Rational Design of Stable Lyophilized Protein Formulations: Some Practical Advice


Early in the development of a protein therapeutic it 1s essential to design a formulation that is stable during shipping and long-term storage. Obviously, an aqueous liquid formulation is the easiest and most economical to handle during manufacturing, and is the most convenient for the end user. However, many proteins are susceptible to chemical  (e.g., deamidation or oxidation) and/or physical degradation (e.g., aggregation and precipitation) in liquid formulations (1,2). It may be possible to design an aqueous formulation to slow protein degradation adequately, under controlled storage conditions (i.e., constant temperature and minimal agitation). However, during shipping, when precise control of conditions is not always feasible, prod­ucts can be subjected to numerous stresses that denature pro­teins. These include agitation, high and low temperatures, and freezing (2). Furthermore, although a formulation and shipping system might be designed to circumvent damage from these stresses, it still may not be possible to inhibit damage suffi­ciently during long-term storage. For example, there are cases where conditions that minimize chemical degradation foster physical damage and vice versa (1,2). Then, conditions that provide a compromise affording the requisite long-term stability cannot be found.

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