Three key components of QbD for Biologics
Three key components of the QbD approach have been previously defined as:
1. Process knowledge with an understanding of inputs and their impact on process performance.
2. Understanding the relationship between the process and the product’s critical quality attributes (CQAs)
3. Understanding the connection between CQAs and a products clinical properties (Rathore & Winkle, 2009, Nat Biotechnology 27(1) 26-34)
Tom Hayes from Genzyme will be presenting on the ‘Application of Quality by Design principles to the development, characterization and scale-up of a late stage perfusion cell culture process” at BPI Boston, 2015 as part of the Process Characterization, QbD and Technology Transfer session.
It will be interesting to see the extent to which it draws on the work of Abhinav Shukla and co-workers from Bristol-Myers Squibb published in 2010 entitled “Defining process design space for monoclonal antibody cell culture” (Abu-Absi et al., Biotechnol Bioeng, 106: 894-905)
A four step approach to defining a design-space for cell culture
Shukla and the team developed process understanding in which the effect of varying input variable on CQAs was understood for a non-continuous cell culture step with the following approach:
1. Use of failure modes effects analysis (FMEA) to identify and allocate a risk priority number to process parameters and that could influence cell culture performance.
2. Qualification of a 7L scale-down production bioreactor model.
3. Two stage design of experiments methodology (2-level Resolution IV and face-centered central composite designs) with the scale-down model to map the design space.
4. Performance of linking studies to show the effect of upstream conditions on process- and product-related impurity clearance by downstream purification steps.
The link between cell culture process parameters and CQAs
The group found that production bioreactor pH, temperature and initial viable cell density impacted product glycosylation and basic banding on isoelectric-focussing gels. Bioreactor temperature also affected product deamination. Host cell protein levels in Protein A eluates was shown to be impacted by the cell viability at harvest.
Have your say
To what extent to you think the industries approach to QbD for cell culture steps has developed since the Shukla paper from 2010? How applicable is a study such as this, based on non-continuous culture, be too continuous cell culture?
Dr Nick Hutchinson
Join me at #BPIconf
Dr Nick Hutchinson has a Masters and Doctorate in Biochemical Engineering from University College London, UK where he focused on laboratory tools for rapid bioprocess development and characterization. He then worked at Lonza Biologics in an R&D function investigating novel methods for large-scale antibody purification before moving to an operational role scaling-up and transferring manufacturing processes between Lonza sites in the UK, Spain and USA. Nick now works in Market Development at Parker domnick hunter where his focus is in bringing Parker's strengths in Motion & Control to Bioprocessing. This will enable customers to improve the quality and deliverability of existing and future biopharmaceuticals.
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