Abstract: An in vitro release test (IVRT) method and system is provided for drug release testing. The IVRT method, referred to herein as adaptive perfusion, employ tangential-flow filtration (TFF), where released drug products that are smaller than a molecular weight cutoff (MWCO) of a membrane filter pass therethrough into the permeate. Unreleased drug products are retained by the pores of the filter and are recirculated to a retentate reservoir. Fresh media is provided to the retentate in order to maintain a constant total volume for the sample as well as to maintain sink conditions for the drug release. Drug concentration in the retentate and permeate are evaluated by in situ monitoring with one or more sensors and/or by periodic removal of aliquots from the respective reservoirs. In some embodiments, the membrane filter can be conditioned prior to use in order to improve the accuracy, precision, or both of the subsequent testing.