implementing in-line cell culture monitoring
- Speeding up process development, scale-up and transfer to production
- Fulfilling regulatory requests
Quality by Design (QbD), including Process Analytical Technology (PAT) tools are expected to highly contribute to face these challenges by designing, analyzing and controlling pharmaceutical manufacturing processes, in particular for vaccines and biologics. This is achieved through the robust measurement of Critical Process Parameters (CPP) which are used to ensure that the resulting product will comply with the required Critical Quality Attributes (CQA). MultiVariate Data Analysis (MVDA) is the cornerstone of information processing in these systems, with mathematical tools such as Principal Components Analysis (PCA) and Partial Least-Squares (PLS) or Support Vector Machine (SVM). The right choice of sensing technology, methodology of measurement, and mathematical tools is essential to implement an efficient and reliable Process Analytical Technology solution. This is particularly true for material such as CHO cell culture used for biodrug manufacturing, because variability can be significant with living organisms.
Raman spectroscopy has been recently demonstrated as a very efficient Process Analytical Technology instrumental technics for upstream development and bioprocess monitoring, in particular for predicting concentration of conventional metabolites in the cell culture (monitoring of lactate, etc.) and then for monitoring the feeding nutrients (monitoring of glucose, medium feeding, etc.). However dissemination of this solution needs a Process Analytical Technology sensor, understood as integrated, robust and easy-to-use system.
The challenge of implementing in-line Raman monitoring of bioprocess also deals with the combination of instrumental, data processing and bioprocess skills.