title: Comparability and biosimilarity: considerations for the healthcare provider.
abstract: BACKGROUND
  Healthcare providers use recombinant biologics such as monoclonal antibodies to treat a variety of serious illnesses. Manufacturing of approved biotechnology products is complex, and the quality of the resulting biologic is dependent on careful control of process inputs and operating conditions. Biosimilars, which are similar but not identical to innovator biologics, are entering regulatory evaluation, approval, and marketing in regions with biosimilar approval pathways.
  This article describes the evaluation and potential impact of manufacturing process changes and biosimilar product development, and explores the similarities and distinctions between the two. Regulatory agencies generally require a comparability exercise following a manufacturing process change. This comparability is focused primarily on analytical characterization of the approved product before and after the manufacturing process change, with non-clinical and clinical confirmation required when determined necessary. When developing a biosimilar, the manufacturer does not have access to key information including the innovator manufacturer's cell line, cell culture conditions, purification procedures, and fill and finish processes. Further, the biosimilar manufacturer does not have access to information about the innovator manufacturer's product development history, including knowledge about the quality attributes of lots used in non-clinical and clinical development. We define the biosimilar manufacturer's lack of information as the knowledge gap. As a result, a biosimilarity exercise to compare a biosimilar to an approved innovator biologic requires a rigorous evaluation to ensure the safety and efficacy of the biosimilar.
  
  
  CONCLUSIONS
  Given the knowledge gap under which biosimilars are developed, data to establish biosimilarity should go beyond a simple comparability exercise.
authors.affiliation: Drug Product Development, Amgen Inc., Thousand Oaks, CA 91320, USA. jaymil@amgen.com
authors.forename: Jaymi F
authors.initials: JF
authors.lastname: Lee
authors.forename: Jason B
authors.initials: JB
authors.lastname: Litten
authors.forename: Gustavo
authors.initials: G
authors.lastname: Grampp
mesh_terms: D001688:Biological Products / Q000627:therapeutic use; D059451:Biosimilar Pharmaceuticals / Q000627:therapeutic use*; D017277:Drug Approval; D005060:Europe; D006282:Health Personnel; D006801:Humans; D008954:Models, Biological; D010818:Practice Patterns, Physicians'; D013810:Therapeutic Equivalency
chemical_list: D001688:Biological Products; D059451:Biosimilar Pharmaceuticals