title: Statistical Approaches to Assess Biosimilarity from Analytical Data.
abstract: Protein therapeutics have unique critical quality attributes (CQAs) that define their purity, potency, and safety. The analytical methods used to assess CQAs must be able to distinguish clinically meaningful differences in comparator products, and the most important CQAs should be evaluated with the most statistical rigor. High-risk CQA measurements assess the most important attributes that directly impact the clinical mechanism of action or have known implications for safety, while the moderate- to low-risk characteristics may have a lower direct impact and thereby may have a broader range to establish similarity. Statistical equivalence testing is applied for high-risk CQA measurements to establish the degree of similarity (e.g., highly similar fingerprint, highly similar, or similar) of selected attributes. Notably, some high-risk CQAs (e.g., primary sequence or disulfide bonding) are qualitative (e.g., the same as the originator or not the same) and therefore not amenable to equivalence testing. For biosimilars, an important step is the acquisition of a sufficient number of unique originator drug product lots to measure the variability in the originator drug manufacturing process and provide sufficient statistical power for the analytical data comparisons. Together, these analytical evaluations, along with PK/PD and safety data (immunogenicity), provide the data necessary to determine if the totality of the evidence warrants a designation of biosimilarity and subsequent licensure for marketing in the USA. In this paper, a case study approach is used to provide examples of analytical similarity exercises and the appropriateness of statistical approaches for the example data.
authors.affiliation: Elion Labs, 1450 Infinite Drive, Louisville, Colorado, 80027, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Burdick
authors.affiliation: Washington State University, PO Box 643113, Pullman, Washington, 99164, USA.
authors.forename: Todd
authors.initials: T
authors.lastname: Coffey
authors.affiliation: Oncobiologics Inc., 7 Clarke Drive, Cranbury, New Jersey, 08536, USA.
authors.forename: Hiten
authors.initials: H
authors.lastname: Gutka
authors.affiliation: West-Ward Pharmaceuticals (A Hikma Company), 300 Northfield Rd., Bedford, Ohio, 44146, USA.
authors.forename: Gyöngyi
authors.initials: G
authors.lastname: Gratzl
authors.affiliation: Pfizer Inc., 1 Burtt Road, Andover, Massachusetts, 01810, USA.
authors.forename: Hugh D
authors.initials: HD
authors.lastname: Conlon
authors.affiliation: CTH Analytical Consulting, 1 Broadway, Cambridge, Massachusetts, 02142, USA.
authors.forename: Chi-Ting
authors.initials: CT
authors.lastname: Huang
authors.affiliation: BioTechLogic, 717 Indian Rd, Glenview, Illinois, 60025, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Boyne
authors.affiliation: Coherus BioSciences, 4014 Camino Ranchero Ste A, Camarillo, California, 93012, USA. hkuehne@coherus.com.
authors.forename: Henriette
authors.identifier: 0000-0002-9802-9033
authors.initials: H
authors.lastname: Kuehne
mesh_terms: D059451:Biosimilar Pharmaceuticals / Q000592:standards*; D017277:Drug Approval; D004341:Drug Evaluation / Q000706:statistics & numerical data*; D004345:Drug Industry / Q000592:standards* / Q000639:trends; D011786:Quality Control; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D059451:Biosimilar Pharmaceuticals
keywords: analytical methods; comparability and AAPS commentary; protein therapeutics; similarity