Storage & Handling

Peer-reviewed stability literature on lyophilised (solid) versus liquid (aqueous / reconstituted) peptide and protein samples, and on temperature, light, and freeze–thaw as experimental variables, is summarised below. Findings were reported in in vitro chemical and pharmaceutical studies, not as handling instructions for a named catalogue lot. In a review of solid-state chemical stability of proteins and peptides, the authors stated that peptide and protein drugs are often formulated in the solid state to provide stabilization during storage, while chemical reactions including deamidation, peptide-bond cleavage, oxidation, the Maillard reaction, beta-elimination, and dimerization or aggregation can still occur in the solid state; temperature, moisture content, excipients, and amorphous versus crystalline physical state were listed as influencing factors.[1] In a review of protein stabilization in the solid state, the solid state was described as preferred for many proteins because of marginal stability in solution, while chemical and physical degradation were still reported to occur on the time scale of drying, distribution, and use.[2] In a review of freeze-drying of bioproducts, product and process parameters that determine successful freeze-drying were related to thermochemical and thermomechanical properties of water-soluble amorphous materials.[3] In a review of liquid protein pharmaceuticals, protein instability was described as a reason protein pharmaceuticals are stored under cold conditions or freeze-dried to achieve an acceptable shelf life, and chemical and physical instability of proteins in liquid formulations was summarised.[4] A 1989 review of protein-pharmaceutical stability summarised chemical pathways including proteolysis, deamidation, oxidation, racemization, and beta-elimination, and physical processes including aggregation, precipitation, denaturation, and adsorption to surfaces.[5] In a review of photodegradation of protein biologics, residues reported to undergo primary photooxidation included tryptophan, tyrosine, phenylalanine, and cysteine or cystine, and photodegradation was described as able to change primary, secondary, and tertiary structure.[6] In an in vitro study of proteins in aqueous solutions, freezing and thawing rates were reported to affect denaturation of the test proteins under the compared freeze–thaw conditions.[7]