A scale-down model must be statistically similar to its corresponding large-scale process. In this article from BioProcess International magazine, authors from Genzyme report on using 12-L bench-top bioreactors to model a 2,000-L microcarrier-based perfusion cell culture process. They scaled down agitation rate based on a power/working-volume ratio and matched scale-independent parameters to the commercial-scale process. A two one-sided test (TOST) helped them establish statistical equivalency to qualify the scale-down model. Comparing critical product-quality attributes showed that cell culture performance of the model was within specified ranges.
A range of factors are currently conspiring to push the field of pharmaceutical manufacturing toward wider use of SUSs. While factors specific to the fill/finish stage have meant that it has taken the longest to be affected by such changes, recent developments in the associated materials, technology and regulatory landscape are making possible rapid development on this front. Disposables have the potential to render substantial benefits in respect of savings of time and expense, and enhancements to safety and clinical rigor. All this makes it almost certain that they will see continued growth in the immediate future, and anyone with a stake in the industry would do well to keep a finger on the pulse of this transformation.
The CMO Patheon has installed an entirely disposable fill/finish system that is fully validated, scalable from 2 liters to 200 liters, and meets all requirements in respect of E&Ls. Fill sets of three different sizes were manufactured in collaboration with suppliers. An initial saving of 10% on capital investment was achieved through the implementation of a single-use system, and subsequent continuing benefits include a reduction in personnel hours required for changeover from 19 hours to 1.5. Further, the flexibility offered by SUSs in terms of size means that excess or wasted capacity is greatly reduced, and Tony Pidgeon, senior manager of global science and technology at Patheon, claims, “At this point, whenever we can, we will opt for single-use systems, and single-use technology has become the preferred approach for new facilities.”
Please can you introduce yourself?
SM: Hi I’m Sigma Mostafa vice president for Upstream and Downstream process development at KBI biopharma. We are a CDMO (Contract Development and Manufacturing Organisation) and we have two locations in North Carolina, as well as in Colorado.
What is process robustness?
SM: The general definition of robustness is the ability of a process to tolerate the expected variabilities, and this comes from raw materials or process conditions or human factors or equipment. Essentially, robustness is something we need to demonstrate prior to a molecule going into market. A lot of the process characterisation work gets done later in the life cycle of a molecule to ensure that data is generated. So what we are talking about here is bringing in the sort of studies of robustness as well as understanding around the cell line process very early on so that there aren’t any surprises in the late phases of the molecule.
With such a fast paced industry, it is sometimes hard to keep up with the most current trends in the industry. We asked a selection of the speakers here at the conference what they saw as the emerging trends in the industry; here is what they had to say.
By: Dr. Nick Hutchinson
Biopharmaceutical companies are placing great focus on the way they perform process development activities at the earliest stages of the product lifecycle. It is a field in which considerable research and innovation is taking place as firms attempt to make best use of their resources and gain competitive advantage. To find out more about the way in which companies are adapting their early stage development approach I spoke to Dr Will Lewis, Head of Purification Research, Biopharm Process Research at GSK.
In today’s podcast, Nobel Vale, Research Scientist at Bristol-Myers Squibb takes you through his presentation ‘Techniques for real-time monitoring of CHO Cell bioprocess.’
“Various methods have been developed to monitor cell metabolism in CHO upstream bioprocesses. We are currently evaluating the potential for these techniques to routinely support cell-line selection and process development DoEs. The spectroscopic technologies we used include Raman and Near-Infrared, along with capacitance measurements. Potential benefits from these techniques are the ability to have optimised feeding strategies, automated sampling procedures, improved temporal resolution of cell metabolism, and highly precise measurements. Commonly measured attributes in CHO upstream bioprocesses through sampling include nutrient and metabolite levels, protein production, and viable/total cell density. The ability for spectroscopic methods to resolve and predict different analytes online and offline will be described, as will the feasibility of using capacitance measurement to infer viable cell density. One unique aspect of this work is the development of preliminary models for prediction using standards developed offline. Calibrations developed using standards can accelerate the calibration process and potentially eliminate spurious correlations from the model that would otherwise occur during multiple bioreactor runs.
In an effort to get an industry insight into the geographical differences in the regenerative medicines market segments we spoke to Dr. Larry Couture, Vice President of the Center for Applied Technology Development, City of Hope.
KNect365 Bioprocessing: In your opinion, what are the key differences in the regenerative medicine industry between North America, Europe and Asia?
Dr. Couture: I kind of touched on the big one. The biggest difference between Europe and the United States – I can’t speak as much to Asia, but I can speak to Europe and the United States – the big difference is the focus on pre-clinical animal modelling. In the United States the trend – the focus – is on testing the human product – the actual product that will go into humans – in animal models. That is our culture. That’s how we’ve been doing this for a long time and it’s the logic that has applied to all biologics. If you are not testing the human product, you are really not testing the product.