title: Protein isolated from biopharmaceutical formulations cannot be used for comparative studies: Follow-up to "a case study using Epoetin Alfa from Epogen and EPREX".
abstract: In the biotechnology area, the issue of comparability with an innovator product is complex. Ideally, a side-by-side comparison of physical properties would be part of the demonstration of comparability. However, biogeneric companies do not have access to the bulk drug substance from the innovator company for biophysical comparison, and isolation of protein from marketed product cannot be guaranteed to produce material that is identical to the bulk drug substance from which it was prepared. In a recently published study, protein was isolated from marketed product and comparative studies performed. In a follow-up investigation of the published work, we demonstrate here that even a simple isolation procedure can significantly compromise the protein, which raises serious questions about the interpretation of that study, and in a broader context the value of any studies done with such "out-of-process" protein.
authors.affiliation: Centocor R&D, 145 King of Prussia Road, Radnor, PA 19087, USA. gheavner@cntus.jnj.com
authors.forename: G A
authors.initials: GA
authors.lastname: Heavner
authors.forename: T
authors.initials: T
authors.lastname: Arakawa
authors.forename: J S
authors.initials: JS
authors.lastname: Philo
authors.forename: M A
authors.initials: MA
authors.lastname: Calmann
authors.forename: S
authors.initials: S
authors.lastname: Labrenz
mesh_terms: D016477:Artifacts; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004339:Drug Compounding; D004340:Drug Contamination; D004355:Drug Stability; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000737:chemistry* / Q000302:isolation & purification; D006397:Hematinics / Q000737:chemistry* / Q000302:isolation & purification; D006863:Hydrogen-Ion Concentration; D011489:Protein Denaturation; D011786:Quality Control; D011994:Recombinant Proteins; D015203:Reproducibility of Results; D013056:Spectrophotometry, Ultraviolet; D013678:Technology, Pharmaceutical / Q000379:methods* / Q000592:standards; D014461:Ultracentrifugation
chemical_list: D006397:Hematinics; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa