mAbxience | Biosimilar characterization


Biologic medicine

Biological products are a diverse category of products and are generally large, complex molecules. These products may be produced through biotechnology in a living system, such as a microorganism, plant cell, or animal cell, and are often more difficult to characterize than small molecule drugs. 1
The nature of biological products, including the inherent variations that can result from the manufacturing process, can present challenges in characterizing and manufacturing these products that often do not exist in the development of small molecule drugs. Slight differences between manufactured lots of the same biological product (i.e., acceptable within-product variations) are normal and expected within the manufacturing process. 1

Biosimilar medicine

A biosimilar is a biological medicinal product that contains a version of the active substance of an already authorized original biological medicinal product (reference medicinal product) in the European Economic Area (EEA). 2
Similarity to the reference medicinal product in terms of quality characteristics, biological activity, safety and efficacy based on a comprehensive comparability exercise needs to be established.2

Unlike generic medicines, manufactured through chemical synthesis, biologic medicines contain one or more active principles produced or derived from a biologic source, include a wide range of products like vaccines, allergens or recombinant proteins. 3
Most biological medicines in current clinical use contain active substances made of proteins. These can differ in size and structural complexity, from simple proteins like insulin or growth hormone to more complex ones such as coagulation factors or monoclonal antibodies (figure 1). 4
The manufacture of biological medicines tends to be more complex than for chemically-derived molecules. Most biological medicines are made by biotechnology, often using sophisticated cell systems and recombinant DNA technology.4

Figure 1. Examples of types of proteins in biological medicines approved in the EU4

Biosimilars are biological medicines manufactured through biotechnology and which have demonstrated their equivalence in quality, efficacy and safety to the reference product.3,4
One of the key differences between biosimilars and reference biologics is how clinical trials operate during the development process. With biologics, the goal of trials is to ascertain the clinical efficacy of the product. With biosimilars the goal is to demonstrate that the product is comparable to the reference biologic product in terms of its pharmacokinetics, pharmacodynamics, safety and immunogenicity. In other words, the goal is to demonstrate the scientific concept of comparability to show that minor differences between the two do not have a relevant impact on the final therapeutic result. 3

Figure 2. Comparison of data requirements of approval of a biosimilar versus the reference medicine4


Figure 3. Main differences generic, biologic and biosimilar (Figure combined from different resources. mAbxience)3,9


  1. Food and Drug Administration. Available on:
  2. European Medicines Agency: Guideline on similar biological medicinal products. EMEA/CHMP/437/04 Rev. 1. Available on:
  3. BioSim. Guía de medicamentos biosimilares para médicos. 2017. ISBN: 978-84-697-2838-3. Available on:
  4. Biosimilars in the EU. Information guide for healthcare professionals. 2019.
  5. Halimi V. et all., Clinical and Regulatory Concerns of Biosimilars: A Review of Literature. Int. J. Environ. Res. Public Health 2020, 17, 5800; doi:10.3390/ijerph17165800.
  6. Wouters OJ, McKee M, Luyten J. Estimated Research and Development Investment Needed to Bring a New Medicine to Market, 2009-2018. JAMA. 2020;323(9):844–853. doi:10.1001/jama.2020.1166.
  7. Agbogbo F. et all., Current perspectives on biosimilars. Journal of Industrial Microbiology & Biotechnology (2019) 46:1297–1311.
  8. Windisch J. et all. Biosimilars versus originators: similarities and differences from development to approval. Int. J. Clin. Rheumatol. (2015) 10(6), 00–00.
  9. Covance guideline. Continuous safety monitoring: risk management plan including Pharmacovigilance and post-approval studies. 2020.