ABSTRACT
As discussed in Chapter 4, the formulation of peptide and protein drugs is a difcult task and the formulation scientist has to overcome several challenges to develop a stable and efcacious formulation. Once a formulation is identied, it needs to be scaled up for large-scale manufacturing. During such scale-up and subsequent manufacture, the peptide or protein is exposed to several types of stresses. Also, production of the pure protein itself prior to its formulation also exposes the protein to several stress situations. These stress situations can be loosely dened as pharmaceutical processing. These include the generation of extensive air-water interfaces due to the turbulence in mixing tanks, foaming, adsorption to lters or tubing, freezing and drying stress during lyophilization, and other unique situations such as exposure to light, organic solvents, or heavy metals (Akers & Nail, 1994). This chapter discusses the stress imposed on peptide and protein drugs during pharmaceutical processing and means to minimize the resulting deleterious effects on protein stability. Emphasis will be placed on protein lyophilization. In addition, handling of therapeutic peptides and proteins in other settings such as in a hospital will also be discussed. A quality by design approach (see Section 4.8) has been described to understand the effect of various variables and their interactions for a lyophilized monoclonal antibody (Awotwe-Otoo et al., 2012).
