Biosimilars vs Generics

Important distinctions between biosimilars and generics.

Unlike generic medicines in which the active ingredients are identical to the reference small–molecule drug, biosimilars will not be identical to the reference biologics.1

Due to processes associated with translating biologics from living cells in the laboratory to mass-production molecules, biosimilars can only be highly similar to the reference product they are designed to resemble; there is no way to make identical copies of biologics. A generic drug, by legal definition, is an exact copy of its reference medicine and must have the same chemical structure.


Why do the Differences Between Biosimilars and Generics Matter?

Because of the complexity of biosimilars, and the differentiation from smallmolecule drugs, medical practice with these products may differ from generics:2

  • Some biosimilars may have approval for all, a few, or only one indication of its reference product. Extrapolation to indications not studied for the biosimilar will be evaluated and approved by regulatory authorities on a product-by-product basis2

  • The US biosimilars pathway offers the opportunity for a drug manufacturer to demonstrate “interchangeability,” which is a separate standard than “biosimilarity” and requires additional evidence to achieve. To obtain this designation, a biosimilar must be expected to produce the same clinical result as the reference product and have undergone successful switching studies in which patients alternate between the reference product and biosimilar with no loss of safety, efficacy, or immunogenicity. An interchangeable biologic is one that the US Food and Drug Administration (FDA) has determined is safe for a pharmacist to substitute for the reference biologic product without the intervention of the prescriber3

Biosimilars differ from generics in complexity, manufacturing processes, and in the data needed to demonstrate similarity for approval1,4-9

PROPERTIES GENERICS BIOSIMILARS
SIZE Small Large
MOLECULAR WEIGHT ~150 Daltons ~150,000 Daltons
STRUCTURE Simple and well-defined Complex with potential structural variations
MANUFACTURING Predictable chemical process to make identical copy Specialized biological process to make similar copy
COMPLEXITY Easy to fully characterize Difficult to characterize
STABILITY Relatively stable Sensitive to storage and handling conditions
ADVERSE IMMUNE REACTION Lower potential Higher potential
MANUFACTURING QUALITY TESTS ≤ 50 ≥ 250
APPROVAL REQUIREMENTS Small clinical trials in healthy volunteers Large clinical trials in patients

References:

  1. Camacho LH, Frost CP, Abella E, Morrow PK, Whittaker S. Biosimilars 101: considerations for U.S. oncologists in clinical practice. Cancer Medicine. 2014;3:889-899.
  2. US Department of Health and Human Services. Scientific considerations in demonstrating biosimilarity to a reference product. Guidance for industry. http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm291128.pdf. Accessed November 23, 2016.
  3. Kozlowski S. US FDA Perspectives on Biosimilar Biological Products. Presented at: 2014 Biotechnology Technology Summit; June 13, 2014; Rockville, MD.
  4. Niederwieser D, Schmitz S. Biosimilar agents in oncology/haematology: from approval to practice. Eur J Haematol. 2011;86:277-288.
  5. Aspirin Prescribing Information, Bayer.
  6. Taltz (ixekizumab) Prescribing Information, Eli Lilly.
  7. Lybecker KM. Essay: when patents aren't enough: why biologics necessitate date exclusivity protection. William Mitchell Law Rev. 2014;40:1427-1442.
  8. EuropaBio. Guide to biological medicines: a focus on biosimilar medicines. European Medicines Agency. 2005.
  9. Alten R, Cronstein BN. Clinical trial development for biosimilars. Semin Arthritis Rheum. 2015;44:S2-S8.