title: Recommendations regarding technical standards for follow-on biologics: comparability, similarity, interchangeability.
abstract: BACKGROUND
  Policy makers around the world are currently considering the creation of a regulatory pathway for follow-on biologics (FOB), which will have to account for the substantial technical challenges associated with FOB development. These challenges will likely involve more complexity than comparability assessments of process changes made by the same manufacturer. The history of industry-regulator comparability discussions helps explain why the same degree of testing and flexibility now applied to change-control within a manufacturer's own process, at this time, cannot be extrapolated to the observed and possibly unknown differences between two manufacturing processes that are independently developed by different (non-collaborating) parties.
  
  
  OBJECTIVE
  This commentary provides recommendations on the technical aspects that should be considered in the creation of an approval pathway for FOB products.
  
  
  CONCLUSIONS
  In the authors' view, analytical methodology in its current state cannot alone provide full assurance that the FOB is sufficiently similar to the innovator product. Moreover, the FOB manufacturer will not have access to the extensive knowledge accumulated by the innovator manufacturer from early development through marketing. Thus, extensive clinical evaluation will likely be necessary to provide assurance that the FOB is safe and efficacious. If such testing demonstrates the FOB is safe and efficacious per existing regulatory standards, the product should receive marketing approval as a 'similar' product. Since 'similarity' is a fundamentally different determination than establishing interchangeability between the two products, an interchangeability determination must be based on additional testing and market experience to ensure patient safety. Post-marketing surveillance of the FOB should be conducted to ensure that the approved molecule has similar clinical safety and efficacy as the innovator product, prior to any consideration of interchangeability.
authors.affiliation: Eli Lilly and Company, Lilly Research Laboratories, Indianapolis, IN 46285, USA. davis_gregory_c@lilly.com
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Davis
authors.forename: John M
authors.initials: JM
authors.lastname: Beals
authors.forename: Craig
authors.initials: C
authors.lastname: Johnson
authors.forename: Mark H
authors.initials: MH
authors.lastname: Mayer
authors.forename: Bruce I
authors.initials: BI
authors.lastname: Meiklejohn
authors.forename: Bruce H
authors.initials: BH
authors.lastname: Mitlak
authors.forename: Jody L
authors.initials: JL
authors.lastname: Roth
authors.forename: John K
authors.initials: JK
authors.lastname: Towns
authors.forename: Melissa
authors.initials: M
authors.lastname: Veenhuizen
mesh_terms: D001688:Biological Products / Q000493:pharmacokinetics / Q000592:standards*; D019411:Clinical Laboratory Techniques / Q000592:standards*; D017277:Drug Approval / Q000331:legislation & jurisprudence; D004341:Drug Evaluation / Q000331:legislation & jurisprudence / Q000592:standards; D006287:Health Planning Guidelines; D006801:Humans; D011358:Product Surveillance, Postmarketing / Q000592:standards*; D013810:Therapeutic Equivalency
chemical_list: D001688:Biological Products