Data analysis in stability studies of biopharmaceutical drugs with isothermal and non-isothermal assays

Stability is a particular problem for biopharmaceutical products because the efficacy of peptides and proteins as therapeutic or diagnostic agents can be affected during preparation, shipping, and storage. A particular formulation may have no immediately apparent effect on physical or chemical stability, and the time required for these studies at ambient temperature can be very lengthy because chemical reactions proceed relatively slowly at low temperatures. Undoubtedly, accelerated and stress testing of stability can provide useful information for future product development. The many methods used to study kinetics in aqueous solution may be experimental or computational. Experimental approaches may be isothermal or non-isothermal. Non-linear and linear regression methods can be used to analyze data from these experimental approaches, and the Monte Carlo method could be useful to obtain information about uncertainties in experimental data.The purpose of this review is to describe and to discuss options for the accelerated study of peptide and protein drugs. These options are not necessarily the same as those used for regulatory testing to set expiration dates. We also review statistical techniques to estimate kinetic parameters (rate constant, activation energy, and pre-exponential factor). Further, we establish the advantages and the limitations of both thermal approaches. We analyze and discuss all aspects using the most recent examples of peptide and protein stability.