To retain biological activity, proteins generally must be maintained in a specific, three-dimensional conformation. This conformation
is only marginally stable, and thus relatively minor perturbing forces can disrupt protein structure, causing loss of biological
activity, as well as formation of non-native protein aggregates. Such perturbations are commonly encountered as proteins are
produced, stored, transported, and delivered to patients. For example, it is well known that during common industrial processes
such as filtering (Maa and Hsu, 1998), storage (Mcleod et al., 2000), agitation (Thurow and Geisen, 1984; Maa and Hsu, 1997) freeze/thawing (Eckhardt, Oeswein et al., 1991; Nema and Avis, 1993; Izutsu et al., 1994), lyophilization (Carpenter and Chang, 1996; Carpenter et al., 1997), nebulization (Ip et al., 1995) and spray-drying (Broadhead et al., 1994; Mumenthaler et al., 1994; Maa et al., 1998; Adler and Lee, 1999; Millqvist-Fureby, Malmsten et al., 1999; Tzannis and Prestrelski, 1999) proteins can suffer damage to their native conformation. Further, delivery of protein pharmaceuticals to patients may also
provoke losses of conformational integrity via unfavorable interactions of proteins with surfaces (e.g., inner walls of catheter
tubing or syringes (Tzannis et al., 1996)).