The phenomenon of protein aggregation during the production of a bio therapeutic drug is an increasing challenge to many pharmaceutical research and development groups and companies.Aggregation may cause a number of deleterious effects on protein drugs

including the loss of efficacy

the induction of immunogenicity

alteration of pharmacokinetics and reduction of shelf life.Size exclusion chromatography(SEC) is a traditional technique widely employed for the qualitative and quantitative evaluation on pharmaceutical proteins and their aggregates

which possesses some advantages such as easy operation

mild mobile phase conditions and nondestructive detection of the conformational structure and local environment

etc.However

SEC method still remains a number of limitations

in which the most important one is the adsorption of protein to resin.The theory for SEC separation is outlined in this review

and some methods how to reduce the nonspecific adsorption problem are described.Some techniques mutually comlementary with SEC are listed

which could be used in the analysis on pharmaceutical protein aggregates.Finally

the future development and outlook for SEC technique are described.