title: Cleaning characterization of protein drug products using UV-vis spectroscopy.
abstract: This study uses on-line absorbance monitoring to evaluate cleanability of protein drug products. Characterization and validation of equipment cleanliness is a key requirement for a biopharmaceutical facility. A manufacturing-scale cleaning cycle has to be developed and validated for its ability to clean all of the equipment parts for a given soil. Cleaning validation in a multiproduct fill-finish facility could benefit from using a worst-case-based approach that involves validating the cleaning process for the most difficult to clean product. Such an approach minimizes the number of required validation runs. Scaled-down cleaning evaluations can provide helpful information for evaluating multiple products and determine the worst case. This study presents a simple and rapid technique for bench-scale characterization of cleanability of protein drug products. On-line A280 (UV absorbance at 280 nm) measurements are performed using a fiber optic probe, and the data are used to establish the dynamics of protein dissolution in cleaning solution. The model not only helps to estimate cleaning time of different formulated proteins (and peptides) but also provides insights into the kinetics of cleaning under different thermal and chemical conditions. Protein product degradation during cleaning is also evaluated through gel electrophoresis. Such information is useful in designing new cleaning cycles. While the study is performed using drug products, the model as well as the findings are also applicable for characterization of final purified bulk soils relevant to bulk drug manufacturing.
authors.affiliation: Drug Product and Device Development, Amgen Inc., Thousand Oaks, California 91320, USA. nrathore@amgen.com
authors.forename: Nitin
authors.initials: N
authors.lastname: Rathore
authors.forename: Wei
authors.initials: W
authors.lastname: Qi
authors.forename: Wenchang
authors.initials: W
authors.lastname: Ji
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000295:instrumentation / Q000379:methods; D003902:Detergents / Q000737:chemistry*; D004340:Drug Contamination / Q000517:prevention & control*; D004866:Equipment Contamination / Q000517:prevention & control*; D011506:Proteins / Q000032:analysis* / Q000737:chemistry*; D012987:Soil / Q000032:analysis*; D013056:Spectrophotometry, Ultraviolet / Q000379:methods*
chemical_list: D003902:Detergents; D011506:Proteins; D012987:Soil