Product analysis - Pharmaceutical Biotechnology: Concepts and Aapplications - page 204

of the product with a vast excess of DNA is counterproductive, in that it may render subsequent
downstream processing unrepresentative of standard production runs.
For more comprehensive validation studies, the molecular mass profi le of the DNA spike should
roughly approximate to the molecular mass range of endogenous contaminant DNA in the crude prod-
uct. Obviously, the true DNA clearance rate attained by downstream processing procedures (e.g. gel
fi ltration) will depend to some extent on the molecular mass characteristics of the contaminant DNA.
Other manufacturing procedures requiring validation include cleaning, decontamination and
sanitation (CDS) procedures developed for specifi c items of equipment/processing areas. Of par-
ticular importance is the ability of such procedures to remove bioburden. This may be assessed by
monitoring levels of microbial contamination before and after application of CDS protocols to the
equipment item in question.
Further reading
Books
Aguilar, M. 2003. HPLC of Peptides and Proteins . Humana Press.
Dass, C. 2000. Principles and Practice of Biological Mass Spectrometry. Wiley.
Kellner, R. 1999. Micorcharacterization of Proteins . Wiley.
Kinter, M. and Sherman, N. 2005. Protein Sequencing and Identifi cation Using Tandem Mass Spectrometry.
Wiley.
Ramstorp, M. 2000. Contamination Control and Cleanroom Technology . Wiley.
Rathore, A. and Sofer, G. (eds). 2005. Process Validation in Manufacturing of Biopharmaceuticals: Guidelines,
Current Practices, and Industrial Case Studies . Taylor and Francis.
Rosenberg, I. 2004. Protein Analysis and Purifi cation . Birkhauser.
Venn, R. 2000. Principles and Practice of Bioanalysis . Taylor and Francis.
Whyte, W. 2001. Cleanroom Technology . Wiley.
Wild, D. (ed.) 2005. The Immunoassay Handbook . Elsevier.
Articles
Dabbah, R. and Grady, L. 1998. Pharmacopoeial harmonization in biotechnology. Current Opinion in Biotech-
nology 9 , 307-311.
Darling, A. 2002. Validation of biopharmaceutical purifi cation processes for virus clearance evaluation. Molecu-
lar Biotechnology 21 , 57-83.
Ding, J. and Ho, B. 2001. A new era in pyrogen testing. Trends in Biotechnology 18 (8), 277-280.
Domon, B. and Aebersold, R. 2006. Review - mass spectrometry and protein analysis. Science 312, 212-217.
Geisow, M.J. 1991. Characterizing recombinant proteins. Bio/Technology 9 , 921-924.
Geng, D., Shankar, G., Schantz, A., Rajadhyaksha, M., Davis, H., and Wagner, C. 2005. Validation of immu-
noassays used to assess immunogenicity to therapeutic monoclonal antibodies. Journal of Pharmaceutical and
Biomedical Analysis 39 , 364-375.
Glennon, B. 1997. Control system validation in multipurpose biopharmaceutical facilities. Journal of Biotechnol-
ogy 59 (1-2), 53- 61.
Hu, S. and Dovichi, N. 2002. Capillary electrophoresis for the analysis of biopolymers. Analytical Chemistry
74 (12), 2833-2850.