Proteins accelerated stability testing

Finally, the protein assay for the drug product will also be used for realtime and accelerated stability testing if it has been validated to be stability indicating. A stability-indicating protein concentration method usually translates to a method that can reveal how much protein can be recovered from the dosage form. Many protein instabilities result in precipitation of the protein and adsorption to the container. An instability that results in only a modification of the protein structure but not in loss of protein from solution will not be detected by a sequence-independent protein assay such as a colorimetric assay. 

Stamper GF, Lambert WJ. Accelerated stability testing of proteins and peptides pH-stability profile of insulinoptropin using traditional Arrhenius and non-linear fitting analysis. Drug Dev Ind Pharm 1995 21 1503-1511. 

Once the formulation scientist has narrowed the list of excipients to test in a formulation, an accelerated stability study is initiated. In this study, potential formulations are exposed to conditions such as elevated temperature, harsh light, mechanical stress, and freezing to assess which formulation provides the most stability to the active protein. 

Stability prediction for peptide and protein drugs under accelerated testing conditions is possible if the temperature dependence of the degradation rate is determined and found to be well behaved. The temperature dependence can often be represented by the Arrhenius equation, as was seen with small-molecule drugs. Linear Arrhenius plots and the values of apparent activation energy calculated from the slopes have been reported for chemical degradation of various peptides in aqueous solutions. Values of approximately 20 kcal/mol... 

Accelerated shelf life tests take at least 48 hr or one week to provide results. More rapid predictions of beer stability are sometimes obtained using chemical precipitants such as ethanol [185] or formaldehyde [186]. Proteins can be precipitated with ammonium sulphate [187], magnesium sulphate, or gallic tannic acid [188]. 

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