The similarity question for biologicals and non-biological complex drugs

Eur J Pharm Sci. 2015 Aug 30;76:10-7. doi: 10.1016/j.ejps.2015.04.010. Epub 2015 Apr 23.


For small - low molecular weight - molecule medicines a robust regulatory system has evolved over the years. This system guarantees high and constant quality of our (generic) medicines. Pharmaceutical equivalence and bioequivalence assessment are the pillars under that system. But there are complex medicines where the question of equivalence is more challenging to answer. For biologicals the paradigm of similarity rather than equality (the emergence of 'biosimilars') was developed in the past decade. This has been a program where an evolutionary, science based approach has been chosen by the frontrunner regulatory body, the EMA, with a 'learn and confirm' character. In addition, there is another group of complex drugs, the non-biological complex drugs, NBCDs, where the generic paradigm can be challenged as well. The NBCDs are defined as: 1. consisting of a complex multitude of closely related structures; 2. the entire multitude is the active pharmaceutical ingredient; 3. the properties cannot be fully characterized by physicochemical analysis and 4. the consistent, tightly controlled manufacturing process is fundamental to reproduce the product. NBCDs encompass product families such as the glatiramoids, liposomes, iron-carbohydrate colloids and many candidates of the group of the upcoming nanoparticulate systems. Following the main principles of regulatory pathways for biologicals (with appropriate product-by-product adjustments), instead of that for small molecules, would be the more logical strategy for these NBCDs. The status and outstanding regulatory issues for biosimilars and NBCD-similars/follow on versions were discussed at a conference in Budapest, Hungary (October 2014) and this commentary touches upon the issues brought up in the presentations, deliberations and conclusions.

Keywords: Biologicals; Biosimilars; Glatiramoids; Iron–carbohydrate complexes; Liposomes; Nanomedicines; Non-biological complex drugs.

Publication types

  • Congress

MeSH terms

  • Animals
  • Biological Products / adverse effects
  • Biological Products / chemistry
  • Biological Products / classification
  • Biological Products / therapeutic use*
  • Biosimilar Pharmaceuticals / adverse effects
  • Biosimilar Pharmaceuticals / chemistry
  • Biosimilar Pharmaceuticals / classification
  • Biosimilar Pharmaceuticals / therapeutic use*
  • Drug Approval*
  • Drugs, Generic / adverse effects
  • Drugs, Generic / chemistry
  • Drugs, Generic / classification
  • Drugs, Generic / therapeutic use*
  • Guidelines as Topic
  • Humans
  • Molecular Structure
  • Patient Safety
  • Pharmaceutical Preparations* / chemistry
  • Pharmaceutical Preparations* / classification
  • Risk Assessment
  • Structure-Activity Relationship
  • Terminology as Topic
  • Therapeutic Equivalency


  • Biological Products
  • Biosimilar Pharmaceuticals
  • Drugs, Generic
  • Pharmaceutical Preparations