Biosimilars

Biosimilars: Development, Approval & Interchangeability

1. Definition & terminology

• A biosimilar ("similar biologic" in Indian regulatory parlance) is a biological/biotechnology-derived product that is highly similar to an already-licensed reference biologic (innovator product), with no clinically meaningful differences in terms of safety, purity, potency and efficacy, despite minor differences in clinically inactive components (Shargel 8e Ch.29, pp.26–27).
• The Indian term of art is "Similar Biologic", defined as a product "similar in terms of quality, safety and efficacy to an already authorized Reference Biologic" (CDSCO–DBT Similar Biologics 2016, §3 [CDSCO]).
• A biosimilar is, by definition, similar and NOT identical to its reference biologic — even two batches/lots of the same reference biologic are not identical to each other (Shargel 8e Ch.29, p.28).
• Regulators coined "biosimilar" to denote a follow-on biologic "as close as possible to a reference biologic, in an almost analogous way that a generic drug is versus a reference drug" — but the analogy is deliberately loose because the active substance cannot be proven identical (Shargel 8e Ch.29, p.26).
• Distinguish related "follow-on" terms (Shargel 8e Ch.29, pp.9–11):
  • Generic — follow-on of a small-molecule (chemically synthesised) drug; API is identical to the reference; demonstrates bioequivalence (BE).
  • Biosimilar / Similar Biologic — follow-on of a biologic; API is highly similar but not identical; demonstrates biosimilarity via a comparability exercise.
  • "Biobetter" (not a formal regulatory term) — an intentionally engineered improvement over the reference biologic (e.g. modified glycosylation, longer half-life); regulated as a new biologic / stand-alone product, NOT as a biosimilar.
  • A "supergeneric" is the small-molecule analogue of a biobetter — an improvement (less frequent dosing, combination) filed as a new drug application/submission, not a generic (Shargel 8e Ch.29, p.9).
• Reference biologic (CDSCO term) = the innovator's product approved after evaluation of a complete (full safety, efficacy, quality) dossier. Another similar biologic can NEVER serve as the reference (CDSCO 2016 §6.1 [CDSCO]).