Analytical techniques for the evaluation of liquid protein therapeutics.
A common problem in the manufacture of liquid protein therapeutics is the tendency for aggregation and particle formation on extended storage. Analytical techniques are required to study the propensity of solutions to form aggregates and particles and to allow the investigation of the effect of conditions encountered during manufacture and storage. A key challenge is to utilize appropriate specific and sensitive techniques to allow the early detection of initial aggregation events, thereby avoiding the need to resort to extended stability trials. The present review evaluates a range of techniques for the detection of changes in protein conformation and the formation of aggregates and particles. It is hoped that the availability of this information will encourage and facilitate studies to resolve stability issues associated with protein therapeutics.
Research and Development Department, CSL Bioplasma, 189-209 Camp Road, Broadmeadows, Vic. 3047, Australia.
Owen C
OC
Tatford
Peter T
PT
Gomme
Joseph
J
Bertolini
D002623:Chemistry Techniques, Analytical / Q000379:methods; D045424:Complex Mixtures / Q000032:analysis / Q000737:chemistry; D003257:Consumer Product Safety; D003461:Crystallography / Q000379:methods*; D004340:Drug Contamination / Q000517:prevention & control*; D004355:Drug Stability; D004356:Drug Storage; D046912:Multiprotein Complexes / Q000032:analysis* / Q000737:chemistry / Q000627:therapeutic use*; D011487:Protein Conformation; D011489:Protein Denaturation; D011506:Proteins / Q000032:analysis* / Q000737:chemistry / Q000627:therapeutic use*; D017751:Safety Management / Q000379:methods; D012996:Solutions / Q000032:analysis* / Q000737:chemistry
D045424:Complex Mixtures; D046912:Multiprotein Complexes; D011506:Proteins; D012996:Solutions