EMA and HMA Issue Joint Statement on the Interchangeability of Biosimilars with Reference Medicinal Products and Equivalent Biosimilars

A biosimilar is a biological imitation medicinal product that is very similar to, but not identical to, another biological medicinal product that has already been authorised (the "reference medicine"). A biosimilar is not considered to be a generic biological medicine. This is mainly due to the fact that the natural variability and the more complex production of biological medicines do not permit an exact reproduction of their molecular microheterogeneity. Biological medicines contain active substances from a biological source, e.g. from living cells or organisms, and are often produced using state-of-the-art technologies. Most biological medicines currently in clinical use contain proteins or monoclonal antibodies as active ingredients.

The interchangeable use of biosimilars is already practised in many Member States. Interchangeability means that the reference medicinal product can be replaced by a biosimilar without changing the clinical effect on the patient.

The recently published opinion harmonises this approach in the EU. It provides more clarity for healthcare professionals and thus contributes to more patients having access to biological medicines across the EU.

"Our experts from the national medicines authorities of the EU Member States have thoroughly examined 86 authorised biosimilar medicinal products in the Committee for Medicinal Products for Human Use (CHMP) at the EMA over the past 15 years and have also monitored them after they have been authorised. Experience has shown that biosimilar medicines are comparable to and interchangeable with their reference products," said Klaus Cichutek, President of the Paul-Ehrlich-Institut, responsible for vaccines and biomedicines. "Monoclonal antibodies and their biosimilars enable effective treatments for diseases such as cancer, neurological diseases and autoimmune diseases such as rheumatoid arthritis," he added.

The statement drafted by the experts of the national medicines authorities of the EU in the CHMP's Biosimilar Working Party and in the Heads of Medicines Agencies Working Group of Biosimilars was approved by the Committee for Human Medicinal Products at the EMA, the CHMP on 22 July 2022.

The European position is based on the experience gained from clinical practice, where it has become common for doctors to switch their patients between different biological medicines. Approved biosimilars have shown similar efficacy, safety and immunogenicity compared to their reference medicinal products and the analysis of safety data from more than one million patient treatment years has not given rise to safety concerns. Therefore, experts from the EU medicines authorities consider that a biosimilar, if it is authorised in the EU, can be used instead of the reference product (or vice versa) or that it can be replaced by another biosimilar of the same reference product.

Decisions on substitution at the pharmacy level (i.e. dispensing one medicine instead of another, without consulting the prescribing physician) are not addressed here and are taken by the individual EU Member States.

Background

Safety, Immunogenicity and Interchangeability of Biosimilars

The short-term and long-term data on the safety and exchangeability of biosimilars from the field of monoclonal antibodies and fusion proteins with antibody components was analysed in an article published in 2021 in the scientific journal "Drugs". The most important findings of this study were presented in the Bulletin on Drug Safety, issue 4/2021 (see further information). This study and previous reports also confirmed that the concerns about safety and increased, unwanted immunogenicity in the event of a switch are unfounded. Additional systematic switch studies are therefore not required.

References

1. Kurki P et al.: BioDrugs 2017 Apr;31(2):83-91
2. Barbier L et al.: Frontiers in Medicine 2022, Vol 9, 820755
3. Kurki P et al.: Safety, Immunogenicity and Interchangeability of Biosimilar Monoclonal Antibodies and Fusion Proteins: A Regulatory Perspective. Drugs 2021 Nov;81(16):1881-1896
4. Ebbers H et al.: The safety of switching between therapeutic proteinsExpert Opinion Biol Ther. 2012;12:1473-1485
5. Biosimilars in the EU - Information guide for healthcare professionals (europa.eu)

Further Information

Biosimilar medicines can be interchanged
Statement on the scientific rationale supporting interchangeability of biosimilar medicines in the EU
Safety, immunogenicity and interchangeability of biosimilars - focus on monoclonal antibodies and fusion proteins with antibody moieties - Drug Safety Bulletin, Issue 4-2021