title: A methodical approach to ultra-scale-down of process sequences: application to casein removal from the milk of transgenic animals.
abstract: Scale-down models of individual operations are widely used in biopharmaceutical process development to obtain information about the performance of production-scale equipment on the basis of inexpensive and efficient laboratory-scale tests, for the purposes of validation or optimization or characterization studies. We have investigated the ability of scale-down models of whole process sequences to provide reliable information for process scale-up from laboratory- to pilot-scales of operation. Using the example of the recovery of a protein from transgenic milk, we have conducted an a priori scale-down analysis of a projected pilot-scale process sequence. A systematic approach was developed to ensure that all critical aspects of process behavior were included in the scale-down model, resulting in the creation of an accurate and reliable scale-down representation of the pilot-scale process. The data from scale-down process trials conducted at 70 and 200 mL scales of operation served to highlight crucial factors determining process performance, and proved reliable in predicting the performance of the pilot-scale process over a scaling factor of 1000.
authors.affiliation: Amgen Process & Analytical Sciences, Thousand Oaks, California 91320, USA.
authors.forename: Lars W
authors.initials: LW
authors.lastname: Pampel
authors.forename: Rihab
authors.initials: R
authors.lastname: Boushaba
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Titchener-Hooker
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002364:Caseins / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism; D002417:Cattle; D005524:Food Technology / Q000379:methods*; D007784:Lactoperoxidase / Q000302:isolation & purification / Q000378:metabolism; D008892:Milk / Q000737:chemistry*; D008894:Milk Proteins / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism
chemical_list: D002364:Caseins; D008894:Milk Proteins; D007784:Lactoperoxidase