This article presents an approach for managing raw materials in the QbD paradigm. It should be understood that risk assessments
are limited by what is known at a given point in time. In a recent example, it was noted that the distribution of peaks on
a column in the purification train showed differences after a process transfer from one site to another. Although it caused
no difference in product functionality, the cause of the variability was sought. After investigation, the two sites were found
to be using different sources for a media component. Further investigation showed that the two sources differed in their content
of a trace metal ion, which was a cofactor for an enzyme whose activity could explain the differences in peak distribution.
Continuous monitoring of processes and the use of techniques such as multivariate data analysis are prerequisites for continuous
improvement and superior process performance.9–12
The authors would like to thank Jennifer Mercer, Amgen Inc., Thousand Oaks, CA, for her review of the manuscript and her helpful
Anurag S. Rathore, PhD, is a biotech CMC consultant and a faculty member at the Indian Institute of Delhi, India, +91-9650770650, firstname.lastname@example.org
. Rathore also is a member of BioPharm International's editorial advisory board. Duncan Low is a scientific executive director in process development at Amgen Inc., Thousand Oaks, CA.
1. International Conference on Harmonization. Q9, Quality risk management. Geneva, Switzerland; 2005.
2. ASTM Standard E-2476. Standard guide for Risk Assessment and Risk Control as it Impacts the Design, Development, and Control
of PAT Processes for Pharmaceutical Manufacture. ASTM International. West Conshohocken, PA; 2009.
3. Rathore AS, Winkle H. Quality by Design for pharmaceuticals: regulatory perspective and approach. Nature Biotechnol. 2009;27:26–34.
4. Rathore AS. A roadmap for implementation of Quality by Design (QbD) for biotechnology products. Trends Biotechnol. 2009
5. Rathore AS. Follow-on protein products: scientific issues, developments and challenges. Trends Biotechnol. 2009 Dec;27(12):698–705.
6. CMC Biotech Working Group A-Mab: a Case Study in Bioprocess Development. 2009. Available from: http://www.ispe.org/cs/explore_by_topic/pqli_resources and http://www.casss.org/displaycommon.cfm?an=1&subarticlenbr=286.
7. Low D, Phillips J. 2009. Evolution and integration of Quality by Design and process analytical technology. In: Rathore
AS, Mhatre R, editors. Quality by Design for biopharmaceuticals. Hoboken, NJ: Wiley Interscience; 2009. p. 255–86.
8. Toro A, Colon J, Melendez-Colon V, Rivera JH. Changes in raw material sources from suppliers. Bioprocess Int. 2010 Apr;8(4):50–5.
9. Kirdar AO, Chen G, Rathore AS. Combining near-infrared (NIR) spectroscopy and multivariate data analysis (MVDA) for screening
of raw materials used in the cell culture medium for the production of a recombinant therapeutic protein. Biotechnol Progr.
10. Lanan M. QbD for raw materials. In: Rathore AS, Mhatre R, editors. Quality by Design for biopharmaceuticals. Hoboken,
NJ: Wiley Interscience; 2009. p. 193-210.
11. Kirdar AO, Green KD, Rathore AS. Application of multivariate analysis for identification and resolution of a root cause
for a bioprocessing application. Biotechnol Prog. 2008;24:720–6.
12. Rathore A, Johnson R, Yu O, Kirdar, A, Annamalai A, Ahuja S, et al. Applications of multivariate data analysis in biotech
processing. BioPharm Int. 2007;20(10):130–4.