title: Differentiating biosimilarity and comparability in biotherapeutics.
abstract: The manufacture of biologics is a complex process involving numerous steps. Over time, differences may arise as a result of planned changes to the manufacturing processes of a biologic from the same manufacturer. Comparability is the regulatory process that outlines the scope of an assessment required of an already licensed biologic after a manufacturing process change made by the same manufacturer. The aim of a comparability assessment is to demonstrate that any pre-manufacturing and post-manufacturing changes have no adverse impact on quality, safety, and efficacy of the biologic. A comparability assessment is distinct from a biosimilarity assessment, which involves extensive assessment of a biologic that is highly similar to the originator (reference product) in terms of quality, safety, and efficacy. The US Food and Drug Administration, European Medicines Agency, and World Health Organization have applied the fundamental comparability concepts into their respective biosimilarity guidance documents. In this review, we examine the rationale behind the distinct, highly regulated approval processes governing changes that may occur over time to an originator biologic due to planned manufacturing changes (as described by a comparability exercise) and those that outline the approval of a proposed biosimilar drug, based on its relationship with the reference product (biosimilarity evaluations).
authors.affiliation: Federal University of Paraná, Curitiba, PR, Brazil.
authors.forename: Valderilio
authors.initials: V
authors.lastname: Azevedo
authors.affiliation: Pfizer Biotech, Dublin, Ireland.
authors.forename: Brian
authors.initials: B
authors.lastname: Hassett
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa and Hospital de Santa Maria, Lisbon Medical Academic Medical Centre, Lisbon, Portugal.
authors.forename: João Eurico
authors.initials: JE
authors.lastname: Fonseca
authors.affiliation: Division of Rheumatology, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Atsumi
authors.affiliation: Pfizer Inc., New York, NY, USA.
authors.forename: Javier
authors.initials: J
authors.lastname: Coindreau
authors.affiliation: Pfizer Inc., New York, NY, USA.
authors.forename: Ira
authors.initials: I
authors.lastname: Jacobs
authors.affiliation: Pfizer Inc., Collegeville, PA, USA.
authors.forename: Ehab
authors.initials: E
authors.lastname: Mahgoub
authors.affiliation: Pfizer Worldwide Safety and Regulatory, EU and International Regulatory Policy, Dublin, Ireland.
authors.forename: Julie
authors.initials: J
authors.lastname: O'Brien
authors.affiliation: Pfizer Inc., Collegeville, PA, USA.
authors.forename: Ena
authors.initials: E
authors.lastname: Singh
authors.affiliation: Pfizer Biotech, Andover, MA, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Vicik
authors.affiliation: Pfizer Biotech, Dublin, Ireland. Brian.Fitzpatrick@pfizer.com.|Pfizer Biotech, Global Supply, Grange Castle, Dublin 22, Ireland. Brian.Fitzpatrick@pfizer.com.
authors.forename: Brian
authors.initials: B
authors.lastname: Fitzpatrick
mesh_terms: D059451:Biosimilar Pharmaceuticals / Q000737:chemistry* / Q000627:therapeutic use*; D017277:Drug Approval; D055808:Drug Discovery / Q000331:legislation & jurisprudence / Q000379:methods*; D004345:Drug Industry / Q000331:legislation & jurisprudence / Q000639:trends; D006801:Humans; D012016:Reference Values; D013810:Therapeutic Equivalency; D014481:United States; D014486:United States Food and Drug Administration; D014944:World Health Organization
chemical_list: D059451:Biosimilar Pharmaceuticals
keywords: Biosimilar; Biosimilarity; Biotherapeutics; Comparability