By Carol Kirchhoff and Shefali Kakar
Biosimilar is the term used to describe a biological therapeutic that has been developed to be highly similar to a marketed biological therapeutic (reference) product that has exhausted its patent protection and is approved via a stringent regulatory pathway. By 2020, biologics that have exhausted their patents are estimated to represent over $80 billion in sales. Development of biosimilars potentially represents not only billions of dollars in health care savings but also a significant increase in patient access. This concept has been well recognized for small molecule reference products and their corresponding generics and is beginning to translate to large molecules with recently developed approval pathways globally.
Biosimilars have been approved and on the market in much of Europe since 2006. While these products have been proven to be safe and effective, their global acceptance varies. Many health care providers still have less confidence in a biosimilar than in a small molecule generic. This may, in part, be due to lack of understanding of how biosimilars are developed, as well as the currently marketed “intended copies” (also known as noncomparable biologics). Unlike biosimilars, developers of intended copies may conduct only limited similarity assessments against the reference product. The International Federation of Pharmaceutical Manufacturers & Associations (IFPMA) recently published a policy statement on noncomparable biotherapeutic products, in which the typical differences between an intended copy and a biosimilar in the depth and breadth of similarity assessments back to the originator are outlined.
Since pharmacokinetic (PK) equivalence can be a good surrogate for the efficacy and safety of a small molecule, a PK equivalence study is sufficient to confirm the extent and duration of the effect. The effect (safety and efficacy) of a biological therapeutic, however, is affected by not only the molecule but also possibly the formulation, impurities, and posttranslational modifications (e.g., glycosylation); therefore, the efficacy and safety of a protein therapeutic requires a more comprehensive assessment to confirm a similar clinical safety and efficacy profile. These include extensive analytical characterization and similarity assessments between the proposed biosimilar and the biological reference product, nonclinical in vivo and/or ex vivo studies, as well as safety and efficacy studies in patients or healthy subjects. The overall license application submission is not based on sequential hierarchy of assessments, but rather, the totality of evidence supporting biosimilarity.
The cover article in the May issue of the AAPS Newsmagazine examines multiple aspects of biosimilarity and how they are achieved. Read Achieving Biosimilarity through “the Totality of Evidence,” from the BIOTEC section, and then participate in the discussion point below.
What do you envision to be the greatest challenge in achieving biosimilarity?