title: Establishing analytical comparability for "biosimilars": filgrastim as a case study.
abstract: Biosimilars are defined as biotherapeutic drugs that have been shown to have comparable quality, safety, and efficacy to the original product. Fuelled by the patent cliff in the next 5 years, the focus of the biopharmaceutical industry is gradually shifting towards production of biosimilars. Scientific and regulatory issues around development and approval of these biosimilars have been a topic of great interest and debate recently. Unlike the conventional small molecular weight drugs, biosimilars exhibit high complexity at the molecular level. Slight variations during the manufacturing of these complex protein molecules may lead to the significant changes in the safety and efficacy profile of the therapeutic product. Establishing comparability to the reference product is essential for successful approval of a biosimilar product. Analytical comparability provides the foundation to this exercise. This paper presents data from such an exercise involving use of several orthogonal analytical tools for establishing analytical comparability. Granulocyte colony-stimulating factor (GCSF/Filgrastim) expressed in Escherichia coli has been selected as the model protein. The approach would be of interest to those engaged in development and commercialization of biosimilars.
authors.affiliation: Department of Chemical Engineering, Indian Institute of Technology, Hauz Khas, New Delhi, 110016, India, asrathore@biotechcmz.com.
authors.forename: Anurag S
authors.initials: AS
authors.lastname: Rathore
authors.forename: Rahul
authors.initials: R
authors.lastname: Bhambure
mesh_terms: D000595:Amino Acid Sequence; D059451:Biosimilar Pharmaceuticals / Q000737:chemistry* / Q000378:metabolism; D056148:Chromatography, Reverse-Phase; D002942:Circular Dichroism; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli / Q000235:genetics; D000069585:Filgrastim; D015870:Gene Expression; D016179:Granulocyte Colony-Stimulating Factor / Q000737:chemistry* / Q000235:genetics; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics
chemical_list: D059451:Biosimilar Pharmaceuticals; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim