A biological drug revolution
Biological medicines (biologicals) contain active substances from a biological source, such as living cells or organisms2. Biological medicines are well-established in clinical practice and in many cases they are indispensable for the treatment of serious and chronic conditions such as diabetes, autoimmune diseases and cancer2. Compared with small chemical substances, biological medicines consist of large and often complex molecular structures2.
Monoclonal antibody (lgG1)
adjusted from Biologic Therapies:Optimizing Therapies Online Monograph Bioengineering and Biosimilars, Gregg Silverman, MD et al.
A biosimilar is a biological medicine highly similar to another already approved biological medicine (the ‘reference medicine’)3. Biosimilars are approved according to the same standards of pharmaceutical quality, safety and efficacy that apply to all biological medicines3.
No previous knowledge of safety and efficacy2
Builds on knowledge of safety and efficacy from years of clinical use with reference medicine2
Comparability studies only for manufacturing changes during development (e.g. producing larger batches for clinical trials)2
Comprehensive comparability studies with the reference medicine2
Conventional clinical trials to demonstrate efficacy and safety in all claimed therapeutic indications2
Comparative clinical trials to exclude clinically meaningful differences2
Positive benefit-risk balance mainly established on the basis of safety and efficacy studies in the intended population2
Positive benefit-risk balance based on demonstrating biosimilarity (using comparability studies)2
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The biosimilar has physical, chemical and biological properties highly similar to those of the reference medicine. There may be minor differences from the reference medicine which are not clinically meaningful in terms of safety or efficacy.2
No differences are expected in clinical performance.
Clinical studies that support the approval of a biosimilar confirm that any differences will not have an effect on safety and efficacy.2
Minor variability is only allowed when scientific evidence shows that it does not affect the safety and efficacy of the biosimilar. The range of variability allowed for a biosimilar is the same as that allowed between batches of the reference medicine. This is achieved with a robust manufacturing process to ensure that all batches of the medicine are of proven quality.2
Biosimilars are approved according to the same strict standards of quality, safety and efficacy that apply to any other medicine.2
The evidence acquired over 10 years of clinical experience shows that biosimilars approved through EMA can be used as safely and effectively in all their approved indications as other biological medicines and in many cases they are indispensable for the treatment of serious and chronic conditions such as diabetes, autoimmune diseases and cancers.2
The growth of the biosimilar market can provide multiple sourcing options for healthcare professionals and may provide broader patient access to high-quality and effective treatment options.2
Biosimilar competition can offer advantages to EU healthcare systems, as it is expected to improve patients’ access to safe and effective biological medicines with proven quality.2
The introduction of biosimilars on the market means more treatment options and increased competition. This competition may lead to high-value therapies at reduced prices. The savings obtained with biosimilars could free up healthcare funding for coverage of new medicines or other healthcare needs.2
Medicines are approved when studies on their pharmaceutical quality, safety and efficacy convincingly demonstrate that the medicine’s benefits outweigh the risks. For any biological medicine with a new active substance, a positive benefit-risk balance is determined mainly from evidence of safety and efficacy in pivotal trials in humans, supported by solid pharmaceutical quality data and non-clinical data.2
Adapted from Biologic Therapies:Optimizing Therapies Online Monograph Bioengineering and Biosimilars, Gregg Silverman, MD et al.
Guidance for the regulatory review and approval of biosimilars has been developed by the World Health Organization, the European Medicines Agency, Health Canada, the United States Food and Drug Administration (FDA), and several other national regulatory agencies.4
In contrast to that of an originator biopharmaceutical, for which phase II and large phase III clinical studies must be conducted, the development of a biosimilar is based on extensive physicochemical and functional characterization comparing it to its reference product.4
Animal toxicology studies, pharmacokinetic and pharmacodynamic studies and at least one clinical trial comparing the biosimilar to its reference product are then conducted. However, phase II clinical trials are not needed because the biosimilar must be administered at the same dose as its reference product.4
1. Hakan Mellstedt, EJC supplements 11, no. 3 (2013): 1–11.
2. Biosimilars in the EU, Information guide for healthcare professionals, European Medicines Agency, 2017.
3. Biosimilar medicines, European Medicines Agency, http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/general/general_content_001832.jsp&mid=WC0b01ac0580bb8fda, last access 06/2018.
4. Biologic Therapies:Optimizing Therapies Online Monograph Bioengineering and Biosimilars, Gregg Silverman, MD et al: http://www.clevelandclinicmeded.com/online/monograph/biologicsvi-optimizing-therapies/biosimilars.htm, last access 06/2018.