title: Biosimilar monoclonal antibodies: preclinical and clinical development aspects.
abstract: Biological drugs and their originated biosimilars are large, highly complex molecules derived from living cells or organisms. Traditional medicines, by contrast, are usually simple molecules of low molecular weight, synthesised by chemical means. The distinct complexities and methods of manufacture create an important difference between biosimilars and conventional generic drugs: while chemical generics can be fully characterised as identical to the originator product, biosimilars cannot. In addition, biological therapies are inherently variable, creating unavoidable differences between even subsequent batches of the same product. An expiring patent does not necessarily mean that the manufacturing process of the originator product becomes available to the biosimilar developers (for instance, the relevant cell line clone and growth medium). Therefore, it cannot be guaranteed that biosimilar products are identical to their reference product on a molecular level. This difference has important implications for the regulation and licensing of biosimilars. While conventional generic drugs require only a limited comparison and demonstration of identical chemical structure to the reference product, biosimilars require far more rigorous testing. In general, there must be a thorough comparison of structural and functional characteristics between biosimilar and originator drug. Stepwise nonclinical in vitro and in vivo approaches are recommended to evaluate the similarity of both drugs and any identified micro-heterogeneities must then be assessed for their impact on safety and clinical performance. Subsequently, clinical pharmacokinetic (PK) studies need to be performed in order to demonstrate a similar PK profile, prior to conducting clinical efficacy trials.
authors.affiliation: iMed-Research Institute of Medicines, Faculdade de Farmácia da Universidade de Lisboa, Lisboa, Portugal. jgoncalv@ff.ulisboa.pt.
authors.forename: João
authors.initials: J
authors.lastname: Gonçalves
authors.affiliation: Rheumatology Unit, Hospital Ortopédico de Sant'Ana, SCML; and Institute of Microbiology, Faculdade de Medicina da Universidade de Lisboa, Portugal.
authors.forename: Filipe
authors.initials: F
authors.lastname: Araújo
authors.affiliation: Research Laboratory and Division of Clinical Rheumatology, Department of Internal Medicine, University of Genova, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cutolo
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa and Rheumatology Department, Hospital de Santa Maria, Lisbon Academic Medical Centre, Portugal.
authors.forename: João Eurico
authors.initials: JE
authors.lastname: Fonseca
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000592:standards / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000592:standards / Q000627:therapeutic use*; D059451:Biosimilar Pharmaceuticals / Q000009:adverse effects / Q000493:pharmacokinetics / Q000592:standards / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D017277:Drug Approval / Q000379:methods*; D004353:Drug Evaluation, Preclinical; D016568:Drugs, Generic / Q000009:adverse effects / Q000592:standards / Q000627:therapeutic use*; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000592:standards / Q000627:therapeutic use*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D010330:Patents as Topic; D061214:Patient Safety; D011786:Quality Control; D012216:Rheumatic Diseases / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D018570:Risk Assessment; D013810:Therapeutic Equivalency; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D059451:Biosimilar Pharmaceuticals; D016568:Drugs, Generic; D005765:Gastrointestinal Agents